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Sample records for neurodegenerative disorders affecting

  1. [Sleep in neurodegenerative disorders].

    Science.gov (United States)

    Happe, S; Mayer, G

    2006-10-01

    Neurodegenerative disorders are a group of heterogeneous, progressive disorders of varying etiology that affect one or more systems. They occur predominantly at older age, during which the structure and amount of sleep undergo changes. Neurodegenerative processes cause structural changes of the sleep/wake generators in the brainstem which result in disorders such as daytime sleepiness, insomnia, sleep-related movement and breathing disturbances, and disorders of the circadian rhythms. Some sleep disorders manifest years before the onset of neurodegenerative disorders and may serve as predictors. Polysomnography shows sleep fragmentation, tonic or phasic movements of the extremities, alteration of respiratory muscles, reduced slow wave sleep, REM sleep absence or without muscle atonia, increased arousal or wake activity, epileptiform EEG activity, and changes in sleep-related breathing. Very frequently, REM sleep behaviour disorder is associated with neurodegenerative disorders. In this overview we present symptoms, pathophysiology, and polysomnographic findings of sleep disorders in prevalent neurodegenerative disorders.

  2. Sleep disorders in neurodegenerative diseases.

    Science.gov (United States)

    Raggi, A; Ferri, R

    2010-11-01

    The aim of this review is to provide data on sleep disturbances in three categories of neurodegenerative disorders: synucleinopathies, tauopathies, and other diseases (this heterogeneous group includes also spinocerebellar degeneration and amyotrophic lateral sclerosis). Analysing and knowing sleep disorders in neurodegenerative diseases may offer important insights into the pathomechanism of some of these diseases and calls attention to the still insufficiently known 'sleep neurology'. The identification of sleep disorders in some neurodegenerative conditions may make their diagnosis easier and earlier; for example, rapid eye movements sleep behaviour disorder may precede any other clinical manifestation of synucleinopathies by more than 10 years. © 2010 The Author(s). Journal compilation © 2010 EFNS.

  3. Molecular diagnostics of neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Megha eAgrawal

    2015-09-01

    Full Text Available Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer’s and Parkinson’s disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

  4. Endocannabinoid system in neurodegenerative disorders.

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    Basavarajappa, Balapal S; Shivakumar, Madhu; Joshi, Vikram; Subbanna, Shivakumar

    2017-09-01

    Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well-defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may proceed concurrently or successively, and they differ among cell types at different developmental stages in distinct brain regions. The endocannabinoid system, which involves cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), endogenous cannabinoids and the enzymes that catabolize these compounds, has been shown to contribute to the development of NDDs in several animal models and human studies. In this review, we discuss the functions of the endocannabinoid system in NDDs and converse the therapeutic efficacy of targeting the endocannabinoid system to rescue NDDs. © 2017 International Society for Neurochemistry.

  5. Sleep in Neurodevelopmental and Neurodegenerative Disorders.

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    Kotagal, Suresh

    2015-06-01

    There is a close relationship between sleep and childhood neurodevelopmental/neurodegenerative disorders. Understanding the sleep issues may provide greater insight into pathophysiology and treatment of these disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Neurobiology of sleep disturbances in neurodegenerative disorders.

    Science.gov (United States)

    Gagnon, J-F; Petit, D; Latreille, V; Montplaisir, J

    2008-01-01

    This review presents sleep disturbances and their underlying pathophysiology in three categories of neurodegenerative disorders namely tauopathies, synucleinopathies, and Huntington's disease (HD) and prion-related diseases. Sleep abnormalities are a major and early feature of neurodegenerative disorders, especially for synucleinopathies, HD and prion-related diseases, in which the sleep-related brainstem regions are severely altered and impaired sooner than in most of the tauopathies. In synucleinopathies, HD and prion-related diseases, specific sleep disturbances, different from those observed in tauopathies, are considered as core manifestations of the disease and in some cases, as preclinical signs. For this reason, the evaluation of sleep components in these neurodegenerative disorders may be useful to make a diagnosis and to assess the efficacy of pharmacotherapy. Since sleep disruption may occur early in the course of neurodegeneration, sleep disturbance may serve as groundwork to study the efficacy of neuroprotective agents to prevent or delay the development of a full-blown neurodegenerative disorder. The cause of sleep disturbances in neurodegenerative disorders may be attributed to several factors, including age-related modifications, symptoms of the disease, comorbid conditions and the neurodegenerative process itself.

  7. Recent Patent Advances For Neurodegenerative Disorders And Its Treatment.

    Science.gov (United States)

    Kumar, Bhavna; Sharma, Deepika

    2017-10-10

    Neurodegenerative disorders are one of the common diseases that affect our society with tremendous medical and financial burdens. As a whole, neurodegeneration affects individuals of all ages, but becomes increasingly frequent with age, coming to affect a very large share of our elderly population which is severely affecting the patient, caregivers, and enormously increasing the financial burden of the nation. These diseases share a very complex nature, which often result from combined genetic, environment and pathogenic factors. Various challenges are faced by the scientific community that researches on the pathogenesis and the therapy of neurodegenerative disorder. The review has been analysed for recent patent documents and treatment approaches for neurodegenerative disorders. The study design is based on updating the international and national literatures and an exhaustive patent search and compiling of various patented documents for the treatment of neurodegenerative disorders (EP2282779 A1, US20110229555 A1) to provide information in the state of technological innovation in terms of research and development. In the present review, the authors described various neurodegenerative diseases, there treatment strategies and emphasized on various patented approaches for age-related neurodegenerative disorders such as New therapeutic approaches for treating Alzheimer disease and related disorders through a modulation of cell stress response EP2282779 A1, through combined therapies that modulate angiogenesis US20120058992 A1. The review will attract the interest of academics, researchers, students and pharmaceutical companies in the recent on-going activities in neurodegenerative disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Genetically modified pig models for neurodegenerative disorders.

    Science.gov (United States)

    Holm, Ida E; Alstrup, Aage Kristian Olsen; Luo, Yonglun

    2016-01-01

    Increasing incidence of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease has become one of the most challenging health issues in ageing humans. One approach to combat this is to generate genetically modified animal models of neurodegenerative disorders for studying pathogenesis, prognosis, diagnosis, treatment, and prevention. Owing to the genetic, anatomic, physiologic, pathologic, and neurologic similarities between pigs and humans, genetically modified pig models of neurodegenerative disorders have been attractive large animal models to bridge the gap of preclinical investigations between rodents and humans. In this review, we provide a neuroanatomical overview in pigs and summarize and discuss the generation of genetically modified pig models of neurodegenerative disorders including Alzheimer's diseases, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and ataxia-telangiectasia. We also highlight how non-invasive bioimaging technologies such as positron emission tomography (PET), computer tomography (CT), and magnetic resonance imaging (MRI), and behavioural testing have been applied to characterize neurodegenerative pig models. We further propose a multiplex genome editing and preterm recloning (MAP) approach by using the rapid growth of the ground-breaking precision genome editing technology CRISPR/Cas9 and somatic cell nuclear transfer (SCNT). With this approach, we hope to shorten the temporal requirement in generating multiple transgenic pigs, increase the survival rate of founder pigs, and generate genetically modified pigs that will more closely resemble the disease-causing mutations and recapitulate pathological features of human conditions. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. REM behaviour disorder and neurodegenerative diseases.

    Science.gov (United States)

    Zanigni, Stefano; Calandra-Buonaura, Giovanna; Grimaldi, Daniela; Cortelli, Pietro

    2011-12-01

    Rapid-eye movement (REM) sleep behaviour disorder (RBD) is an REM sleep parasomnia characterized by enactment of dream content during REM sleep associated with loss of muscle atonia. RBD can be either idiopathic or secondary to drugs or other diseases. The best recognized association is with neurodegenerative diseases, namely alpha-synucleinopathies. RBD may represent the first feature of neurodegeneration and can be considered an early marker of these disorders. This review describes the main clinical, pathogenetic, and therapeutic features of RBD, pointing to its association with neurodegenerative diseases and emphasizing the clinical and prognostic implications. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Sleep-disordered breathing in neurodegenerative diseases.

    Science.gov (United States)

    Gaig, Carles; Iranzo, Alex

    2012-04-01

    Sleep disorders are common in neurodegenerative diseases such as Parkinson's disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), hereditary ataxias, and Alzheimer's disease (AD). Type, frequency, and severity of sleep disturbances vary depending on each of these diseases. Cell loss of the brainstem nuclei that modulates respiration, and dysfunction of bulbar and diaphragmatic muscles increase the risk for sleep-disordered breathing (SDB) in MSA and ALS. The most relevant SDB in MSA is stridor, whereas in ALS nocturnal hypoventilation due to diaphragmatic weakness is the most common sleep breathing abnormality. Stridor and nocturnal hypoventilation are associated with reduced survival in MSA and ALS. In contrast, sleep apnea seems not to be more prevalent in PD than in the general population. In some PD patients, however, coincidental obstructive sleep apnea (OSA) can be the cause of excessive daytime sleepiness (EDS). SDB can also occur in some hereditary ataxias, such as stridor in spinocerebellar ataxia type 3 (Machado-Joseph disease). The presence of concomitant OSA in patients with AD can have deleterious effects on nocturnal sleep, may result in EDS, and might aggravate the cognitive deficits inherent to the disease. However, whether OSA is more frequent in patients with AD than in the general population is uncertain. Recognition of SDB in neurodegenerative disease is important because they are associated with significant morbidity and potential effective treatments are available.

  11. Ghrelin and Neurodegenerative Disorders-a Review.

    Science.gov (United States)

    Shi, Limin; Du, Xixun; Jiang, Hong; Xie, Junxia

    2017-03-01

    Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor 1a (GHS-R1a), is a gut-derived, orexigenic peptide hormone that primarily regulates growth hormone secretion, food intake, and energy homeostasis. With the wide expression of GHS-R1a in extra-hypothalamic regions, the physiological role of ghrelin is more extensive than solely its involvement in metabolic function. Ghrelin has been shown to be involved in numerous higher brain functions, such as memory, reward, mood, and sleep. Some of these functions are disrupted in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). This link between ghrelin and these neurodegenerative diseases is supported by numerous studies. This review aims to provide a comprehensive overview of the most recent evidence of the novel neuromodulatory role of ghrelin in PD, AD, and HD. Moreover, the changes in circulating and/or central ghrelin levels that are associated with disease progression are also postulated to be a biomarker for clinical diagnosis and therapy.

  12. Localization of Axonal Motor Molecules Machinery in Neurodegenerative Disorders

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    Fulvio Florenzano

    2012-04-01

    Full Text Available Axonal transport and neuronal survival depend critically on active transport and axon integrity both for supplying materials and communication to different domains of the cell body. All these actions are executed through cytoskeleton, transport and regulatory elements that appear to be disrupted in neurodegenerative diseases. Motor-driven transport both supplies and clears distal cellular portions with proteins and organelles. This transport is especially relevant in projection and motor neurons, which have long axons to reach the farthest nerve endings. Thus, any disturbance of axonal transport may have severe consequences for neuronal function and survival. A growing body of literature indicates the presence of alterations to the motor molecules machinery, not only in expression levels and phosphorylation, but also in their subcellular distribution within populations of neurons, which are selectively affected in the course of neurodegenerative diseases. The implications of this altered subcellular localization and how this affects axon survival and neuronal death still remain poorly understood, although several hypotheses have been suggested. Furthermore, cytoskeleton and transport element localization can be selectively disrupted in some disorders suggesting that specific loss of the axonal functionality could be a primary hallmark of the disorder. This can lead to axon degeneration and neuronal death either directly, through the functional absence of essential axonal proteins, or indirectly, through failures in communication among different cellular domains. This review compares the localization of cytoskeleton and transport elements in some neurodegenerative disorders to ask what aspects may be essential for axon survival and neuronal death.

  13. Comparative Incidence of Conformational, Neurodegenerative Disorders.

    Directory of Open Access Journals (Sweden)

    Jesús de Pedro-Cuesta

    Full Text Available The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs.We identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD. We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD forms, amyotrophic lateral sclerosis (ALS, and sporadic rapidly progressing neurodegenerative dementia (sRPNDd. For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined.Based on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from ≤1.5 for sRPNDd, different CJD forms and Huntington's disease (HD, to 1589 and 2589 for AMD and Alzheimer's disease (AD respectively. Age-specific profiles varied from (a symmetrical, inverted V-shaped curves for low incidences to (b those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20-24 to ≥90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration.These results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to incidence magnitude and survival might

  14. Connected Speech in Neurodegenerative Language Disorders: A Review.

    Science.gov (United States)

    Boschi, Veronica; Catricalà, Eleonora; Consonni, Monica; Chesi, Cristiano; Moro, Andrea; Cappa, Stefano F

    2017-01-01

    Language assessment has a crucial role in the clinical diagnosis of several neurodegenerative diseases. The analysis of extended speech production is a precious source of information encompassing the phonetic, phonological, lexico-semantic, morpho-syntactic, and pragmatic levels of language organization. The knowledge about the distinctive linguistic variables identifying language deficits associated to different neurodegenerative diseases has progressively improved in the last years. However, the heterogeneity of such variables and of the way they are measured and classified limits any generalization and makes the comparison among studies difficult. Here we present an exhaustive review of the studies focusing on the linguistic variables derived from the analysis of connected speech samples, with the aim of characterizing the language disorders of the most prevalent neurodegenerative diseases, including primary progressive aphasia, Alzheimer's disease, movement disorders, and amyotrophic lateral sclerosis. A total of 61 studies have been included, considering only those reporting group analysis and comparisons with a group of healthy persons. This review first analyzes the differences in the tasks used to elicit connected speech, namely picture description, story narration, and interview, considering the possible different contributions to the assessment of different linguistic domains. This is followed by an analysis of the terminologies and of the methods of measurements of the variables, indicating the need for harmonization and standardization. The final section reviews the linguistic domains affected by each different neurodegenerative disease, indicating the variables most consistently impaired at each level and suggesting the key variables helping in the differential diagnosis among diseases. While a large amount of valuable information is already available, the review highlights the need of further work, including the development of automated methods, to

  15. Transmission of Neurodegenerative Disorders Through Blood Transfusion

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Hjalgrim, Henrik; Rostgaard, Klaus

    2016-01-01

    : Multivariable Cox regression models were used to estimate hazard ratios for dementia of any type, Alzheimer disease, and Parkinson disease in patients receiving blood transfusions from donors who were later diagnosed with any of these diseases versus patients who received blood from healthy donors. Whether...... excess occurrence of neurodegenerative disease occurred among recipients of blood from a subset of donors was also investigated. As a positive control, transmission of chronic hepatitis before and after implementation of hepatitis C virus screening was assessed. RESULTS: Among included patients, 2.......9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy...

  16. Interaction between -Synuclein and Other Proteins in Neurodegenerative Disorders

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    Kurt A. Jellinger

    2011-01-01

    Full Text Available Protein aggregation is a common characteristic of many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, evidence increasingly indicates considerable overlap between synucleinopathies and tauopathies or other protein-misfolding diseases. Inclusions, characteristics of these disorders, also occurring in other neurodegenerative diseases, suggest interactions of pathological proteins engaging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Parkinson and Alzheimer diseases have confirmed correlations/overlaps between these and other neurodegenerative disorders. The synergistic effects of α-synuclein, hyperphosphorylated tau, amyloid-β, and other pathologic proteins, and the underlying molecular pathogenic mechanisms, including induction and spread of protein aggregates, are critically reviewed, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, although the etiology of most of these processes is still mysterious.

  17. Ghrelin: a link between ageing, metabolism and neurodegenerative disorders

    NARCIS (Netherlands)

    Stoyanova, Irina

    2014-01-01

    Along with the increase in life expectancy over the last century comes the increased risk for development of age-related disorders, including metabolic and neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. These chronic disorders share two main characteristics:

  18. The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

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    Yajin Liao

    2017-02-01

    Full Text Available The mitochondrial calcium uniporter (MCU—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP; however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.

  19. Global warming and neurodegenerative disorders: speculations on their linkage.

    Science.gov (United States)

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

  20. Melatonin for Sleep Disorders in Patients with Neurodegenerative Diseases.

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    Trotti, Lynn Marie; Karroum, Elias G

    2016-07-01

    In patients with neurodegenerative diseases, sleep disorders are common; they impair the quality of life for patients and caregivers and are associated with poorer clinical outcomes. Melatonin has circadian, hypnotic, and free radical-scavenging effects, and preclinical data suggest benefits of melatonin on neurodegeneration. However, randomized, controlled trials of melatonin in patients with neurodegenerative diseases have not shown strong effects. Trials in Alzheimer's patients demonstrate a lack of benefit on sleep quantity. Subjective measures of sleep quality are mixed, with possible symptomatic improvements seen only on some measures or at some time points. Benefits on cognition have not been observed across several studies. In Parkinson's patients, there may be minimal benefit on objective sleep measures, but a suggestion of subjective benefit in few, small studies. Effective treatments for the sleep disorders associated with neurodegenerative diseases are urgently needed, but current data are insufficient to establish melatonin as such a treatment.

  1. DNA triplex structures in neurodegenerative disorder, Friedreich's ...

    Indian Academy of Sciences (India)

    2012-06-25

    Jun 25, 2012 ... 3. DNA triplet repeat expansions in human genome. In the beginning of the last decade, expanded DNA-trinucleotide repeats in genes were identified as unstable and responsible for a large number of neurological disorders like FRDA, fragile X syndrome, spinocerebellar ataxia and muscular dystrophy.

  2. Neurotrophin Therapy of Neurodegenerative Disorders with Mitochondrial Dysfunction

    Science.gov (United States)

    2007-09-01

    TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Table of Contents 1 Narrative...neurodegenerative disorders including Wernicke -Korsakoff syndrome (reviewed in Martin et al., 2005). 2. Results At E15.5, Ts16 brains are slightly

  3. Predictive gene testing for Huntington disease and other neurodegenerative disorders.

    Science.gov (United States)

    Wedderburn, S; Panegyres, P K; Andrew, S; Goldblatt, J; Liebeck, T; McGrath, F; Wiltshire, M; Pestell, C; Lee, J; Beilby, J

    2013-12-01

    Controversies exist around predictive testing (PT) programmes in neurodegenerative disorders. This study sets out to answer the following questions relating to Huntington disease (HD) and other neurodegenerative disorders: differences between these patients in their PT journeys, why and when individuals withdraw from PT, and decision-making processes regarding reproductive genetic testing. A case series analysis of patients having PT from the multidisciplinary Western Australian centre for PT over the past 20 years was performed using internationally recognised guidelines for predictive gene testing in neurodegenerative disorders. Of 740 at-risk patients, 518 applied for PT: 466 at risk of HD, 52 at risk of other neurodegenerative disorders - spinocerebellar ataxias, hereditary prion disease and familial Alzheimer disease. Thirteen percent withdrew from PT - 80.32% of withdrawals occurred during counselling stages. Major withdrawal reasons related to timing in the patients' lives or unknown as the patient did not disclose the reason. Thirty-eight HD individuals had reproductive genetic testing: 34 initiated prenatal testing (of which eight withdrew from the process) and four initiated pre-implantation genetic diagnosis. There was no recorded or other evidence of major psychological reactions or suicides during PT. People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  4. Nanomedicine and neurodegenerative disorders: so close yet so far.

    Science.gov (United States)

    Tosi, Giovanni; Vandelli, Maria Angela; Forni, Flavio; Ruozi, Barbara

    2015-07-01

    This editorial provides an overview of the main advantages of the use of nanomedicine-based approach for innovation in the treatment of neurodegenerative diseases. Besides these aspects, a critical analysis on the main causes that slow the application of nanomedicine to brain disorders is given along with the identification of possible solutions and possible interventions. Better communication between the main players of research in this field and a detailed understanding of the most critical issues to be addressed should help in defining future directions towards the improvement and, finally, the clinical application of nanomedicine to neurodegenerative diseases.

  5. Evidence-based therapy for sleep disorders in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    LIU Ling

    2013-08-01

    Full Text Available Objective To evaluate the effectiveness of the treatments for sleep disorders in neurodegenerative diseases so as to provide the best therapeutic regimens for the evidence-based treatment. Methods Search PubMed, MEDLINE, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases with "sleep disorder or sleep disturbance", "neurodegenerative diseases", "Parkinson's disease or PD", "Alzheimer's disease or AD", "multiple system atrophy or MSA" as retrieval words. The quality of the articles were evaluated with Jadad Scale. Results A total of 35 articles, including 2 systematic reviews, 5 randomized controlled trials, 13 clinical controlled trials, 13 case series and 2 epidemiological investigation studies were included for evaluation, 13 of which were high grade and 22 were low grade articles. Clinical evidences showed that: 1 advice on sleep hygiene, careful use of dopaminergic drugs and hypnotic sedative agents should be considered for PD. Bright light therapy (BLT may improve circadian rhythm sleep disorders and clonazepam may be effective for rapid eye movement sleep behavior disorder (RBD. However, to date, very few controlled studies are available to make a recommendation for the management of sleep disorders in PD; 2 treatments for sleep disorders in AD include drug therapy (e.g. melatonin, acetylcholinesterase inhibitors, antipsychotic drugs, antidepressants and non-drug therapy (e.g. BLT, behavior therapy, but very limited evidence shows the effectiveness of these treatments; 3 the first line treatment for sleep-related breathing disorder in MSA is nasal continuous positive airway pressure (nCPAP, and clonazepam is effective for RBD in MSA; 4 there is rare evidence related to the treatment of sleep disorders in dementia with Lewy body (DLB and amyotrophic lateral sclerosis (ALS. Conclusion Evidence-based medicine can provide the best clinical evidence on sleep disorders' treatment in neurodegenerative

  6. Yeast buddies helping to unravel the complexity of neurodegenerative disorders.

    Science.gov (United States)

    Fruhmann, Gernot; Seynnaeve, David; Zheng, Ju; Ven, Karen; Molenberghs, Sofie; Wilms, Tobias; Liu, Beidong; Winderickx, Joris; Franssens, Vanessa

    2017-01-01

    Neurodegenerative disorders have a profound effect on the quality of life of patients and their environment. However, the development of adequate therapies requires accurate understanding of the underlying disease pathogenesis. On that account, yeast models can play an important role, as they enable the elucidation of the mechanisms leading to neurodegenerative disorders. Furthermore, by using so-called humanized yeast systems, the findings in yeast can be interpolated to humans. In this review, we will give an overview of the current body of knowledge on the use of yeast models with regard to Huntington's, Parkinson's and Alzheimer's disease. In addition to the results, obtained with the baker's yeast Saccharomyces cerevisiae, we also consider the existing literature on the less common but promising fission yeast Schizosaccharomyces pombe. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Transposable elements in TDP-43-mediated neurodegenerative disorders.

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    Wanhe Li

    Full Text Available Elevated expression of specific transposable elements (TEs has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.

  8. Need to improve clinical trials in rare neurodegenerative disorders.

    Science.gov (United States)

    Puopolo, Maria; Pocchiari, Maurizio

    2011-01-01

    Rare neurodegenerative diseases are fatal and no therapy is available to cure or slow down the progression of disease. We report possibly weaknesses in the management of clinical studies in these diseases, ranging from poor preclinical studies, difficulties in the recruitment of patients, delay in the onset of treatment because of lack in early disease-specific biomarkers, and suboptimal design of Phase II clinical trials. The adoption of innovative statistical approaches in early Phase II trials might improve the screening of drugs in rare neurodegenerative disorders, but this implicates efforts from clinical researchers, statisticians, and regulatory people to the development of new strategies that should maintain rigorous scientific integrity together with a more ethical approach to human experimentations.

  9. Need to improve clinical trials in rare neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Maria Puopolo

    2011-01-01

    Full Text Available Rare neurodegenerative diseases are fatal and no therapy is available to cure or slow down the progression of disease. We report possibly weaknesses in the management of clinical studies in these diseases, ranging from poor preclinical studies, difficulties in the recruitment of patients, delay in the onset of treatment because of lack in early disease-specific biomarkers, and suboptimal design of Phase II clinical trials. The adoption of innovative statistical approaches in early Phase II trials might improve the screening of drugs in rare neurodegenerative disorders, but this implicates efforts from clinical researchers, statisticians, and regulatory people to the development of new strategies that should maintain rigorous scientific integrity together with a more ethical approach to human experimentations.

  10. Potential future neuroprotective therapies for neurodegenerative disorders and stroke.

    Science.gov (United States)

    Tarawneh, Rawan; Galvin, James E

    2010-02-01

    The cellular mechanisms underlying neuronal loss and neurodegeneration have been an area of interest in the last decade. Although neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and Huntington disease each have distinct clinical symptoms and pathologies, they all share common mechanisms such as protein aggregation, oxidative injury, inflammation, apoptosis, and mitochondrial injury that contribute to neuronal loss. Although cerebrovascular disease has different causes from the neurodegenerative disorders, many of the same common disease mechanisms come into play following a stroke. Novel therapies that target each of these mechanisms may be effective in decreasing the risk of disease, abating symptoms, or slowing down their progression. Although most of these therapies are experimental, and require further investigation, a few seem to offer promise.

  11. DNA methylation in neurodegenerative disorders: a missing link between genome and environment?

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    Iraola-Guzmán, S; Estivill, X; Rabionet, R

    2011-07-01

    The risk of developing neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease is influenced by genetic and environmental factors. Environmental events occurring during development or later in life can be related to disease susceptibility. One way by which the environment may exert its effect is through epigenetic modifications, which might affect the functioning of genes. These include nucleosome positioning, post-translational histone modifications, and DNA methylation. In this review we will focus in the potential role of DNA methylation in neurodegenerative disorders and in the approaches to explore such epigenetic changes. Advances in deciphering the role of epigenetic modifications in phenotype are being uncovered for a variety of diseases, including cancer, autoimmune, neurodevelopmental and cognitive disorders. Epigenetic modifications are now being also associated with cardiovascular and metabolic traits, and they are expected to be especially involved in learning and memory processes, as well as in neurodegenerative disease. The study of the role of methylation and other epigenetic modifications in disease development will provide new insights in the etiopathogenesis of neurodegenerative disorders, and should hopefully shape new avenues in the development of therapeutic strategies. © 2011 John Wiley & Sons A/S.

  12. Vestibular Deficits in Neurodegenerative Disorders: Balance, Dizziness, and Spatial Disorientation.

    Science.gov (United States)

    Cronin, Thomas; Arshad, Qadeer; Seemungal, Barry M

    2017-01-01

    The vestibular system consists of the peripheral vestibular organs in the inner ear and the associated extensive central nervous system projections-from the cerebellum and brainstem to the thalamic relays to cortical projections. This system is important for spatial orientation and balance, both of critical ecological importance, particularly for successful navigation in our environment. Balance disorders and spatial disorientation are common presenting features of neurodegenerative diseases; however, little is known regarding central vestibular processing in these diseases. A ubiquitous aspect of central vestibular processing is its promiscuity given that vestibular signals are commonly found in combination with other sensory signals. This review discusses how impaired central processing of vestibular signals-typically in combination with other sensory and motor systems-may account for the impaired balance and spatial disorientation in common neurodegenerative conditions. Such an understanding may provide for new diagnostic tests, potentially useful in detecting early disease while a mechanistic understanding of imbalance and spatial disorientation in these patients may enable a vestibular-targeted therapy for such problems in neurodegenerative diseases. Studies with state of the art central vestibular testing are now much needed to tackle this important topic.

  13. Vestibular Deficits in Neurodegenerative Disorders: Balance, Dizziness, and Spatial Disorientation

    Directory of Open Access Journals (Sweden)

    Thomas Cronin

    2017-10-01

    Full Text Available The vestibular system consists of the peripheral vestibular organs in the inner ear and the associated extensive central nervous system projections—from the cerebellum and brainstem to the thalamic relays to cortical projections. This system is important for spatial orientation and balance, both of critical ecological importance, particularly for successful navigation in our environment. Balance disorders and spatial disorientation are common presenting features of neurodegenerative diseases; however, little is known regarding central vestibular processing in these diseases. A ubiquitous aspect of central vestibular processing is its promiscuity given that vestibular signals are commonly found in combination with other sensory signals. This review discusses how impaired central processing of vestibular signals—typically in combination with other sensory and motor systems—may account for the impaired balance and spatial disorientation in common neurodegenerative conditions. Such an understanding may provide for new diagnostic tests, potentially useful in detecting early disease while a mechanistic understanding of imbalance and spatial disorientation in these patients may enable a vestibular-targeted therapy for such problems in neurodegenerative diseases. Studies with state of the art central vestibular testing are now much needed to tackle this important topic.

  14. Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank.

    Science.gov (United States)

    Bieniek, Kevin F; Ross, Owen A; Cormier, Kerry A; Walton, Ronald L; Soto-Ortolaza, Alexandra; Johnston, Amelia E; DeSaro, Pamela; Boylan, Kevin B; Graff-Radford, Neill R; Wszolek, Zbigniew K; Rademakers, Rosa; Boeve, Bradley F; McKee, Ann C; Dickson, Dennis W

    2015-12-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future

  15. Ghrelin: a link between ageing, metabolism and neurodegenerative disorders.

    Science.gov (United States)

    Stoyanova, I I

    2014-12-01

    Along with the increase in life expectancy over the last century comes the increased risk for development of age-related disorders, including metabolic and neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. These chronic disorders share two main characteristics: 1) neuronal loss in motor, sensory or cognitive systems, leading to cognitive and motor decline; and 2) a strong correlation between metabolic changes and neurodegeneration. In order to treat them, a better understanding of their complexity is required: it is necessary to interpret the neuronal damage in light of the metabolic changes, and to find the disrupted link between the peripheral organs governing energy metabolism and the CNS. This review is an attempt to present ghrelin as part of molecular regulatory interface between energy metabolism, neuroendocrine and neurodegenerative processes. Ghrelin takes part in lipid and glucose metabolism, in higher brain functions such as sleep-wake state, learning and memory consolidation; it influences mitochondrial respiration and shows neuroprotective effect. All these make ghrelin an attractive target for development of biomarkers or therapeutics for prevention or treatment of disorders, in which cell protection and recruitment of new neurons or synapses are needed. Copyright © 2014. Published by Elsevier Inc.

  16. REM behaviour disorder detection associated with neurodegenerative diseases

    DEFF Research Database (Denmark)

    Kempfner, Jacob; Sorensen, Gertrud; Zoetmulder, Marielle

    2010-01-01

    Abnormal skeleton muscle activity during REM sleep is characterized as REM Behaviour Disorder (RBD), and may be an early marker for different neurodegenerative diseases. Early detection of RBD is therefore highly important, and in this ongoing study a semi-automatic method for RBD detection......, a computerized algorithm has been attempted implemented. By analysing the REM and non-REM EMG activity, using advanced signal processing tools combined with a statistical classifier, it is possible to discriminate normal and abnormal EMG activity. Due to the small number of patients, the overall performance...

  17. Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Disease.

    Science.gov (United States)

    Howell, Michael Joseph; Schenck, Carlos Hugh

    2015-06-01

    The dream enactment of rapid eye movement sleep behavior disorder (RBD) is often the first indication of an impending α-synuclein disorder, such as Parkinson disease, multiple-system atrophy, or dementia with Lewy bodies. To provide an overview of RBD from the onset of dream enactment through the emergence of a parkinsonian disorder. Peer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized trials, and basic science investigations, were identified in a PubMed search of articles on RBD from January 1, 1986, through July 31, 2014. Under normal conditions, vivid dream mentation combined with skeletal muscle paralysis characterizes rapid eye movement sleep. In RBD, α-synuclein abnormalities in the brainstem disinhibit rapid eye movement sleep motor activity, leading to dream enactment. The behaviors of RBD are often theatrical, with complexity, aggression, and violence; fighting and fleeing actions can be injurious to patients as well as bed partners. Rapid eye movement sleep behavior disorder is distinguished from other parasomnias by clinical features and the demonstration of rapid eye movement sleep without atonia on polysomnography. Consistent with early neurodegeneration, patients with RBD demonstrate subtle motor, cognitive, and autonomic impairments. Approximately 50% of patients with spontaneous RBD will convert to a parkinsonian disorder within a decade. Ultimately, nearly all (81%-90%) patients with RBD develop a neurodegenerative disorder. Among patients with Parkinson disease, RBD predicts a non-tremor-predominant subtype, gait freezing, and an aggressive clinical course. The most commonly cited RBD treatments include low-dose clonazepam or high-dose melatonin taken orally at bedtime. Treatment of RBD can prevent injury to patients and bed partners. Because RBD is a prodromal syndrome of Parkinson disease (or related disorder), it represents a unique opportunity for developing and testing disease

  18. Support system and method for detecting neurodegenerative disorder

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to a system and a method for detection of abnormal motor activity during REM sleep, and further to systems and method for assisting in detecting neurodegenerative disorders such as Parkinson's. One embodiment relates to a method for detection of abnormal motor activity...... during REM sleep comprising the steps of: performing polysomnographic recordings of a sleeping subject, thereby obtaining one or more electromyography (EMG) derivations, preferably surface EMG recordings, and one or more EEG derivations, and/or one or more electrooculargraphy (EOG) derivations, detecting...... one or more REM sleep stages, preferably based on the one or more EEG and/or EOG derivations, determining the level of muscle activity during the one or more REM sleep stages based on the one or more EMG derivations, wherein a subject having an increased level of muscle activity during REM sleep...

  19. Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

    Science.gov (United States)

    Perluigi, Marzia; Reed, Tanea; Muharib, Tasneem; Hughes, Christopher P.; Robinson, Renã A.S.; Sultana, Rukhsana

    2012-01-01

    Abstract Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidative-stress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610–1655. PMID:22115501

  20. Melatonin in Alzheimer's disease and other neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Poeggeler B

    2006-05-01

    Full Text Available Abstract Increased oxidative stress and mitochondrial dysfunction have been identified as common pathophysiological phenomena associated with neurodegenerative disorders such as Alzheimer's disease (AD, Parkinson's disease (PD and Huntington's disease (HD. As the age-related decline in the production of melatonin may contribute to increased levels of oxidative stress in the elderly, the role of this neuroprotective agent is attracting increasing attention. Melatonin has multiple actions as a regulator of antioxidant and prooxidant enzymes, radical scavenger and antagonist of mitochondrial radical formation. The ability of melatonin and its kynuramine metabolites to interact directly with the electron transport chain by increasing the electron flow and reducing electron leakage are unique features by which melatonin is able to increase the survival of neurons under enhanced oxidative stress. Moreover, antifibrillogenic actions have been demonstrated in vitro, also in the presence of profibrillogenic apoE4 or apoE3, and in vivo, in a transgenic mouse model. Amyloid-β toxicity is antagonized by melatonin and one of its kynuramine metabolites. Cytoskeletal disorganization and protein hyperphosphorylation, as induced in several cell-line models, have been attenuated by melatonin, effects comprising stress kinase downregulation and extending to neurotrophin expression. Various experimental models of AD, PD and HD indicate the usefulness of melatonin in antagonizing disease progression and/or mitigating some of the symptoms. Melatonin secretion has been found to be altered in AD and PD. Attempts to compensate for age- and disease-dependent melatonin deficiency have shown that administration of this compound can improve sleep efficiency in AD and PD and, to some extent, cognitive function in AD patients. Exogenous melatonin has also been reported to alleviate behavioral symptoms such as sundowning. Taken together, these findings suggest that melatonin

  1. Few patients with neurodegenerative disorders require spinal surgery

    Science.gov (United States)

    Epstein, Nancy E.; Gottesman, Malcolm

    2014-01-01

    Background: Few patients with neurodegenerative disorders (ND) (e.g., Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Postpolio Syndrome (PPS)) require spinal surgery. Typically, their neurological symptoms and signs reflect their underlying neurologic disorders rather than structural spinal pathology reported on magnetic resonance images (MR) or computed tomographic scans (CT). Methods: The first author, a neurosurgeon, reviewed 437 spinal consultations performed over a 20-month period. Of 254 patients seen in first opinion (e.g., had not been seen by a spinal surgeon), 9 had MS, while 2 had ALS. Of 183 patients seen in second opinion (e.g., prior spinal surgeons recommended surgery), 4 had MS, 2 had ALS, and 1 had PPS. We performed this study to establish how often patients with ND, seen in first or second opinion, require spinal surgery. We focused on whether second opinions from spinal surgeons would limit the number of operations offered to these patients. Results: Two of 11 patients with ND seen in first opinion required surgery. The first patient required a C5-7 laminectomy/C2-T2 fusion, followed by a L2-S1 laminectomy/L5S1 fusion. The second patient required a L2-L3 laminectomy/diskectomy/fusion. However, none of the seven patients seen in second opinion, who were previously told by outside surgeons they needed spinal surgery, required operations. Conclusions: Few patients with neurodegenerative syndromes (MS, ALS, PPS) and reported “significant” spondyloitic spinal disease interpreted on MR/CT studies required surgery. Great caution should be exercised in offering patients with ND spinal surgery, and second opinions should be encouraged to limit “unnecessary” procedures. PMID:24843817

  2. Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases.

    Science.gov (United States)

    Irwin, Michael H; Moos, Walter H; Faller, Douglas V; Steliou, Kosta; Pinkert, Carl A

    2016-05-01

    Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders?

    Science.gov (United States)

    Kocot, Joanna; Luchowska-Kocot, Dorota; Kiełczykowska, Małgorzata; Musik, Irena; Kurzepa, Jacek

    2017-06-27

    Vitamin C (Vit C) is considered to be a vital antioxidant molecule in the brain. Intracellular Vit C helps maintain integrity and function of several processes in the central nervous system (CNS), including neuronal maturation and differentiation, myelin formation, synthesis of catecholamine, modulation of neurotransmission and antioxidant protection. The importance of Vit C for CNS function has been proven by the fact that targeted deletion of the sodium-vitamin C co-transporter in mice results in widespread cerebral hemorrhage and death on post-natal day one. Since neurological diseases are characterized by increased free radical generation and the highest concentrations of Vit C in the body are found in the brain and neuroendocrine tissues, it is suggested that Vit C may change the course of neurological diseases and display potential therapeutic roles. The aim of this review is to update the current state of knowledge of the role of vitamin C on neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic sclerosis, as well as psychiatric disorders including depression, anxiety and schizophrenia. The particular attention is attributed to understanding of the mechanisms underlying possible therapeutic properties of ascorbic acid in the presented disorders.

  4. Idiopathic REM sleep behavior disorder as a long-term predictor of neurodegenerative disorders.

    Science.gov (United States)

    Fulda, Stephany

    2011-12-01

    REM sleep behavior disorder (RBD) is a parasomnia characterized by dream-enacting behavior and loss of muscle atonia during REM sleep. Idiopathic RBD occurs in the absence of any neurological disease or other possible cause, is male-predominant and its clinical course is generally chronic progressive. Secondary RBD may be related to neurodegenerative disorders such as multiple system atrophy, Parkinson's disease and Lewy body dementia. Recent long-term prospective studies have shown that 30% to 65% of patients with idiopathic RBD will eventually develop a neurodegenerative disorder with the rate of emergence depending on the length of the follow-up period. RBD may therefore be one of the earliest signs of and/or a long-term predictor for neurodegenerative disorders. Because RBD antecedes the development of these disorders by several years or decades, its recognition may enable the delay or prevention of neurodegenerative disorders through the early application of neuroprotective or disease-modifying therapies in the future.

  5. Therapeutic potential of cannabinoids in neurodegenerative disorders: a selective review.

    Science.gov (United States)

    Velayudhan, Latha; Van Diepen, Erik; Marudkar, Mangesh; Hands, Oliver; Suribhatla, Srinivas; Prettyman, Richard; Murray, Jonathan; Baillon, Sarah; Bhattacharyya, Sagnik

    2014-01-01

    The endocannabinoid system (ECS) is now recognised as an important modulator of various central nervous system processes. More recently, an increasing body of evidence has accumulated to suggest antioxidant, anti-inflammatory and neuroprotective roles of ECS. In this review we discuss the role and therapeutic potential of ECS in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, Huntington's disease, Tourette's syndrome, brain ischemia and amyotrophic lateral sclerosis (ALS). Elements of the ECS, such as fatty acid amide hydrolase or the cannabinoid receptors are now considered as promising pharmacological targets for some diseases. Although still preliminary, recent reports suggest that modulation of the ECS may constitute a novel approach for the treatment of AD. There are windows of opportunity in conditions caused by acute events such as trauma and ischemia as well in conditions that may involve altered functionality of the target receptors of the ECS, such as in AD. The ECS changes in Parkinson's disease could be compensatory as well as pathogenic of the illness process and needs further understanding and clinical studies are still in the preliminary stage. There is not enough evidence to support use of cannabinoids in treating Huntington's disease, tics and obsessive compulsive behaviour in Tourette's syndrome. Evidence on therapeutic use of cannabinoids in multiple sclerosis and ALS is currently limited. A major challenge for future research is the development of novel compounds with more selectivity for various components of the ECS which could target different neurotoxic pathways and be used in combination therapy.

  6. The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders.

    Science.gov (United States)

    Eira, Jessica; Silva, Catarina Santos; Sousa, Mónica Mendes; Liz, Márcia Almeida

    2016-06-01

    Cytoskeleton defects, including alterations in microtubule stability, in axonal transport as well as in actin dynamics, have been characterized in several unrelated neurodegenerative conditions. These observations suggest that defects of cytoskeleton organization may be a common feature contributing to neurodegeneration. In line with this hypothesis, drugs targeting the cytoskeleton are currently being tested in animal models and in human clinical trials, showing promising effects. Drugs that modulate microtubule stability, inhibitors of posttranslational modifications of cytoskeletal components, specifically compounds affecting the levels of tubulin acetylation, and compounds targeting signaling molecules which regulate cytoskeleton dynamics, constitute the mostly addressed therapeutic interventions aiming at preventing cytoskeleton damage in neurodegenerative disorders. In this review, we will discuss in a critical perspective the current knowledge on cytoskeleton damage pathways as well as therapeutic strategies designed to revert cytoskeleton-related defects mainly focusing on the following neurodegenerative disorders: Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis and Charcot-Marie-Tooth Disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Environmental Pollutants as Risk Factors for Neurodegenerative Disorders

    OpenAIRE

    Miguel eChin-Chan; Juliana eNavarro-Yepes; Betzabet eQuintanilla-Vega

    2015-01-01

    Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment, from diet to the new nanomaterials as putative risk factors has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metal...

  8. Gene Therapy-Based Modeling of Neurodegenerative Disorders: Huntington's Disease.

    Science.gov (United States)

    Young, Deborah

    2016-01-01

    Huntington's disease is a fatal neurodegenerative disease characterized by impairments in motor control, and cognitive and psychiatric disturbances. In this chapter, viral vector-mediated approaches used in modeling the key neuropathological features of the disease including the production of abnormal intracellular protein aggregates, neuronal dysfunction and degeneration and motor impairments in rodents are described.

  9. Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools

    Science.gov (United States)

    Silva, Juliana; Monge-Fuentes, Victoria; Gomes, Flávia; Lopes, Kamila; dos Anjos, Lilian; Campos, Gabriel; Arenas, Claudia; Biolchi, Andréia; Gonçalves, Jacqueline; Galante, Priscilla; Campos, Leandro; Mortari, Márcia

    2015-01-01

    Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer’s Disease, Parkinson’s Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. PMID:26295258

  10. Environmental Pollutants as Risk Factors for Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Miguel eChin-Chan

    2015-04-01

    Full Text Available Neurodegenerative diseases including Alzheimer (AD and Parkinson (PD have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment, from diet to the new nanomaterials as putative risk factors has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ peptide and the phosphorylation of Tau protein (P-Tau, causing senile/amyloid plaques and neurofibrillary tangles characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn, which is a key constituent of Lewy bodies, a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzymes such as neprilysin or insulin degrading enzyme. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.

  11. REM Sleep Behavior Disorder (RBD) as a marker of neurodegenerative disorders.

    Science.gov (United States)

    Ferini-Strambi, L; Marelli, S; Galbiati, A; Rinaldi, F; Giora, E

    2014-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) can occur in the absence of any other obvious associated neurologic disorder or in association with a neurodegenerative disease, in which case it is considered as symptomatic RBD. RBD is frequently associated with Parkinson's disease (PD), Lewy body dementia or multiple system atrophy (MSA), and in several cases may even antedate the occurrence of motor symptoms by decades. When no neurologic disorder is obvious, RBD can be considered as idiopathic (iRBD). Several studies have looked at neurophysiologic and neuropsychological functions in iRBD and have found evidence of CNS dysfunction during both wakefulness and sleep in a variable proportion of these patients, challenging the concept of iRBD. Identifying subjects with a high risk of developing a neurodegenerative process may be crucial in order to develop early intervention strategies. Some prospective results in iRBD showed that potential markers of neurodegeneration are the following: 1) marked EEG slowing on spectral analysis; 2) decreased striatal 123I-FPCIT; 3) impaired color vision.

  12. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder.

    Science.gov (United States)

    Postuma, R B; Gagnon, J F; Vendette, M; Fantini, M L; Massicotte-Marquez, J; Montplaisir, J

    2009-04-14

    Idiopathic REM sleep behavior disorder (RBD) is a potential preclinical marker for the development of neurodegenerative diseases, particularly Parkinson disease (PD) and Lewy body dementia. However, the long-term risk of developing neurodegeneration in patients with idiopathic RBD has not been established. Obtaining an accurate picture of this risk is essential for counseling patients and for development of potential neuroprotective therapies. We conducted a follow-up study of all patients seen at the sleep disorders laboratory at the Hôpital du Sacré Coeur with a diagnosis of idiopathic RBD. Diagnoses of parkinsonism and dementia were defined according to standard criteria. Survival curves were constructed to estimate the 5-, 10-, and 12-year risk of developing neurodegenerative disease. Of 113 patients, 93 (82%) met inclusion criteria. The mean age of participants was 65.4 years and 75 patients (80.4%) were men. Over the follow-up period, 26/93 patients developed a neurodegenerative disorder. A total of 14 patients developed PD, 7 developed Lewy body dementia, 4 developed dementia that met clinical criteria for AD, and 1 developed multiple system atrophy. The estimated 5-year risk of neurodegenerative disease was 17.7%, the 10-year risk was 40.6%, and the 12-year risk was 52.4%. Although we have found a slightly lower risk than other reports, the risk of developing neurodegenerative disease in idiopathic REM sleep behavior disorder is substantial, with the majority of patients developing Parkinson disease and Lewy body dementia.

  13. Cognitive performance in REM sleep behaviour disorder: a possible early marker of neurodegenerative disease?

    Science.gov (United States)

    Terzaghi, Michele; Sinforiani, Elena; Zucchella, Chiara; Zambrelli, Elena; Pasotti, Chiara; Rustioni, Valter; Manni, Raffaele

    2008-05-01

    Rapid eye movement [REM] sleep behaviour disorder (RBD) may herald neurodegenerative diseases. Neurobiological deficits similar to those identified in neurodegenerative diseases have been reported in idiopathic RBD. Researchers are looking for early markers supporting a possible role of RBD as a harbinger of impending neurodegenerative disease. To examine the neuropsychological functions in idiopathic RBD subjects. Should they be found to present a neuropsychological dysfunction that overlaps that reported in neurodegenerative diseases, it would be possible to consider cognitive deficits as possible early markers of an underlying degenerative process. Twenty-three subjects with idiopathic RBD (21 males, mean age 67.0+/-7.0 years) and a group of healthy controls matched for sex, age and education underwent a neuropsychological battery evaluating different cognitive domains. Considering mean values, poorer performances were observed in the Word Span (pneurodegenerative disease, but until more prolonged long-term follow-up data are available, the true neurobiological significance of cognitive deficits in RBD will remain unknown.

  14. Molecular underpinnings of neurodegenerative disorders: striatal-enriched protein tyrosine phosphatase signaling and synaptic plasticity.

    Science.gov (United States)

    Lombroso, Paul J; Ogren, Marilee; Kurup, Pradeep; Nairn, Angus C

    2016-01-01

    This commentary focuses on potential molecular mechanisms related to the dysfunctional synaptic plasticity that is associated with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Specifically, we focus on the role of striatal-enriched protein tyrosine phosphatase (STEP) in modulating synaptic function in these illnesses. STEP affects neuronal communication by opposing synaptic strengthening and does so by dephosphorylating several key substrates known to control synaptic signaling and plasticity. STEP levels are elevated in brains from patients with Alzheimer's and Parkinson's disease. Studies in model systems have found that high levels of STEP result in internalization of glutamate receptors as well as inactivation of ERK1/2, Fyn, Pyk2, and other STEP substrates necessary for the development of synaptic strengthening. We discuss the search for inhibitors of STEP activity that may offer potential treatments for neurocognitive disorders that are characterized by increased STEP activity. Future studies are needed to examine the mechanisms of differential and region-specific changes in STEP expression pattern, as such knowledge could lead to targeted therapies for disorders involving disrupted STEP activity.

  15. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients.

    Science.gov (United States)

    Iranzo, Alex; Fernández-Arcos, Ana; Tolosa, Eduard; Serradell, Mónica; Molinuevo, José Luis; Valldeoriola, Francesc; Gelpi, Ellen; Vilaseca, Isabel; Sánchez-Valle, Raquel; Lladó, Albert; Gaig, Carles; Santamaría, Joan

    2014-01-01

    To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD) patients with long follow-up. Using the Kaplan-Meier method, we estimated the disease-free survival rate from defined neurodegenerative syndromes in all the consecutive IRBD patients diagnosed and followed-up in our tertiary referal sleep center between November 1991 and July 2013. The cohort comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a median follow-up of four years. The risk of a defined neurodegenerative syndrome from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and 90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses (37.4%) were dementia with Lewy bodies (DLB) in 29 subjects, Parkinson disease (PD) in 22, multiple system atrophy (MSA) in two, and mild cognitive impairment (MCI) in 12. In six cases, in whom postmortem was performed, neuropathological examination disclosed neuronal loss and widespread Lewy-type pathology in the brain in each case. In a large IRBD cohort diagnosed in a tertiary referal sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA. IRBD represented the prodromal period of these conditions. Our findings in IRBD have important implications in clinical practice, in the investigation of the early pathological events occurring in the synucleinopathies, and for the design of interventions with potential disease-modifying agents.

  16. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients.

    Directory of Open Access Journals (Sweden)

    Alex Iranzo

    Full Text Available OBJECTIVE: To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD patients with long follow-up. METHODS: Using the Kaplan-Meier method, we estimated the disease-free survival rate from defined neurodegenerative syndromes in all the consecutive IRBD patients diagnosed and followed-up in our tertiary referal sleep center between November 1991 and July 2013. RESULTS: The cohort comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a median follow-up of four years. The risk of a defined neurodegenerative syndrome from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and 90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses (37.4% were dementia with Lewy bodies (DLB in 29 subjects, Parkinson disease (PD in 22, multiple system atrophy (MSA in two, and mild cognitive impairment (MCI in 12. In six cases, in whom postmortem was performed, neuropathological examination disclosed neuronal loss and widespread Lewy-type pathology in the brain in each case. CONCLUSIONS: In a large IRBD cohort diagnosed in a tertiary referal sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA. IRBD represented the prodromal period of these conditions. Our findings in IRBD have important implications in clinical practice, in the investigation of the early pathological events occurring in the synucleinopathies, and for the design of interventions with potential disease-modifying agents.

  17. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease.

    Science.gov (United States)

    Boeve, B F; Silber, M H; Saper, C B; Ferman, T J; Dickson, D W; Parisi, J E; Benarroch, E E; Ahlskog, J E; Smith, G E; Caselli, R C; Tippman-Peikert, M; Olson, E J; Lin, S-C; Young, T; Wszolek, Z; Schenck, C H; Mahowald, M W; Castillo, P R; Del Tredici, K; Braak, H

    2007-11-01

    REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep with prominent motor activity accompanying dreaming. The terminology relating to RBD, and mechanisms underlying REM sleep without atonia and RBD based on data in cat and rat are presented. Neuroimaging data from the few published human cases with RBD associated with structural lesions in the brainstem are presented, in which the dorsal midbrain and pons are implicated. Pharmacological manipulations which alter RBD frequency and severity are reviewed, and the data from human neuropathological studies are presented. An anatomic framework and new schema for the pathophysiology of RBD are proposed based on recent data in rat regarding the putative flip-flop switch for REM sleep control. The structure in man analogous to the subcoeruleus region in cat and sublaterodorsal nucleus in rat is proposed as the nucleus (and its associated efferent and afferent pathways) crucial to RBD pathophysiology. The association of RBD with neurological disease ('secondary RBD') is presented, with emphasis on RBD associated with neurodegenerative disease, particularly the synucleinopathies. The hypothesized pathophysiology of RBD is presented in relation to the Braak staging system for Parkinson's disease, in which the topography and temporal sequence of synuclein pathology in the brain could explain the evolution of parkinsonism and/or dementia well after the onset of RBD. These data suggest that many patients with 'idiopathic' RBD are actually exhibiting an early clinical manifestation of an evolving neurodegenerative disorder. Such patients may be appropriate for future drug therapies that affect synuclein pathophysiology, in which the development of parkinsonism and/or dementia could be delayed or prevented. We suggest that additional clinicopathological studies be performed in patients with dementia or parkinsonism, with and without RBD, as well as in

  18. Research progress on the pathogenesis of rapid eye movement sleep behavior disorder and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Hai-yang JIANG

    2017-10-01

    Full Text Available Rapid eye movement sleep behavior disorder (RBD is a sleep disorder characterized by the disappearance of muscle relaxation and enacting one's dreams during rapid eye movement (REM, with most of the dreams being violent or aggressive. Prevalence of RBD, based on population, is 0.38%-2.01%, but it becomes much higher in patients with neurodegenerative diseases, especially α - synucleinopathies. RBD may herald the emergence of α-synucleinopathies by decades, thus it may be used as an effective early marker of neurodegenerative diseases. In this review, we summarized the progress on the pathogenesis of RBD and its relationship with neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2017.10.003

  19. Exogenous melatonin for sleep disorders in neurodegenerative diseases: a meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Zhang, Wei; Chen, Xue-yan; Su, Su-wen; Jia, Qing-zhong; Ding, Tao; Zhu, Zhong-ning; Zhang, Tong

    2016-01-01

    The purpose of this work is to investigate the efficacy of exogenous melatonin in the treatment of sleep disorders in patients with neurodegenerative disease. We searched Pubmed, the Cochrane Library, and ClinicalTrials.gov, from inception to July 2015. We included randomized clinical trials (RCTs) that compared melatonin with placebo and that had the primary aim of improving sleep in people with neurodegenerative diseases, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). We pooled data with the weighted mean difference in sleep outcomes. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I (2) statistic. 9 RCTs were included in this research. We found that the treatment with exogenous melatonin has positive effects on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) in PD patients (MD: 4.20, 95 % CI: 0.92-7.48; P = 0.01), and by changes in PSQI component 4 in AD patients (MD: 0.67, 95 % CI: 0.04-1.30; P = 0.04), but not on objective sleep outcomes in both AD and PD patients. Treatment with melatonin effectively improved the clinical and neurophysiological aspects of rapid eye movement (REM) sleep behavior disorder (RBD), especially elderly individuals with underlying neurodegenerative disorders. This meta-analysis provided some evidence that melatonin improves sleep quality in patients with AD and PD, and melatonin can be considered as a possible sole or add-on therapy in neurodegenerative disorders patients with RBD.

  20. [Sleep disorder, a potential early diagnostic marker for psychiatric and neurodegenerative diseases].

    Science.gov (United States)

    Chen, Yan-Mei; Qin, Dong-Dong; Jiang, Hui-Hui; Hu, Xin-Tian; Ma, Yuan-Ye

    2011-02-01

    Sleep/circadian timing depends on several neurotransmitter systems, including 5-HT, NE, DA, Ach, GABA, etc. These neurotransmitter systems play critical roles in mental, emotional and cognitive functions in the brain. Dysfunctions of these systems not only result in sleep disorder, but are also related to many psychiatric and neurodegenerative diseases. Sleep disruption is tightly associated with an increased susceptibility to a broad range of psychiatric and neurodegenerative diseases, such as depression and Parkinson diseases. Non-human primates, especially the rhesus monkey is an excellent biomedical model for human sleep and CNS diseases. Establishing nonhuman primates' model of mental disorders and monitoring the sleep changes during the development of the model will help us to know more about the relationships between sleep disorder and psychiatric and neurodegenerative diseases. Sleep disorder as an early marker for psychiatric and neurodegenerative diseases would permit early intervention of these diseases and draw attention to the potential therapeutic benefits of normalizing sleep rhythms in individuals with brain pathologies.

  1. Abnormal red cell features associated with hereditary neurodegenerative disorders: the neuroacanthocytosis syndromes

    NARCIS (Netherlands)

    Franceschi, L. De; Bosman, G.J.C.G.M.; Mohandas, N.

    2014-01-01

    PURPOSE OF REVIEW: This review discusses the mechanisms involved in the generation of thorny red blood cells (RBCs), known as acanthocytes, in patients with neuroacanthocytosis, a heterogenous group of neurodegenerative hereditary disorders that include chorea-acanthocytosis (ChAc) and McLeod

  2. Motor Abnormalities: From Neurodevelopmental to Neurodegenerative Through "Functional" (Neuro)Psychiatric Disorders.

    Science.gov (United States)

    Peralta, Victor; Cuesta, Manuel J

    2017-09-01

    Motor abnormalities (MAs) of severe mental disorders have been traditionally neglected both in clinical practice and research, although they are an increasing focus of attention because of their clinical and neurobiological relevance. For historical reasons, most of the literature on MAs has been focused to a great extent on schizophrenia, and as a consequence their prevalence and featural properties in other psychiatric or neuropsychiatric disorders are poorly known. In this article, we evaluated the extent to which catatonic, extrapyramidal and neurological soft signs, and their associated clinical features, are present transdiagnostically. We examined motor-related features in neurodevelopmental (schizophrenia, obsessive compulsive disorder, autism spectrum disorders), "functional" (nonschizophrenic nonaffective psychoses, mood disorders) and neurodegenerative (Alzheimer's disease) disorders. Examination of the literature revealed that there have been very few comparisons of motor-related features across diagnoses and we had to rely mainly in disorder-specific studies to compare it transdiagnostically. One or more motor domains had a substantial prevalence in all the diagnoses examined. In "functional" disorders, MAs, and particularly catatonic signs, appear to be markers of episode severity; in chronic disorders, although with different degree of strength or evidence, all motor domains are indicators of both disorder severity and poor outcome; lastly, in Alzheimer's disease they are also indicators of disorder progression. MAs appear to represent a true transdiagnostic domain putatively sharing neurobiological mechanisms of neurodevelopmental, functional or neurodegenerative origin.

  3. Role of nucleolar dysfunction in neurodegenerative disorders: a game of genes?

    Directory of Open Access Journals (Sweden)

    Rosanna Parlato

    2015-05-01

    Full Text Available Within the cell nucleus the nucleolus is the site of rRNA transcription and ribosome biogenesis and its activity is clearly essential for a correct cell function, however its specific role in neuronal homeostasis remains mainly unknown. Here we review recent evidence that impaired nucleolar activity is a common mechanism in different neurodegenerative disorders. We focus on the specific causes and consequences of impaired nucleolar activity to better understand the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD, Parkinson's disease (PD, Huntington's disease (HD and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD. In particular, we discuss the genetic and epigenetic factors that might regulate nucleolar function in these diseases. In addition, we describe novel animal models enabling the dissection of the context-specific series of events triggered by nucleolar disruption, also known as nucleolar stress. Finally, we suggest how this novel mechanism could help to identify strategies to treat these still incurable disorders.

  4. Tracking the progression of social cognition in neurodegenerative disorders.

    Science.gov (United States)

    Kumfor, Fiona; Irish, Muireann; Leyton, Cristian; Miller, Laurie; Lah, Suncica; Devenney, Emma; Hodges, John R; Piguet, Olivier

    2014-10-01

    Behavioural-variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) patients experience behavioural and emotion recognition alterations, yet understanding of how socioemotional processing is affected with disease progression is minimal. Additionally, evidence suggests that bvFTD patients with limited brain atrophy on neuroimaging at presentation (bvFTD-la) have a more benign course than those with marked atrophy (bvFTD-ma). Longitudinal investigation of these patients, however, is lacking. We investigated general cognition, emotion recognition and sarcasm detection in 20 bvFTD (8 with limited brain atrophy) and 17 AD patients longitudinally and used mixed models analyses to determine the level and rates of decline across groups over time. At baseline, all patient groups performed worse than controls on general cognition and emotion recognition measures. The bvFTD-ma group showed significant impairment on the sarcasm detection task compared with controls. Longitudinally, an overall effect of time was present for general cognition (psarcasm detection task, the bvFTD-ma and AD patients declined, whereas bvFTD-la patients remained stable over time (p=0.002). Tasks of sarcasm detection represent a clinically useful tool to differentiate between bvFTD and AD at baseline. Furthermore, tasks of socioemotional functioning can track progression within bvFTD and identify bvFTD patients more likely to show a faster rate of decline. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?

    Science.gov (United States)

    Postuma, Ronald B; Gagnon, Jean-Francois; Tuineaig, Maria; Bertrand, Josie-Anne; Latreille, Veronique; Desjardins, Catherine; Montplaisir, Jacques Y

    2013-11-01

    Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. Prospective cohort study. Tertiary sleep disorders center. 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.

  6. The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases.

    Science.gov (United States)

    Iranzo, Alex; Santamaria, Joan; Tolosa, Eduard

    2009-12-01

    REM sleep behavior disorder (RBD) is characterized by vigorous movements associated with unpleasant dreams and increased electromyographic activity during REM sleep. Polysomnography with audiovisual recording is needed to confirm the diagnosis of RBD and to exclude other sleep disorders that can mimic its symptoms including obstructive sleep apnea, nocturnal hallucinations and confusional awakenings. RBD may be idiopathic or related to neurodegenerative diseases, particularly multiple system atrophy, Parkinson's disease and dementia with Lewy bodies. RBD may be the first manifestation of these disorders, antedating the onset of parkinsonism, cerebellar syndrome, dysautonomia, and dementia by several years. RBD should thus be considered an integral part of the disease process. When effective, neuroprotective strategies should be considered in subjects with idiopathic RBD. Patients with other neurodegenerative diseases, though, such as spinocerebellar ataxias, may also present with RBD. When clinically required, clonazepam at bedtime is effective in decreasing the intensity of dream-enacting behaviors and unpleasant dreams in both the idiopathic and secondary forms. When part of a neurodegenerative disorder the development of RBD is thought to reflect the location and extent of the underlying lesions involving the REM sleep centers of the brain (e.g., locus subceruleus, amygdala, etc.), leading to a complex multiple neurotransmitter dysfunction that involves GABAergic, glutamatergic and monoaminergic systems. RBD is mediated neither by direct abnormal alpha-synuclein inclusions nor by striatonigral dopaminergic deficiency alone.

  7. Hydrogel-Based Nanocomposites and Mesenchymal Stem Cells: A Promising Synergistic Strategy for Neurodegenerative Disorders Therapy

    Directory of Open Access Journals (Sweden)

    Diego Albani

    2013-01-01

    Full Text Available Hydrogel-based materials are widely employed in the biomedical field. With regard to central nervous system (CNS neurodegenerative disorders, the design of injectable nanocomposite hydrogels for in situ drug or cell release represents an interesting and minimally invasive solution that might play a key role in the development of successful treatments. In particular, biocompatible and biodegradable hydrogels can be designed as specific injectable tools and loaded with nanoparticles (NPs, to improve and to tailor their viscoelastic properties upon injection and release profile. An intriguing application is hydrogel loading with mesenchymal stem cells (MSCs that are a very promising therapeutic tool for neurodegenerative or traumatic disorders of the CNS. This multidisciplinary review will focus on the basic concepts to design acellular and cell-loaded materials with specific and tunable rheological and functional properties. The use of hydrogel-based nanocomposites and mesenchymal stem cells as a synergistic strategy for nervous tissue applications will be then discussed.

  8. Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders.

    Science.gov (United States)

    Fagherazzi, Elen V; Garcia, Vanessa A; Maurmann, Natasha; Bervanger, Thielly; Halmenschlager, Luis H; Busato, Stefano B; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Schröder, Nadja

    2012-02-01

    Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

  9. Endocannabinoids and Neurodegenerative Disorders: Parkinson's Disease, Huntington's Chorea, Alzheimer's Disease, and Others.

    Science.gov (United States)

    Fernández-Ruiz, Javier; Romero, Julián; Ramos, José A

    2015-01-01

    This review focuses on the role of the endocannabinoid signaling system in controlling neuronal survival, an extremely important issue to be considered when developing new therapies for neurodegenerative disorders. First, we will describe the cellular and molecular mechanisms, and the signaling pathways, underlying these neuroprotective properties, including the control of glutamate homeostasis, calcium influx, the toxicity of reactive oxygen species, glial activation and other inflammatory events; and the induction of autophagy. We will then concentrate on the preclinical studies and the few clinical trials that have been carried out targeting endocannabinoid signaling in three important chronic progressive neurodegenerative disorders (Parkinson's disease, Huntington's chorea, and Alzheimer's disease), as well as in other less well-studied disorders. We will end by offering some ideas and proposals for future research that should be carried out to optimize endocannabinoid-based treatments for these disorders. Such studies will strengthen the possibility that these therapies will be investigated in the clinical scenario and licensed for their use in specific disorders.

  10. Recent Updates in the Treatment of Neurodegenerative Disorders Using Natural Compounds

    Directory of Open Access Journals (Sweden)

    Mahmood Rasool

    2014-01-01

    Full Text Available Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS. Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer’s disease, Parkinson’s disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

  11. Glucose 6 phosphatase dehydrogenase (G6PD and neurodegenerative disorders: Mapping diagnostic and therapeutic opportunities

    Directory of Open Access Journals (Sweden)

    Manju Tiwari

    2017-12-01

    Full Text Available Glucose 6 phosphate dehydrogenase (G6PD is a key and rate limiting enzyme in the pentose phosphate pathway (PPP. The physiological significance of enzyme is providing reduced energy to specific cells like erythrocyte by maintaining co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH. There are preponderance research findings that demonstrate the enzyme (G6PD role in the energy balance, and it is associated with blood-related diseases and disorders, primarily the anemia resulted from G6PD deficiency. The X-linked genetic deficiency of G6PD and associated non-immune hemolytic anemia have been studied widely across the globe. Recent advancement in biology, more precisely neuroscience has revealed that G6PD is centrally involved in many neurological and neurodegenerative disorders. The neuroprotective role of the enzyme (G6PD has also been established, as well as the potential of G6PD in oxidative damage and the Reactive Oxygen Species (ROS produced in cerebral ischemia. Though G6PD deficiency remains a global health issue, however, a paradigm shift in research focusing the potential of the enzyme in neurological and neurodegenerative disorders will surely open a new avenue in diagnostics and enzyme therapeutics. Here, in this study, more emphasis was made on exploring the role of G6PD in neurological and inflammatory disorders as well as non-immune hemolytic anemia, thus providing diagnostic and therapeutic opportunities.

  12. BLOOD GROUPS AND AFFECTIVE DISORDERS

    OpenAIRE

    Reddy, P. Lakshmi; Puttaram, Sowbhagya; Rao, B.S. Sridhara Rama; Khanna, Sumant; Channabasavanna, S.M.

    1988-01-01

    SUMMARY An analysis was made of the distribution of various blood groups in subjects with affective disorders. A group of healthy subjects served as controls. The distribution showed lack of association of affective disorder and any blood groups.

  13. High-speed video gait analysis reveals early and characteristic locomotor phenotypes in mouse models of neurodegenerative movement disorders.

    Science.gov (United States)

    Preisig, Daniel F; Kulic, Luka; Krüger, Maik; Wirth, Fabian; McAfoose, Jordan; Späni, Claudia; Gantenbein, Pascal; Derungs, Rebecca; Nitsch, Roger M; Welt, Tobias

    2016-09-15

    Neurodegenerative diseases of the central nervous system frequently affect the locomotor system resulting in impaired movement and gait. In this study we performed a whole-body high-speed video gait analysis in three different mouse lines of neurodegenerative movement disorders to investigate the motor phenotype. Based on precise computerized motion tracking of all relevant joints and the tail, a custom-developed algorithm generated individual and comprehensive locomotor profiles consisting of 164 spatial and temporal parameters. Gait changes observed in the three models corresponded closely to the classical clinical symptoms described in these disorders: Muscle atrophy due to motor neuron loss in SOD1 G93A transgenic mice led to gait characterized by changes in hind-limb movement and positioning. In contrast, locomotion in huntingtin N171-82Q mice modeling Huntington's disease with basal ganglia damage was defined by hyperkinetic limb movements and rigidity of the trunk. Harlequin mutant mice modeling cerebellar degeneration showed gait instability and extensive changes in limb positioning. Moreover, model specific gait parameters were identified and were shown to be more sensitive than conventional motor tests. Altogether, this technique provides new opportunities to decipher underlying disease mechanisms and test novel therapeutic approaches. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. [Etiology of affective disorders].

    Science.gov (United States)

    Shinohara, M; Kariya, T

    1994-05-01

    We discussed mainly neurochemical etiology of affective disorders (A.D.). Neurochemically, decreased 5-HT uptake in the platelet, increased 5-HT2 receptor in the platelet and cortex of suicides, increased beta receptor in the brains of suicide, functional abnormality of alpha 2 receptor in clonidine, DMI test, GABAB receptor up-regulation after chronic administration of antidepressants and mood stabilizers, participation of neuropeptide Y, and abnormality of HPA axis were recognized. Moreover, we referred to the importance of psychosocial and genetic factors. As for the etiology of A.D., while predisposition and environment participate, the method of participation will be different in subtypes. Frailty to stress in a broad sense, however is commonly seen in A.D. Though psychosocial factors are important, the physical condition, which involves fatigue, cannot be ignored. And, it is the most important that the biological and genetical factors which cause A.D., in the face of stimuli, must first be elucidated.

  15. Potential for targeting dopamine/DARPP-32 signaling in neuropsychiatric and neurodegenerative disorders.

    Science.gov (United States)

    Nishi, Akinori; Shuto, Takahide

    2017-03-01

    Alterations in dopamine neurotransmission has been implicated in pathophysiology of neuropsychiatric and neurodegenerative disorders, and DARPP-32 plays a pivotal role in dopamine neurotransmission. DARPP-32 likely influences dopamine-mediated behaviors in animal models of neuropsychiatric and neurodegenerative disorders and therapeutic effects of pharmacological treatment. Areas covered: We will review animal studies on the biochemical and behavioral roles of DARPP-32 in drug addiction, schizophrenia and Parkinson's disease. In general, under physiological and pathophysiological conditions, DARPP-32 in D1 receptor expressing (D1R) -medium spiny neurons (MSNs) promotes dopamine/D1 receptor/PKA signaling, whereas DARPP-32 in D2 receptor expressing (D2R)-MSNs counteracts dopamine/D2 receptor signaling. However, the function of DARPP-32 is differentially regulated in acute and chronic phases of drug addiction; DARPP-32 enhances D1 receptor/PKA signaling in the acute phase, whereas DARPP-32 suppresses D1 receptor/PKA signaling in the chronic phase through homeostatic mechanisms. Therefore, DARPP-32 plays a bidirectional role in dopamine neurotransmission, depending on the cell type and experimental conditions, and is involved in dopamine-related behavioral abnormalities. Expert opinion: DARPP-32 differentially regulates dopamine signaling in D1R- and D2R-MSNs, and a shift of balance between D1R- and D2R-MSN function is associated with behavioral abnormalities. An adjustment of this imbalance is achieved by therapeutic approaches targeting DARPP-32-related signaling molecules.

  16. Does any drug to treat cancer target mTOR and iron hemostasis in neurodegenerative disorders?

    Science.gov (United States)

    Jodeiri Farshbaf, Mohammad; Ghaedi, Kamran

    2017-02-01

    The prevalence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease are increased by age. Alleviation of their symptoms and protection of normal neurons against degeneration are the main aspects of the research to establish novel therapeutic strategies. Iron as the one of most important cation not only play important role in the structure of electron transport chain proteins but also has pivotal duties in cellular activities. But disruption in iron hemostasis can make it toxin to neurons which causes lipid peroxidation, DNA damage and etc. In patients with Alzheimer and Parkinson misbalancing in iron homeostasis accelerate neurodegeneration and cause neuroinflmmation. mTOR as the common signaling pathway between cancer and neurodegenerative disorders controls iron uptake and it is in active form in both diseases. Anti-cancer drugs which target mTOR causes iron deficiency and dual effects of mTOR inhibitors can candidate them as a therapeutic strategy to alleviate neurodegeneration/inflammation because of iron overloading.

  17. Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Chanshuai Han

    2018-02-01

    Full Text Available Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop “first-of-their-kind” disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI and its partners are piloting an “Open Science” model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

  18. Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders

    Science.gov (United States)

    Iturria-Medina, Yasser; Sotero, Roberto C.; Toussaint, Paule J.; Evans, Alan C.

    2014-01-01

    Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders. PMID:25412207

  19. Lower urinary tract dysfunction in patients with parkinsonism and other neurodegenerative disorders

    DEFF Research Database (Denmark)

    Winge, Kristian

    2015-01-01

    be present, most commonly in disorders with spinal cord involvement. The systematic and careful tracking of symptoms, evaluation using non-invasive techniques, and conservative management including pharmacologic treatments can often markedly improve the lives of patients and their caregivers....... of dopaminergic neurons in the substantia nigra and possibly also in the ventral tegmental area induces loss of neurogenic bladder control through dysfunction of a complex network in which selective disinhibition of bladder reflexes is lost. In PD, more than 60% of patients have troublesome bladder symptoms...... of incontinence in Alzheimer's disease, but higher cognitive function including attention and self-management may play a role. Incontinence is a major risk factor for loss of independence. The complex pathophysiologic mechanisms of neurodegenerative disorders and hence complex symptoms play important roles...

  20. Structural disorder and the loss of RNA homeostasis in aging and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Douglas eGray

    2013-08-01

    Full Text Available Whereas many cases of neurodegenerative disease feature the abnormal accumulationof protein, an abundance of recent literature highlights loss of RNA homeostasis as aubiquitous and central feature of pathological states. In some diseases expandedrepeats have been identified in non-coding regions of disease-associated transcripts,calling into question the relevance of protein in the disease mechanism. We review theliterature in support of a hypothesis that intrinsically disordered proteins (proteins thatlack a stable three dimensional conformation are particularly sensitive to an age-relateddecline in maintenance of protein homeostasis. The potential consequences forstructurally disordered RNA binding proteins are explored, including their aggregationinto complexes that could be transmitted through a prion-like mechanism. We proposethat the spread of ribonucleoprotein complexes through the nervous system couldpropagate a neuronal error catastrophe at the level of RNA metabolism.

  1. Behavioral Phenotyping Assays for Genetic Mouse Models of Neurodevelopmental, Neurodegenerative, and Psychiatric Disorders.

    Science.gov (United States)

    Sukoff Rizzo, Stacey J; Crawley, Jacqueline N

    2017-02-08

    Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent behavioral symptoms. Mouse behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse behavioral tests available in the established behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategies can be employed to test hypotheses about environmental causes and gene × environment interactions.

  2. Application of monoterpenoids and their derivatives for treatment of neurodegenerative disorders.

    Science.gov (United States)

    Volcho, Konstantin P; Laev, Sergey S; Ashraf, Ghulam Md; Aliev, Gjumrakch; Salakhutdinov, Nariman F

    2017-01-11

    Neurodegenerative disorders (NDDs) like Alzheimer disease, Parkinson's disease and Huntington's disease are a heterogeneous group of disorders with the progressive and severe loss of neurons. There are no full proof cures for these diseases, and only medicines are available that can alleviate some of the symptoms. Developing effective treatments for the NDDs is a difficult but necessary task. Hence, the investigation of monoterpenoids which modulate targets applicable to many NDDs is highly relevant. Many monoterpenoids have demonstrated promising neuroprotective activity mediated by various systems. It can form the basis for elaboration of agents which will be useful both for the alleviation of symptoms of NDDs and for the treatment of diseases progression and also for prevention of neurodegeneration. The further developments including detections of monoterpenoids and their derivatives with high neuroprotective or neurotrophic activity as well as the results of qualified clinical trials are needed to draw solid conclusions regarding the efficacy of these agents.

  3. Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8

    Directory of Open Access Journals (Sweden)

    Sehgal SA

    2016-05-01

    Full Text Available Sheikh Arslan Sehgal,1–4 Shazia Mannan,1 Sannia Ali1 1Department of Bioscience, COMSATS Institute of Information Technology, Sahiwal, Pakistan; 2State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, 3University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan Abstract: Charcot–Marie–Tooth (CMT disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by homology modeling and pharmacophore identification. Detailed screening analyses were carried out by 2-D similarity search against prescribed antidepressant drugs with physicochemical properties. LigandScout was employed to ascertain novel molecules and pharmacophore properties. In this study, we report three novel compounds that showed maximum binding affinity with HSPB8. Docking analysis elucidated that Met37, Ser57, Ser58, Trp60, Thr63, Thr114, Lys115, Asp116, Gly117, Val152, Val154, Leu186, Asp189, Ser190, Gln191, and Glu192 are critical residues for ligand–receptor interactions. Our analyses suggested paroxetine as a potent compound for targeting HSPB8. Selected compounds have more effective energy scores than the selected drug analogs. Additionally, site-directed mutagenesis could be significant for further analysis of the binding pocket. The novel findings based on an in silico approach may be momentous for potent drug design against depression and CMT. Keywords: bioinformatics, computer

  4. Targeting innate immunity for neurodegenerative disorders of the central nervous system.

    Science.gov (United States)

    Andreasson, Katrin I; Bachstetter, Adam D; Colonna, Marco; Ginhoux, Florent; Holmes, Clive; Lamb, Bruce; Landreth, Gary; Lee, Daniel C; Low, Donovan; Lynch, Marina A; Monsonego, Alon; O'Banion, M Kerry; Pekny, Milos; Puschmann, Till; Russek-Blum, Niva; Sandusky, Leslie A; Selenica, Maj-Linda B; Takata, Kazuyuki; Teeling, Jessica; Town, Terrence; Van Eldik, Linda J

    2016-09-01

    Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview of physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia and astrocyte cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer's disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview on physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of

  5. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Amin Mottahedin

    2017-07-01

    Full Text Available The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function. In this article, we will review the role of glia cells in synaptic physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following perinatal inflammatory challenges and potential implications for neurodevelopmental and neurodegenerative disorders.

  6. Overcoming Seasonal Affective Disorder.

    Science.gov (United States)

    Leahy, Laura G

    2017-11-01

    Seasonal affective disorder (SAD) significantly impacts the lives of individuals around the world. The mood fluctuations that occur are not only exhibited during the winter months but also during the spring and summer. The key to identifying SAD is the distinct seasonal onset and spontaneous remission of symptoms over the course of a season. Nurses are in a unique position to identify the symptoms of SAD and offer treatment recommendations to reduce the negative impact of these seasonal mood fluctuations. As holistic health care practitioners, nurses provide patient education regarding healthy lifestyle interventions, which can aid in minimizing the disruptive symptoms of SAD. Advanced practice nurses can offer pharmacotherapy interventions to address symptoms contributing to the individual's inability to function across domains-individual, family, and social. Finally, after reading the article, nurses of all disciplines will have a better understanding of the evidence-based bright light therapy (also known as light box therapy) and how to incorporate this treatment when caring for patients with SAD. [Journal of Psychosocial Nursing and Mental Health Services, 55(11), 10-14.]. Copyright 2017, SLACK Incorporated.

  7. Proline-rich polypeptides in Alzheimer's disease and neurodegenerative disorders -- therapeutic potential or a mirage?

    Science.gov (United States)

    Gladkevich, A; Bosker, F; Korf, J; Yenkoyan, K; Vahradyan, H; Aghajanov, M

    2007-10-01

    The development of effective and safe drugs for a growing Alzheimer disease population is an increasing need at present. Both experimental and clinical evidence support a beneficial effect of proline-rich polypeptides in a number of neurodegenerative diseases, including Alzheimer disease. Experimental data have shown that proline-rich polypeptides isolated from bovine neurohypophisis possess neuroprotective and neuromodulatory properties in mice with aluminum neurotoxicosis or neuronal damage caused by venoms and toxins. Proline-rich polypeptides from ovine colostrums, so called Colostrinin, have been shown to produce cognitive improvement in an experimental model and in patients with Alzheimer disease. However, the precise mechanism underlying the neuroprotective action of proline-rich polypeptides is not very well established. Moreover, studies pointing at a neuroprotective effect of proline-rich polypeptides from bovine neurohypophisis in humans have not been reported thus far. The authors conclude that more detailed information on the mode of action of proline-rich polypeptides is needed as well as confirmation of their efficacy in broad clinical trials before this approach can really show its potential in the treatment of neurodegenerative disorders.

  8. Assessing Executive Dysfunction in Neurodegenerative Disorders: A Critical Review of Brief Neuropsychological Tools

    Directory of Open Access Journals (Sweden)

    Helena S. Moreira

    2017-11-01

    Full Text Available Executive function (EF has been defined as a multifaceted construct that involves a variety of high-level cognitive abilities such as planning, working memory, mental flexibility, and inhibition. Being able to identify deficits in EF is important for the diagnosis and monitoring of several neurodegenerative disorders, and thus their assessment is a topic of much debate. In particular, there has been a growing interest in the development of neuropsychological screening tools that can potentially provide a reliable quick measure of EF. In this review, we critically discuss the four screening tools of EF currently available in the literature: Executive Interview-25 (EXIT 25, Frontal Assessment Battery (FAB, INECO Frontal Screening (IFS, and FRONTIER Executive Screen (FES. We first describe their features, and then evaluate their psychometric properties, the existing evidence on their neural correlates, and the empirical work that has been conducted in clinical populations. We conclude that the four screening tools generally present appropriate psychometric properties, and are sensitive to impairments in EF in several neurodegenerative conditions. However, more research will be needed mostly with respect to normative data and neural correlates, and to determine the extent to which these tools add specific information to the one provided by global cognition screening tests. More research directly comparing the available tools with each other will also be important to establish in which conditions each of them can be most useful.

  9. Assessing Executive Dysfunction in Neurodegenerative Disorders: A Critical Review of Brief Neuropsychological Tools.

    Science.gov (United States)

    Moreira, Helena S; Costa, Ana S; Castro, São L; Lima, César F; Vicente, Selene G

    2017-01-01

    Executive function (EF) has been defined as a multifaceted construct that involves a variety of high-level cognitive abilities such as planning, working memory, mental flexibility, and inhibition. Being able to identify deficits in EF is important for the diagnosis and monitoring of several neurodegenerative disorders, and thus their assessment is a topic of much debate. In particular, there has been a growing interest in the development of neuropsychological screening tools that can potentially provide a reliable quick measure of EF. In this review, we critically discuss the four screening tools of EF currently available in the literature: Executive Interview-25 (EXIT 25), Frontal Assessment Battery (FAB), INECO Frontal Screening (IFS), and FRONTIER Executive Screen (FES). We first describe their features, and then evaluate their psychometric properties, the existing evidence on their neural correlates, and the empirical work that has been conducted in clinical populations. We conclude that the four screening tools generally present appropriate psychometric properties, and are sensitive to impairments in EF in several neurodegenerative conditions. However, more research will be needed mostly with respect to normative data and neural correlates, and to determine the extent to which these tools add specific information to the one provided by global cognition screening tests. More research directly comparing the available tools with each other will also be important to establish in which conditions each of them can be most useful.

  10. Epigenetic Research of Neurodegenerative Disorders Using Patient iPSC-Based Models

    Science.gov (United States)

    2016-01-01

    Epigenetic mechanisms play a role in human disease but their involvement in pathologies from the central nervous system has been hampered by the complexity of the brain together with its unique cellular architecture and diversity. Until recently, disease targeted neural types were only available as postmortem materials after many years of disease evolution. Current in vitro systems of induced pluripotent stem cells (iPSCs) generated by cell reprogramming of somatic cells from patients have provided valuable disease models recapitulating key pathological molecular events. Yet whether cell reprogramming on itself implies a truly epigenetic reprogramming, the epigenetic mechanisms governing this process are only partially understood. Moreover, elucidating epigenetic regulation using patient-specific iPSC-derived neural models is expected to have a great impact to unravel the pathophysiology of neurodegenerative diseases and to hopefully expand future therapeutic possibilities. Here we will critically review current knowledge of epigenetic involvement in neurodegenerative disorders focusing on the potential of iPSCs as a promising tool for epigenetic research of these diseases. PMID:26697081

  11. [Affective disorders and impulsivity].

    Science.gov (United States)

    Belzeaux, R; Correard, N; Mazzola-Pomietto, P; Adida, M; Cermolacce, M; Azorin, J-M

    2014-12-01

    Impulsivity is a complex and important phenomenon in mood disorders. Impulse control disorders, as defined in DSM, are more frequent in mood disorders especially in Bipolar Disorder type I, and are associated with a more severe course of illness. Dimensional studies demonstrate that impulsivity is a core manifestation of bipolar disorder both as state- and trait-dependent markers in patients. Comorbid substance use disorders are often associated with a higher level of impulsivity whereas the relation between suicidal behaviors and higher impulsivity remains uncertain. Moreover, neuropsychological tests were used to study correlation between clinical impulsivity and laboratory measurements of impulsivity. Level of correlation remains weak and several explanations are proposed in the literature. Copyright © 2014 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  12. Cellular stress responses, mitostress and carnitine insufficiencies as critical determinants in aging and neurodegenerative disorders: role of hormesis and vitagenes.

    Science.gov (United States)

    Calabrese, Vittorio; Cornelius, Carolin; Stella, Anna Maria Giuffrida; Calabrese, Edward J

    2010-12-01

    The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. A prediction of this theory is that, among species, differential rates of aging may be apparent on the basis of intrinsic differences in oxidative damage accrual. Although widely accepted, there is a growing number of exceptions to this theory, most contingently related to genetic model organism investigations. Proteins are one of the prime targets for oxidative damage and cysteine residues are particularly sensitive to reversible and irreversible oxidation. The adaptation and survival of cells and organisms requires the ability to sense proteotoxic insults and to coordinate protective cellular stress response pathways and chaperone networks related to protein quality control and stability. The toxic effects that stem from the misassembly or aggregation of proteins or peptides, in any cell type, are collectively termed proteotoxicity. Despite the abundance and apparent capacity of chaperones and other components of homeostasis to restore folding equilibrium, the cell appears poorly adapted for chronic proteotoxic stress which increases in cancer, metabolic and neurodegenerative diseases. Pharmacological modulation of cellular stress response pathways has emerging implications for the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. A critical key to successful medical intervention is getting the dose right. Achieving this goal can be extremely challenging due to human inter-individual variation as affected by age, gender, diet, exercise, genetic factors and health status. The nature of the dose response in and adjacent to the therapeutic zones, over the past decade has received considerable advances. The hormetic dose-response, challenging long-standing beliefs about the nature of the dose-response in a lowdose zone, has the potential to affect significantly the design of pre

  13. Mood and affect disorders.

    Science.gov (United States)

    Tang, Michael H; Pinsky, Elizabeth G

    2015-02-01

    Depressive disorders are common in children and adolescents, with estimates for depressive episodes as high as 18.2% for girls and 7.7% for boys by age 17 years, and are a major cause of morbidity and even mortality. The primary care pediatrician should be able to (1) diagnose depressive disorders and use standardized instruments; (2) ask about suicide, self-harm, homicide, substance use, mania, and psychosis; (3) triage the severity of illness; (4) be aware of the differential diagnosis, including normal development, other depressive disorders, bipolar disorders, and comorbid disorders, such as anxiety and substance use; (5) refer to evidenced-based psychotherapies; (6) prescribe first-line medications; and (7) provide ongoing coordination in a medical home. Pediatric bipolar disorders and the new disruptive mood dysregulation disorder (DMDD) diagnoses are controversial but not uncommon, with prevalence estimates ranging from 0.8% to 4.3% in children at various ages. Although the pediatrician is not likely to be prescribing medications for children with bipolar disorder and DMDD diagnoses, all clinicians should be familiar with common neuroleptics and other mood stabilizers, including important potential adverse effects. Basic management of depressive and bipolar disorders is an important skill for primary care pediatricians. © American Academy of Pediatrics, 2015. All rights reserved.

  14. Metabolic control of the proteotoxic stress response: implications in diabetes mellitus and neurodegenerative disorders.

    Science.gov (United States)

    Su, Kuo-Hui; Dai, Chengkai

    2016-11-01

    Proteome homeostasis, or proteostasis, is essential to maintain cellular fitness and its disturbance is associated with a broad range of human health conditions and diseases. Cells are constantly challenged by various extrinsic and intrinsic insults, which perturb cellular proteostasis and provoke proteotoxic stress. To counter proteomic perturbations and preserve proteostasis, cells mobilize the proteotoxic stress response (PSR), an evolutionarily conserved transcriptional program mediated by heat shock factor 1 (HSF1). The HSF1-mediated PSR guards the proteome against misfolding and aggregation. In addition to proteotoxic stress, emerging studies reveal that this proteostatic mechanism also responds to cellular energy state. This regulation is mediated by the key cellular metabolic sensor AMP-activated protein kinase (AMPK). In this review, we present an overview of the maintenance of proteostasis by HSF1, the metabolic regulation of the PSR, particularly focusing on AMPK, and their implications in the two major age-related diseases-diabetes mellitus and neurodegenerative disorders.

  15. Brain Atrophy of Secondary REM-Sleep Behavior Disorder in Neurodegenerative Disease.

    Science.gov (United States)

    Kim, Hee-Jin; Im, Hyung Kyun; Kim, Juhan; Han, Jee-Young; de Leon, Mony; Deshpande, Anup; Moon, Won-Jin

    2016-04-05

    Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy. We investigated that dementia with RBD might show distinctive cortical atrophic patterns. A total of 31 patients with idiopathic Parkinson's disease (IPD), 23 with clinically probable Alzheimer's disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for detection of regional brain atrophy among groups of subjects. Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes. The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α-synucleinopathy.

  16. Niemann-Pick C disease gene mutations and age-related neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Michael Zech

    Full Text Available Niemann-Pick type C (NPC disease is a rare autosomal-recessively inherited lysosomal storage disorder caused by mutations in NPC1 (95% or NPC2. Given the highly variable phenotype, diagnosis is challenging and particularly late-onset forms with predominantly neuropsychiatric presentations are likely underdiagnosed. Pathophysiologically, genetic alterations compromising the endosomal/lysosomal system are linked with age-related neurodegenerative disorders. We sought to examine a possible association of rare sequence variants in NPC1 and NPC2 with Parkinson's disease (PD, frontotemporal lobar degeneration (FTLD and progressive supranuclear palsy (PSP, and to genetically determine the proportion of potentially misdiagnosed NPC patients in these neurodegenerative conditions. By means of high-resolution melting, we screened the coding regions of NPC1 and NPC2 for rare genetic variation in a homogenous German sample of patients clinically diagnosed with PD (n = 563, FTLD (n = 133 and PSP (n = 94, and 846 population-based controls. The frequencies of rare sequence variants in NPC1/2 did not differ significantly between patients and controls. Disease-associated NPC1/2 mutations were found in six PD patients (1.1% and seven control subjects (0.8%, but not in FTLD or PSP. All rare variation was detected in the heterozygous state and no compound heterozygotes were observed. Our data do not support the hypothesis that rare NPC1/2 variants confer susceptibility for PD, FTLD, or PSP in the German population. Misdiagnosed NPC patients were not present in our samples. However, further assessment of NPC disease genes in age-related neurodegeneration is warranted.

  17. Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases.

    Science.gov (United States)

    Shan, Ling; Hofman, Michel A; van Wamelen, Daniel J; Van Someren, Eus J W; Bao, Ai-Min; Swaab Dick, F

    2012-05-01

    Neuronal histamine shows diurnal rhythms in rodents and plays a major role in the maintenance of vigilance. No data are available on its diurnal fluctuation in humans, either in health or in neurodegenerative disorders such as Parkinson disease (PD), Alzheimer disease (AD), or Huntington disease (HD), all of which are characterized by sleep-wake disturbances. Quantitative in situ hybridization was used to study the mRNA expression of histidine decarboxylase (HDC), the key enzyme of histamine production in the tuberomammillary nucleus (TMN) in postmortem human hypothalamic tissue, obtained from 33 controls and 31 patients with a neurodegenerative disease-PD (n = 15), AD (n = 9), and HD (n = 8)-and covering the full 24-h cycle with respect to clock time of death. HDC-mRNA levels in controls were found to be significantly higher during the daytime than at night (e.g., 08:01-20:00 versus 20:01-08:00, P = 0.004). This day-night fluctuation was markedly different in patients with neurodegenerative diseases. The diurnal fluctuation of HDC-mRNA expression in human TMN supports a role for neuronal histamine in regulating day-night rhythms. Future studies should investigate histamine rhythm abnormalities in neurodegenerative disorders. Shan L; Hofman MA; van Wamelen DJ; Van Someren EJW; Bao AM; Swaab DF. Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases.

  18. Family psychoeducation for affective disorders

    DEFF Research Database (Denmark)

    Timmerby, Nina; Austin, Stephen; Bech, Per

    2017-01-01

    The aim of this article was to examine the evidence of family psychoeducation (FPE) for affective disorders. Evidence indicates that FPE can be an effective supplement to the standard treatment of patients with affective disorders. FPE can effectively reduce the patients' risk of relapse and reduce...

  19. Low-dose, continuous enzyme replacement therapy ameliorates brain pathology in the neurodegenerative lysosomal disorder mucopolysaccharidosis type IIIA.

    Science.gov (United States)

    King, Barbara; Hassiotis, Sofia; Rozaklis, Tina; Beard, Helen; Trim, Paul J; Snel, Marten F; Hopwood, John J; Hemsley, Kim M

    2016-05-01

    Repeated replacement of sulphamidase via cerebrospinal fluid injection is an effective treatment for pathological changes in the brain in mice and dogs with the lysosomal storage disorder, mucopolysaccharidosis type IIIA (MPS IIIA). Investigational trials of this approach are underway in children with this condition, however, infusions require attendance at a specialist medical facility. We sought to comprehensively evaluate the effectiveness of sustained-release (osmotic pump-delivered) enzyme replacement therapy in murine MPS IIIA as this method, if applied to humans, would require only subcutaneous administration of enzyme once the pump was installed. Six-week-old MPS IIIA and unaffected mice were implanted with subcutaneous mini-osmotic pumps connected to an infusion cannula directed at the right lateral ventricle. Either recombinant human sulphamidase or vehicle were infused over the course of 7 weeks, with pumps replaced part-way through the experimental period. We observed near-normalisation of primarily stored substrate (heparan sulphate) in both hemispheres of the MPS IIIA brain and cervical spinal cord, as determined using tandem mass spectrometry. Immunohistochemistry indicated a reduction in secondarily stored GM 3 ganglioside and neuroinflammatory markers. A bias towards the infusion side was seen in some, but not all outcomes. The recombinant enzyme appears stable under pump-like conditions for at least 1 month. Given that infusion pumps are in clinical use in other nervous system disorders, e.g. for treatment of spasticity or brain tumours, this treatment method warrants consideration for testing in large animal models of MPS IIIA and other lysosomal storage disorders that affect the brain. Clinical trials of repeated injection of replacement enzyme into CSF are underway in patients with the inherited neurodegenerative disorder mucopolysaccharidosis type IIIA. In this pre-clinical study, we examined an alternative approach - slow, continual infusion

  20. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders.

    Science.gov (United States)

    Sas, Katalin; Robotka, Hermina; Toldi, József; Vécsei, László

    2007-06-15

    The mitochondria have several important functions in the cell. A mitochondrial dysfunction causes an abatement in ATP production, oxidative damage and the induction of apoptosis, all of which are involved in the pathogenesis of numerous disorders. This review focuses on mitochondrial dysfunctions and discusses their consequences and potential roles in the pathomechanism of neurodegenerative disorders. Other pathogenetic factors are also briefly surveyed. The second part of the review deals with the kynurenine metabolic pathway, its alterations and their potential association with cellular energy impairment in certain neurodegenerative diseases. During energy production, most of the O(2) consumed by the mitochondria is reduced fully to water, but 1-2% of the O(2) is reduced incompletely to give the superoxide anion (O(2)(-)). If the function of one or more respiratory chain complexes is impaired for any reason, the enhanced production of free radicals further worsens the mitochondrial function by causing oxidative damage to macromolecules, and by opening the mitochondrial permeability transition pores thereby inducing apoptosis. These high-conductance pores offer a pathway which can open in response to certain stimuli, leading to the induction of the cells' own suicide program. This program plays an essential role in regulating growth and development, in the differentiation of immune cells, and in the elimination of abnormal cells from the organism. Both failure and exaggeration of apoptosis in a human body can lead to disease. The increasing amount of superoxide anions can react with nitric oxide to yield the highly toxic peroxynitrite anion, which can destroy cellular macromolecules. The roles of oxidative, nitrative and nitrosative damage are discussed. Senescence is accompanied by a higher degree of reactive oxygen species production, and by diminished functions of the endoplasmic reticulum and the proteasome system, which are responsible for maintenance of the

  1. Non-opioid nociceptive activity of human dynorphin mutants that cause neurodegenerative disorder spinocerebellar ataxia type 23

    NARCIS (Netherlands)

    Watanabe, Hiroyuki; Mizoguchi, Hirokazu; Verbeek, Dineke S.; Kuzmin, Alexander; Nyberg, Fred; Krishtal, Oleg; Sakurada, Shinobu; Bakalkin, Georgy

    We previously identified four missense mutations in the prodynorphin gene that cause human neurodegenerative disorder spinocerebellar ataxia type 23 (SCA23). Three mutations substitute Leu(5), Arg(6), and Arg(9) to Ser (L5S), Trp (R6W) and Cys (R9C) in dynorphin A(1-17) (Dyn A), a peptide with both

  2. Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program.

    Science.gov (United States)

    Beach, Thomas G; Adler, Charles H; Sue, Lucia I; Serrano, Geidy; Shill, Holly A; Walker, Douglas G; Lue, LihFen; Roher, Alex E; Dugger, Brittany N; Maarouf, Chera; Birdsill, Alex C; Intorcia, Anthony; Saxon-Labelle, Megan; Pullen, Joel; Scroggins, Alexander; Filon, Jessica; Scott, Sarah; Hoffman, Brittany; Garcia, Angelica; Caviness, John N; Hentz, Joseph G; Driver-Dunckley, Erika; Jacobson, Sandra A; Davis, Kathryn J; Belden, Christine M; Long, Kathy E; Malek-Ahmadi, Michael; Powell, Jessica J; Gale, Lisa D; Nicholson, Lisa R; Caselli, Richard J; Woodruff, Bryan K; Rapscak, Steven Z; Ahern, Geoffrey L; Shi, Jiong; Burke, Anna D; Reiman, Eric M; Sabbagh, Marwan N

    2015-08-01

    The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0-hour median post-mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200

  3. Seasonal Affective Disorder

    Science.gov (United States)

    ... look different in women, men, seniors, and children. Depression and College Students : This booklet describes what depression is, how it affects college students, and treatment options. Teen Depression : This flier for ...

  4. Mesenchymal stem cells-based therapy as a potential treatment in neurodegenerative disorders: is the escape from senescence an answer?

    Directory of Open Access Journals (Sweden)

    Alessandro Castorina

    2015-01-01

    Full Text Available Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration.Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during long-term culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-related transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.

  5. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders

    NARCIS (Netherlands)

    Kos, Claire; van Tol, Marie-Jose; Marsman, Jan-Bernard C.; Knegtering, Henderikus; Aleman, Andre

    2016-01-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar

  6. Recommendations for the Use of Serious Games in Neurodegenerative Disorders: 2016 Delphi Panel

    Directory of Open Access Journals (Sweden)

    Valeria Manera

    2017-07-01

    Full Text Available The use of Serious Games (SG in the health domain is expanding. In the field of neurodegenerative disorders (ND such as Alzheimer’s disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients’ treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014. The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI. SG are more adapted for use with trained caregivers (both at home and in clinical settings, with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game, and should be personalized with the help of a clinician.

  7. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Adriana Covarrubias-Pinto

    2015-11-01

    Full Text Available Ascorbic acid is a key antioxidant of the Central Nervous System (CNS. Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders.

  8. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders.

    Science.gov (United States)

    Covarrubias-Pinto, Adriana; Acuña, Aníbal Ignacio; Beltrán, Felipe Andrés; Torres-Díaz, Leandro; Castro, Maite Aintzane

    2015-11-27

    Ascorbic acid is a key antioxidant of the Central Nervous System (CNS). Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS) generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders.

  9. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders

    Science.gov (United States)

    Covarrubias-Pinto, Adriana; Acuña, Aníbal Ignacio; Beltrán, Felipe Andrés; Torres-Díaz, Leandro; Castro, Maite Aintzane

    2015-01-01

    Ascorbic acid is a key antioxidant of the Central Nervous System (CNS). Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS) generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders. PMID:26633354

  10. DNA damage in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Coppedè, Fabio, E-mail: fabio.coppede@med.unipi.it; Migliore, Lucia, E-mail: lucia.migliore@med.unipi.it

    2015-06-15

    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  11. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

    Science.gov (United States)

    Fernández-Ruiz, Javier; Sagredo, Onintza; Pazos, M Ruth; García, Concepción; Pertwee, Roger; Mechoulam, Raphael; Martínez-Orgado, José

    2013-01-01

    Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ9-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ9-tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels. PMID:22625422

  12. Imaging of neurodegenerative cognitive and behavioral disorders: practical considerations for dementia clinical practice.

    Science.gov (United States)

    Atri, Alireza

    2016-01-01

    This chapter reviews clinical applications and imaging findings useful in medical practice relating to neurodegenerative cognitive/dementing disorders. The preponderance of evidence and consensus guidelines support an essential role of multitiered neuroimaging in the evaluation and management of neurodegenerative cognitive/dementia syndrome that range in severity from mild impairments to frank dementia. Additionally, imaging features are incorporated in updated clinical and research diagnostic criteria for most dementias, including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Frontotemporal Lobar Degenerations/Frontotemporal Dementia (FTD), and Vascular Cognitive Impairment (VCI). Best clinical practices dictate that structural imaging, preferably with magnetic resonance imaging (MRI) when possible and computed tomography when not, be obtained as a first-tier approach during the course of a thorough clinical evaluation to improve diagnostic confidence and assess for nonneurodegenerative treatable conditions that may cause or substantially contribute to cognitive/behavioral symptoms or which may dictate a substantial change in management. These conditions include less common structural (e.g., mass lesions such as tumors and hematomas; normal-pressure hydrocephalus), inflammatory, autoimmune and infectious conditions, and more common comorbid contributing conditions (e.g., vascular cerebral injury causing leukoaraiosis, infarcts, or microhemorrhages) that can produce a mixed dementia syndrome. When, after appropriate clinical, cognitive/neuropsychologic, and structural neuroimaging assessment, a dementia specialist remains in doubt regarding etiology and appropriate management, second-tier imaging with molecular methods, preferably with fluorodexoyglucose positron emission tomography (PET) (or single-photon emission computed tomography if PET is unavailable) can provide more diagnostic specificity (e.g., help differentiate between atypical AD and FTD as

  13. Skin disorders affecting the feet

    African Journals Online (AJOL)

    Skin disorders on the feet can affect the glabrous skin on the dorsal aspects, or the thick skin on the plantar aspects, thereof, or both. Some can affect one foot, and others both of them. These diseases can be inflammatory, genetically inherited, infectious and neoplastic in origin. It is important to identify them and to.

  14. Bipolar Affective Disorder and Migraine

    Directory of Open Access Journals (Sweden)

    Birk Engmann

    2012-01-01

    Full Text Available This paper consists of a case history and an overview of the relationship, aetiology, and treatment of comorbid bipolar disorder migraine patients. A MEDLINE literature search was used. Terms for the search were bipolar disorder bipolar depression, mania, migraine, mood stabilizer. Bipolar disorder and migraine cooccur at a relatively high rate. Bipolar II patients seem to have a higher risk of comorbid migraine than bipolar I patients have. The literature on the common roots of migraine and bipolar disorder, including both genetic and neuropathological approaches, is broadly discussed. Moreover, bipolar disorder and migraine are often combined with a variety of other affective disorders, and, furthermore, behavioural factors also play a role in the origin and course of the diseases. Approach to treatment options is also difficult. Several papers point out possible remedies, for example, valproate, topiramate, which acts on both diseases, but no first-choice treatments have been agreed upon yet.

  15. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders.

    Science.gov (United States)

    Kos, Claire; van Tol, Marie-José; Marsman, Jan-Bernard C; Knegtering, Henderikus; Aleman, André

    2016-10-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. Copyright © 2016. Published by Elsevier Ltd.

  16. [Affective disorders and biological rhythms].

    Science.gov (United States)

    Le Strat, Y; Ramoz, N; Gorwood, P

    2008-06-01

    Disruptions of circadian rhythms are described in affective disorders, including unipolar and bipolar disorder, but also seasonal affective disorder. Sleep-wake and hormone circadian rhythms are among the most quoted examples. Depression could be conceptualized as a desynchronization between the endogenous circadian pacemaker and the exogenous stimuli, such as sunlight and social rhythms. Accordingly, Clock genes have been studied and the literature suggests that variants in these genes confer a higher risk of relapse, more sleep disturbances associated with depression, as well as incomplete treatment response. Most of therapeutic interventions in depression have an impact on biological rhythms. Some of them exclusively act via a biological pathway, such as sleep deprivation or light therapy. Some psychosocial interventions are specifically focusing on social rhythms, particularly in bipolar disorder, in which the promotion of stabilization is emphasized. Finally, all antidepressant medications could improve biological rhythms, but some new agents are now totally focusing this novel approach for the treatment of depression.

  17. Cannabinoids and value-based decision making: Implications for neurodegenerative disorders

    NARCIS (Netherlands)

    Lee, AM; Oleson, E.B.; Diergaarde, L.; Cheer, J.F.; Pattij, T.

    2012-01-01

    In recent years, disturbances in cognitive function have been increasingly recognized as important symptomatic phenomena in neurodegenerative diseases, including Parkinson's disease (PD). Value-based decision making in particular is an important executive cognitive function that is not only impaired

  18. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

    OpenAIRE

    Chin-Chan, Miguel; Navarro-Yepes, Juliana; Quintanilla-Vega, Betzabet

    2015-01-01

    Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, ...

  19. Gut Microbiota, Nitric Oxide, and Microglia as Prerequisites for Neurodegenerative Disorders.

    Science.gov (United States)

    Tse, Joyce K Y

    2017-07-19

    Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer's disease (AD) and Parkinson's disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g., superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation. NO also instigates a down-regulated secretion of brain-derived neurotrophic factor, which is essential for neuronal survival, development and differentiation, synaptogenesis, and learning and memory. The gut-brain axis denotes communication between the enteric nervous system (ENS) of the GI tract and the central nervous system (CNS) of the brain, and the modes of communication include the vagus nerve, passive diffusion and carrier by oxyhemoglobin. Amyloid precursor protein that forms amyloid beta plaques in AD is normally expressed in the ENS by gut bacteria, but when amyloid beta accumulates, it compromises CNS functions. Escherichia coli and Salmonella enterica are among the many bacterial strains that express and secrete amyloid proteins and contribute to AD pathogenesis. Gut microbiota is essential for regulating microglia maturation and activation, and activated microglia secrete significant amounts of iNOS. Pharmacological interventions and lifestyle modifications to rectify aberrant NO signaling in AD include NOS inhibitors, NMDA receptor antagonists, potassium channel modulators, probiotics, diet, and exercise.

  20. The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies: a review.

    Science.gov (United States)

    Pang, Shirley Yin-Yu; Teo, Kay-Cheong; Hsu, Jacob Shujui; Chang, Richard Shek-Kwan; Li, Miaoxin; Sham, Pak-Chung; Ho, Shu-Leong

    2017-01-01

    The clinical diagnosis of neurodegenerative disorders based on phenotype is difficult in heterogeneous conditions with overlapping symptoms. It does not take into account the disease etiology or the highly variable clinical course even amongst patients diagnosed with the same disorder. The advent of next generation sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all gene variants in the genome simultaneously. With the plethora of new genes being identified, genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia (SCA), hereditary spastic paraplegia (HSP) and Charcot-Marie-Tooth disease (CMT) has become widely accepted. It has also become clear that gene variants play a role in common and predominantly sporadic neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). The observation of pleiotropy has emerged, with mutations in the same gene giving rise to diverse phenotypes, which further increases the complexity of phenotype-genotype correlation. Possible mechanisms of pleiotropy include different downstream effects of different mutations in the same gene, presence of modifier genes, and oligogenic inheritance. Future directions include development of bioinformatics tools and establishment of more extensive public genotype/phenotype databases to better distinguish deleterious gene variants from benign polymorphisms, translation of genetic findings into pathogenic mechanisms through in-vitro and in-vivo studies, and ultimately finding disease-modifying therapies for neurodegenerative disorders.

  1. Executive dysfunction affects word list recall performance: Evidence from amyotrophic lateral sclerosis and other neurodegenerative diseases.

    Science.gov (United States)

    Consonni, Monica; Rossi, Stefania; Cerami, Chiara; Marcone, Alessandra; Iannaccone, Sandro; Francesco Cappa, Stefano; Perani, Daniela

    2017-03-01

    The Rey Auditory Verbal Learning Test (RAVLT) is widely used in clinical practice to evaluate verbal episodic memory. While there is evidence that RAVLT performance can be influenced by executive dysfunction, the way executive disorders affect the serial position curve (SPC) has not been yet explored. To this aim, we analysed immediate and delayed recall performances of 13 non-demented amyotrophic lateral sclerosis (ALS) patients with a specific mild executive dysfunction (ALSci) and compared their performances to those of 48 healthy controls (HC) and 13 cognitively normal patients with ALS. Moreover, to control for the impact of a severe dysexecutive syndrome and a genuine episodic memory deficit on the SPC, we enrolled 15 patients with a diagnosis of behavioural variant of frontotemporal dementia (bvFTD) and 18 patients with probable Alzheimer's disease (AD). Results documented that, compared to cognitively normal subjects, ALSci patients had a selective mid-list impairment for immediate recall scores. The bvFTD group obtained low performances with a selectively increased forgetting rate for terminal items, whereas the AD group showed a disproportionately large memory loss on the primary and middle part of the SPC for immediate recall scores and were severely impaired in the delayed recall trial. These results suggested that subtle executive dysfunctions might influence the recall of mid-list items, possibly reflecting deficiency in control strategies at retrieval of word lists, whereas severer dysexecutive syndrome might also affect the recall of terminal items possibly due to attention deficit or retroactive interference. © 2015 The British Psychological Society.

  2. Phosphorylation of collapsin response mediator protein-2 disrupts neuronal maturation in a model of adult neurogenesis: Implications for neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Rockenstein Edward

    2011-09-01

    Full Text Available Abstract Background Recent studies suggest that the pathogenic process in neurodegenerative disorders may disrupt mature neuronal circuitries and neurogenesis in the adult brain. Abnormal activation of CDK5 is associated with neurodegenerative disorders, and recently a critical role for CDK5 in adult neurogenesis has been identified. We have developed an in vitro model of abnormal CDK5 activation during adult hippocampal neurogenesis, and here we used this model to investigate aberrantly phosphorylated downstream targets of CDK5. Results Abnormal CDK5 activation in an in vitro model of adult neurogenesis results in hyperphosphorylation of collapsin-response mediator protein-2 (CRMP2 and impaired neurite outgrowth. Inhibition of CDK5, or expression of a non-phosphorylatable (S522A CRMP2 construct reduced CRMP2 hyperphosphorylation, and reversed neurite outgrowth deficits. CRMP2 plays a role in microtubule dynamics; therefore we examined the integrity of microtubules in this model using biochemical and electron microscopy techniques. We found that microtubule organization was disrupted under conditions of CDK5 activation. Finally, to study the relevance of these findings to neurogenesis in neurodegenerative conditions associated with HIV infection, we performed immunochemical analyses of the brains of patients with HIV and transgenic mice expressing HIV-gp120 protein. CDK5-mediated CRMP2 phosphorylation was significantly increased in the hippocampus of patients with HIV encephalitis and in gp120 transgenic mice, and this effect was rescued by genetic down-modulation of CDK5 in the mouse model. Conclusions These results reveal a functional mechanism involving microtubule destabilization through which abnormal CDK5 activation and CRMP2 hyperphosphorylation might contribute to defective neurogenesis in neurodegenerative disorders such as HIV encephalitis.

  3. Combination Comprising Parthenolide For Use In The Treatment Of Alzheimer's Disease And Other Neurodegenerative Disorders

    KAUST Repository

    Bajic, Vladimir B.

    2015-06-18

    The present invention generally concerns particular methods and compositions for treatment of a neurodegenerative disease, such as Alzheimer\\'s Disease. In particular embodiments, there is a composition comprising Parthenolide and a second agent, including an inhibitor of TLR4/MD-2/CD14, nAChR agonist, Resatorvid, Curcumin, Tilorone or a Tilorone analog, or a combination thereof.

  4. Proline-rich polypeptides in Alzheimer's disease and neurodegenerative disorders - Therapeutic potential or a mirage?

    NARCIS (Netherlands)

    Gladkevich, A.; Bosker, F.; Korf, J.; Yenkoyan, K.; Vahradyan, H.; Aghajanov, M.

    2007-01-01

    The development of effective and safe drugs for a growing Alzheimer disease population is an increasing need at present. Both experimental and clinical evidence support a beneficial effect of proline-rich polypeptides in a number of neurodegenerative diseases, including Alzheimer disease.

  5. Visual Hallucinations in the Psychosis Spectrum and Comparative Information From Neurodegenerative Disorders and Eye Disease

    NARCIS (Netherlands)

    Waters, Flavie; Collerton, Daniel; Ffytche, Dominic H.; Jardri, Renaud; Pins, Delphine; Dudley, Robert; Blom, Jan Dirk; Mosimann, Urs Peter; Eperjesi, Frank; Ford, Stephen; Laroi, Frank

    Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding

  6. PET Imaging of the Peripheral Benzodiazepine Receptor : Monitoring Disease Progression and Therapy Response in Neurodegenerative Disorders

    NARCIS (Netherlands)

    Doorduin, Janine; de Vries, Erik F. J.; Dierckx, Rudi A.; Klein, Hans C.

    2008-01-01

    It is important to gain more insight into neurodegenerative diseases, because these debilitating diseases can not be cured. A common characteristic of many neurological diseases is neuroinflammation, which is accompanied by the presence of activated microglia cells. In activated microglia cells, an

  7. Pig Models of Neurodegenerative Disorders: Utilization in Cell Replacement-Based Preclinical Safety and Efficacy Studies

    Czech Academy of Sciences Publication Activity Database

    Doležalová, D.; Hruška-Plocháň, M.; Bjarkam, C. R.; Sorensen, J. C. H.; Cunningham, M.; Weingarten, D.; Ciacci, J. D.; Juhás, Štefan; Juhásová, Jana; Motlík, Jan; Hefferan, M. P.; Hazel, T.; Johe, K.; Carromeu, C.; Muotri, A.; Bui, J. D.; Strnádel, J.; Marsala, M.

    2014-01-01

    Roč. 522, č. 12 (2014), s. 2784-2801 ISSN 0021-9967 R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : pig * neurodegenerative models * stem cells Subject RIV: FH - Neurology Impact factor: 3.225, year: 2014

  8. Treatment of seasonal affective disorders

    Science.gov (United States)

    Praschak-Rieder, Nicole; Willeit, Matthäus

    2003-01-01

    Seasonal affective disorder (SAD) is a subform of major depressive disorder, recurrent, or bipolar disorder with a regular onset of depressive episodes at a certain time of year, usually the winter. The treatment of SAD is similar to that of other forms of affective disorder, except that bright light therapy is recommended as the first-line option. Light therapy conventionally involves exposure to visible light of at least 2500 lux intensity at eye level. The effects of light therapy are thought to be mediated exclusively by the eyes, not the skin, although this assumption has not yet been verified. Morning light therapy has proven to be superior to treatment regimens in the evening. Response rates to light therapy are about 80% in selected patient populations, with atypical depressive symptoms being the best predictor of a favorable treatment outcome. Data from randomized, controlled trials suggest that antidepressants are effective in the treatment of SAD. Three double-blind, placebo-controlled trials have been conducted showing promising results for the selective serotonin reuptake inhibitors (SSRIs) sertraline and fluoxetine, as well as for moclobemide, a reversible inhibitor of monoamine oxidase A. PMID:22033639

  9. Depressive symptoms in neurodegenerative diseases

    Science.gov (United States)

    Baquero, Miquel; Martín, Nuria

    2015-01-01

    Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer’s disease and related conditions like Parkinson’s disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have a particular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment. PMID:26301229

  10. Heteronemin, a marine sponge terpenoid, targets TDP-43, a key factor in several neurodegenerative disorders.

    Science.gov (United States)

    Cassiano, Chiara; Esposito, Roberta; Tosco, Alessandra; Zampella, Angela; D'Auria, Maria Valeria; Riccio, Raffaele; Casapullo, Agostino; Monti, Maria Chiara

    2014-01-14

    Trans-activation response DNA-binding protein of 43 kDa (TDP-43), a key factor in several neurodegenerative conditions, was discovered as a novel target of heteronemin by chemical proteomics. Combining bio-physical orthogonal approaches with biological analysis, heteronemin was found to influence the binding of TDP-43-cognate nucleic acids and to modulate the TDP-43 aggregation state and its cellular localization.

  11. Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Martin Hofmann-Apitius

    2015-12-01

    Full Text Available Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biological mechanisms, causally driving diseases, has been limited, in part due to the inherent complexity of biological systems. Whereas we have witnessed progress in the areas of cancer, cardiovascular and metabolic diseases, the area of neurodegenerative diseases has proved to be very challenging. This is in part because the aetiology of neurodegenerative diseases such as Alzheimer´s disease or Parkinson´s disease is unknown, rendering it very difficult to discern early causal events. Here we describe a panel of bioinformatics and modeling approaches that have recently been developed to identify candidate mechanisms of neurodegenerative diseases based on publicly available data and knowledge. We identify two complementary strategies—data mining techniques using genetic data as a starting point to be further enriched using other data-types, or alternatively to encode prior knowledge about disease mechanisms in a model based framework supporting reasoning and enrichment analysis. Our review illustrates the challenges entailed in integrating heterogeneous, multiscale and multimodal information in the area of neurology in general and neurodegeneration in particular. We conclude, that progress would be accelerated by increasing efforts on performing systematic collection of multiple data-types over time from each individual suffering from neurodegenerative disease. The work presented here has been driven by project AETIONOMY; a project funded in the course of the Innovative Medicines Initiative (IMI; which is a public-private partnership of the European Federation of Pharmaceutical Industry Associations

  12. Light Therapy Boxes for Seasonal Affective Disorder

    Science.gov (United States)

    Seasonal affective disorder treatment: Choosing a light therapy box Light therapy boxes can offer an effective treatment for seasonal affective disorder. Features such as light intensity, safety, cost and ...

  13. The interplay between iron accumulation, mitochondrial dysfunction and inflammation during the execution step of neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Pamela J. Urrutia

    2014-03-01

    Full Text Available A growing set of observations points to mitochondrial dysfunction, iron accumulation, oxidative damage and chronic inflammation as common pathognomonic signs of a number of neurodegenerative diseases that includes Alzheimer's disease, Huntington disease, amyotrophic lateral sclerosis, Friedrich’s ataxia and Parkinson’s disease. Particularly relevant for neurodegenerative processes is the relationship between mitochondria and iron. The mitochondrion upholds the synthesis of iron-sulfur clusters and heme, the most abundant iron-containing prosthetic groups in a large variety of proteins, so a fraction of incoming iron must go through this organelle before reaching its final destination. In turn, the mitochondrial respiratory chain is the source of reactive oxygen species (ROS derived from leaks in the electron transport chain. The co-existence of both iron and ROS in the secluded space of the mitochondrion makes this organelle particularly prone to hydroxyl radical-mediated damage. In addition, a connection between the loss of iron homeostasis and inflammation is starting to emerge; thus, inflammatory cytokines like TNF-alpha and IL-6 induce the synthesis of the divalent metal transporter 1 and promote iron accumulation in neurons and microglia. Here, we review the recent literature on mitochondrial iron homeostasis and the role of inflammation on mitochondria dysfunction and iron accumulation on the neurodegenerative process that lead to cell death in Parkinson’s disease. We also put forward the hypothesis that mitochondrial dysfunction, iron accumulation and inflammation are part of a synergistic self-feeding cycle that ends in apoptotic cell death, once the antioxidant cellular defense systems are finally overwhelmed.

  14. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases.

    Science.gov (United States)

    Chin-Chan, Miguel; Navarro-Yepes, Juliana; Quintanilla-Vega, Betzabet

    2015-01-01

    Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.

  15. FDTD-based Transcranial Magnetic Stimulation model applied to specific neurodegenerative disorders.

    Science.gov (United States)

    Fanjul-Vélez, Félix; Salas-García, Irene; Ortega-Quijano, Noé; Arce-Diego, José Luis

    2015-01-01

    Non-invasive treatment of neurodegenerative diseases is particularly challenging in Western countries, where the population age is increasing. In this work, magnetic propagation in human head is modelled by Finite-Difference Time-Domain (FDTD) method, taking into account specific characteristics of Transcranial Magnetic Stimulation (TMS) in neurodegenerative diseases. It uses a realistic high-resolution three-dimensional human head mesh. The numerical method is applied to the analysis of magnetic radiation distribution in the brain using two realistic magnetic source models: a circular coil and a figure-8 coil commonly employed in TMS. The complete model was applied to the study of magnetic stimulation in Alzheimer and Parkinson Diseases (AD, PD). The results show the electrical field distribution when magnetic stimulation is supplied to those brain areas of specific interest for each particular disease. Thereby the current approach entails a high potential for the establishment of the current underdeveloped TMS dosimetry in its emerging application to AD and PD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. RBD and Neurodegenerative Diseases.

    Science.gov (United States)

    Jiang, Haiyang; Huang, Jinsha; Shen, Yan; Guo, Shiyi; Wang, Luxi; Han, Chao; Liu, Ling; Ma, Kai; Xia, Yun; Li, Jie; Xu, Xiaoyun; Xiong, Nian; Wang, Tao

    2017-05-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disorder characterized by enacting one's dreams during the REM sleep, with most of the dreams being violent or aggressive, so that patients often come to see the doctor complaining hurting themselves or bed partners during sleep. Prevalence of RBD, based on population, is 0.38-2.01 %, but much higher in patients with neurodegenerative diseases, especially synucleinopathies. RBD may herald the emergence of synucleinopathies by decades, such that it may be used as an effective early marker of neurodegenerative diseases. Pharmaceutical treatment of RBD includes clonazepam, melatonin, pramipexole, and some newly reported medications. In this review, we summarized the clinical and PSG features of RBD, the pathophysiology and the therapy of it, focusing on the correlation between neurodegenerative diseases and RBD, in order to emphasize the significance of RBD as an early marker of neurodegenerative diseases.

  17. Progressive and self-limiting neurodegenerative disorders in Africa: a new prominent field of research led by South Africa but without strong health policy.

    Science.gov (United States)

    Poreau, Brice

    2016-01-01

    Neurodegenerative disorders are involved in mortality and morbidity of every country. A high prevalence is estimated in Africa. Neurodegenerative disorders are defined by a progressive or self-limiting alteration of neurons implied in specific functional and anatomical functions. It encompasses a various range of clinical disorders from self-limiting to progressive. Focus on public health policies and scientific research is needed to understand the mechanisms to reduce this high prevalence. We use bibliometrics and mapping tools to explore the area studies and countries involved in scientific research on neurodegenerative disorders in Africa. We used two databases: Web of Science and Pubmed. We analyzed the journals, most cited articles, authors, publication years, organizations, funding agencies, countries and keywords in Web of Science Core collection database and publication years and Medical Subject Headings in Pubmed database. We mapped the data using VOSviewer. We accessed 44 articles published between 1975 and 2014 in Web of Science Core collection Database and 669 from Pubmed database. The majority of which were after 2006. The main countries involved in research on neurodegenerative disorders in Africa the USA, the United Kingdom, France and South Africa representing the main network collaboration. Clinical neurology and Genetics hereditary are the main Web of Science categories whereas Neurosciences and Biochemistry and Molecular Biology are the main Web of Science categories for the general search "neurodegenerative disorders" not restrained to Africa. This is confirmed by Medical Subject Headings analysis from Pubmed with one more area study: Treatment. Neurodegenerative disorders research is leaded by South Africa with a network involving the USA, the UK, as well as African countries such Zambia. The chief field that emerged was on patient and hereditary as well as treatment. Public health policies were lacking fields in research whereas prevalence is

  18. REM sleep behavior disorder: Updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions.

    Science.gov (United States)

    Boeve, Bradley F

    2010-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. The polysomnographic features of RBD include increased electromyographic tone +/- dream enactment behavior during REM sleep. Management with counseling and pharmacologic measures is usually straightforward and effective. In this review, the terminology, clinical and polysomnographic features, demographic and epidemiologic features, diagnostic criteria, differential diagnosis, and management strategies are discussed. Recent data on the suspected pathophysiologic mechanisms of RBD are also reviewed. The literature and our institutional experience on RBD are next discussed, with an emphasis on the RBD-neurodegenerative disease association and particularly the RBD-synucleinopathy association. Several issues relating to evolving concepts, controversies, and future directions are then reviewed, with an emphasis on idiopathic RBD representing an early feature of a neurodegenerative disease and particularly an evolving synucleinopathy. Planning for future therapies that impact patients with idiopathic RBD is reviewed in detail.

  19. S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding.

    Science.gov (United States)

    Nakamura, T; Lipton, S A

    2007-07-01

    Although activation of glutamate receptors is essential for normal brain function, excessive activity leads to a form of neurotoxicity known as excitotoxicity. Key mediators of excitotoxic damage include overactivation of N-methyl-D-aspartate (NMDA) receptors, resulting in excessive Ca(2+) influx with production of free radicals and other injurious pathways. Overproduction of free radical nitric oxide (NO) contributes to acute and chronic neurodegenerative disorders. NO can react with cysteine thiol groups to form S-nitrosothiols and thus change protein function. S-nitrosylation can result in neuroprotective or neurodestructive consequences depending on the protein involved. Many neurodegenerative diseases manifest conformational changes in proteins that result in misfolding and aggregation. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. Molecular chaperones - such as protein-disulfide isomerase, glucose-regulated protein 78, and heat-shock proteins - can provide neuroprotection by facilitating proper protein folding. Here, we review the effect of S-nitrosylation on protein function under excitotoxic conditions, and present evidence that NO contributes to degenerative conditions by S-nitrosylating-specific chaperones that would otherwise prevent accumulation of misfolded proteins and neuronal cell death. In contrast, we also review therapeutics that can abrogate excitotoxic damage by preventing excessive NMDA receptor activity, in part via S-nitrosylation of this receptor to curtail excessive activity.

  20. Improvement of Oxidative and Metabolic Parameters by Cellfood Administration in Patients Affected by Neurodegenerative Diseases on Chelation Treatment

    Directory of Open Access Journals (Sweden)

    Alessandro Fulgenzi

    2014-01-01

    Full Text Available Objective. This prospective pilot study aimed at evaluating the effects of therapy with antioxidant compounds (Cellfood, and other antioxidants on patients affected by neurodegenerative diseases (ND, who displayed toxic metal burden and were subjected to chelation treatment with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA or EDTA. Methods. Two groups of subjects were studied: (a 39 patients affected by ND and (b 11 subjects unaffected by ND (controls. The following blood parameters were analyzed before and after three months’ treatment with chelation + Cellfood or chelation + other antioxidants: oxidative status (reactive oxygen species, ROS; total antioxidant capacity, TAC; oxidized LDL, oxLDL; glutathione, homocysteine, vitamin B12, and folate. Results. After 3-months’ chelation + Cellfood administration oxLDL decreased, ROS levels were significantly lower, and TAC and glutathione levels were significantly higher than after chelation + other antioxidants treatment, both in ND patients and in controls. Moreover, homocysteine metabolism had also improved in both groups. Conclusions. Chelation + Cellfood treatment was more efficient than chelation + other antioxidants improving oxidative status and homocysteine metabolism significantly in ND patients and controls. Although limited to a small number of cases, this study showed how helpful antioxidant treatment with Cellfood was in improving the subjects’ metabolic conditions.

  1. Affective disorders among patients with borderline personality disorder.

    Science.gov (United States)

    Sjåstad, Hege Nordem; Gråwe, Rolf W; Egeland, Jens

    2012-01-01

    The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar spectrum. This association may reflect

  2. Affective disorders among patients with borderline personality disorder.

    Directory of Open Access Journals (Sweden)

    Hege Nordem Sjåstad

    Full Text Available BACKGROUND: The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. METHODS: In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773, we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043 had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636. Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. RESULTS: More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. CONCLUSIONS: The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than

  3. Affective Disorders among Patients with Borderline Personality Disorder

    Science.gov (United States)

    Sjåstad, Hege Nordem; Gråwe, Rolf W.; Egeland, Jens

    2012-01-01

    Background The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. Methods In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. Results More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. Conclusions The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar

  4. Role of serotonin in seasonal affective disorder.

    Science.gov (United States)

    Gupta, A; Sharma, P K; Garg, V K; Singh, A K; Mondal, S C

    2013-01-01

    This review was prepared with an aim to show role of serotonin in seasonal affective disorder. Seasonal affective disorder, which is also called as winter depression or winter blues, is mood disorder in which persons with normal mental health throughout most of the year will show depressive symptoms in the winter or, less commonly, in the summer. Serotonin is an important endogenous neurotransmitter which also acts as neuromodulator. The least invasive, natural, and researched treatment of seasonal affective disorder is natural or otherwise is light therapy. Negative air ionization, which acts by liberating charged particles on the sleep environment, has also become effective in treatment of seasonal affective disorder.  

  5. Application of PIXE in medical study. Environmental minerals and neurodegenerative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, S. [Department of Neurology, Wakayama Medical College, Wakayama (Japan)

    1999-07-01

    Comparative study on amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PDC) in the Kii Peninsula of Japan and Guam was conducted to evaluate the participatory role of environmental minerals in the pathogenesis of the above neurodegenerative diseases, using particle-induced x-ray emission (PIXE) spectrometry and morphometric-statistical analysis. A significantly high content of Al in the hippocampus and spinal cord or Kii and Guamanian ALS/PD cases was found with a positive correlation for Fe and Cu, and a negative correlation for Zn. The numbers of hippocampal neurons in Guamanian PDC, Alzheimer's disease, and Parkinson's disease were significantly decreased with a high Al content. Al content significantly and positively correlated with the number of Alzheimer's neurofibrillary tangles (NFTs) in the hippocampus of ALS cases and controls in both foci, especially in Guamanian cases. The slope of best linear regression of Guamanian cases was markedly steeper than that of Japanese cases (p < 0,001), Morin staining for Al showed green fluorescence on the nucleolus, cytoplasm, and NFT in the hippocampus of Kii ALS cases. These findings suggest that Guamanian and Kii people have a predisposition to develop ALS/PDC precipitated by their geological/geochemical environmental status, i.e., a prolonged low intake or Ca and Mg together with excess exposure to Al and other environmental minerals. (author)

  6. In search of innovative therapeutics for neuropsychiatric disorders: the case of neurodegenerative diseases.

    Science.gov (United States)

    Féger, J; Hirsch, E C

    2015-01-01

    The recent medical literature highlights the lack of new drugs able to prevent or treat neurodegenerative diseases such as Alzheimer disease or Parkinson disease. Yet, the prevalence of these diseases is growing, related to increasing life expectancy, and is leading to a rise in their economic and social cost. At the same time, pharmaceutical companies are reducing or halting their investment in neuropharmacological research. Why have advances in basic neuroscience and our understanding of these diseases not allowed innovative discoveries in drug research? This review will try to explain this failure and suggest possible solutions: develop basic and clinical research but with the emphasis on translational and truly collaborative research; improve preclinical studies by developing more appropriate animal models, using new biomarkers and methodologies such as imaging suitable for clinical trials, providing worthwhile information on the ability of the drug to reach its intended target and induce significant pharmacological changes; build a new system of research management, based on stronger interdisciplinary relations between preclinical and clinical research and including the introduction of international precompetitive research between academic teams, start-up companies and pharmaceutical laboratories; hold early discussions with the regulatory authorities during preclinical studies and at the beginning of clinical trials in order to validate the methodological approaches; involve patients' associations in this new organization of research. These changes should help to ensure the discovery of effective treatments for these pathologies. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. Heritability of bipolar affective disorder: Family study

    Directory of Open Access Journals (Sweden)

    Obradović Tanja

    2011-01-01

    Full Text Available Background/Aim. Bipolar affective disorder is mental disorder with polygenic type of heredity. Heritability - relation between genetic and environmental variance is used to estimate the level of influence of genetic variance to phenotype variance. Study results show decreasing trend in the value of heritability of bipolar affective disorder, thus indicating that this disorder is a complex behavioral threshold characteristic. Therefore, the aim of this study was to estimate the contribution of genetic variance to phenotype variance of bipolar affective disorder, i.e. to estimate heritability of this disorder. Methods. By the use of a questionnaire, 80 patients with over crossed threshold for bipolar affective disorder were asked for functional information about the members of their families belonging to the first degree of relation (fathers, mothers and full- sibs. By using ”Applet for calculating heritability for threshold traits (disease“, and regression analysis, heritability of bipolar affective disorder as well as its statistical significance, were estimated (χ2 test. Results. Heritability and relationship of genetic and environmental variance of bipolar affective disorder is 0.2 with statistically significant difference from zero (p < 0.001. Conclusion. The estimated contribution of genetic variance to phenotype variance of bipolar affective disorder is low being 20%, while the contribution of environmental variance is 80%. This result contributes to the understanding of bipolar affective disorder as a complex behavioral threshold trait.

  8. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders.

    Science.gov (United States)

    Romanucci, Mariarita; Della Salda, Leonardo

    2015-01-01

    Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.

  9. Sleep and circadian dysfunction in neurodegenerative disorders: insights from a mouse model of Huntington's disease.

    Science.gov (United States)

    Kuljis, Dika; Schroeder, Analyne M; Kudo, Takashi; Loh, Dawn H; Willison, David L; Colwell, Christopher S

    2012-09-01

    Sleep disorders are common in patients with neurogenerative diseases and manifest early in the disease process. Among a number of possible mechanisms underlying the sleep disturbances, there is evidence that dysfunction in the circadian system is a contributing factor. Focusing on a mouse model of Huntington's disease has enabled us to determine that at the onset of symptoms, spontaneous electrical activity of neurons within the central clock is disrupted even though the molecular clockwork is still functional. These findings suggest that the fundamental deficit contributing to disordered sleep is reduced SCN output. The mechanism underlying this deficit is not yet known, but mitochondrial dysfunction and oxidative stress are likely involved. Disruption of circadian output from the SCN would be expected to have wide ranging impact on the body including SCN regulated brain regions and the heart. In fact, there is a great deal of overlap in the non-motor symptoms experienced by HD patients and the consequences of circadian disruption. This raises the possibility that the disordered sleep and circadian function experienced by HD patients may be an integral part of the disease. Furthermore, we speculate that circadian dysfunction may accelerate the pathology underlying HD. If these hypotheses are correct, we should focus on treating circadian misalignment and sleep disruptions early in disease progression.

  10. Increased Understanding of Stem Cell Behavior in Neurodegenerative and Neuromuscular Disorders by Use of Noninvasive Cell Imaging

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    Bryan Holvoet

    2016-01-01

    Full Text Available Numerous neurodegenerative and neuromuscular disorders are associated with cell-specific depletion in the human body. This imbalance in tissue homeostasis is in healthy individuals repaired by the presence of endogenous stem cells that can replace the lost cell type. However, in most disorders, a genetic origin or limited presence or exhaustion of stem cells impairs correct cell replacement. During the last 30 years, methods to readily isolate and expand stem cells have been developed and this resulted in a major change in the regenerative medicine field as it generates sufficient amount of cells for human transplantation applications. Furthermore, stem cells have been shown to release cytokines with beneficial effects for several diseases. At present however, clinical stem cell transplantations studies are struggling to demonstrate clinical efficacy despite promising preclinical results. Therefore, to allow stem cell therapy to achieve its full potential, more insight in their in vivo behavior has to be achieved. Different methods to noninvasively monitor these cells have been developed and are discussed. In some cases, stem cell monitoring even reached the clinical setting. We anticipate that by further exploring these imaging possibilities and unraveling their in vivo behavior further improvement in stem cell transplantations will be achieved.

  11. Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder.

    Science.gov (United States)

    Barber, Thomas R; Lawton, Michael; Rolinski, Michal; Evetts, Samuel; Baig, Fahd; Ruffmann, Claudio; Gornall, Aimie; Klein, Johannes C; Lo, Christine; Dennis, Gary; Bandmann, Oliver; Quinnell, Timothy; Zaiwalla, Zenobia; Ben-Shlomo, Yoav; Hu, Michele T M

    2017-08-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is the most specific marker of prodromal alpha-synucleinopathies. We sought to delineate the baseline clinical characteristics of RBD and evaluate risk stratification models. Clinical assessments were performed in 171 RBD, 296 control, and 119 untreated Parkinson's (PD) participants. Putative risk measures were assessed as predictors of prodromal neurodegeneration, and Movement Disorders Society (MDS) criteria for prodromal PD were applied. Participants were screened for common leucine-rich repeat kinase 2 (LRRK2)/glucocerebrosidase gene (GBA) gene mutations. Compared to controls, participants with RBD had higher rates of solvent exposure, head injury, smoking, obesity, and antidepressant use. GBA mutations were more common in RBD, but no LRRK2 mutations were found. RBD participants performed significantly worse than controls on Unified Parkinson's Disease Rating Scale (UPDRS)-III, timed "get-up-and-go", Flamingo test, Sniffin Sticks, and cognitive tests and had worse measures of constipation, quality of life (QOL), and orthostatic hypotension. For all these measures except UPDRS-III, RBD and PD participants were equally impaired. Depression, anxiety, and apathy were worse in RBD compared to PD participants. Stratification of people with RBD according to antidepressant use, obesity, and age altered the odds ratio (OR) of hyposmia compared to controls from 3.4 to 45.5. 74% (95% confidence interval [CI] 66%, 80%) of RBD participants met the MDS criteria for probable prodromal Parkinson's compared to 0.3% (95% CI 0.009%, 2%) of controls. RBD are impaired across a range of clinical measures consistent with prodromal PD and suggestive of a more severe nonmotor subtype. Clinical risk stratification has the potential to select higher risk patients for neuroprotective interventions.

  12. Sleep in Neurodegenerative Diseases.

    Science.gov (United States)

    Iranzo, Alex

    2016-03-01

    Disorders of sleep are an integral part of neurodegenerative diseases and include insomnia, sleep-wake cycle disruption, excessive daytime sleepiness that may be manifested as persistent somnolence or sudden onset of sleep episodes, obstructive and central sleep apnea, rapid eye movement sleep behavior disorder, and restless legs syndrome. The origin of these sleep disorders is multifactorial including degeneration of the brain areas that modulate sleep, the symptoms of the disease, and the effect of medications. Treatment of sleep disorders in patients with neurodegenerative diseases should be individualized and includes behavioral therapy, sleep hygiene, bright light therapy, melatonin, hypnotics, waking-promoting agents, and continuous positive airway pressure. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Multifaceted Roles of Metzincins in CNS Physiology and Pathology: From Synaptic Plasticity and Cognition to Neurodegenerative Disorders

    Science.gov (United States)

    Brzdak, Patrycja; Nowak, Daria; Wiera, Grzegorz; Mozrzymas, Jerzy W.

    2017-01-01

    The extracellular matrix (ECM) and membrane proteolysis play a key role in structural and functional synaptic plasticity associated with development and learning. A growing body of evidence underscores the multifaceted role of members of the metzincin superfamily, including metalloproteinases (MMPs), A Disintegrin and Metalloproteinases (ADAMs), A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs) and astacins in physiological and pathological processes in the central nervous system (CNS). The expression and activity of metzincins are strictly controlled at different levels (e.g., through the regulation of translation, limited activation in the extracellular space, the binding of endogenous inhibitors and interactions with other proteins). Thus, unsurprising is that the dysregulation of proteolytic activity, especially the greater expression and activation of metzincins, is associated with neurodegenerative disorders that are considered synaptopathies, especially Alzheimer’s disease (AD). We review current knowledge of the functions of metzincins in the development of AD, mainly the proteolytic processing of amyloid precursor protein, the degradation of amyloid β (Aβ) peptide and several pathways for Aβ clearance across brain barriers (i.e., blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB)) that contain specific receptors that mediate the uptake of Aβ peptide. Controlling the proteolytic activity of metzincins in Aβ-induced pathological changes in AD patients’ brains may be a promising therapeutic strategy. PMID:28713245

  14. Multifaceted Roles of Metzincins in CNS Physiology and Pathology: From Synaptic Plasticity and Cognition to Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Patrycja Brzdak

    2017-06-01

    Full Text Available The extracellular matrix (ECM and membrane proteolysis play a key role in structural and functional synaptic plasticity associated with development and learning. A growing body of evidence underscores the multifaceted role of members of the metzincin superfamily, including metalloproteinases (MMPs, A Disintegrin and Metalloproteinases (ADAMs, A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs and astacins in physiological and pathological processes in the central nervous system (CNS. The expression and activity of metzincins are strictly controlled at different levels (e.g., through the regulation of translation, limited activation in the extracellular space, the binding of endogenous inhibitors and interactions with other proteins. Thus, unsurprising is that the dysregulation of proteolytic activity, especially the greater expression and activation of metzincins, is associated with neurodegenerative disorders that are considered synaptopathies, especially Alzheimer’s disease (AD. We review current knowledge of the functions of metzincins in the development of AD, mainly the proteolytic processing of amyloid precursor protein, the degradation of amyloid β (Aβ peptide and several pathways for Aβ clearance across brain barriers (i.e., blood-brain barrier (BBB and blood-cerebrospinal fluid barrier (BCSFB that contain specific receptors that mediate the uptake of Aβ peptide. Controlling the proteolytic activity of metzincins in Aβ-induced pathological changes in AD patients’ brains may be a promising therapeutic strategy.

  15. Relevance of the chronobiological and non-chronobiological actions of melatonin for enhancing therapeutic efficacy in neurodegenerative disorders.

    Science.gov (United States)

    Cecon, Erika; Markus, Regina P

    2011-05-01

    Melatonin is an indolamine with a large spectrum of functions that can be divided into chronobiotic and nonchronobiotic. Chronobiotic effects are mediated by the daily rhythm of melatonin in the plasma due to nocturnal pineal synthesis, whereas the melatonin produced by other cells, such as gastrointestinal and immune competent cells, is independent of the light/dark cycle and exert non-chronobiotic effects. The concentrations achieved by the two sources are significantly different, varying in the pM-nM range in the plasma, and may achieve concentrations in the mM range when released locally by activated immune-competent cells. Consequently, the effects of the melatonin produced in these two situations are distinct. Much has been reported about the beneficial response to exogenous melatonin administration in several pathological conditions. However, the relationship between the establishment of a disease and the state of the physiological activity of the pineal gland is still poorly understood. Here, we review the state of art in the modulation of pineal melatonin synthesis, relevant patents, and discuss its relationship with neurodegenerative disorders that involve a central inflammatory response, such as Alzheimer's disease, to suggest the putative relevance of new therapeutic protocols that replace this pineal hormone.

  16. Synopsis on Managment Strategies for Neurodegenerative Disorders: Challenges from Bench to Bedside in Successful Drug Discovery and Development.

    Science.gov (United States)

    Bhat, Sheraz Ahmad; Kamal, Mohammad Amjad; Yarla, Nagendra Sastry; Ashraf, Ghulam Md

    2017-01-01

    The maintenance of health requires successful cell functioning, which in turn depends upon the proper and active conformation of proteins besides other biomolecules. However, occasionally these proteins may misfold and lead to the appearance and progression of protein conformational diseases. These diseases apart from others include several neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, and other lesser known diseases. Although much knowledge has been gained, these NDDs still warrant advance research in the elucidation of their mechanisms as well as effective therapeutic interventions and proper management. There is an ever-growing and urgent need to improve the diagnosis and management of NDDs due to their devastating nature, serious social impact and neuropsychiatric symptoms. It is also envisioned that we may be able to encourage, develop, and strengthen the cell defenses against amyloid toxicity and prevent neuronal destruction and consequently neurodegeneration. In this review, the implications of protein misfolding and aggregation in NDDs are discussed along with some of the most recent findings on the curative and beneficial effects of natural molecules such as polyphenols. This paper also reviews the anti-aggregation and protective effects of some organic and peptidic compounds duly supported experimentally, as prospective future therapeutics for NDDs. The synopses presented in this review shall prove helpful in further understanding of the causes, cures and management of lethal NDDs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Potential contribution of the neurodegenerative disorders risk loci to cognitive performance in an elderly male gout population.

    Science.gov (United States)

    Han, Lin; Jia, Zhaotong; Cao, Chunwei; Liu, Zhen; Liu, Fuqiang; Wang, Lin; Ren, Wei; Sun, Mingxia; Wang, Baoping; Li, Changgui; Chen, Li

    2017-09-01

    Cognitive impairment has been described in elderly subjects with high normal concentrations of serum uric acid. However, it remains unclear if gout confers an increased poorer cognition than those in individuals with asymptomatic hyperuricemia. The present study aimed at evaluating cognitive function in patients suffering from gout in an elderly male population, and further investigating the genetic contributions to the risk of cognitive function.This study examined the cognitive function as assessed by Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in 205 male gout patients and 204 controls. The genetic basis of these cognitive measures was evaluated by genome-wide association study (GWAS) data in 102 male gout patients. Furthermore, 7 loci associated with cognition in GWAS were studied for correlation with gout in 1179 male gout patients and 1848 healthy male controls.Compared with controls, gout patients had significantly lower MoCA scores [22.78 ± 3.01 vs 23.42 ± 2.95, P = .023, adjusted by age, body mass index (BMI), education, and emotional disorder]. GWAS revealed 7 single-nucleotide polymorphisms (SNPs) associations with MoCA test at a level of conventional genome-wide significance (P gout in further analysis (all P > .05).Elderly male subjects with gout exhibit accelerated decline in cognition performance. Several neurodegenerative disorders risk loci were identified for genetic contributors to cognitive performance in our Chinese elderly male gout population. Larger prospective studies of the cognitive performance and genetic analysis in gout subjects are recommended.

  18. Thyroid Functions and Bipolar Affective Disorder

    Directory of Open Access Journals (Sweden)

    Subho Chakrabarti

    2011-01-01

    Full Text Available Accumulating evidence suggests that hypothalamo-pituitary-thyroid (HPT axis dysfunction is relevant to the pathophysiology and clinical course of bipolar affective disorder. Hypothyroidism, either overt or more commonly subclinical, appears to the commonest abnormality found in bipolar disorder. The prevalence of thyroid dysfunction is also likely to be greater among patients with rapid cycling and other refractory forms of the disorder. Lithium-treatment has potent antithyroid effects and can induce hypothyroidism or exacerbate a preexisting hypothyroid state. Even minor perturbations of the HPT axis may affect the outcome of bipolar disorder, necessitating careful monitoring of thyroid functions of patients on treatment. Supplementation with high dose thyroxine can be considered in some patients with treatment-refractory bipolar disorder. Neurotransmitter, neuroimaging, and genetic studies have begun to provide clues, which could lead to an improved understanding of the thyroid-bipolar disorder connection, and more optimal ways of managing this potentially disabling condition.

  19. Seasonal affective disorder, grief reaction, and adjustment disorder.

    Science.gov (United States)

    Osborn, Justin; Raetz, Jacqueline; Kost, Amanda

    2014-09-01

    Seasonal affective disorder is a subtype of other affective disorders. The most studied treatment is light therapy, although second-generation antidepressants are also an option. Grief reactions are normal for patients experiencing loss, and primary care providers (PCPs) should be aware of both the expected course of grief and the more severe symptoms that indicate complex grief. Adjustment disorder is a time-limited abnormal response to a stressor. PCPs can manage patients with adjustment disorder by arranging counseling, screening for suicidality, assessing for substance abuse, and ruling out other psychiatric diagnoses. At present there are no reliable data to suggest medication management. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Genetics Home Reference: seasonal affective disorder

    Science.gov (United States)

    ... is genetic testing? How can I find a genetics professional in my area? Other Names for This Condition affective disorder, seasonal depression in a seasonal pattern depression; seasonal major depressive ...

  1. Seasonal affective disorder and non-seasonal affective disorders : Results from the NESDA study

    NARCIS (Netherlands)

    Winthorst, Wim H; Roest, Annelieke M; Bos, Elisabeth H; Meesters, Ybe; Penninx, Brenda W J H; Nolen, Willem A; de Jonge, Peter

    BACKGROUND: Seasonal affective disorder (SAD) is considered to be a subtype of depression. AIMS: To compare the clinical picture of SAD to non-seasonal affective disorders (non-SADs). METHOD: Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were established

  2. [Life style and affective disorders].

    Science.gov (United States)

    Raboch, Jiří

    2017-01-01

    Life style significantly affects the health status of each person. Life style medicine is an evidence based practice, which is trying to develop patterns of healthy behavior. Most evidence exists about the effect of suitable diet (eg. unsaturated fatty acids) and adequate aerobic exercise. Combination of lifestyle modification to standard psychopharmacologic and psychotherapeutic techniques can improve the results of preventive and therapeutic programs for people with depressive issues.

  3. [Comorbidity of affective disorders and alcohol use disorder].

    Science.gov (United States)

    Pringuey, D; Cherikh, F; Lunacek, S; Giordana, B; Fakra, E; Belzeaux, R; Adida, M; Azorin, J-M

    2014-12-01

    The comorbidity of affective disorders with alcohol use disorder remains insufficiently taken into account. In spite of the well-known frequency of the addict comorbidity in most psychiatric disorders, the level of association between affective disorders and alcohol is still underestimated and poorly understood. The label of "double diagnosis" relates to a simple addition of two independent pathologies. It is suggested to consider a "dual psychopathology" combining the effects of one disorder on the other. Interactions between the two disorders commit a complex state calling a new clinical reading, an adapted therapeutic strategy through a necessary integration of care. Association of alcohol use disorder and affective disorder, particularly in bipolar disorders, is correlated with severity, unstable course, treatment resistance and a greater risk of suicide. Alcohol aggravates depression and hampers therapeutics. Alcohol and mania remain a dreaded danger. The mechanism of the comorbid association does not only refer to a behavioral strategy of compensation but seems strongly based on a shared and crossed vulnerability, related to the genetics of the 5HT carrier and gene Clock. Therapeutic limitations do suggest the implementation of an "integrated" device which supposes a new organization of care and facilitation of collaborations between Addiction and Psychiatry. Copyright © 2014 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  4. Sleep disturbance in mental health problems and neurodegenerative disease

    National Research Council Canada - National Science Library

    Anderson, Kirstie N; Bradley, Andrew J

    2013-01-01

    ... and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative...

  5. Using the WHOQOL-DIS to measure quality of life in persons with physical disabilities caused by neurodegenerative disorders.

    Science.gov (United States)

    Lucas-Carrasco, Ramona; Pascual-Sedano, Berta; Galán, Ingrid; Kulisevsky, Jaime; Sastre-Garriga, Jaume; Gómez-Benito, Juana

    2011-01-01

    Neurodegenerative disorders (ND) have a major impact on quality of life (QoL) and place a substantial burden on patients, their families and carers; they are the second leading cause of disability. The objective of this study was to examine QoL in persons with ND. A battery of subjective assessments was used, including the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) and the World Health Organization Quality of Life - Disability (WHOQOL-DIS). Psychometric properties of the WHOQOL-BREF and WHOQOL-DIS were investigated using classical psychometric methods. Participants (n = 149) were recruited and interviewed at two specialized centers to obtain information on health and disability perceptions, depressive symptoms (Hospital Anxiety and Depression Scale - Depression, HADS-D), Fatigue Assessment Scale (FAS), Satisfaction with Life (SWL), generic QoL (WHOQOL-BREF, WHOQOL-DIS), specific QoL (Multiple Sclerosis Impact Scale, MSIS-29; Parkinson's Disease Questionnaire, PDQ-39) and sociodemographics. Internal consistency was acceptable, except for the WHOQOL-BREF social (0.67). Associations, using Pearson's and Spearman's rho correlations, were confirmed between WHOQOL-BREF and WHOQOL-DIS with MSIS-29, PDQ-39, HADS-D, FAS and SWL. Regarding 'known group' differences, Student's t tests showed that WHOQOL-BREF and WHOQOL-DIS scores significantly discriminated between depressed and nondepressed and those perceiving a more severe impact of the disability on their lives. This study is the first to report on use of the WHOQOL-BREF and WHOQOL-DIS in Spanish persons with ND; they are promising useful tools in assessing persons with ND through the continuum of care, as they include important dimensions commonly omitted from other QoL measures. Copyright © 2010 S. Karger AG, Basel.

  6. Genomic Characteristics of Genetic Creutzfeldt-Jakob Disease Patients with V180I Mutation and Associations with Other Neurodegenerative Disorders.

    Science.gov (United States)

    Lee, Sol Moe; Chung, Myungguen; Hyeon, Jae Wook; Jeong, Seok Won; Ju, Young Ran; Kim, Heebal; Lee, Jeongmin; Kim, SangYun; An, Seong Soo A; Cho, Sung Beom; Lee, Yeong Seon; Kim, Su Yeon

    2016-01-01

    Inherited prion diseases (IPDs), including genetic Creutzfeldt-Jakob disease (gCJD), account for 10-15% of cases of prion diseases and are associated with several pathogenic mutations, including P102L, V180I, and E200K, in the prion protein gene (PRNP). The valine to isoleucine substitution at codon 180 (V180I) of PRNP is the most common pathogenic mutation causing gCJD in East Asian patients. In this study, we conducted follow-up analyses to identify candidate factors and their associations with disease onset. Whole-genome sequencing (WGS) data of five gCJD patients with V180I mutation and 145 healthy individuals were used to identify genomic differences. A total of 18,648,850 candidate variants were observed in only the patient group, 29 of them were validated as variants. Four of these validated variants were nonsense mutations, six were observed in genes directly or indirectly related to neurodegenerative disorders (NDs), such as LPA, LRRK2, and FGF20. More than half of validated variants were categorized in Gene Ontology (GO) terms of binding and/or catalytic activity. Moreover, we found differential genome variants in gCJD patients with V180I mutation, including one uniquely surviving 10 years after diagnosis of the disease. Elucidation of the relationships between gCJD and Alzheimer's disease or Parkinson's disease at the genomic level will facilitate further advances in our understanding of the specific mechanisms mediating the pathogenesis of NDs and gold standard therapies for NDs.

  7. Fetal programming of the human brain: is there a link with insurgence of neurodegenerative disorders in adulthood?

    Science.gov (United States)

    Faa, G; Marcialis, M A; Ravarino, A; Piras, M; Pintus, M C; Fanos, V

    2014-01-01

    In recent years, evidence is growing on the role played by gestational factors in shaping brain development and on the influence of intrauterine experiences on later development of neurodegenerative diseases including Parkinson's (PD) and Alzheimer's disease (AD). The nine months of intrauterine development and the first three years of postnatal life are appearing to be extremely critical for making connections among neurons and among neuronal and glial cells that will shape a lifetime of experience. Here, the multiple epigenetic factors acting during gestation - including maternal diet, malnutrition, stress, hypertension, maternal diabetes, fetal hypoxia, prematurity, low birth weight, prenatal infection, intrauterine growth restriction, drugs administered to the mother or to the baby - are reported, and their ability to modulate brain development, resulting in interindividual variability in the total neuronal and glial burden at birth is discussed. Data from recent literature suggest that prevention of neurodegeneration should be identified as the one method to halt the diffusion of neurodegenerative diseases. The "two hits" hypothesis, first introduced for PD and successfully applied to AD and other neurodegenerative human pathologies, should focus our attention on a peculiar period of our life: the intrauterine and perinatal periods. The first hit to our nervous system occurs early in life, determining a PD or AD imprinting to our brain that will condition our resistance or, alternatively, our susceptibility to develop a neurodegenerative disease later in life. In conclusion, how early life events contribute to late-life development of adult neurodegenerative diseases, including PD and AD, is emerging as a new fascinating research focus. This assumption implies that research on prevention of neurodegenerative diseases should center on events taking place early in life, during gestation and in the perinatal periods, thus presenting a new challenge to

  8. [Etiopathology and therapy of seasonal affective disorder].

    Science.gov (United States)

    Molnar, Eszter; Gonda, Xenia; Rihmer, Zoltan; Bagdy, Gyorgy

    2010-12-01

    To understand the etiology of seasonal affective disorder (SAD) heterogeneous biological, psychological and environmental mechanisms needs to be considered. The aim of our study was to review theoretical hypotheses and therapeutic possibilities for seasonal affective disorder, which focus on alterations of circadian rhythms and monoaminergic neurotransmitter function as well as the role of vitamin D3 and possible implications of the cognitive-behavioral model. These discrepant hypotheses are insufficient alone to interpret the pathophysiology of SAD, but the integrative dual vulnerability hypothesis is an option to explain emergence of seasonal affective disorder. In addition to summarizing theoretical approaches we also review and evaluate the therapeutic possibilities derive form these hypotheses. In practice the most effective treatment for SAD is the combination of light therapy, antidepressants and psychotherapy.

  9. Affect regulation and Depressive Personality Disorder.

    Science.gov (United States)

    Chen, Yung-Tsen; Huprich, Steven K; Hsiao, Wei-Cheng

    2011-12-01

    Depressive Personality Disorder (DPD) has been under consideration for inclusion in the Diagnostic and Statistical Manual of Mental Disorders since 1994; yet, few studies have been published that test whether those with DPD have affective experiences that are characterized exclusively by depression and negative affect. One hundred ninety-seven undergraduate students were interviewed for DPD and Borderline Personality Disorder with the Personality Disorder Interview for DSM-IV (Widiger, Mangine, Corbitt, Ellis, & Thomas, 1995), in order to control for frequently co-occurring BPD which is characterized by affective lability. Participants also were administered measures of affective lability, affective intensity, anxious and depressive states, and more trait-like manifestations of depression, anxiety, and anger. Results indicate that those with DPD may be described as having a mood state characterized by transitions from a baseline neutral mood to one of anxiety, with their experiences being more prominently depressed and dysphoric. They also have tendencies toward angry hostility, though they may not report frequent shifts from a baseline neutral mood to anger. Those with DPD also report intense, frequent experiences of depression and dysphoria, with many shifts between depression and anxiety.

  10. Affective Bipolar Disorder and Borderline Personality Disorder - Comorbidity or Continuum

    Directory of Open Access Journals (Sweden)

    Berta Ferreira

    2014-10-01

    Full Text Available The association between bipolar disorder and borderline personality has been studied by several researchers. Comorbidity has been emphasized by some authors which observe a prognostic impairment of bipolar disorder because the delay of the diagnostic. Symptoms related with alcohol and drugs abuse, suicidary behaviour and impulsivity, often present in borderline patients, make the treatment difficult. Other authors consider these symptoms as being part of the bipolar disease, proposing a continuum between the two entities. In this case, borderline personality would be a mild form of an affective disorder. We will discuss different opinions and their cli- nical and therapeutic consequences.

  11. Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha.

    Science.gov (United States)

    Ven Murthy, M R; Ranjekar, Prabhakar K; Ramassamy, Charles; Deshpande, Manasi

    2010-09-01

    nontoxic medication that normalizes physiological functions, disturbed by chronic stress, through correction of imbalances in the neuroendocrine and immune systems [9, 10]. The scientific research that has been carried out on Ashwagandha and other ayurvedic herbal medicines may be classified into three major categories, taking into consideration the endogenous or exogenous phenomena that are known to cause physiological disequilibrium leading to the pathological state; (A) pharmacological and therapeutic effects of extracts, purified compounds or multi-herbal mixtures on specific non-neurological diseases; (B) pharmacological and therapeutic effects of extracts, purified compounds or multi-herbal mixtures on neurodegenerative disorders; and (C) biochemical, physiological and genetic studies on the herbal plants themselves, in order to distinguish between those originating from different habitats, or to improve the known medicinal quality of the indigenous plant. Some of the major points on its use in the treatment of neurodegenerative disorders are described below.

  12. Circadian polymorphisms associated with affective disorders

    Directory of Open Access Journals (Sweden)

    Shekhtman Tatyana

    2009-01-01

    Full Text Available Abstract Background Clinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective disorders, we explored whether circadian gene polymorphisms were associated with affective disorders in four complementary studies. Methods Four groups of subjects were recruited from several sources: 1 bipolar proband-parent trios or sib-pair-parent nuclear families, 2 unrelated bipolar participants who had completed the BALM morningness-eveningness questionnaire, 3 sib pairs from the GenRed Project having at least one sib with early-onset recurrent unipolar depression, and 4 a sleep clinic patient group who frequently suffered from depression. Working mainly with the SNPlex assay system, from 2 to 198 polymorphisms in genes related to circadian function were genotyped in the participant groups. Associations with affective disorders were examined with TDT statistics for within-family comparisons. Quantitative trait associations were examined within the unrelated samples. Results In NR1D1, rs2314339 was associated with bipolar disorder (P = 0.0005. Among the unrelated bipolar participants, 3 SNPs in PER3 and CSNK1E were associated with the BALM score. A PPARGC1B coding SNP, rs7732671, was associated with affective disorder with nominal significance in bipolar family groups and independently in unipolar sib pairs. In TEF, rs738499 was associated with unipolar depression; in a replication study, rs738499 was also associated with the QIDS-SR depression scale in the sleep clinic patient sample. Conclusion Along with anti-manic effects of lithium and the antidepressant effects of bright light, these findings suggest that perturbations of the circadian gene network at several levels may

  13. Ophthalmic implications of seasonal affective disorder

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, J.E.; King, V.M. (Ferris State Univ., Big Rapids, MI (USA))

    1989-07-01

    A review of seasonal affective disorder (SAD) is presented with a discussion of its standard treatment of phototherapy. A number of ophthalmic implications related to SAD are proposed. These implications relate to both the condition and the phototherapy used in its treatment, especially the use of full spectrum light which contains ultraviolet and near ultraviolet radiation. 12 references.

  14. On the chronobiology of seasonal affective disorder

    NARCIS (Netherlands)

    Koorengevel, Kathelijne Mara

    2002-01-01

    Chronobiological hypotheses about the pathogenesis of affective disorders have a long history. According to the modern variants, abnormalities of either a sleep-wake cycle dependent process S, or a circadian pacemaker related process C, or an abnor-mal interaction between these two processes

  15. Novel mutations in PANK2 and PLA2G6 genes in patients with neurodegenerative disorders: two case reports.

    Science.gov (United States)

    Dastsooz, Hassan; Nemati, Hamid; Fard, Mohammad Ali Farazi; Fardaei, Majid; Faghihi, Mohammad Ali

    2017-08-18

    Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous group of disorders associated with progressive impairment of movement, vision, and cognition. The disease is initially diagnosed on the basis of changes in brain magnetic resonance imaging which indicate an abnormal brain iron accumulation in the basal ganglia. However, the diagnosis of specific types should be based on both clinical findings and molecular genetic testing for genes associated with different types of NBIA, including PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, WDR45, COASY, FTL, CP, and DCAF17. The purpose of this study was to investigate disease-causing mutations in two patients with distinct NBIA disorders. Whole Exome sequencing using Next Generation Illumina Sequencing was used to enrich all exons of protein-coding genes as well as some other important genomic regions in these two affected patients. A deleterious homozygous four-nucleotide deletion causing frameshift deletion in PANK2 gene (c.1426_1429delATGA, p.M476 fs) was identified in an 8 years old girl with dystonia, bone fracture, muscle rigidity, abnormal movement, lack of coordination and chorea. In addition, our study revealed a novel missense mutation in PLA2G6 gene (c.3G > T:p.M1I) in one and half-year-old boy with muscle weakness and neurodevelopmental regression (speech, motor and cognition). The novel mutations were also confirmed by Sanger sequencing in the proband and their parents. Current study uncovered two rare novel mutations in PANK2 and PLA2G6 genes in patients with NBIA disorder and such studies may help to conduct genetic counseling and prenatal diagnosis more accurately for individuals at the high risk of these types of disorders.

  16. Idiopathic REM sleep behavior disorder and neurodegenerative risk: To tell or not to tell to the patient? How to minimize the risk?

    Science.gov (United States)

    Arnaldi, Dario; Antelmi, Elena; St Louis, Erik K; Postuma, Ronald B; Arnulf, Isabelle

    2016-11-10

    Most people with idiopathic REM sleep behavior disorder (iRBD) have an underlying synucleinopathy, mainly Parkinson's disease (PD) or dementia with Lewy bodies, with median conversion time of 4-9 y from iRBD diagnosis and of 11-16 y from symptom onset. Subtle signs and imaging tests indicate concomitant neurodegeneration in widespread brain areas. Risk factor studies suggest that iRBD patients may have prior head injury, occupational farming, pesticide exposure, low education level and possibly more frequent family history of dream-enactment behavior (but not of PD), plus unexpected risk factors (smoking, ischemic heart disease and inhaled corticosteroid use). Unlike PD, caffeine and smoking appear not to have a protective role. Prior depression and antidepressant use may be early neurodegenerative signs rather than exclusively causative factors. Age, hyposmia, impaired color vision, abnormal dopaminergic imaging, mild cognitive impairment and possibly sleepiness, may identify patients at greater risk of more rapid conversion. The consensus is to generally disclose the neurodegenerative risk to patients (with the caveat that phenoconversion and its temporal course remain uncertain in individuals without "soft neurodegenerative signs" and those under 50 y of age), to suggest a healthy lifestyle and to take part in prospective cohort studies in anticipation of eventual neuroprotective trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Brain Networks Implicated in Seasonal Affective Disorder

    DEFF Research Database (Denmark)

    Nørgaard, Martin; Ganz, Melanie; Svarer, Claus

    2017-01-01

    Background: Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder characterized by seasonally occurring depression that often presents with atypical vegetative symptoms such as hypersomnia and carbohydrate craving. It has recently been shown that unlike healthy people......, patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT) in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption...

  18. No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001-2010.

    Science.gov (United States)

    Forrester, Joseph D; Kugeler, Kiersten J; Perea, Anna E; Pastula, Daniel M; Mead, Paul S

    2015-11-01

    Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were identified. Lyme disease incidence per US state was not correlated with rates of death due to ALS, MS, or Parkinson disease; however, an inverse correlation was detected between Lyme disease and Alzheimer disease. The absence of a positive correlation between the geographic distribution of Lyme disease and the distribution of deaths due to Alzheimer disease, ALS, MS, and Parkinson disease provides further evidence that Lyme disease is not associated with the development of these neurodegenerative conditions.

  19. No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001?2010

    OpenAIRE

    Forrester, Joseph D; Kugeler, Kiersten J.; Perea, Anna E.; Pastula, Daniel M.; Mead, Paul S.

    2015-01-01

    Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were i...

  20. Climatic factors and bipolar affective disorder

    DEFF Research Database (Denmark)

    Christensen, Ellen Margrethe; Larsen, Jens Knud; Gjerris, Annette

    2008-01-01

    In bipolar disorder, the factors provoking a new episode are unknown. As a seasonal variation has been noticed, it has been suggested that weather conditions may play a role. The aim of the study was to elucidate whether meteorological parameters influence the development of new bipolar phases....... A group of patients with at least three previous hospitalizations for bipolar disorder was examined every 3 months for up to 3 years. At each examination an evaluation of the affective phase was made according to the Hamilton Depression Scale (HAM-D(17)), and the Bech-Rafaelsen Mania Rating Scale (MAS......). In the same period, daily recordings from the Danish Meteorological Institute were received. We found no correlations between onset of bipolar episodes [defined as MAS score of 11 or more (mania) and as HAM-D(17) score of 12 or more (depression)] and any meteorological parameters. We found a statistical...

  1. Role of 4-hydroxy-2-nonenal (HNE) in the pathogenesis of alzheimer disease and other selected age-related neurodegenerative disorders.

    Science.gov (United States)

    Di Domenico, Fabio; Tramutola, Antonella; Butterfield, D Allan

    2017-10-01

    Oxidative stress is involved in various and numerous pathological states including several age-related neurodegenerative diseases. Peroxidation of the membrane lipid bilayer is one of the major sources of free radical-mediated injury that directly damages neurons causing increased membrane rigidity, decreased activity of membrane-bound enzymes, impairment of membrane receptors and altered membrane permeability and eventual cell death. Moreover, the peroxidation of polyunsaturated fatty acids leads to the formation of aldehydes, which can act as toxic by-products. One of the most abundant and cytotoxic lipid -derived aldehydes is 4-hydroxy 2-nonenal (HNE). HNE toxicity is mainly due to the alterations of cell functions by the formation of covalent adducts of HNE with proteins. A key marker of lipid peroxidation, HNE-protein adducts, were found to be elevated in brain tissues and body fluids of Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis subjects and/or models of the respective age-related neurodegenerative diseases. Although only a few proteins were identified as common targets of HNE modification across all these listed disorders, a high overlap of these proteins occurs concerning the alteration of common pathways, such as glucose metabolism or mitochondrial function that are known to contribute to cognitive decline. Within this context, despite the different etiological and pathological mechanisms that lead to the onset of different neurodegenerative diseases, the formation of HNE-protein adducts might represent the shared leit-motif, which aggravates brain damage contributing to disease specific clinical presentation and decline in cognitive performance observed in each case. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. New strategies for the treatment of Parkinson's disease hold considerable promise for future management of neurodegenerative disorders

    DEFF Research Database (Denmark)

    Bjarkam, Carsten Reidies; Sørensen, Jens Christian; Sunde, Niels Å

    2001-01-01

    or more. Parkinson's disease ischaracterized by a massive loss of dopaminergicneurons in the substantia nigra, leading tosevere functional disturbance of the neuronalcircuitry in the basal ganglia. A thoroughdescription of basal ganglia circuitry inhealth and disease is presented. We describehow...... the functional disturbances seen inParkinson's disease may be corrected atspecific sites in this circuitry by medicaltreatment or, in advanced stages of Parkinson'sdisease, by neurosurgical methods. The latterinclude lesional surgery, neuraltransplantation and deep brain stimulation,together with future......Neurodegenerative diseases are often consideredincurable with no efficient therapies to modifyor halt the progress of disease, and ultimatelylead to reduced quality of life and to death.Our knowledge of the nervous system in healthand disease has, however, increasedconsiderably during the last...

  3. REM Sleep Behavior Disorder: Updated Review of the Core Features, the RBD-Neurodegenerative Disease Association, Evolving Concepts, Controversies, and Future Directions

    Science.gov (United States)

    Boeve, Bradley F.

    2010-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. Patients appear to “act out their dreams,” in which the exhibited behaviors mirror the content of the dreams, and the dream content often involves a chasing or attacking theme. The polysomnographic features of RBD include increased electromyographic tone +/- dream enactment behavior during REM sleep. Management with counseling and pharmacologic measures is usually straight-forward and effective. In this review, the terminology, clinical and polysomnographic features, demographic and epidemiologic features, diagnostic criteria, differential diagnosis, and management strategies are discussed. Recent data on the suspected pathophysiologic mechanisms of RBD are also reviewed. The literature and our institutional experience on RBD are next discussed, with an emphasis on the RBD-neurodegenerative disease association and particularly the RBD-synucleinopathy association. Several issues relating to evolving concepts, controversies, and future directions are then reviewed, with an emphasis on idiopathic RBD representing an early feature of a neurodegenerative disease and particularly an evolving synucleinopathy. Planning for future therapies that impact patients with idiopathic RBD is reviewed in detail. PMID:20146689

  4. Neurodegenerative Diseases: Multifactorial Conformational Diseases and Their Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Saba Sheikh

    2013-01-01

    Full Text Available Neurodegenerative diseases are multifactorial debilitating disorders of the nervous system that affect approximately 30 millionindividuals worldwide. Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis diseases are the consequence of misfolding and dysfunctional trafficking of proteins. Beside that, mitochondrial dysfunction, oxidative stress, and/or environmental factors strongly associated with age have also been implicated in causing neurodegeneration. After years of intensive research, considerable evidence has accumulated that demonstrates an important role of these factors in the etiology of common neurodegenerative diseases. Despite the extensive efforts that have attempted to define the molecular mechanisms underlying neurodegeneration, many aspects of these pathologies remain elusive. However, in order to explore the therapeutic interventions directed towards treatment of neurodegenerative diseases, neuroscientists are now fully exploiting the data obtained from studies of these basic mechanisms that have gone awry. The novelty of these mechanisms represents a challenge to the identification of viable drug targets and biomarkers for early diagnosis of the diseases. In this paper, we are reviewing various aspects associated with the disease and the recent trends that may have an application for the treatment of the neurodegenerative disorders.

  5. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study.

    Science.gov (United States)

    Iranzo, Alex; Tolosa, Eduard; Gelpi, Ellen; Molinuevo, José Luis; Valldeoriola, Francesc; Serradell, Mónica; Sanchez-Valle, Raquel; Vilaseca, Isabel; Lomeña, Francisco; Vilas, Dolores; Lladó, Albert; Gaig, Carles; Santamaria, Joan

    2013-05-01

    We postulated that idiopathic rapid-eye-movement (REM) sleep behaviour disorder (IRBD) represents the prodromal phase of a Lewy body disorder and that, with sufficient follow-up, most cases would eventually be diagnosed with a clinical defined Lewy body disorder, such as Parkinson's disease (PD) or dementia with Lewy bodies (DLB). Patients from an IRBD cohort recruited between 1991 and 2003, and previously assessed in 2005, were followed up during an additional period of 7 years. In this original cohort, we sought to identify the nature and frequency of emerging defined neurodegenerative syndromes diagnosed by standard clinical criteria. We estimated rates of survival free from defined neurodegenerative disease by means of the Kaplan-Meier method. We further characterised individuals who remained diagnosed as having only IRBD, through dopamine transporter (DAT) imaging, transcranial sonography (TCS), and olfactory testing. We did a neuropathological assessment in three patients who died during follow-up and who had the antemortem diagnosis of PD or DLB. Of the 44 participants from the original cohort, 36 (82%) had developed a defined neurodegenerative syndrome by the 2012 assessment (16 patients were diagnosed with PD, 14 with DLB, one with multiple system atrophy, and five with mild cognitive impairment). The rates of neurological-disease-free survival from time of IRBD diagnosis were 65·2% (95% CI 50·9 to 79·5) at 5 years, 26·6% (12·7 to 40·5) at 10 years, and 7·5% (-1·9 to 16·9) at 14 years. Of the four remaining neurological-disease-free individuals who underwent neuroimaging and olfactory tests, all four had decreased striatal DAT uptake, one had substantia nigra hyperechogenicity on TCS, and two had impaired olfaction. In three patients, the antemortem diagnoses of PD and DLB were confirmed by neuropathological examination showing widespread Lewy bodies in the brain, and α-synuclein aggregates in the peripheral autonomic nervous system in one case

  6. Affective Priming in Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Joelle eLeMoult

    2012-10-01

    Full Text Available Research on cognitive biases in depression has provided considerable evidence for the impact of emotion on cognition. Individuals with depression tend to preferentially process mood-congruent material and to show deficits in the processing of positive material leading to biases in attention, memory, and judgments. More research is needed, however, to fully understand which cognitive processes are affected. The current study further examines the impact of emotion on cognition using a priming design with facial expressions of emotion. Specifically, this study tested whether the presentation of facial expressions of emotion affects subsequent processing of affective material in participants with major depressive disorder (MDD and healthy controls (CTL. Facial expressions displaying happy, sad, angry, disgusted, or neutral expressions were presented as primes for 500ms, and participants’ speed to identify a subsequent target’s emotional expression was assessed. All participants displayed greater interference from emotional versus neutral primes, marked by slower response times to judge the emotion of the target face when it was preceded by an emotional prime. Importantly, the CTL group showed the strongest interference when happy emotional expressions served as primes whereas the MDD group failed to show this bias. These results add to a growing literature that shows that depression is associated with difficulties in the processing of positive material.

  7. Cerebral blood flow and Aβ-amyloid estimates by WARM analysis of [11C]PiB uptake distinguish among and between neurodegenerative disorders and aging

    DEFF Research Database (Denmark)

    Rodell, Anders B.; O'Keefe, Graeme; Rowe, Christopher C.

    2017-01-01

    Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [11C]Pittsburgh Compound B ([11C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including...... metabolism and reduction of blood flow by neurovascular coupling in neurodegenerative disorders, including Alzheimer's disease. Methods: Previously reported images of [11C]PiB retention in brain of 29 subjects with cognitive impairment or dementia [16 Alzheimer's Disease (AD), eight subjects with dementia......) and correlated surrogate cerebral blood flow (sCBF) estimates, based on the [11C]PiB images, compared to estimates by conventional Standard Uptake Value Ratio (SUVR) of [11C]PiB retention with cerebellum gray matter as reference. Receiver Operating Characteristics (ROC) revealed the power of discrimination among...

  8. Pain in Neurodegenerative Disease : Current Knowledge and Future Perspectives

    NARCIS (Netherlands)

    de Tommaso, Marina; Arendt-Nielsen, Lars; Defrin, Ruth; Kunz, Miriam; Pickering, Gisele; Valeriani, Massimiliano

    2016-01-01

    Neurodegenerative diseases are going to increase as the life expectancy is getting longer. The management of neurodegenerative diseases such as Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD related disorders, motor neuron diseases (MND), Huntington's disease (HD),

  9. [Neuropathological diagnosis of neurodegenerative and dementia diseases].

    Science.gov (United States)

    Kretzschmar, H A; Neumann, M

    2000-09-01

    Neurodegenerative and dementing disorders such as Parkinson disease and Alzheimer disease are among the most common diseases of advanced age. Despite progress in the clinical diagnosis of neurodegenerative disorders, definite diagnosis for most of these disorders is still possible only by neuropathological examination of the brain. The neuropathological diagnosis and classification of neurodegenerative disorders has made clear advances in recent years, particularly due to the results of genetic and biochemical studies, resulting in the development of new disease-specific antibodies. Internationally recognized consensus criteria for most neurodegenerative disorders allow a definite and standardized diagnosis to be made. To obtain further knowledge about the etiopathogenesis, particularly with regard to new therapeutic strategies, studies with clinically and neuropathologically well-documented cases are needed. The project "Brain-Net" has therefore been established with the aim of setting up a German Brain and Tissue Bank for Diseases of the Central Nervous System. The project is funded by the Federal Ministry of Education and Research.

  10. Somatic therapies for seasonal affective disorder.

    Science.gov (United States)

    Howland, Robert H

    2009-01-01

    The syndrome of seasonal affective disorder (SAD) is defined as a history of major depressive episodes that recur regularly at a particular time of year, typically fall or winter, and completely remit in the spring. It has been hypothesized that photoperiod-related changes in the duration of melatonin secretion may be involved in the seasonal mood cycles of SAD in human beings, suggesting that artificial bright lights (mimicking daylight) might be used to treat SAD. This article reviews studies on the use of bright light therapy and antidepressant medication for the treatment of SAD. Studies have found that bright light therapy and antidepressant medication are both effective for the treatment of SAD. Bright light therapy may also be effective for treating nonseasonal depression.

  11. Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism.

    NARCIS (Netherlands)

    Steinfeld, R.; Grapp, M.; Kraetzner, R.; Dreha-Kulaczewski, S.; Helms, G.; Dechent, P.; Wevers, R.A.; Grosso, S.; Gartner, J.

    2009-01-01

    Sufficient folate supplementation is essential for a multitude of biological processes and diverse organ systems. At least five distinct inherited disorders of folate transport and metabolism are presently known, all of which cause systemic folate deficiency. We identified an inherited

  12. Seasonal affective disorder: a clinical update.

    Science.gov (United States)

    Westrin, Asa; Lam, Raymond W

    2007-01-01

    Seasonal affective disorder (SAD) consists of recurrent major depressive episodes in the fall/winter with remissions in spring/summer. A Medline search was conducted to identify studies relating to clinical management of SAD using the Medical Subject Heading, seasonal affective disorder, and key words, depress* and season*, focusing on studies published in the past 10 years. The Cochrane library of systematic reviews was also searched for relevant studies. A careful history is important to make the diagnosis and differentiate SAD from other similar conditions such as subsyndromal SAD and atypical depression. Seasonal patterns with winter worsening are also recognized in "nonseasonal" depression as well as many other psychiatric conditions, and comorbidity with SAD is common. The pathophysiology of SAD seems to be heterogeneous as research on circadian, neurotransmitter function and genetic hypotheses have shown discrepant results. A dual vulnerability model with differential loading on separate seasonal and depression factors has been proposed to explain these findings. Recent systematic reviews have shown that light therapy is an efficacious and well-tolerated treatment for SAD. There is also evidence for efficacy of pharmacotherapy to treat and prevent SAD. Clinical studies show equal effectiveness with light and antidepressants, so patient preference should be considered in the selection of initial treatment. Dawn stimulation, negative air ions, exercise and cognitve behaviour therapy are under investigation and may also be helpful treatments for SAD. SAD is a common condition with significant psychosocial impairment. Clinicians should be vigilant in recognizing seasonal patterns of depressive episodes because there are effective, evidence-based treatments for SAD.

  13. Eyelid Dysfunction in Neurodegenerative, Neurogenetic, and Neurometabolic Disease

    Directory of Open Access Journals (Sweden)

    Ali G. Hamedani

    2017-07-01

    Full Text Available Eye movement abnormalities are among the earliest clinical manifestations of inherited and acquired neurodegenerative diseases and play an integral role in their diagnosis. Eyelid movement is neuroanatomically linked to eye movement, and thus eyelid dysfunction can also be a distinguishing feature of neurodegenerative disease and complements eye movement abnormalities in helping us to understand their pathophysiology. In this review, we summarize the various eyelid abnormalities that can occur in neurodegenerative, neurogenetic, and neurometabolic diseases. We discuss eyelid disorders, such as ptosis, eyelid retraction, abnormal spontaneous and reflexive blinking, blepharospasm, and eyelid apraxia in the context of the neuroanatomic pathways that are affected. We also review the literature regarding the prevalence of eyelid abnormalities in different neurologic diseases as well as treatment strategies (Table 1.

  14. Potential animal models of seasonal affective disorder.

    Science.gov (United States)

    Workman, Joanna L; Nelson, Randy J

    2011-01-01

    Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. The vitamin D, ionised calcium and parathyroid hormone axis of cerebral capillary function: therapeutic considerations for vascular-based neurodegenerative disorders.

    Science.gov (United States)

    Lam, Virginie; Takechi, Ryusuke; Pallabage-Gamarallage, Menuka; Giles, Corey; Mamo, John C L

    2015-01-01

    Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones. This study utilised an integrated approach and investigated the effects of vitamin D supplementation, parathyroid tissue ablation (PTX), or exogenous infusion of parathyroid hormone (PTH) on cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG) was used as a marker of cerebral capillary permeability. In C57BL/6J mice and Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance of IgG within cerebral cortex (CTX) and hippocampal formation (HPF). Vitamin D was also associated with increased plasma ionised calcium (iCa) and decreased PTH. A response to dose was suggested and parenchymal effects persisted for up to 24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels increased, however the PTH treated animals did not show increased cerebral permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation showed modestly increased parenchymal abundance of glial-fibrillary acidic protein (GFAP), a marker of astroglial activation. PTH infusion attenuated GFAP abundance. The findings suggest that vitamin D can compromise capillary integrity via a mechanism that is independent of calcium homeostasis. The effects of exogenous vitamin D supplementation on capillary function and in the context of prevention of vascular

  16. The vitamin D, ionised calcium and parathyroid hormone axis of cerebral capillary function: therapeutic considerations for vascular-based neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Virginie Lam

    Full Text Available Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones. This study utilised an integrated approach and investigated the effects of vitamin D supplementation, parathyroid tissue ablation (PTX, or exogenous infusion of parathyroid hormone (PTH on cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG was used as a marker of cerebral capillary permeability. In C57BL/6J mice and Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance of IgG within cerebral cortex (CTX and hippocampal formation (HPF. Vitamin D was also associated with increased plasma ionised calcium (iCa and decreased PTH. A response to dose was suggested and parenchymal effects persisted for up to 24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels increased, however the PTH treated animals did not show increased cerebral permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation showed modestly increased parenchymal abundance of glial-fibrillary acidic protein (GFAP, a marker of astroglial activation. PTH infusion attenuated GFAP abundance. The findings suggest that vitamin D can compromise capillary integrity via a mechanism that is independent of calcium homeostasis. The effects of exogenous vitamin D supplementation on capillary function and in the context of prevention of

  17. Neuroprotective effects of the anti-cancer drug sunitinib in models of HIV neurotoxicity suggests potential for the treatment of neurodegenerative disorders.

    Science.gov (United States)

    Wrasidlo, Wolf; Crews, Leslie A; Tsigelny, Igor F; Stocking, Emily; Kouznetsova, Valentina L; Price, Diana; Paulino, Amy; Gonzales, Tania; Overk, Cassia R; Patrick, Christina; Rockenstein, Edward; Masliah, Eliezer

    2014-12-01

    Anti-retrovirals have improved and extended the life expectancy of patients with HIV. However, as this population ages, the prevalence of cognitive changes is increasing. Aberrant activation of kinases, such as receptor tyrosine kinases (RTKs) and cyclin-dependent kinase 5 (CDK5), play a role in the mechanisms of HIV neurotoxicity. Inhibitors of CDK5, such as roscovitine, have neuroprotective effects; however, CNS penetration is low. Interestingly, tyrosine kinase inhibitors (TKIs) display some CDK inhibitory activity and ability to cross the blood-brain barrier. We screened a small group of known TKIs for a candidate with additional CDK5 inhibitory activity and tested the efficacy of the candidate in in vitro and in vivo models of HIV-gp120 neurotoxicity. Among 12 different compounds, sunitinib inhibited CDK5 with an IC50 of 4.2 μM. In silico analysis revealed that, similarly to roscovitine, sunitinib fitted 6 of 10 features of the CDK5 pharmacophore. In a cell-based model, sunitinib reduced CDK5 phosphorylation (pCDK5), calpain-dependent p35/p25 conversion and protected neuronal cells from the toxic effects of gp120. In glial fibrillary acidic protein-gp120 transgenic (tg) mice, sunitinib reduced levels of pCDK5, p35/p25 and phosphorylated tau protein, along with amelioration of the neurodegenerative pathology. Compounds such as sunitinib with dual kinase inhibitory activity could ameliorate the cognitive impairment associated with chronic HIV infection of the CNS. Moreover, repositioning existing low MW compounds holds promise for the treatment of patients with neurodegenerative disorders. © 2014 The British Pharmacological Society.

  18. Essential Tremor: A Neurodegenerative Disease?

    Directory of Open Access Journals (Sweden)

    Julian Benito-Leon

    2011-08-01

    Full Text Available Background: Essential tremor (ET is one of the most common neurological disorders among adults, and is the most common of the many tremor disorders. It has classically been viewed as a benign monosymptomatic condition, yet over the past decade, a growing body of evidence indicates that ET is a progressive condition that is clinically heterogeneous, as it may be associated with a spectrum of clinical features, with both motor and non‐motor elements. In this review, I will describe the most significant emerging milestones in research which, when taken together, suggest that ET is a neurodegenerative condition.Methods: A PubMed search conducted in June 2014 crossing the terms “essential tremor” (ET and “neurodegenerative” yielded 122 entries, 20 of which included the term “neurodegenerative” in the article title. This was supplemented by articles in the author's files that pertained to this topic.Results/Discussion: There is an open and active dialogue in the medical community as to whether ET is a neurodegenerative disease, with considerable evidence in favor of this. Specifically, ET is a progressive disorder of aging associated with neuronal loss (reduction in Purkinje cells as well as other post‐mortem changes that occur in traditional neurodegenerative disorders. Along with this, advanced neuroimaging techniques are now demonstrating distinct structural changes, several of which are consistent with neuronal loss, in patients with ET. However, further longitudinal clinical and neuroimaging longitudinal studies to assess progression are required.

  19. Seasonal affective disorder and non-seasonal affective disorders: results from the NESDA study

    Science.gov (United States)

    Roest, Annelieke M.; Bos, Elisabeth H.; Meesters, Ybe; Penninx, Brenda W.J.H.; Nolen, Willem A.; de Jonge, Peter

    2017-01-01

    Background Seasonal affective disorder (SAD) is considered to be a subtype of depression. Aims To compare the clinical picture of SAD to non-seasonal affective disorders (non-SADs). Method Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were established in 2185 participants of the Netherlands Study of Depression and Anxiety. The Seasonal Pattern Assessment Questionnaire was administered to diagnose SAD. Symptoms of depression and anxiety were measured with the Inventory of Depressive Symptoms, the Beck Anxiety Inventory and the Fear Questionnaire. Results Participants with SAD, participants with a lifetime bipolar disorder and participants with a lifetime comorbid anxiety and depressive disorder scored highest in terms of psychopathology in the past year. The seasonal distribution of major depressive episodes was not different for participants with or without SAD. Conclusions SAD may be a measure of severity of depression with a subjectively perceived worsening of symptoms in the winter months. Declaration of interest Y.M. has received research funding and served as a consultant for Royal Philips Electronics NV and The Litebook Company Ltd. W.A.N. has received grants from the Netherlands Organization for Health Research and Development, the European Union, the Stanley Medical Research Institute, Astra Zeneca, Eli Lilly, GlaxoSmithKline and Wyeth; has received honoraria/speaker’s fees from Astra Zeneca, Pfizer, Servier and Wyeth; and has served in advisory boards for Astra Zeneca, Pfizer and Servier. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28904813

  20. Seasonal affective disorder and non-seasonal affective disorders: results from the NESDA study.

    Science.gov (United States)

    Winthorst, Wim H; Roest, Annelieke M; Bos, Elisabeth H; Meesters, Ybe; Penninx, Brenda W J H; Nolen, Willem A; de Jonge, Peter

    2017-07-01

    Seasonal affective disorder (SAD) is considered to be a subtype of depression. To compare the clinical picture of SAD to non-seasonal affective disorders (non-SADs). Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were established in 2185 participants of the Netherlands Study of Depression and Anxiety. The Seasonal Pattern Assessment Questionnaire was administered to diagnose SAD. Symptoms of depression and anxiety were measured with the Inventory of Depressive Symptoms, the Beck Anxiety Inventory and the Fear Questionnaire. Participants with SAD, participants with a lifetime bipolar disorder and participants with a lifetime comorbid anxiety and depressive disorder scored highest in terms of psychopathology in the past year. The seasonal distribution of major depressive episodes was not different for participants with or without SAD. SAD may be a measure of severity of depression with a subjectively perceived worsening of symptoms in the winter months. Y.M. has received research funding and served as a consultant for Royal Philips Electronics NV and The Litebook Company Ltd. W.A.N. has received grants from the Netherlands Organization for Health Research and Development, the European Union, the Stanley Medical Research Institute, Astra Zeneca, Eli Lilly, GlaxoSmithKline and Wyeth; has received honoraria/speaker's fees from Astra Zeneca, Pfizer, Servier and Wyeth; and has served in advisory boards for Astra Zeneca, Pfizer and Servier. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

  1. The Neurobiology of Retinoic Acid in Affective Disorders

    OpenAIRE

    Bremner, J. Douglas; McCaffery, Peter

    2007-01-01

    Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from Vitamin A that perform a large nu...

  2. Salivary cortisol in unaffected twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj; Bennike, Bente; Kyvik, Kirsten Ohm

    2008-01-01

    Dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a biological endophenotype for affective disorders. In the present study the hypothesis that a high genetic liability to affective disorder is associated with higher cortisol levels was tested in a cross-sectional h......Dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a biological endophenotype for affective disorders. In the present study the hypothesis that a high genetic liability to affective disorder is associated with higher cortisol levels was tested in a cross...

  3. Oxytocin and social cognition in affective and psychotic disorders.

    Science.gov (United States)

    Mercedes Perez-Rodriguez, M; Mahon, Katie; Russo, Manuela; Ungar, Allison K; Burdick, Katherine E

    2015-02-01

    Impairments in social cognition are now recognized as core illness features in psychotic and affective disorders. Despite the significant disability caused by social cognitive abnormalities, treatments for this symptom dimension are lacking. Here, we describe the evidence demonstrating abnormalities in social cognition in schizophrenia, major depressive disorder, and bipolar disorder, as well as the neurobiology of social cognition including the role of oxytocin. We then review clinical trials of oxytocin administration in psychotic and affective disorders and the impact of this agent on social cognition. To date, several studies have demonstrated that oxytocin may improve social cognition in schizophrenia; too few studies have been conducted in affective disorders to determine the effect of oxytocin on social cognition in these disorders. Future work is needed to clarify which aspects of social cognition may be improved with oxytocin treatment in psychotic and affective disorders. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  4. Oxytocin and Social Cognition in Affective and Psychotic Disorders

    Science.gov (United States)

    Perez-Rodriguez, M. Mercedes; Mahon, Katie; Russo, Manuela; Ungar, Allison K.; Burdick, Katherine E.

    2014-01-01

    Impairments in social cognition are now recognized as core illness features in psychotic and affective disorders. Despite the significant disability caused by social cognitive abnormalities, treatments for this symptom dimension are lacking. Here, we describe the evidence demonstrating abnormalities in social cognition in schizophrenia, major depressive disorder, and bipolar disorder, as well as the neurobiology of social cognition including the role of oxytocin. We then review clinical trials of oxytocin administration in psychotic and affective disorders and the impact of this agent on social cognition. To date, several studies have demonstrated that oxytocin may improve social cognition in schizophrenia; too few studies have been conducted in affective disorders to determine the effect of oxytocin on social cognition in these disorders. Future work is needed to clarify which aspects of social cognition may be improved with oxytocin treatment in psychotic and affective disorders. PMID:25153535

  5. Automatic sleep scoring in normals and in individuals with neurodegenerative disorders according to new international sleep scoring criteria

    DEFF Research Database (Denmark)

    Jensen, Peter S.; Sørensen, Helge Bjarup Dissing; Jennum, P. J.

    2010-01-01

    Introduction: Reliable polysomnographic classification is the basis for evaluation of sleep disorders in neurological diseases. Aim: To develop a fully automatic sleep scoring algorithm on the basis of a reproduction of new international sleep scoring criteria from the American Academy of Sleep...... Medicine (AASM). Methods: A biomedical signal processing algorithm was developed, allowing for automatic sleep depth quantification of routine polysomnographic (PSG) recordings through feature extraction, supervised probabilistic Bayesian classification, and heuristic rule-based smoothing. The performance...... of the algorithm was tested using 28 manually classified day-night PSGs from 18 normal subjects and 10 patients with Parkinson's disease (PD) or multiple system atrophy (MSA). This led to quantification of automaticversus- manual epoch-by-epoch agreement rates for both normal and abnormal recordings. Results...

  6. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

    2012-01-01

    Iron and copper are important co-factors for a number of enzymes in the brain, including enzymes involved in neurotransmitter synthesis and myelin formation. Both shortage and an excess of iron or copper will affect the brain. The transport of iron and copper into the brain from the circulation...... is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead......) is involved in the uptake of both iron and copper. Furthermore, copper is an essential co-factor in numerous proteins that are vital for iron homeostasis and affects the binding of iron-response proteins to iron-response elements in the mRNA of the transferrin receptor, DMT1, and ferroportin, all highly...

  7. Meditation and neurodegenerative diseases

    National Research Council Canada - National Science Library

    Newberg, Andrew B; Serruya, Mijail; Wintering, Nancy; Moss, Aleezé Sattar; Reibel, Diane; Monti, Daniel A

    2014-01-01

    .... Meditation techniques present an interesting potential adjuvant treatment for patients with neurodegenerative diseases and have the advantage of being inexpensive, and easy to teach and perform...

  8. Descriptive epidemiology of affective disorders in multiple sclerosis.

    Science.gov (United States)

    Patten, Scott B; Svenson, Lawrence W; Metz, Luanne M

    2005-05-01

    Affective disorders present an important clinical challenge in multiple sclerosis (MS). Due to prohibitive sample size requirements, population-based studies have not yet provided an adequate description of the underlying epidemiology of this association. To describe the epidemiology of affective disorders in MS in a general population sample. The study presented here accessed administrative data from a universal healthcare insurance plan in the Canadian province of Alberta. Physician billing data recorded in the Alberta Health Care Insurance Plan was used to identify members of the population >15 years of age with and without MS. Crude and stratified estimates of the association between affective disorders and MS were made. Logistic regression analysis was used to evaluate statistical interactions and to provide adjusted estimates of the association. The estimated prevalence of MS in the population within the targeted age range (2.3 million individuals) was 386/100,000 and that of affective disorders was 7.7%. As expected, an association between MS and affective disorders was identified (crude relative prevalence: 2.2). The association varied in strength over age-sex categories. Although the prevalence of affective disorder was higher in women with MS than men with MS, the association of MS with affective disorders was stronger in men. The strength of association declined with age in both men and women. Affective disorder prevalence in people with MS becomes similar to that of the general population in older age groups. Affective disorders occur with an increased frequency in MS. This is true in men and women and across all relevant age groups, although the association gets weaker with advancing age. Higher frequencies of affective disorder occur in women with MS than in men with MS. The frequency of affective disorder in people with MS is highest in the 25-44 age group, and declines in older age categories.

  9. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    DEFF Research Database (Denmark)

    Mottahedin, Amin; Ardalan, Maryam; Chumak, Tetyana

    2017-01-01

    The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly...... physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following...

  10. Sleep-wake changes and cognition in neurodegenerative disease.

    Science.gov (United States)

    Naismith, Sharon L; Lewis, Simon J G; Rogers, Naomi L

    2011-01-01

    With the increasing aging population, neurodegenerative disorders will become more common in clinical practice. These disorders involve multiple pathophysiological mechanisms that differentially affect cognition, mood, and physical functions. Possibly due to the involvement of common underlying neurobiological circuits, sleep and/or circadian (sleep-wake) changes are also common in this disease group. Of significance, sleep-wake changes are often a prodromal feature and are predictive of cognitive decline, psychiatric symptoms, quality of life, need for institutional care, and caregiver burden. Unfortunately, in neurodegenerative disease, few studies have included detailed polysomnography or neuropsychological assessments although some data indicate that sleep and neurocognitive features are related. Further studies are also required to address the effects of pharmacological and nonpharmacological treatments on cognitive functioning. Such research will hopefully lead to targeted early intervention approaches for cognitive decline in older people. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Treatment-refractory, juvenile-onset bipolar affective disorder

    OpenAIRE

    Vijay Sagar, K. John

    2005-01-01

    A case of juvenile-onset bipolar affective disorder with a childhood history of attention-deficit hyperactivity disorder (ADHD) is presented. As the patient was refractory to treatment with mood stabilizers, clozapine was given, which succeeded in achieving remission. The disorder's natural history needs further study. Data also need to be collected for optimal pharmacotherapeutic guidance.

  12. The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile

    Directory of Open Access Journals (Sweden)

    Di Benedetto Giulia

    2008-09-01

    Full Text Available Abstract This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects.

  13. A review of the potential role of nano-enabled drug delivery technologies in amyotrophic lateral sclerosis: lessons learned from other neurodegenerative disorders.

    Science.gov (United States)

    Mazibuko, Zamanzima; Choonara, Yahya E; Kumar, Pradeep; Du Toit, Lisa C; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

    2015-04-01

    Amyotrophic lateral sclerosis (ALS) has a multitude of factors implicated in its etiology. The complex neuro-etiology and the restrictive nature of the blood-brain barrier (BBB) have significantly hindered the drug therapy of ALS. Riluzole, a moderately performing drug, is the only agent approved for treating ALS. However, several promising nanocarrier approaches are surfacing that can provide more efficient drug delivery. In addition, biologicals such as stem cells are able to carry neurotrophic factors to their target site, providing motor neurons with the benefits of both, stem cells and neurotrophic factors. This review examines the current drug delivery strategies investigated for optimally treating ALS and related neurodegenerative disorders. Examples include cerium oxide nanoparticles in Alzheimer's disease, odorranalectin, and lactoferrin-coupled PEG-PLGA nanoparticles for urocortin transportation in Parkinson's disease that can also be employed in ALS to bypass the BBB and increase drug bioavailability. A concise incursion into the progress (and lack thereof) made in ALS clinical trials is also discussed. Nanocarriers can potentially eliminate the challenges of poor drug bioavailability in ALS as they have been proven to cross the BBB and reach target sites while minimizing systemic side-effects. Nanocarrier-based delivery of ALS drugs is an area that requires much needed investigation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. When Cytokinin, a Plant Hormone, Meets the Adenosine A2A Receptor: A Novel Neuroprotectant and Lead for Treating Neurodegenerative Disorders?

    Science.gov (United States)

    Huang, Chuen-Lin; Kuo, Tsun-Yung; Lin, Jung-Hsin; Yang, De-Ming; Huang, Nai-Kuei

    2012-01-01

    It is well known that cytokinins are a class of phytohormones that promote cell division in plant roots and shoots. However, their targets, biological functions, and implications in mammalian systems have rarely been examined. In this study, we show that one cytokinin, zeatin riboside, can prevent pheochromocytoma (PC12) cells from serum deprivation-induced apoptosis by acting on the adenosine A2A receptor (A2A-R), which was blocked by an A2A-R antagonist and a protein kinase A (PKA) inhibitor, demonstrating the functional ability of zeatin riboside by mediating through A2A-R signaling event. Since the A2A-R was implicated as a therapeutic target in treating Huntington’s disease (HD), a cellular model of HD was applied by transfecting mutant huntingtin in PC12 cells. By using filter retardation assay and confocal microscopy we found that zeatin riboside reversed mutant huntingtin (Htt)-induced protein aggregations and proteasome deactivation through A2A-R signaling. PKA inhibitor blocked zeatin riboside-induced suppression of mutant Htt aggregations. In addition, PKA activated proteasome activity and reduced mutant Htt protein aggregations. However, a proteasome inhibitor blocked both zeatin riboside-and PKA activator-mediated suppression of mutant Htt aggregations, confirming mediation of the A2A-R/PKA/proteasome pathway. Taken together, zeatin riboside might have therapeutic potential as a novel neuroprotectant and a lead for treating neurodegenerative disorders. PMID:22719969

  15. Copy number variations in affective disorders and meta-analysis

    DEFF Research Database (Denmark)

    Olsen, Line; Hansen, Thomas; Djurovic, Srdjan

    2011-01-01

    In two recent studies 10 copy number variants (CNV) were found to be overrepresented either among patients suffering from affective disorders in an Amish family or in the Wellcome Trust Case-Control Consortium study. Here, we investigate if these variants are associated with affective disorders...

  16. Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson's disease.

    Science.gov (United States)

    Wang, Yan-Hong; Samoylenko, Volodymyr; Tekwani, Babu L; Khan, Ikhlas A; Miller, Loren S; Chaurasiya, Narayan D; Rahman, Md Mostafizur; Tripathi, Lalit M; Khan, Shabana I; Joshi, Vaishali C; Wigger, Frank T; Muhammad, Ilias

    2010-04-21

    Banisteriopsis caapi, a woody vine from the Amazonian basin, is popularly known as an ingredient of a sacred drink ayahuasca, widely used throughout the Amazon as a medicinal tea for healing and spiritual exploration. The usefulness of Banisteriopsis caapi has been established for alleviating symptoms of neurological disorders including Parkinson's disease. Primary objective of this study was to develop the process for preparing standardized extracts of Banisteriopsis caapi to achieve high potency for inhibition of human monoamine oxidases (MAO) and antioxidant properties. The aqueous extracts prepared from different parts of the plant collected from different geographical locations and seasons were analyzed by HPLC for principal bioactive markers. The extracts were simultaneously tested in vitro for inhibition of human MAOs and antioxidant activity for analysis of correlation between phytochemical composition of the extracts and bioactivities. Reversed-phase HPLC with photodiode array detection was employed to profile the alkaloidal and non-alkaloidal components of the aqueous extract of Banisteriopsis caapi. The Banisteriopsis caapi extracts and standardized compositions were tested in vitro for inhibition of recombinant preparations of human MAO-A and MAO-B. In vitro cell-based assays were employed for evaluation of antioxidant property and mammalian cell cytotoxicity of these preparations. Among the different aerial parts, leaves, stems/large branches and stem bark of Banisteriopsis caapi, HPLC analysis revealed that most of the dominant chemical and bioactive markers (1, 2, 5, 7-9) were present in high concentrations in dried bark of large branch. A library of HPLC chromatograms has also been generated as a tool for fingerprinting and authentication of the studied Banisteriopsis caapi species. The correlation between potency of MAO inhibition and antioxidant activity with the content of the main active constituents of the aqueous Banisteriopsis caapi extracts

  17. Epigenetic programming of neurodegenerative diseases by an adverse environment.

    Science.gov (United States)

    Babenko, Olena; Kovalchuk, Igor; Metz, Gerlinde A

    2012-03-20

    Experience and environment can critically influence the risk and progression of neurodegenerative disorders. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications, readily respond to experience and environmental factors. Here we propose that epigenetic regulation of gene expression and environmental modulation thereof may play a key role in the onset and course of common neurological conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. For example, epigenetic mechanisms may mediate long-term responses to adverse experience, such as stress, to affect disease susceptibility and the course of neurodegenerative events. This review introduces the epigenetic components and their possible role in mediating neuropathological processes in response to stress. We argue that epigenetic modifications will affect neurodegenerative events through altered gene function. The study of epigenetic states in neurodegenerative diseases presents an opportunity to gain new insights into risk factors and pathogenic mechanisms. Moreover, research into epigenetic regulation of disease may revolutionize health care by opening new avenues of personalized, preventive and curative medicine. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Bipolar Disorder and Early Affective Trauma.

    Science.gov (United States)

    de Codt, Aloise; Monhonval, Pauline; Bongaerts, Xavier; Belkacemi, Ikram; Tecco, Juan Martin

    2016-09-01

    Bipolar disorder is a chronic psychiatric disease with a high prevalence and is a major psychosocial and medical burden. The exact etiological pathways of bipolar disorder are not fully understood. Genetic factors are known to play an important role in the etiology of bipolar disorder. However, high rates of discordance among identical twins and a growing body of evidence that environmental factors such as early stress can influence the onset and course of psychiatric diseases underline the importance of additional etiological mechanisms of bipolar disorders. There has been little investigation about early trauma in bipolar disorder. The aim of this study was to review the literature on the association between early traumatic interactions like child neglect, mistreatment, abuse or early parental separation and the occurrence of bipolar disorder in adulthood or impact on the course of the disease. Studies investigating associations between child neglect, mistreatment, abuse or early parental separation and occurrence of bipolar disorder in adulthood or impact on the course of the disease were searched in the Pubmed database. More than 700 articles were sorted independently by two of the authors using predefined criteria. Only research articles, reviews and meta-analyses were selected for this review. 53 articles met the inclusion criteria. To date, four systematic reviews partially addressed our research question. Early trauma is more frequently found in the past of bipolar patients than in the general population. Studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a worse prognosis. Early trauma is more often found in the past of bipolar adult patients than the general population and studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a

  19. Psychological therapies for preventing seasonal affective disorder.

    Science.gov (United States)

    Forneris, Catherine A; Nussbaumer, Barbara; Kaminski-Hartenthaler, Angela; Morgan, Laura C; Gaynes, Bradley N; Sonis, Jeffrey H; Greenblatt, Amy; Wipplinger, Jörg; Lux, Linda J; Winkler, Dietmar; Van Noord, Megan G; Hofmann, Julia; Gartlehner, Gerald

    2015-11-11

    Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on psychological therapies as preventive interventions. To assess the efficacy and safety of psychological therapies (in comparison with no treatment, other types of psychological therapy, second-generation antidepressants (SGAs), light therapy, melatonin or agomelatine or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. We conducted a search of the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We conducted a grey literature search (e.g. in clinical trial registries) and handsearched the reference lists of all included studies and pertinent review articles. To examine efficacy, we planned to include randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. To examine adverse events, we intended to include non-randomised studies. We planned to include studies that compared psychological therapy versus any other type of psychological therapy, placebo, light therapy, SGAs, melatonin, agomelatine or lifestyle changes. We also intended to

  20. Non-coding RNA and pseudogenes in neurodegenerative diseases: “The (un)Usual Suspects”

    OpenAIRE

    Costa, Valerio; Esposito, Roberta; Aprile, Marianna; Ciccodicola, Alfredo

    2012-01-01

    Neurodegenerative disorders and cancer are severe diseases threatening human health. The glaring differences between neurons and cancer cells mask the processes involved in their pathogenesis. Defects in cell cycle, DNA repair, and cell differentiation can determine unlimited proliferation in cancer, or conversely, compromise neuronal plasticity, leading to cell death and neurodegeneration. Alteration in regulatory networks affecting gene expression contribute to human diseases onset, includi...

  1. Low-dose, continual enzyme delivery ameliorates some aspects of established brain disease in a mouse model of a childhood-onset neurodegenerative disorder.

    Science.gov (United States)

    King, Barbara; Setford, Meghan L; Hassiotis, Sofia; Trim, Paul J; Duplock, Stephen; Tucker, Justin N; Hattersley, Kathryn; Snel, Marten F; Hopwood, John J; Hemsley, Kim M

    2016-04-01

    To determine the capacity of continual low-dose lysosomal enzyme infusion into the cerebrospinal fluid of mucopolysaccharidosis type IIIA (MPS IIIA) mice to reverse established neurodegenerative disease. The rationale behind the study is that there is only limited animal model-derived evidence supporting treatment of symptomatic patients, principally because few studies have been designed to examine disease reversibility. Twelve-week old MPS IIIA mice were implanted with indwelling unilateral intra-ventricular cannulae. These were connected to subcutaneous mini-osmotic pumps infusing recombinant human sulphamidase. Pump replacement was carried out in some mice at 16-weeks of age, enabling treatment to continue for a further month. Control affected/unaffected mice received vehicle via the same method. Behavioural, neuropathological and biochemical parameters of disease were assessed. Improvement in some, but not all, behavioural parameters occurred. Sulphamidase infusion mediated a statistically significant reduction in primary (heparan sulphate) and secondary (gangliosides GM2, GM3) substrate accumulation in the brain, with small reductions in micro- but not astro-gliosis. There was no change in axonal spheroid number. All mice developed a humoural response, however the antibodies were non-neutralising and no adverse clinical effects were observed. Continual infusion of replacement enzyme partially ameliorates clinical, histological and biochemical aspects of MPS IIIA mice, when treatment begins at an early symptomatic stage. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Bipolar affective disorder, pregnancy and childbirth: clinical characteristics and heredity

    Directory of Open Access Journals (Sweden)

    Rositsa Vladimirova

    2016-09-01

    Full Text Available Bipolar affective disorder has higher frequency among women of reproductive age and can relapse both during pregnancy and immediately after childbirth. The presence of family history is one of the leading risk factors for bipolar affective disorder. A cross-sectional study was performed as part of a large naturalistic study. It included 81 women with pronounced symptoms of bipolar disorder who required hospitalization. The clinical method included comprehensive assessment of patients in the cohort, assessment of the severity of symptoms and the family history. The results showed that more than 50% of the women were at an average age of 25 years and experienced bipolar affective disorder mostly in the first and third trimester, whereas, in the puerperal period, the risk was highest in the first two weeks after childbirth. There was previous history of bipolar affective disorder in about 50% of the women. In 55.6% of the women, there was family history of bipolar affective disorder. The presence of previous history of bipolar affective disorder, first-degree family history and pregnancy at later age were shown to be risk factors for a new relapse during pregnancy and after childbirth. Clinical expression of manic–psychotic symptoms was more typical of the period of lactation than manic symptoms, which were associated rather with younger age and the period of pregnancy. In the studied cohort of patients, the risk of repeatability of affective episodes was significantly higher with each subsequent pregnancy.

  3. Bipolar Affective Disorder and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Birk Engmann

    2011-01-01

    Full Text Available Little is known about comorbidities of bipolar disorder such as Parkinson's disease. A case history and a literature survey indicate that bipolar disorder is linked with or influences Parkinson's disease and vice versa. Underlying mechanisms are poorly understood, and, more importantly, no treatment options are established in such double diagnoses. The few data in comorbid Parkinson cases seem to point to a rapid cycling pattern of bipolar symptoms. With regard to therapeutic intervention, the literature supports pramipexole for treatment of both Parkinson and depressive symptoms in bipolar depression. Lithium, the mood stabilizer of choice for treating manic states, is problematical for use in Parkinson patients because of its side effects. Valproate might be an alternative, especially for treatment of rapid cycling.

  4. Studies of anticipation in bipolar affective disorder.

    Science.gov (United States)

    Lange, Kezia J; McInnis, Melvin G

    2002-03-01

    Anticipation refers to the increase in disease severity or decrease in age of onset in successive generations. The concept evolved from the theories and dogma of degeneration that were pervasive in psychiatry and medicine in the late 19th century and into the early 20th century. The term was set aside with the criticism of geneticist Lionel Penrose, who argued that anticipation was the result of ascertainment biases. The renewed interest in anticipation followed the identification of its molecular genetic basis in the form of unstable trinucleotide repeats. Subsequently, several diseases have been studied clinically for the presence of anticipation. Although anticipation has been identified in many diseases, including bipolar disorder, only diseases showing a pattern of progressive neurodegeneration have been associated with unstable trinucleotide repeats. This review summarizes the research on anticipation in bipolar disorder and other secular trends in the patterns of the illness such as the cohort effect. The changing nature of bipolar disorder is likely to be a result of combined influences from several genes, some of which are likely to be in a state of flux, as well as environmental or cultural forces that converge to give the clinical picture of anticipation.

  5. Longitudinal Study of Neurodegenerative Disorders

    Science.gov (United States)

    2018-01-31

    MLD; Krabbe Disease; ALD; MPS I; MPS II; MPS III; Vanishing White Matter Disease; GM3 Gangliosidosis; PKAN; Tay-Sachs Disease; NP Deficiency; Osteopetrosis; Alpha-Mannosidosis; Sandhoff Disease; Niemann-Pick Diseases; MPS IV; Gaucher Disease; GAN; GM1 Gangliosidoses; Morquio Disease; S-Adenosylhomocysteine Hydrolase Deficiency; Batten Disease; Pelizaeus-Merzbacher Disease; Leukodystrophy; Lysosomal Storage Diseases; Purine Nucleoside Phosphorylase Deficiency; Multiple Sulfatase Deficiency Disease

  6. Diagnostic Value of Isolated Mentalis Versus Mentalis Plus Upper Limb Electromyography in Idiopathic REM Sleep Behavior Disorder Patients Eventually Developing a Neurodegenerative Syndrome.

    Science.gov (United States)

    Fernández-Arcos, Ana; Iranzo, Alex; Serradell, Mónica; Gaig, Carles; Guaita, Marc; Salamero, Manel; Santamaria, Joan

    2017-04-01

    To compare two electromyographic (EMG) montages, isolated mentalis muscle versus mentalis in combination with upper limb muscles in the baseline diagnostic video-polysomnography (V-PSG) of patients with idiopathic REM sleep behaviors disorder (IRBD) who eventually were diagnosed with a clinically defined neurodegenerative syndrome. Forty-nine patients were included. At baseline, diagnosis of RBD was based on a typical history of dream enactment behaviors plus V-PSG showing REM sleep with qualitative increased EMG activity and/or abnormal behaviors. Quantification of EMG activity (tonic, phasic and "any") in the mentalis and upper limb muscles (biceps brachii-BB, n = 36 or flexor digitorum superficialis-FDS, n = 13) was performed manually and compared with published cut-offs. Nine (18.4%) patients had either tonic or phasic EMG below the cut-offs for the isolated mentalis and four of them (11.1 %) also had values below the cut-off for the mentalis combined with BB. All 13 patients recorded with the FDS were above the mentalis combined with FDS cut-off. For the diagnosis of IRBD, sensitivity of isolated mentalis was 81.6% and of the combination of mentalis plus upper limb muscles was 91.8% (p = .03). Audiovisual analysis showed abnormal REM sleep behaviors in all nine patients with values below the cut-offs. Quantification of EMG activity in the upper limbs combined with the mentalis increases the ability to diagnose IRBD when compared with the isolated measurement of the mentalis. Detection of typical abnormal behaviors during REM sleep with audiovisual analysis is essential for the diagnosis of IRBD in patients with EMG values below the published cut-offs.

  7. Fractality of sensations and the brain health: the theory linking neurodegenerative disorder with distortion of spatial and temporal scale-invariance and fractal complexity of the visible world

    Science.gov (United States)

    Zueva, Marina V.

    2015-01-01

    The theory that ties normal functioning and pathology of the brain and visual system with the spatial–temporal structure of the visual and other sensory stimuli is described for the first time in the present study. The deficit of fractal complexity of environmental influences can lead to the distortion of fractal complexity in the visual pathways of the brain and abnormalities of development or aging. The use of fractal light stimuli and fractal stimuli of other modalities can help to restore the functions of the brain, particularly in the elderly and in patients with neurodegenerative disorders or amblyopia. Non-linear dynamics of these physiological processes have a strong base of evidence, which is seen in the impaired fractal regulation of rhythmic activity in aged and diseased brains. From birth to old age, we live in a non-linear world, in which objects and processes with the properties of fractality and non-linearity surround us. Against this background, the evolution of man took place and all periods of life unfolded. Works of art created by man may also have fractal properties. The positive influence of music on cognitive functions is well-known. Insufficiency of sensory experience is believed to play a crucial role in the pathogenesis of amblyopia and age-dependent diseases. The brain is very plastic in its early development, and the plasticity decreases throughout life. However, several studies showed the possibility to reactivate the adult’s neuroplasticity in a variety of ways. We propose that a non-linear structure of sensory information on many spatial and temporal scales is crucial to the brain health and fractal regulation of physiological rhythms. Theoretical substantiation of the author’s theory is presented. Possible applications and the future research that can experimentally confirm or refute the theoretical concept are considered. PMID:26236232

  8. Light therapy for preventing seasonal affective disorder.

    Science.gov (United States)

    Nussbaumer, Barbara; Kaminski-Hartenthaler, Angela; Forneris, Catherine A; Morgan, Laura C; Sonis, Jeffrey H; Gaynes, Bradley N; Greenblatt, Amy; Wipplinger, Jörg; Lux, Linda J; Winkler, Dietmar; Van Noord, Megan G; Hofmann, Julia; Gartlehner, Gerald

    2015-11-08

    Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on light therapy as a preventive intervention. Light therapy is a non-pharmacological treatment that exposes people to artificial light. Mode of delivery (e.g. visors, light boxes) and form of light (e.g. bright white light) vary. To assess the efficacy and safety of light therapy (in comparison with no treatment, other types of light therapy, second-generation antidepressants, melatonin, agomelatine, psychological therapies, lifestyle interventions and negative ion generators) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. A search of the Specialised Register of the Cochrane Depression, Anxiety and Neuorosis Review Group (CCDANCTR) included all years to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials derived from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trails (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We also conducted a grey literature search and handsearched the reference lists of all included studies and pertinent review articles. For efficacy, we included randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we also intended to include non-randomised studies. We intended to include studies that compared any type of

  9. Obstructive sleep apnea and neurodegenerative diseases: A bidirectional relation

    OpenAIRE

    Christianne Martins Corrêa da Silva Bahia; João Santos Pereira

    2015-01-01

    Sleep disorders are common during the clinical course of the main neurodegenerative diseases. Among these disorders, obstructive sleep apnea has been extensively studied in the last decade and recent knowledge regarding its relationship with the neurodegenerative process points a bidirectional relationship. Neurodegenerative diseases can lead to functional changes in the respiratory system that facilitate the emergence of apnea. On the other hand, obstructive sleep apnea itself can lead to ac...

  10. Prevalence of Maternal Affective Disorders in Chinese Mothers of Preschool Children with Autism Spectrum Disorders.

    Science.gov (United States)

    Yu, Y W; Chung, K H; Lee, Y K; Lam, W C; Yiu, M Gc

    2016-12-01

    To evaluate the prevalence of affective disorders and identify their associated factors among Chinese mothers of preschool children diagnosed with autism spectrum disorders. This cross-sectional study was conducted at the Autism Spectrum Disorders Multidisciplinary Clinic of the United Christian Hospital from August 2012 to June 2013. All mothers of a consecutive series of preschool children diagnosed with autism spectrum disorders at their first visit to the clinic were recruited. Information regarding the child-related, maternal, and environmental factors was collected. Psychiatric diagnoses were made according to the Chinese-Bilingual Structured Clinical Interview for DSM-IV Axis I Disorders. Independent factors associated with maternal affective disorders were determined by univariate and multivariate analyses. Of the 121 subjects, the point prevalence of affective disorders as a group was 29.8%. The point prevalence of major depressive disorders, adjustment disorders, anxiety disorders, and bipolar affective disorders was 14.9%, 10.7%, 3.3% and 0.8%, respectively. A higher level of disruptive and self-absorbed behaviours in the children (as assessed by the Developmental Behaviour Checklist), a higher level of affiliate stigma (as assessed by 22-item Affiliate Stigma Scale), and a history of psychiatric disorders were independently associated with current affective disorders. Psychiatric disorders, predominantly affective disorders, are common among Chinese mothers of preschool children with autism spectrum disorders. Identification of independent factors associated with maternal affective disorders can aid in the early detection of cases and planning of early intervention programmes to address both child and maternal psychological needs.

  11. Personality traits in unaffected twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Vinberg, M; Kyvik, Kirsten Ohm; Mortensen, E L

    2007-01-01

    OBJECTIVE: To examine whether a high genetic liability to develop affective disorder is associated with specific personality traits. METHOD: A cross-sectional, high-risk, case-control study. Through nation-wide registers, healthy monozygotic (MZ) and dizygotic (DZ) twins with (high-risk twins......) and without (the control group/low-risk twins) a co-twin history of affective disorder were identified. Personality traits were compared for a total of 211 high-risk and low-risk twins. RESULTS: In univariate analyses, the high-risk twins had a higher level of neuroticism than the control twins (P = 0.......03). In multivariate analyses, a high genetic liability to affective disorder was not significantly associated with neuroticism but correlated to sex, minor psychopathology and recent life events. CONCLUSION: A high genetic liability to affective disorder showed an association with neuroticism, but the association...

  12. Seasonal affective disorder, winter type: current insights and treatment options

    National Research Council Canada - National Science Library

    Meesters Y; Gordijn MCM

    2016-01-01

    ...., Groningen, the Netherlands Abstract: Seasonal affective disorder (SAD), winter type, is a seasonal pattern of recurrent major depressive episodes most commonly occurring in autumn or winter and remitting in spring/summer...

  13. Affect regulation and psychopathology in women with borderline personality disorder

    DEFF Research Database (Denmark)

    Simonsen, Erik; Andersen, Rune; Timmerby, Nina

    2012-01-01

    INTRODUCTION: Dysfunction in affect regulation is a prominent feature that grossly impairs behavioural and interpersonal domains of experience and underlies a great deal of the psychopathology in borderline personality disorder (BPD). However, no study has yet been published that evaluates...

  14. Risperidone Mono - Therapy as Prophylaxis in Bipolar Affective Disorders

    OpenAIRE

    Trivedi, Mohit; Pinto, Denzil; Safeekh, A.T.

    2004-01-01

    Risperidone has been found to be useful in the treatment of acute bipolar disorders. This is a case report where risperidone mono therapy has been found to be effective in prophylaxis of bipolar affective disorder. The pharmacological and clinical implications of risperidone in the management of BPAD are discussed

  15. An Autistic Male Presenting Seasonal Affective Disorder (SAD) and Trichotillomania.

    Science.gov (United States)

    Kurita, Hiroshi; Nakayasu, Nobuo

    1994-01-01

    This paper presents a case report of a young adult Japanese male with infantile autism who also met diagnostic criteria for seasonal affective disorder and trichotillomania (compulsive hair pulling). The case report deals with difficulties in diagnosing mood disorder in such individuals, potential treatment effectiveness of valproic acid, and…

  16. Theoretical and clinical overview of affective temperaments in mood disorders

    Directory of Open Access Journals (Sweden)

    Xenia Gonda

    2015-07-01

    Full Text Available Temperaments are imperturbable variations of personality, traits and ways of reacting to the environment that characterize individuals and remain constant throughout several different situations. Temperaments usually play a central role in determining emotional reactions, therefore several temperamental models have attempted to establish the potential relationship between temperaments and affective disorders. According to Hagop Akiskal, affective temperaments are subclinical and subaffective trait-like manifestations of affective disorders. Unlike several models of temperament which were exclusively developed theoretically in order to describe healthy human functioning, later extrapolated to capture the pathological domains of mental and behavioral features, the current model of affective temperaments was developed on classical traditions and mainly based on the observation of subjects with mood disorders and their healthy first degree relatives. There is accumulating evidence concerning the development of affective temperaments based on their adaptive evolutionary characteristics and genetic background, and normative data from large national studies on general and healthy samples indicate their universal characteristics. Studies in affective patient populations indicate that the relationship between affective temperaments and affective illness is more complex than a simple extrapolation from psychopathology and mental health, and affective temperaments may represent a latent state of the staging model, playing a pathoplastic role in mood disorders determining their evolution, clinical features, main characteristics and outcome. A large body of data on affective temperaments has been published during the last decade, deserving a critical analysis presented in this overview.

  17. Implicit affectivity in patients with borderline personality disorder.

    Science.gov (United States)

    Dukalski, Bibiana; Quirin, Markus; Kersting, Anette; Suslow, Thomas; Donges, Uta-Susan

    2017-01-01

    It has been argued that borderline personality disorder (BPD) is related to an enhanced affective reactivity. According to findings from research based on self-report, individuals with BPD develop and feel more negative and less positive affect than healthy individuals. Implicit affectivity, which can be measured using indirect assessment methods, relates to processes of the impulsive, intuitive system. In the present study, implicit and explicit affectivity was examined in patients suffering from BPD compared to healthy persons. Thirty-five women with BPD and 35 healthy women participated in the study. Implicit affectivity was assessed using the Implicit Positive and Negative Affect Test (IPANAT). Measures of explicit state and trait affectivity were also administered. BPD women had lower explicit positive state and trait affect scores and higher negative state and trait affect scores than healthy women. They had also lower implicit positive affect but they did not differ from healthy women regarding implicit negative affect. Total number of comorbid disorders was correlated with both implicit positive and implicit negative affect. According to our data, BPD patients exhibit reduced implicit positive affect as well as reduced explicit positive affect compared to healthy persons. According to our IPANAT data, BPD patients are characterized by a normal disposition to develop negative affective reactions which is in line with a number of findings from psycho-physiological research on BPD. Self-reports of negative affectivity in BPD could be biased by negative distortion.

  18. Animal models of neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Fabiola Mara Ribeiro

    2013-01-01

    Full Text Available The prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD and Parkinson's disease (PD, increases with age, and the number of affected patients is expected to increase worldwide in the next decades. Accurately understanding the etiopathogenic mechanisms of these diseases is a crucial step for developing disease-modifying drugs able to preclude their emergence or at least slow their progression. Animal models contribute to increase the knowledge on the pathophysiology of neurodegenerative diseases. These models reproduce different aspects of a given disease, as well as the histopathological lesions and its main symptoms. The purpose of this review is to present the main animal models for AD, PD, and Huntington's disease.

  19. Coenzyme Q10 effects in neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Meredith Spindler

    2009-11-01

    Full Text Available Meredith Spindler1, M Flint Beal1,2, Claire Henchcliffe1,21Department of Neurology, 2Department of Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Coenzyme Q10 (CoQ10 is an essential cofactor in the mitochondrial respiratory chain, and as a dietary supplement it has recently gained attention for its potential role in the treatment of neurodegenerative disease. Evidence for mitochondrial dysfunction in neurodegenerative disorders derives from animal models, studies of mitochondria from patients, identification of genetic defects in patients with neurodegenerative disease, and measurements of markers of oxidative stress. Studies of in vitro models of neuronal toxicity and animal models of neurodegenerative disorders have demonstrated potential neuroprotective effects of CoQ10. With this data in mind, several clinical trials of CoQ10 have been performed in Parkinson’s disease and atypical Parkinson’s syndromes, Huntington’s disease, Alzheimer disease, Friedreich’s ataxia, and amyotrophic lateral sclerosis, with equivocal findings. CoQ10 is widely available in multiple formulations and is very well tolerated with minimal adverse effects, making it an attractive potential therapy. Phase III trials of high-dose CoQ10 in large sample sizes are needed to further ascertain the effects of CoQ10 in neurodegenerative diseases.Keywords: coenzyme Q10, neurodegenerative disease, Parkinson’s disease, Huntington’s disease, mitochondrial dysfunction

  20. Lysosomal dysfunction in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Klaudia Tomala

    2017-05-01

    Full Text Available Recent data advocate for the implication of lysosomes in the development of programmed cell death. Lysosomal dysfunction decreased the efficiency of autophagosome/lysosome fusion that leads to vacuolation of cells. Autophagic vacuoles containing damaged organelles and altered proteins are hallmarks in most neurodegenerative disorders. These aggregates consequently disrupt cellular homeostasis causing neuronal cell death due apoptosis or necrosis. Moreover calpain mediated or mutation inducted lysosomal rupture result in release of lysosomal cathepsins into the cytoplasm and inducing neuronal cell death. In this review we emphasize the pathophysiological mechanism connecting disrupting autophagy – lysosomal pathway and lysosomal dysfunction in neuronal cell death called lysosomal cell death.

  1. Affective instability in borderline personality disorder: experience sampling findings.

    Science.gov (United States)

    Nica, Elena Irina; Links, Paul S

    2009-02-01

    Affective instability, defined as repeated, rapid, and abrupt shifts in mood, is considered the core pathology in borderline personality disorder. The temporal pattern of affective instability can be best captured with the experience sampling method-longitudinal assessment of people's affective states as they occur in real time and in their natural environment. A review of the experience sampling studies published to date for borderline personality disorder suggests the following mood variability pattern: intense negative mood, more frequent and abrupt mood changes than healthy controls and patients with major depression, and partial triggering of affect by external events. The method also has great potential to investigate the links between affective instability and other psychological and behavioral correlates of the disorder, such as suicide, lack of self-esteem, and erratic behaviors. However, the method requires systematic study to determine best data collection designs and mathematical models of mood variability.

  2. Quality of life in unaffected twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj; Bech, Per; Kyvik, Kirsten Ohm

    2006-01-01

    BACKGROUND: The disability and hardship associated with affective disorder is shared by the family members of affective patients and might affect the family member's quality of life. METHOD: In a cross-sectional, high-risk, case-control study, monozygotic (MZ) and dizygotic (DZ) twins with (High......-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. The aim of the present study was to investigate the hypothesis that a genetic liability to affective disorder is associated with a lower perception of quality...... of life. RESULTS: Univariate analyses showed that quality of life in all domains was impaired for the 121 High-Risk twins compared to the 84 Low-Risk twins. In multiple regression analyses, the differences remained significant after adjustment for sex, age, marital status and years of education. Adjusted...

  3. Coping styles in healthy individuals at risk of affective disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj; Froekjaer, Vibe Gedsoe; Kessing, Lars Vedel

    2010-01-01

    .001) and Avoidance coping (p = 0.04) than individuals not at risk. Adjusted for gender, age, years of education, and recent stressful life events the high-risk individuals used more emotion-oriented coping (p = 0.03). In conclusion, maladaptive coping style may represent a trait marker for mood disorder improving......Coping styles may influence the perceived life stress experienced by an individual and, therefore, also be critical in the development of affective disorders. This study examined whether familial risk of affective disorder is associated with the use of maladaptive coping styles, in healthy...... maladaptive coping styles may be a target for selective prevention focusing on subgroups at high risk of developing an affective disorder....

  4. Coping styles in healthy individuals at risk of affective disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj; Froekjaer, Vibe Gedsoe; Kessing, Lars Vedel

    2010-01-01

    Coping styles may influence the perceived life stress experienced by an individual and, therefore, also be critical in the development of affective disorders. This study examined whether familial risk of affective disorder is associated with the use of maladaptive coping styles, in healthy.......001) and Avoidance coping (p = 0.04) than individuals not at risk. Adjusted for gender, age, years of education, and recent stressful life events the high-risk individuals used more emotion-oriented coping (p = 0.03). In conclusion, maladaptive coping style may represent a trait marker for mood disorder improving...... maladaptive coping styles may be a target for selective prevention focusing on subgroups at high risk of developing an affective disorder....

  5. Analysis of affective disorders in patients with vascular dementia

    Directory of Open Access Journals (Sweden)

    D. V. Zakharchenko

    2012-01-01

    Full Text Available The outpatient records of 147 patients followed up for diagnosed vascular dementia were analyzed to assess the relationship between affective disorders and severe cognitive impairments. It was found that 7% of the examinees had a history of depressive states. Estimating the development time for vascular dementia could divide the patients into 2 groups: 1 60% of the patients in whom cognitive impairments began to determine its clinical picture just within the first 2 years after identification of affective disorders and 2 40%, in whom cognitive impairments occurred 10—20 years later. In both groups, mental disorders occurred at an equal age in the presence of depressive disorders; in Group 1, vascular dementia developed nearly twice as often as that in Group 2. At the same time, the occurrence of cognitive impairments in Group 1 patients just in the early disease stages is indicative of the organic genesis of affective disorders, as confirmed by the moderately rapid progression of psychopathological symptoms, such as sharpening of personality traits, increased rigidity of psychic processes, emotional lability, variations in affective symptomatology, inadequate remissions, and the presence of neurological symptoms. Another type of a ratio of depressive to severe cognitive disorders was found in the elderly persons in Group 2. The long existence of affective disorders without signs of cognitive diminution leads one to say that they have recurrent depressive disorder with further addition of a comorbid vascular process. These patients showed a fairly high severity of affective pathology that was responsible for more frequent admissions, as well as a phase course with relatively pure remissions without any clear intellectual-mnestic reduction and a predominance of hysterical character traits.

  6. Skin disorders affecting the feet | Motswaledi | South African Family ...

    African Journals Online (AJOL)

    Skin disorders of the feet can affect the glabrous skin on the dorsal aspects, or the thick skin on the plantar aspects, thereof, or both. Some can affect one foot, and others both of them. These diseases can be inflammatory, genetically inherited, infectious and neoplastic in origin. It is important to identify them and to start ...

  7. Obstructive sleep apnea and neurodegenerative diseases: A bidirectional relation

    Directory of Open Access Journals (Sweden)

    Christianne Martins Corrêa da Silva Bahia

    Full Text Available Sleep disorders are common during the clinical course of the main neurodegenerative diseases. Among these disorders, obstructive sleep apnea has been extensively studied in the last decade and recent knowledge regarding its relationship with the neurodegenerative process points a bidirectional relationship. Neurodegenerative diseases can lead to functional changes in the respiratory system that facilitate the emergence of apnea. On the other hand, obstructive sleep apnea itself can lead to acceleration of neuronal death due to intermittent hypoxia. Considering that obstructive sleep apnea is a potentially treatable condition, its early identification and intervention could have a positive impact on the management of patients with neurodegenerative diseases.

  8. Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Edyta Paczkowska

    that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.

  9. Course and cognitive outcome in major affective disorder

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel

    2015-01-01

    function as an expression of brain function affected during a longer period. Previous studies of the course of affective episodes are flawed by a number of drawbacks such as various definitions of recovery and recurrence, various kinds of bias and confounders, low statistical power, and statistical...... as an expression of an affective episode. On average, a progressive course with increasing risk of recurrence with every new episode was found for unipolar and bipolar affective disorders. Initially, the two types of disorders followed markedly different courses, but later in the course of the illness the risk...... of illness played a role. The chances of recovery from an episode were found not to change during the course of unipolar or bipolar disorder. In contrast, a review of studies from the era before active treatment revealed that the duration of untreated episodes seemed to increase during the course of illness...

  10. Sleep and neurodegenerative diseases.

    Science.gov (United States)

    Chokroverty, Sudhansu

    2009-09-01

    Sleep disturbances are common in neurodegenerative diseases. Disturbed sleep can result in fatigue, irritability, morning headaches, impaired motor and cognitive skills, depression, and daytime somnolence. The major sleep complaints include insomnia, hypersomnia, parasomnia, excessive nocturnal motor activity, circadian sleep-wake rhythm disturbance, and respiratory dysrhythmia. The pathogenetic mechanisms of sleep disturbances may be secondary to direct structural alteration of the sleep-wake generating neurons or from several other indirect mechanisms. At the biochemical level, neurodegenerative diseases may be largely classified as tauopathies, alpha-synucleinopathies, and other diseases. Overnight polysomnography (PSG), Multiple Sleep Latency Test, Maintenance of Wakefulness Test, and actigraphy are some important diagnostic laboratory tests in the evaluation of sleep disturbances. Management of sleep disturbances is complex and is based primarily on the nature of the sleep disturbance. The clinical profiles, pathogenetic mechanisms, PSG findings, and management issues are discussed here with reference to some common neurodegenerative diseases. Thieme Medical Publishers.

  11. The Role of the Craniocervical Junction in Craniospinal Hydrodynamics and Neurodegenerative Conditions

    Directory of Open Access Journals (Sweden)

    Michael F. Flanagan

    2015-01-01

    Full Text Available The craniocervical junction (CCJ is a potential choke point for craniospinal hydrodynamics and may play a causative or contributory role in the pathogenesis and progression of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, MS, and ALS, as well as many other neurological conditions including hydrocephalus, idiopathic intracranial hypertension, migraines, seizures, silent-strokes, affective disorders, schizophrenia, and psychosis. The purpose of this paper is to provide an overview of the critical role of the CCJ in craniospinal hydrodynamics and to stimulate further research that may lead to new approaches for the prevention and treatment of the above neurodegenerative and neurological conditions.

  12. Abnormal hypothalamic response to light in Seasonal Affective Disorder

    OpenAIRE

    Vandewalle, Gilles; Hébert, M.; C. Beaulieu; Richard, L; Daneault, V.; Garon, M.-L.; LeBlanc, J; Grandjean, D.; Maquet, Pierre; Schwartz, S; M. Dumont; Doyon, J.; Carrier, J

    2011-01-01

    Vulnerability to the reduction in natural light associated with fall/winter is generally accepted as the main trigger of seasonal affective disorder (SAD), whereas light therapy is a treatment of choice of the disorder. However, the relationship between exposure to light and mood regulation remains unclear. As compared with green light, blue light was shown to acutely modulate emotion brain processing in healthy individuals. Here, we investigated the impact of light on emotion brain processin...

  13. Disrupted startle modulation in animal models for affective disorders.

    Science.gov (United States)

    Bijlsma, E Y; Oosting, R S; Olivier, B; Groenink, L

    2010-04-02

    Affective startle modulation is used to study emotional reactivity in humans, and blunted affective startle modulation has been reported in depressed patients. To determine whether blunted affective startle modulation is also a common feature in animal models for affective disorders, light-enhanced startle was studied in three models: inescapable foot shock (IFS), repeated restraint stress (RRS) and olfactory bulbectomy (OBX). In addition, prepulse inhibition was studied in these models. Light-enhanced startle was blunted following IFS and OBX and RRS decreased overall startle responding. Prepulse inhibition, however, was unaffected. These findings indicate that induction models for affective disorders may be associated with long term effects on affective startle modulation. The lack of changes in sensory motor gating suggests that these changes can be ascribed to alterations in emotional reactivity. In conclusion, our results indicate that the blunted affective startle modulation seen in animal models for affective disorders may be used to examine the mechanisms underlying altered emotional reactivity. Copyright 2009 Elsevier B.V. All rights reserved.

  14. Predictors of recurrence in affective disorder - analyses accounting for individual heterogeneity

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Andersen, Elisabeth Anne Wreford; Andersen, Per Kragh

    2000-01-01

    affective disorder, depression, unipolar, bipolar, recurrence, predictors, life event, individual heterogeneity......affective disorder, depression, unipolar, bipolar, recurrence, predictors, life event, individual heterogeneity...

  15. Seasonal Affective Disorder: An Overview of Assessment and Treatment Approaches.

    Science.gov (United States)

    Melrose, Sherri

    2015-01-01

    Seasonal affective disorder or SAD is a recurrent major depressive disorder with a seasonal pattern usually beginning in fall and continuing into winter months. A subsyndromal type of SAD, or S-SAD, is commonly known as "winter blues." Less often, SAD causes depression in the spring or early summer. Symptoms center on sad mood and low energy. Those most at risk are female, are younger, live far from the equator, and have family histories of depression, bipolar disorder, or SAD. Screening instruments include the Seasonal Pattern Assessment Questionnaire (SPAQ). Typical treatment includes antidepressant medications, light therapy, Vitamin D, and counselling. This paper provides an overview of SAD.

  16. Longitudinal associations between mismatch negativity and disability in early schizophrenia- and affective-spectrum disorders.

    Science.gov (United States)

    Kaur, Manreena; Lagopoulos, Jim; Lee, Rico Sze Chun; Ward, Philip B; Naismith, Sharon L; Hickie, Ian B; Hermens, Daniel F

    2013-10-01

    -central P3a amplitudes compared to their peers who did return for repeat assessment. This study provides some evidence of the predictive utility of MMN at the early stages of schizophrenia- and affective-spectrum disorders and demonstrated that MMN impairments in such patients may worsen over time. Specifically, we found that young patients with the most impaired MMN amplitudes at baseline showed the most severe levels of disability at follow-up. Furthermore, in the subset of patients with repeat neurophysiological testing, central MMN was further impaired suggestive of neurodegenerative effects. MMN may serve as a neurophysiological biomarker to more accurately predict functional outcomes and prognosis, particularly at the early stages of illness. © 2013.

  17. Sense of humor disorders in patients with schizophrenia and affective disorders

    Directory of Open Access Journals (Sweden)

    Enikolopov, Sergey N.

    2014-03-01

    Full Text Available The article presents an empirical study of sense of humor disorders in patients with schizophrenia and affective disorders. Several parameters of analysis are distinguished: humor recognition, humor preferences and the level of laughing activity. It is showed that patients with schizophrenia are characterized by inability to recognize humor. As soon as patients with schizotypal disorder do recognize humor, this may be used as a diagnostic criterion in clinical practice. Sense of humor in patients with schizophrenia and affective disorders acquires peculiarities which are defined here as preferences of certain cognitive mechanisms and topics of jokes.

  18. Neuropeptide Y in Alcohol Addiction and Affective Disorders.

    Science.gov (United States)

    Thorsell, Annika; Mathé, Aleksander A

    2017-01-01

    Neuropeptide Y (NPY), a neuropeptide highly conserved throughout evolution, is present at high levels in the central nervous system (CNS), as well as in peripheral tissues such as the gut and cardiovascular system. The peptide exerts its effects via multiple receptor subtypes, all belonging to the G-protein-coupled receptor superfamily. Of these subtypes, the Y1 and the Y2 are the most thoroughly characterized, followed by the Y5 subtype. NPY and its receptors have been shown to be of importance in central regulation of events underlying, for example, affective disorders, drug/alcohol use disorders, and energy homeostasis. Furthermore, within the CNS, NPY also affects sleep regulation and circadian rhythm, memory function, tissue growth, and plasticity. The potential roles of NPY in the etiology and pathophysiology of mood and anxiety disorders, as well as alcohol use disorders, have been extensively studied. This focus was prompted by early indications for an involvement of NPY in acute responses to stress, and, later, also data pointing to a role in alterations within the CNS during chronic, or repeated, exposure to adverse events. These functions of NPY, in addition to the peptide's regulation of disease states, suggest that modulation of the activity of the NPY system via receptor agonists/antagonists may be a putative treatment mechanism in affective disorders as well as alcohol use disorders. In this review, we present an overview of findings with regard to the NPY system in relation to anxiety and stress, acute as well as chronic; furthermore we discuss post-traumatic stress disorder and, in part depression. In addition, we summarize findings on alcohol use disorders and related behaviors. Finally, we briefly touch upon genetic as well as epigenetic mechanisms that may be of importance for NPY function and regulation. In conclusion, we suggest that modulation of NPY-ergic activity within the CNS, via ligands aimed at different receptor subtypes, may be

  19. Neuropeptide Y in Alcohol Addiction and Affective Disorders

    Directory of Open Access Journals (Sweden)

    Annika Thorsell

    2017-07-01

    Full Text Available Neuropeptide Y (NPY, a neuropeptide highly conserved throughout evolution, is present at high levels in the central nervous system (CNS, as well as in peripheral tissues such as the gut and cardiovascular system. The peptide exerts its effects via multiple receptor subtypes, all belonging to the G-protein-coupled receptor superfamily. Of these subtypes, the Y1 and the Y2 are the most thoroughly characterized, followed by the Y5 subtype. NPY and its receptors have been shown to be of importance in central regulation of events underlying, for example, affective disorders, drug/alcohol use disorders, and energy homeostasis. Furthermore, within the CNS, NPY also affects sleep regulation and circadian rhythm, memory function, tissue growth, and plasticity. The potential roles of NPY in the etiology and pathophysiology of mood and anxiety disorders, as well as alcohol use disorders, have been extensively studied. This focus was prompted by early indications for an involvement of NPY in acute responses to stress, and, later, also data pointing to a role in alterations within the CNS during chronic, or repeated, exposure to adverse events. These functions of NPY, in addition to the peptide’s regulation of disease states, suggest that modulation of the activity of the NPY system via receptor agonists/antagonists may be a putative treatment mechanism in affective disorders as well as alcohol use disorders. In this review, we present an overview of findings with regard to the NPY system in relation to anxiety and stress, acute as well as chronic; furthermore we discuss post-traumatic stress disorder and, in part depression. In addition, we summarize findings on alcohol use disorders and related behaviors. Finally, we briefly touch upon genetic as well as epigenetic mechanisms that may be of importance for NPY function and regulation. In conclusion, we suggest that modulation of NPY-ergic activity within the CNS, via ligands aimed at different receptor

  20. Neurodegenerative diseases: exercising towards neurogenesis and neuroregeneration

    Directory of Open Access Journals (Sweden)

    Eng-Tat Ang

    2010-07-01

    Full Text Available Currently, there is still no effective therapy for neurodegenerative diseases (NDD such as Alzheimer’s disease (AD and Parkinson’s disease (PD despite intensive research and on-going clinical trials. Collectively, these diseases account for the bulk of health care burden associated with age-related neurodegenerative disorders. There is therefore an urgent need to further research into the molecular pathogenesis, histological differentiation, and clinical management of NDD. Importantly, there is also an urgency to understand the similarities and differences between these two diseases so as to identify the common or different upstream and downstream signaling pathways. In this review, the role iron play in NDD will be highlighted, as iron is key to a common underlying pathway in the production of oxidative stress. There is increasing evidence to suggest that oxidative stress predisposed cells to undergo damage to DNA, protein and lipid, and as such a common factor involved in the pathogenesis of AD and PD. The challenge then is to minimize elevated and uncontrolled oxidative stress levels while not affecting basal iron metabolism, as iron plays vital roles in sustaining cellular function. However, overload of iron results in increased oxidative stress due to the Fenton reaction. We discuss evidence to suggest that sustained exercise and diet restriction may be ways to slow the rate of neurodegeneration, by perhaps promoting neurogenesis or antioxidant-related pathways. It is also our intention to cover NDD in a broad sense, in the context of basic and clinical sciences to cater for both clinician’s and the scientist’s needs, and to highlight current research investigating exercise as a therapeutic or preventive measure.

  1. Neurodegenerative Diseases: Exercising Toward Neurogenesis and Neuroregeneration

    Science.gov (United States)

    Ang, Eng-Tat; Tai, Yee-Kit; Lo, Shun-Qiang; Seet, Raymond; Soong, Tuck-Wah

    2010-01-01

    Currently, there is still no effective therapy for neurodegenerative diseases (NDD) such as Alzheimer's disease (AD) and Parkinson's disease (PD) despite intensive research and on-going clinical trials. Collectively, these diseases account for the bulk of health care burden associated with age-related neurodegenerative disorders. There is therefore an urgent need to further research into the molecular pathogenesis, histological differentiation, and clinical management of NDD. Importantly, there is also an urgency to understand the similarities and differences between these two diseases so as to identify the common or different upstream and downstream signaling pathways. In this review, the role iron play in NDD will be highlighted, as iron is key to a common underlying pathway in the production of oxidative stress. There is increasing evidence to suggest that oxidative stress predisposed cells to undergo damage to DNA, protein and lipid, and as such a common factor involved in the pathogenesis of AD and PD. The challenge then is to minimize elevated and uncontrolled oxidative stress levels while not affecting basal iron metabolism, as iron plays vital roles in sustaining cellular function. However, overload of iron results in increased oxidative stress due to the Fenton reaction. We discuss evidence to suggest that sustained exercise and diet restriction may be ways to slow the rate of neurodegeneration, by perhaps promoting neurogenesis or antioxidant-related pathways. It is also our intention to cover NDD in a broad sense, in the context of basic and clinical sciences to cater for both clinician's and the scientist's needs, and to highlight current research investigating exercise as a therapeutic or preventive measure. PMID:20725635

  2. Neuromagnetic Indication of Dysfunctional Emotion Regulation in Affective Disorders

    Directory of Open Access Journals (Sweden)

    Christian Pietrek

    2012-01-01

    Full Text Available Dysfunctional emotion regulation is often reported in affective disorders, but it is unclear whether this dysfunction concerns initial processing of emotional input or regulation of resulting emotion. The present study addressed these aspects in 27 depressive and 15 borderline personality disorder patients and 28 healthy controls who were instructed to either passively view unpleasant and neutral pictures or downregulate emotional responses by reappraisal, while neuromagnetic brain activity was measured. All three groups showed more early response to unpleasant than to neutral pictures, whereas patients failed to show subsequent activity suppression under instructions to down-regulate. This deficient emotion regulation was evident primarily in those subjects reporting high childhood adversity. Results support intact emotional input processing but impaired emotion regulation in affective disorders and indicate a moderating influence of early life stress.

  3. Maternal Affective Disorder and Children's Representation of Their Families

    Science.gov (United States)

    Arteche, Adriane; Murray, Lynne

    2011-01-01

    Children's perceptions of family relationship are related to their later emotional and social adjustment. This is of particular relevance in the context of family stressors such as maternal affective disorder. This study investigated the effects of maternal postnatal depression and anxiety on children's family representations. In our sample of…

  4. Light Therapy for Seasonal Affective Disorder. The Effects of Timing

    NARCIS (Netherlands)

    MEESTERS, Y; JANSEN, JHC; BEERSMA, DGM; BOUHUYS, AL; VANDENHOOFDAKKER, RH

    Background. Sixty-eight patients with seasonal affective disorder participated in a 10 000-lux light treatment study in which two questions were addressed: do response rates differ when the light is applied at different times of the day and does short-term rank ordering of morning and evening light

  5. affective, schizophrenic and mood disorders in patients admitted at ...

    African Journals Online (AJOL)

    Findings from clinical, genetic, neuropsychological and neurophysiological studies have failed to highlight a clear demarcation between the two main psychotic syndromes i.e.. MD and SCZ12, while evidence from brain imaging,. The relationship between schizo- affective, schizophrenic and mood disorders in patients ...

  6. Symptom dimensions of affective disorders in migraine patients

    NARCIS (Netherlands)

    Louter, M. A.; Pijpers, J. A.; Wardenaar, K. J.; van Zwet, E. W.; van Hemert, A. M.; Zitman, F. G.; Ferrari, M. D.; Penninx, B. W.; Tervvindt, G. M.

    2015-01-01

    Objective: A strong association has been established between migraine and depression. However, this is the first study to differentiate in a large sample of migraine patients for symptom dimensions of the affective disorder spectrum. Methods: Migraine patients (n = 3174) from the LUMINA (Leiden

  7. affective, schizophrenic and mood disorders in patients admitted at ...

    African Journals Online (AJOL)

    SCZ, SAD and MD regarding: affective and core symptoms of schizophrenia (with the exception of core symptoms of schizophrenia between SCZ and SAD); presence of past trauma; a past suicide attempt; and comorbidity with alcohol and drug abuse disorders. SAD and MD patients took significantly more mood stabilizers ...

  8. Seasonal affective disorder, winter type : current insights and treatment options

    NARCIS (Netherlands)

    Meesters, Ybe; Gordijn, Margaretha

    2016-01-01

    Seasonal affective disorder (SAD), winter type, is a seasonal pattern of recurrent major depressive episodes most commonly occurring in autumn or winter and remitting in spring/summer. The syndrome has been well-known for more than three decades, with light treatment being the treatment of first

  9. Symptom dimensions of affective disorders in migraine patients

    NARCIS (Netherlands)

    Louter, M.A.; Pijpers, J.A.; Wardenaar, K.J.; van Zwet, E.W.; van Hemert, A.M.; Zitman, F. G.; Ferrari, M.D.; Penninx, B.W.; Terwindt, G.M.

    2015-01-01

    Objective: A strong association has been established between migraine and depression. However, this is the first study to differentiate in a large sample of migraine patients for symptom dimensions of the affective disorder spectrum. Methods: Migraine patients (n. =. 3174) from the LUMINA (Leiden

  10. Electronic monitoring of patients with bipolar affective disorder

    DEFF Research Database (Denmark)

    Jacoby, Anne Sophie; Faurholt-Jepsen, Maria; Vinberg, Maj

    2012-01-01

    Bipolar disorder is a great challenge to patients, relatives and clinicians, and there is a need for development of new methods to identify prodromal symptoms of affective episodes in order to provide efficient preventive medical and behavioural intervention. Clinical trials prove that electronic...

  11. Cognitive function in unaffected twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Christensen, Maj Vinberg; Kyvik, Kirsten Ohm; Kessing, Lars Vedel

    2006-01-01

    is associated with cognitive impairment. METHOD: In a cross-sectional high-risk case-control study, healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers...

  12. Melanopsin, photosensitive ganglion cells, and seasonal affective disorder.

    Science.gov (United States)

    Roecklein, Kathryn A; Wong, Patricia M; Miller, Megan A; Donofry, Shannon D; Kamarck, Marissa L; Brainard, George C

    2013-03-01

    In two recent reports, melanopsin gene variations were associated with seasonal affective disorder (SAD), and in changes in the timing of sleep and activity in healthy individuals. New studies have deepened our understanding of the retinohypothalamic tract, which translates environmental light received by the retina into neural signals sent to a set of nonvisual nuclei in the brain that are responsible for functions other than sight including circadian, neuroendocrine and neurobehavioral regulation. Because this pathway mediates seasonal changes in physiology, behavior, and mood, individual variations in the pathway may explain why approximately 1-2% of the North American population develops mood disorders with a seasonal pattern (i.e., Major Depressive and Bipolar Disorders with a seasonal pattern, also known as seasonal affective disorder/SAD). Components of depression including mood changes, sleep patterns, appetite, and cognitive performance can be affected by the biological and behavioral responses to light. Specifically, variations in the gene sequence for the retinal photopigment, melanopsin, may be responsible for significant increased risk for mood disorders with a seasonal pattern, and may do so by leading to changes in activity and sleep timing in winter. The retinal sensitivity of SAD is hypothesized to be decreased compared to controls, and that further decrements in winter light levels may combine to trigger depression in winter. Here we outline steps for new research to address the possible role of melanopsin in seasonal affective disorder including chromatic pupillometry designed to measure the sensitivity of melanopsin containing retinal ganglion cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Daily Interpersonal and Affective Dynamics in Personality Disorder

    Science.gov (United States)

    Wright, Aidan G.C.; Hopwood, Christopher J.; Simms, Leonard J.

    2015-01-01

    In this naturalistic study we adopt the lens of interpersonal theory to examine between-and within-person differences in dynamic processes of daily affect and interpersonal behaviors among individuals (N = 101) previously diagnosed with personality disorders who completed daily diaries over the course of 100 days. Dispositional ratings of interpersonal problems and measures of daily stress were used as predictors of daily shifts in interpersonal behavior and affect in multilevel models. Results indicate that ~40%–50% of the variance in interpersonal behavior and affect is due to daily fluctuations, which are modestly related to dispositional measures of interpersonal problems but strongly related to daily stress. The findings support conceptions of personality disorders as a dynamic form of psychopathology involving the individuals interacting with and regulating in response to the contextual features of their environment. PMID:26200849

  14. The impact of obesity on neurodegenerative diseases.

    Science.gov (United States)

    Mazon, Janaína Niero; de Mello, Aline Haas; Ferreira, Gabriela Kozuchovski; Rezin, Gislaine Tezza

    2017-08-01

    Neurodegenerative diseases are a growing health concern. The increasing incidences of these disorders have a great impact on the patients' quality of life. Although the mechanisms of neurodegenerative diseases are still far from being clarified, several studies look for new discoveries about their pathophysiology and prevention. Furthermore, evidence has shown a strong correlation between obesity and the development of Alzheimer's disease (AD) and Parkinson's disease (PD). Metabolic changes caused by overweight are related to damage to the central nervous system (CNS), which can lead to neural death, either by apoptosis or cell necrosis, as well as alter the synaptic plasticity of the neuron. This review aims to show the association between neurodegenerative diseases, focusing on AD and PD, and metabolic alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Attitudes towards "disorders of sex development" nomenclature among affected individuals.

    Science.gov (United States)

    Johnson, Emilie K; Rosoklija, Ilina; Finlayson, Courtney; Chen, Diane; Yerkes, Elizabeth B; Madonna, Mary Beth; Holl, Jane L; Baratz, Arlene B; Davis, Georgiann; Cheng, Earl Y

    2017-05-08

    Although now commonly used in medicine, the updated "disorders of sex development" (DSD) nomenclature formally introduced in 2006 has never been universally accepted by members of the affected community, particularly advocacy groups. Use of this nomenclature by medical professionals may unintentionally negatively affect access to healthcare and research for individuals with DSD conditions. Among individuals affected by various DSD diagnoses, this study sought to (1) evaluate attitudes towards potentially controversial DSD terminology, (2) determine potential impact of terminology on how affected individuals access healthcare, and (3) explore alternate terms. A web-based survey was developed in collaboration with the AIS-DSDSG (Androgen Insensitivity Syndrome-DSD Support Group) leadership. AIS-DSDSG members (caregivers and affected individuals) were surveyed about attitudes towards DSD, potential impact on healthcare utilization, and alternate terms. A qualitative analysis of reasons for using/avoiding specific terms was performed. Surveys were completed by 202 out of 580 (35%) AIS-DSDSG members (61% affected, 39% caregivers; 16% non-gender binary; age range of affected individuals 0-86 years). Only 24% use disorder of sex development to describe themselves/their child. A majority (69%) had a negative emotional experience because of clinical use of nomenclature; 81% changed their care because of it. Preferred and non-preferred terms for clinical care and research are illustrated in the figure. Preferred diagnostic terms were intersex, variation in sex development, and difference of sex development (55%, 52%, and 50% liked/strongly liked, respectively). Disorder of sex development was not preferred (17% liked/strongly liked). About one-third reported that they would not attend a clinic named the Disorder of Sex Development Clinic. Overall, 81% provided qualitative comments; flexible terminology use was a key theme. These study findings are consistent with previous

  16. Increased mortality among patients admitted with major psychiatric disorders: a register-based study comparing mortality in unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia

    DEFF Research Database (Denmark)

    Laursen, Thomas Munk; Munk-Olsen, Trine; Nordentoft, Merete

    2007-01-01

    disorder has never been examined in a population-based study. OBJECTIVE: Our objective was to examine and compare mortality rates after admission with schizophrenia, schizoaffective disorder, unipolar depressive disorder, or bipolar affective disorder and to examine the impact of family history......: Unipolar depressive disorder, bipolar affective disorder, and schizoaffective disorder were associated with the same pattern of excess mortality. Schizophrenia had a lower mortality from unnatural causes of death and a higher mortality from natural causes compared to the 3 other disorders. Family history......CONTEXT: Persons suffering from severe mental disorder have an excess mortality compared to persons with no mental disorder. However, the magnitude of the excess mortality differs from one mental disorder to another, and the impact on mortality if a first-degree family member suffers from a mental...

  17. Underlying personality differences between alcohol/substance-use disorder patients with and without an affective disorder.

    Science.gov (United States)

    Janowsky, D S; Hong, L; Morter, S; Howe, L

    1999-01-01

    The Myers-Briggs Type Indicator (MBTI), a popular personality test, was used to profile the personalities of in-patient alcoholics/substance-use disorder patients who had, and those who did not have, a concurrent affective disorder diagnosis. The MBTI divides individuals into eight categories: Extroverts and Introverts, Sensors and Intuitives, Thinkers and Feelers, and Judgers and Perceivers. Alcohol/substance-use disorder patients with no affective disorder differed from a normative population only in being significantly more often Sensing and significantly less often Intuitive single-factor types. The Extroverted/Sensing/ Feeling/Judging four-factor type was also significantly over-represented in this group, compared to a normative population. In contrast, mood-disordered alcohol/substance-use disorder patients were significantly more often Introverted, Sensing, Feeling, and Perceiving and significantly less often Extroverted, Intuitive, Thinking, and Judging single-factor types. They were also significantly more often Introverted/Sensing/ Feeling/Perceiving and Introverted/Intuitive/Feeling/Perceiving four-factor types. 'Pure' alcohol/ substance-use disorder patients differed from alcohol/substance-use disorder patients with a mood disorder in that they were significantly more often Extroverted and Thinking and significantly less often Introverted and Feeling single-factor types; and significantly less often were an Introverted/Sensing/ Feeling/Perceiving four-factor type. The above results may have psychogenetic, diagnostic, and psychotherapeutic implications.

  18. Assessing affective variability in eating disorders: affect spins less in anorexia nervosa of the restrictive type.

    Science.gov (United States)

    Vansteelandt, Kristof; Probst, Michel; Pieters, Guido

    2013-08-01

    Differences in affective variability in eating disorders are examined using an ecological momentary assessment (EMA) protocol. It is hypothesized that restriction serves to pre-empt the activation of affect whereas bulimic behavior serves to cope with overwhelming affect once activated. Therefore, we expect anorexia nervosa (AN) patients of the restricting type (AN-RT) to have lower mean levels of affect and less affective variability than Bulimia Nervosa (BN) patients. Patients' successive affective states over time are represented as different positions in a two-dimensional space defined by the orthogonal dimensions of valence and activation. Affective variability is measured by the within person variance and the new concepts of pulse and spin. Results of this exploratory study suggest that the diagnostic groups have the same mean levels of affect but affect spins less in patients with AN-RT. Using an EMA protocol and measures like pulse and spin may reveal insights in eating disorders that remain hidden with more traditional assessment methods. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Daily weather variables and affective disorder admissions to psychiatric hospitals

    Science.gov (United States)

    McWilliams, Stephen; Kinsella, Anthony; O'Callaghan, Eadbhard

    2014-12-01

    Numerous studies have reported that admission rates in patients with affective disorders are subject to seasonal variation. Notwithstanding, there has been limited evaluation of the degree to which changeable daily meteorological patterns influence affective disorder admission rates. A handful of small studies have alluded to a potential link between psychiatric admission rates and meteorological variables such as environmental temperature (heat waves in particular), wind direction and sunshine. We used the Kruskal-Wallis test, ARIMA and time-series regression analyses to examine whether daily meteorological variables—namely wind speed and direction, barometric pressure, rainfall, hours of sunshine, sunlight radiation and temperature—influence admission rates for mania and depression across 12 regions in Ireland over a 31-year period. Although we found some very weak but interesting trends for barometric pressure in relation to mania admissions, daily meteorological patterns did not appear to affect hospital admissions overall for mania or depression. Our results do not support the small number of papers to date that suggest a link between daily meteorological variables and affective disorder admissions. Further study is needed.

  20. Non-coding RNA and pseudogenes in neurodegenerative diseases: "The (un)Usual Suspects".

    Science.gov (United States)

    Costa, Valerio; Esposito, Roberta; Aprile, Marianna; Ciccodicola, Alfredo

    2012-01-01

    Neurodegenerative disorders and cancer are severe diseases threatening human health. The glaring differences between neurons and cancer cells mask the processes involved in their pathogenesis. Defects in cell cycle, DNA repair, and cell differentiation can determine unlimited proliferation in cancer, or conversely, compromise neuronal plasticity, leading to cell death and neurodegeneration. Alteration in regulatory networks affecting gene expression contribute to human diseases onset, including neurodegenerative disorders, and deregulation of non-coding RNAs - particularly microRNAs (miRNAs) - is supposed to have a significant impact. Recently, competitive endogenous RNAs (ceRNAs) - acting as sponges - have been identified in cancer, indicating a new and intricate regulatory network. Given that neurodegenerative disorders and cancer share altered genes and pathways, and considering the emerging role of miRNAs in neurogenesis, we hypothesize ceRNAs may be implicated in neurodegenerative diseases. Here we propose, and computationally predict, such regulatory mechanism may be shared between the diseases. It is predictable that similar regulation occurs in other complex diseases, and further investigation is needed.

  1. Non-coding RNA and pseudogenes in neurodegenerative diseases: "The (unUsual Suspects"

    Directory of Open Access Journals (Sweden)

    Valerio eCosta

    2012-10-01

    Full Text Available Neurodegenerative disorders and cancer are severe diseases threatening human health. The glaring differences between neurons and cancer cells mask the processes involved in their pathogenesis. Defects in cell cycle, DNA repair and cell differentiation can determine unlimited proliferation in cancer, or conversely, compromise neuronal plasticity, leading to cell death and neurodegeneration.Alteration in regulatory networks affecting gene expression contribute to human diseases' onset, including neurodegenerative disorders, and deregulation of non-coding RNAs - particularly microRNAs - is supposed to have a significant impact.Recently, competitive endogenous RNAs - acting as sponges - have been identified in cancer, indicating a new and intricate regulatory network. Given that neurodegenerative disorders and cancer share altered genes and pathways, and considering the emerging role of microRNAs in neurogenesis, we hypothesize competitive endogenous RNAs may be implicated in neurodegenerative diseases. Here we propose, and computationally predict, such regulatory mechanism may be shared between the diseases. It is predictable that similar regulation occurs in other complex diseases, and further investigation is needed.

  2. Seasonal Affective Disorder: An Overview of Assessment and Treatment Approaches

    Directory of Open Access Journals (Sweden)

    Sherri Melrose

    2015-01-01

    Full Text Available Seasonal affective disorder or SAD is a recurrent major depressive disorder with a seasonal pattern usually beginning in fall and continuing into winter months. A subsyndromal type of SAD, or S-SAD, is commonly known as “winter blues.” Less often, SAD causes depression in the spring or early summer. Symptoms center on sad mood and low energy. Those most at risk are female, are younger, live far from the equator, and have family histories of depression, bipolar disorder, or SAD. Screening instruments include the Seasonal Pattern Assessment Questionnaire (SPAQ. Typical treatment includes antidepressant medications, light therapy, Vitamin D, and counselling. This paper provides an overview of SAD.

  3. A Comparative Study of Affective Bipolar Disorder with Schizoaffective Disorder from a Longitudinal Perspective

    Directory of Open Access Journals (Sweden)

    Miruna Milin

    2013-08-01

    Full Text Available Introduction: In the last years there is a great interest for the theory of the “psychotic continuum”, which accepts that there is a transition between schizophrenia and affective pathology, including bipolar disorder with psychotic interferences and the recently introduced diagnosis of schizoaffective disorder. There are few studies that analyze bipolar disorder with mood-incongruent psychosis. The purpose of this study was to observe the way in which the interference of mood-incongruent psychotic symptoms can influence the long term evolution of patients diagnosed with bipolar disorder and the similarities that exists between this type of pathology and schizoaffective disorder. Material and methods: Sixty subjects were selected, who are now diagnosed with schizoaffective disorder and bipolar disorder, with and without psychotic features. All cases have at least 15 years of evolution since the first episode of psychosis and were analyzed in term of their age of onset and longitudinal evolution. Results: The results showed that bipolar patients who had mood incongruent psychotic symptoms had an earlier age of onset and a higher rate of hospitalizations in their long term evolution compared to bipolar patients without psychotic features, which brings them closer to patients with schizoaffective disorder in term of their pattern of evolution. Conclusions: This study has demonstrated that the interference of mood-incongruent psychosis with bipolar disorder determines a worse prognosis of this disease, very similar with the evolution of patients with schizoaffective disorder

  4. Attention deficit hyperactivity disorder (ADHD): an affect-processing and thought disorder?

    Science.gov (United States)

    Günter, Michael

    2014-02-01

    In the literature on child and adolescent psychoanalysis attention deficit hyperactivity disorder (ADHD) is described as complex syndrome with wide-ranging psychodynamic features. Broadly speaking, the disorder is divided into three categories: 1. a disorder in early object relations leading to the development of a maniform defence organization in which object-loss anxieties and depressed affects are not worked through via symbolization but are organized in a body-near manner; 2. a triangulation disorder in which the cathexis of the paternal position is not stable; structures providing little support alternate with excessive arousal, affect regulation is restricted; 3. current emotional stress or a traumatic experience. I suggest taking a fresh look at ADHD from a psychoanalytic vantage point. With respect to the phenomenology of the disorder, the conflict-dynamic approach should be supplemented by a perspective regarding deficits in α-function as constitutive for ADHD. These deficits cause affect-processing and thought disorders compensated for (though not fully) by the symptomatology. At a secondary level, a vicious circle develops through the mutual reinforcement of defective processing of sense data and affects into potential thought content, on the one hand, and secondary, largely narcissistic defence processes on the other. These considerations have major relevance for the improved understanding of ADHD and for psychoanalytic technique. Copyright © 2013 Institute of Psychoanalysis.

  5. Atypical perception of affective prosody in Autism Spectrum Disorder.

    Science.gov (United States)

    Gebauer, Line; Skewes, Joshua; Hørlyck, Lone; Vuust, Peter

    2014-01-01

    Autism Spectrum Disorder (ASD) is characterized by impairments in language and social-emotional cognition. Yet, findings of emotion recognition from affective prosody in individuals with ASD are inconsistent. This study investigated emotion recognition and neural processing of affective prosody in high-functioning adults with ASD relative to neurotypical (NT) adults. Individuals with ASD showed mostly typical brain activation of the fronto-temporal and subcortical brain regions in response to affective prosody. Yet, the ASD group showed a trend towards increased activation of the right caudate during processing of affective prosody and rated the emotional intensity lower than NT individuals. This is likely associated with increased attentional task demands in this group, which might contribute to social-emotional impairments.

  6. Atypical perception of affective prosody in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Line Gebauer

    2014-01-01

    Full Text Available Autism Spectrum Disorder (ASD is characterized by impairments in language and social–emotional cognition. Yet, findings of emotion recognition from affective prosody in individuals with ASD are inconsistent. This study investigated emotion recognition and neural processing of affective prosody in high-functioning adults with ASD relative to neurotypical (NT adults. Individuals with ASD showed mostly typical brain activation of the fronto-temporal and subcortical brain regions in response to affective prosody. Yet, the ASD group showed a trend towards increased activation of the right caudate during processing of affective prosody and rated the emotional intensity lower than NT individuals. This is likely associated with increased attentional task demands in this group, which might contribute to social–emotional impairments.

  7. A Case of Bipolar Affective Disorder and Aspiration Pneumonia

    Directory of Open Access Journals (Sweden)

    Alessandro Gerada

    2013-01-01

    Full Text Available Adults with mental illness are at a higher risk of aspiration pneumonia than the general population. We describe the case of a patient with bipolar affective disorder and two separate episodes of aspiration pneumonia associated with acute mania. We propose that he had multiple predisposing factors, including hyperverbosity, sedative medications, polydipsia (psychogenic and secondary to a comorbidity of diabetes insipidus, and neuroleptic side effects.

  8. Prevalence and correlates of binge eating in seasonal affective disorder

    OpenAIRE

    Donofry, Shannon D.; Kathryn A. Roecklein; Rohan, Kelly J.; Wildes, Jennifer E.; Kamarck, Marissa L.

    2014-01-01

    Eating pathology in Seasonal Affective Disorder (SAD) may be more severe than hyperphagia during winter. Although research has documented elevated rates of subclinical binge eating in women with SAD, the prevalence and correlates of BED in SAD remain largely uncharacterized. We examined the prevalence and correlates of binge eating, weekly binge eating with distress, and BED as defined by the DSM-IV-TR in SAD. We also tested whether binge eating exhibits a seasonal pattern among individuals w...

  9. The neurobiology of retinoic acid in affective disorders.

    Science.gov (United States)

    Bremner, J Douglas; McCaffery, Peter

    2008-02-15

    Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute to

  10. Affective Cognition and its Disruption in Mood Disorders

    Science.gov (United States)

    Elliott, Rebecca; Zahn, Roland; Deakin, J F William; Anderson, Ian M

    2011-01-01

    In this review, we consider affective cognition, responses to emotional stimuli occurring in the context of cognitive evaluation. In particular, we discuss emotion categorization, biasing of memory and attention, as well as social/moral emotion. We discuss limited neuropsychological evidence suggesting that affective cognition depends critically on the amygdala, ventromedial frontal cortex, and the connections between them. We then consider neuroimaging studies of affective cognition in healthy volunteers, which have led to the development of more sophisticated neural models of these processes. Disturbances of affective cognition are a core and specific feature of mood disorders, and we discuss the evidence supporting this claim, both from behavioral and neuroimaging perspectives. Serotonin is considered to be a key neurotransmitter involved in depression, and there is a considerable body of research exploring whether serotonin may mediate disturbances of affective cognition. The final section presents an overview of this literature and considers implications for understanding the pathophysiology of mood disorder as well as developing and evaluating new treatment strategies. PMID:20571485

  11. Tryptophan hydroxylase 2 in seasonal affective disorder: underestimated perspectives?

    Science.gov (United States)

    Kulikov, Alexander V; Popova, Nina K

    2015-01-01

    Seasonal affective disorder (SAD) is characterized by recurrent depression occurring generally in fall/winter. Numerous pieces of evidence indicate the association of SAD with decreased brain neurotransmitter serotonin (5-HT) system functioning. Tryptophan hydroxylase 2 (TPH2) is the key and rate-limiting enzyme in 5-HT synthesis in the brain. This paper concentrates on the relationship between TPH2 activity and mood disturbances, the association between human TPH2 gene expression and the risk of affective disorder, application of tryptophan to SAD treatment and the animal models of SAD. The main conclusions of this review are as follows: (i) the brain 5-HT deficiency contributes to the mechanism underlying SAD, (ii) TPH2 is involved in the regulation of some kinds of genetically defined affective disorders and (iii) the activation of 5-HT synthesis with exogenous l-tryptophan alone or in combination with light therapy could be effective in SAD treatment. The synergic effect of these combined treatments will have several advantages compared to light or tryptophan therapy alone. First, it is effective in the treatment of patients resistant to light therapy. Secondly, l-tryptophan treatment prolongs the antidepressant effect of light therapy.

  12. Risk factors that influence suicidal behavior in affective disorders

    Directory of Open Access Journals (Sweden)

    Stanojević Albina

    2016-01-01

    Full Text Available It is known in the literature that the incidence and prevalence of suicide and attempted suicide in psychiatric patients is significantly higher than in the general population. The paper examined risk factors for suicidal behavior in the category of admitted patients hospitalized with the diagnosis of sleep disorders and affective (Unipolar resp. Bipolar depression. Study activated by 80 patients, 40 in both diagnostic groups received treatment at the Special Psychiatric Hospital in Gornja Toponica near Nis. The work methodology used are: psychiatric interview, Hamilton Depression Rating Scale (HAMD, and the C-SSRS (Columbia-Suicide Severity Rating Scale- assessment tool that assesses suicidal ideation and behavior. The study results show that there is a relationship between suicidal behavior (suicide attempts and suicidal ideation and the diagnosis of bipolar affective disorder, positive history of previous suicide attempts, so that these factors are stronger, to the degree of suicidality higher. On this sample, clearly suicidal behavior, with the same purpose, intensity of suicidal thoughts and medical impairment after suicide attempts were significantly more frequent in patients with Bipolar Affective Disorder in the depressive phase of the illness. Patients with a previous suicide attempt, and poor personal and social circumstances had a higher rate of attempted suicide.

  13. Affective temperaments: familiality and clinical use in mood disorders.

    Science.gov (United States)

    Aguiar Ferreira, Alexandre de; Vasconcelos, Alina Gomide; Neves, Fernando Silva; Laks, Jerson; Correa, Humberto

    2013-05-15

    The affective temperament profiles among patients with mood disorders may be an important parameter in the clinical evaluation of these patients. It has been proposed that temperament traits have familiality and may represent vulnerability markers to identify the risk to developing specific clinical type of mood disorders. To test these theories, measures of temperament were examined in bipolar patients (BP), unipolar major depressive patients (UP), healthy relatives of these patients (HRP) and normal controls (NC). We compared affective temperament scores, using the brief Brazilian version of TEMPS-A--TEMPS-Rio de Janeiro, between 90 BP, 88 UP, 132 HRP and 136 NC. A MANCOVA model was constructed. Dependent variables were the six subscales of the TEMPS-RJ (depressive, cyclothymic, irritable, hyperthymic, anxious and worrying temperaments). The effects of age and gender were adjusted as covariates. Furthermore, we performed a comparison between a subgroup of 68 HRP, relatives of bipolar patients (HRBP), and the remainders 64 HRP, relatives of unipolar patients (HRUP) and controls. The clinical group (BP, UP) showed higher temperament scores than NC, except for hyperthymic scores. BP showed higher cyclothymic (pBipolar I and II subjects were placed in the same group. The cyclothymic and hyperthymic traits were associated with bipolarity in patients and cyclothymic temperament could be a characteristic trait of the healthy relatives of bipolar patients. Our data support that affective temperament might become a useful tool for clinical evaluation and research purposes in mood disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Early noninvasive diagnosis of neurodegenerative diseases.

    Science.gov (United States)

    Danev, Stoyan I; St Stoyanov, Drozdstoy

    2010-01-01

    This paper reviews the contemporary trends in the pathobiochemistry of neurodegenerative disorders with respect to their early predictive diagnosis and possible treatment interventions. If we consider the current epidemiological data related to neurodegenerative disorders, medicine is going to face in the near future latent pandemic situations. The introduction puts an emphasis on the emerging importance of one major cluster of neurodegenerative disorders: diseases of the abnormal protein beta-conformation. The cluster includes such significant diseases as Alzheimer, Pick, Huntington, Parkinson disease, as well as the transmissible spongiform encephalopathies (Creuzfeldt-Jakob disease). The pathogenetic mechanisms in the determination of this group of disorders are explored with an emphasis on the impairment of post-synthetic chaperone correction. The central role of a number of such protein products is discussed. In particular the pathobiochemical mechanisms concerning the formation of beta-amyloid, alpha and beta synucleins, scrapie isoform of the prion protein are presented. A new diagnostic principle allowing the early and specific diagnosis of the conformation diseases protein via amplification techniques is presented. These methods compete in sensitivity with the PCR methods and shows promises for effective treatment. In conclusion, beta-pathies are considered a suitable example for the modern concept of cluster and prototype diagnosis in medicine and especially in clinical neurosciences.

  15. Smooth pursuit deficits in schizophrenia, affective disorder and obsessive-compulsive disorder.

    Science.gov (United States)

    Lencer, R; Trillenberg, P; Trillenberg-Krecker, K; Junghanns, K; Kordon, A; Broocks, A; Hohagen, F; Heide, W; Arolt, V

    2004-04-01

    In schizophrenia, affective disorders, and obsessive-compulsive disorder (OCD) dysfunction of frontal neuronal circuits has been suggested. Such impairments imply corresponding oculomotor deficits. Eye movement response to foveofugal and foveopetal step-ramp stimuli was recorded within the same study design in patients with schizophrenia (N= 16), affective disorder (N= 15), and OCD (N= 18) and compared with controls (N=23) using infra-red reflection oculography. In the foveofugal task steady-state velocity was lower in all patient groups compared with controls. Post-saccadic eye velocity was also decreased in patients with schizophrenia and affective disorder. In the foveopetal stimulus steady-state velocity was reduced in schizophrenic patients, only. Changes of saccadic latencies or position errors were not found in any of the patient groups. Also, pursuit latency was unchanged and initial eye acceleration was not decreased. Unaltered saccadic parameters indicate intact motion perception in cortical visual area V5. Therefore, the observed deficit of pursuit maintenance implies a dysfunction of frontal networks in all patient groups including the pursuit region of the frontal eye field (FEF). In patients with schizophrenia and affective disorder reduced post-saccadic pursuit initiation may indicate an impaired interaction between the pursuit and the saccadic system.

  16. Posttraumatic stress disorder symptom trajectories in Hurricane Katrina affected youth.

    Science.gov (United States)

    Self-Brown, Shannon; Lai, Betty S; Thompson, Julia E; McGill, Tia; Kelley, Mary Lou

    2013-05-01

    This study examined trajectories of posttraumatic stress disorder symptoms in Hurricane Katrina affected youth. A total of 426 youth (51% female; 8-16 years old; mean age=11 years; 75% minorities) completed assessments at 4 time points post-disaster. Measures included Hurricane impact variables (initial loss/disruption and perceived life threat); history of family and community violence exposure, parent and peer social support, and post-disaster posttraumatic stress symptoms. Latent class growth analysis demonstrated that there were three distinct trajectories of posttraumatic stress disorder symptoms identified for this sample of youth (resilient, recovering, and chronic, respectively). Youth trajectories were associated with Hurricane-related initial loss/disruption, community violence, and peer social support. The results suggest that youth exposed to Hurricane Katrina have variable posttraumatic stress disorder symptom trajectories. Significant risk and protective factors were identified. Specifically, youth Hurricane and community violence exposure increased risk for a more problematic posttraumatic stress disorder symptom trajectory, while peer social support served as a protective factor for these youth. Identification of these factors suggests directions for future research as well as potential target areas for screening and intervention with disaster exposed youth. The convenience sample limits the external validity of the findings to other disaster exposed youth, and the self-report data is susceptible to response bias. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Engineering enhanced protein disaggregases for neurodegenerative disease

    OpenAIRE

    Jackrel, Meredith E.; Shorter, James

    2015-01-01

    Abstract Protein misfolding and aggregation underpin several fatal neurodegenerative diseases, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). There are no treatments that directly antagonize the protein-misfolding events that cause these disorders. Agents that reverse protein misfolding and restore proteins to native form and function could simultaneously eliminate any deleterious loss-of-function or toxic gain-of-function caused by...

  18. Synthetic prions and other human neurodegenerative proteinopathies.

    Science.gov (United States)

    Le, Nhat Tran Thanh; Narkiewicz, Joanna; Aulić, Suzana; Salzano, Giulia; Tran, Hoa Thanh; Scaini, Denis; Moda, Fabio; Giachin, Gabriele; Legname, Giuseppe

    2015-09-02

    Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrP(C)) into a β-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrP(Sc) itself is able to recruit and misfold PrP(C) into the pathological conformation. Recent data have shown that recombinant PrP(C) can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrP(C) into PrP(Sc)in vivo. In this review we describe the state-of-the-art of the body of literature in this field. In addition, we describe a cell-based assay to test synthetic prions in cells, providing further evidence that synthetic amyloids are able to template conversion of PrP into prion inclusions. Studying prions might help to understand the pathological mechanisms governing other neurodegenerative diseases. Aggregation and deposition of misfolded proteins is a common feature of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other disorders. Although the proteins implicated in each of these diseases differ, they share a common prion mechanism. Recombinant proteins are able to aggregate in vitro into β-rich amyloid fibrils, sharing some features of the aggregates found in the brain. Several studies have reported that intracerebral inoculation of synthetic aggregates lead to unique pathology, which spread progressively to distal brain regions and reduced survival time in animals. Here, we review the prion-like features of different proteins involved in neurodegenerative disorders, such as α-synuclein, superoxide dismutase-1, amyloid-β and tau. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Skipping breakfast adversely affects menstrual disorders in young college students.

    Science.gov (United States)

    Fujiwara, Tomoko; Sato, Natsuyo; Awaji, Hiroyo; Sakamoto, Hiroko; Nakata, Rieko

    2009-01-01

    In the present study we conducted a questionnaire survey to examine the relationship between dietary habits and menstrual disorders in young women. Subjects were recruited from 315 college students and were classified as: Group I, eating breakfast; Group II, skipping breakfast; Group III, not eating fast foods; Group IV, eating fast foods; Group V, not eating processed foods; and Group VI, eating processed foods. The intensity of dysmenorrhea was scored using three grades. All participants were further divided into groups based on having regular or irregular menstruation, having premenstrual symptoms or not, and self-perception of good or poor general health. General health was poor in Groups II and VI, and dysmenorrhea scores were high in Groups II, IV and VI. The incidence of irregular menses was also high in Group II. However, there was no apparent relation between premenstrual symptoms and dietary habits. These findings suggest that skipping breakfast adversely affects menstrual disorders in young college students.

  20. The chronobiology and neurobiology of winter seasonal affective disorder

    Science.gov (United States)

    Levitan, Robert D.

    2007-01-01

    This review summarizes research on the chronobiology and neurobiology of winter seasonal affective disorder (SAD), a recurrent subtype of depression characterized by a predictable onset in the fall/winter months and spontaneous remission in the spring/summer period. Chronobiological mechanisms related to circadian rhythms, melatonin, and photoperiodism play a significant role in many cases of SAD, and treatment of SAD can be optimized by considering individual differences in key chronobiological markers. Converging evidence also points to a role for the major monoamine neurotransmitters serotonin, norepinephrine, and dopamine in one or more aspects of SAD. Ultimately, as with other psychiatric illnesses, SAD is best considered as a complex disorder resulting from the interaction of several vulnerability factors acting at different levels, the various genetic mechanisms that underlie them, and the physical environment. Models of SAD that emphasize its potential role in human evolution will also be discussed. PMID:17969868

  1. Amygdala response to emotional faces in seasonal affective disorder

    DEFF Research Database (Denmark)

    Borgsted, Camilla; Ozenne, Brice; Mc Mahon, Brenda

    2018-01-01

    BACKGROUND: Seasonal affective disorder (SAD) is characterized by seasonally recurring depression. Heightened amygdala activation to aversive stimuli is associated with major depressive disorder but its relation to SAD is unclear. We evaluated seasonal variation in amygdala activation in SAD...... and healthy controls (HC) using a longitudinal design targeting the asymptomatic/symptomatic phases of SAD. We hypothesized increased amygdala activation to aversive stimuli in the winter in SAD individuals (season-by-group interaction). METHODS: Seventeen SAD individuals and 15 HCs completed an implicit...... emotional faces BOLD-fMRI paradigm during summer and winter. We computed amygdala activation (SPM5) to an aversive contrast (angry & fearful minus neutral) and angry, fearful and neutral faces, separately. Season-by-group and main effects were evaluated using Generalized Least Squares. In SAD individuals...

  2. Cognitions in bipolar affective disorder and unipolar depression: imagining suicide.

    Science.gov (United States)

    Hales, Susie A; Deeprose, Catherine; Goodwin, Guy M; Holmes, Emily A

    2011-01-01

    Bipolar disorder has the highest rate of suicide of all the psychiatric disorders. In unipolar depression, individuals report vivid, affect-laden images of suicide or the aftermath of death (flashforwards to suicide) during suicidal ideation but this phenomenon has not been explored in bipolar disorder. Therefore the authors investigated and compared imagery and verbal thoughts related to past suicidality in individuals with bipolar disorder (n = 20) and unipolar depression (n = 20). The study used a quasi-experimental comparative design. The Structured Clinical Interview for DSM-IV was used to confirm diagnoses. Quantitative and qualitative data were gathered through questionnaire measures (e.g., mood and trait imagery use). Individual interviews assessed suicidal cognitions in the form of (i) mental images and (ii) verbal thoughts. All participants reported imagining flashforwards to suicide. Both groups reported greater preoccupation with these suicide-related images than with verbal thoughts about suicide. However, compared to the unipolar group, the bipolar group were significantly more preoccupied with flashforward imagery, rated this imagery as more compelling, and were more than twice as likely to report that the images made them want to take action to complete suicide. In addition, the bipolar group reported a greater trait propensity to use mental imagery in general. Suicidal ideation needs to be better characterized, and mental imagery of suicide has been a neglected but potentially critical feature of suicidal ideation, particularly in bipolar disorder. Our findings suggest that flashforward imagery warrants further investigation for formal universal clinical assessment procedures. © 2011 John Wiley and Sons A/S.

  3. Sleep disturbance in mental health problems and neurodegenerative disease.

    Science.gov (United States)

    Anderson, Kirstie N; Bradley, Andrew J

    2013-01-01

    Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour) processes and is vital for normal brain function. This review will outline the normal sleep-wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed.

  4. Seasonal affective disorder, winter type: current insights and treatment options.

    Science.gov (United States)

    Meesters, Ybe; Gordijn, Marijke Cm

    2016-01-01

    Seasonal affective disorder (SAD), winter type, is a seasonal pattern of recurrent major depressive episodes most commonly occurring in autumn or winter and remitting in spring/summer. The syndrome has been well-known for more than three decades, with light treatment being the treatment of first choice. In this paper, an overview is presented of the present insights in SAD. Description of the syndrome, etiology, and treatment options are mentioned. Apart from light treatment, medication and psychotherapy are other treatment options. The predictable, repetitive nature of the syndrome makes it possible to discuss preventive treatment options. Furthermore, critical views on the concept of SAD as a distinct diagnosis are discussed.

  5. Post-traumatic stress disorder symptoms, underlying affective vulnerabilities, and smoking for affect regulation.

    Science.gov (United States)

    Mathew, Amanda R; Cook, Jessica W; Japuntich, Sandra J; Leventhal, Adam M

    2015-01-01

    Post-traumatic stress disorder (PTSD) is overrepresented among cigarette smokers. It has been hypothesized that those with PTSD smoke to alleviate negative affect and counteract deficient positive affect commonly associated with the disorder; however, limited research has examined associations between PTSD symptoms, smoking motives, and affective vulnerability factors. In the current study, we examined (1) whether PTSD symptoms were associated with positive reinforcement and negative reinforcement smoking motives; and (2) whether two affective vulnerability factors implicated in PTSD-anxiety sensitivity and anhedonia-mediated relationships between PTSD symptoms and smoking motives. Data were drawn from a community sample of non-treatment-seeking smokers recruited without regard for trauma history (N = 342; 10+ cig/day). We used the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) to assess overall PTSD symptom severity as well as individual PTSD subfactors. Overall, PTSD symptom severity was significantly associated with negative reinforcement, but not positive reinforcement, smoking motives. Variation in anxiety sensitivity significantly mediated the relation between PTSD symptom severity and negative reinforcement smoking motives, whereas anhedonia did not. Regarding PTSD subfactors, emotional numbing was the only PTSD subfactor associated with smoking rate, while re-experiencing symptoms were uniquely associated with both positive reinforcement and negative reinforcement smoking motives. Findings suggest that anxiety sensitivity may be an important feature associated with PTSD that enhances motivation to smoke for negative reinforcement purposes. Smoking cessation interventions that alleviate anxiety sensitivity and enhance coping with negative affect may be useful for smokers with elevated PTSD symptoms. © American Academy of Addiction Psychiatry.

  6. Intensive training of phonological skills in progressive aphasia: a model of brain plasticity in neurodegenerative disease.

    Science.gov (United States)

    Louis, M; Espesser, R; Rey, V; Daffaure, V; Di Cristo, A; Habib, M

    2001-01-01

    Three patients with a typical syndrome of nonfluent primary progressive aphasia (Mesulam's syndrome) were trained daily with a remediation protocol including auditory exercises specifically designed to involve several aspects of phonological processing, a domain known to be specifically affected in the condition. The speech content of the exercises was based on the temporal theory of phonological processes according to which increasing the duration of formant transition should facilitate phoneme discrimination and phoneomic awareness. Significantly improved performance on the trained tasks was demonstrated in the three patients. Improvement further generalized to other tasks such as nonword repetition and reading. We conclude that such results (1) argue for using intensive focused therapy of language impairment in neurodegenerative disorders, (2) may constitute a good model of brain plasticity in neurodegenerative disorders in general, and (3) support theories of phonological processing emphasizing temporal features of the auditory signal.

  7. The Big Bluff of Amyotrophic Lateral Sclerosis Diagnosis: The Role of Neurodegenerative Disease Mimics.

    Science.gov (United States)

    Bicchi, Ilaria; Emiliani, Carla; Vescovi, Angelo; Martino, Sabata

    2015-01-01

    Neurodegenerative diseases include a significant number of pathologies affecting the nervous system. Generally, the primary cause of each disease is specific; however, recently, it was shown that they may be correlated at molecular level. This aspect, together with the exhibition of similar symptoms, renders the diagnosis of these disorders difficult. Amyotrophic lateral sclerosis is one of these pathologies. Herein, we report several cases of amyotrophic lateral sclerosis misdiagnosed as a consequence of features that are common to several neurodegenerative diseases, such as Parkinson's, Huntington's and Alzheimer's disease, spinal muscular atrophy, progressive bulbar palsy, spastic paraplegia and frontotemporal dementia, and mostly with the lysosomal storage disorder GM2 gangliosidosis. Overall reports highlight that the differential diagnosis for amyotrophic lateral sclerosis should include correlated mechanisms. © 2015 S. Karger AG, Basel.

  8. Sleep disturbance in mental health problems and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Anderson KN

    2013-05-01

    Full Text Available Kirstie N Anderson1 Andrew J Bradley2,3 1Department of Neurology, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK; 2Eli Lilly and Company Limited, Lilly House, Basingstoke, UK; 3Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK Abstract: Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour processes and is vital for normal brain function. This review will outline the normal sleep–wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed. Keywords: sleep, mental health, neurodegenerative disorders, cognition

  9. Affective temperaments and neurocognitive functioning in bipolar disorder.

    Science.gov (United States)

    Russo, Manuela; Mahon, Katie; Shanahan, Megan; Ramjas, Elizabeth; Solon, Carly; Braga, Raphael J; Burdick, Katherine E

    2014-12-01

    There is evidence that patients with bipolar disorder (BD) score higher on affective temperament ratings compared to healthy controls (HCs). Moreover, unaffected relatives demonstrate similar patterns as BD patients suggesting that such temperaments are related to the genetic risk for BD and may serve as endophenotypes for the disorder. It is unknown whether affective temperaments are associated with other core features of BD, such as impairments in neurocognition. This study examined the relationship between affective temperaments and neurocognition in patients with BD and in HCs. Temperaments were evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire version (TEMPS-A) in 64 patients with BD and 109 HCs. Neurocognitive functioning was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Correlational analyses between temperaments and cognition were conducted in BD and HC subjects. Data suggest that affective temperaments and neurocognition are correlated. In BD higher ratings of cyclothymia and irritability were associated with better processing speed, working memory, reasoning and problem-solving. In the HC group, increased irritability was related to worse performance on measures of attention and social cognition. Lack of functional outcome measures to evaluate the impact of temperaments and cognition on psychosocial functioning. It would be useful to test these findings on unaffected relatives of BD patients. Cyclothymic and irritable temperaments are correlated with specific aspects of neurocognition in BD. This study is among the few exploring the dimensional relationship between temperaments and cognition in BD, and provides preliminary evidence for future studies investigating the neural and genetic mechanisms underlying the association between these variables. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. [Diagnostic features, epidemiology, and pathophysiology of seasonal affective disorder].

    Science.gov (United States)

    Molnár, Eszter; Gonda, Xénia; Rihmer, Zoltán; Bagdy, György

    2010-01-01

    Seasonal Affective Disorder (SAD) is characterized by patterns of major depressive episodes that occur and remit with the change of seasons. Two seasonal patterns have been identified: summer-type depression with typical depressive signs and symptoms, and winter-type depression with atypical features of depression. In the subsyndromal form of SAD (S-SAD) symptoms are milder, although vegetative symptoms are clinically significant. SAD needs to be differentiated from atypical depression, cyclothymic disorder, and dysthymia or chronic MDD which may be characterized by a winter worsening of symptoms. Full remission of symptoms must occur after the passing of the season for the disorder to merit the diagnosis of SAD. The mean prevalence of SAD in the temperate zone is 3 to 10%, while that of S-SAD is 6 to 20%. In Hungarian general population the occurrence of SAD is 4.6%, and S-SAD is 7.2%. The pathophysiology of SAD seems to be heterogeneous, studies suggest abnormal circadian rhythm and neurotransmitter function (phase shift hypothesis, role of serotonin, dopamin and norepinephrine). Genetic studies focusing on candidate genes involve 5-HTR2A, 5-HTR2C, DRD4, G protein, and clock-related genes.

  11. Dysfunctional affect regulation in borderline personality disorder and in somatoform disorder

    Directory of Open Access Journals (Sweden)

    Annemiek van Dijke

    2012-09-01

    Full Text Available Background: Although affect dysregulation is considered a core component of borderline personality disorder (BPD and somatoform disorders (SoD, remarkably little research has focused on the prevalence and nature of affect dysregulation in these disorders. Also, despite apparent similarities, little is known about how dysfunctional under- and overregulation of affect and positive and negative somatoform and psychoform dissociative experiences inter-relate. Prior studies suggest a clear relationship between early childhood psychological trauma and affect dysregulation, especially when the caretaker is emotionally, sexually, or physically abusing the child, but how these relate to under- and overregulation while differentiating for developmental epochs is not clear. Although an elevated risk of childhood trauma exposure or complex posttraumatic stress disorder (CPTSD symptoms has been reported in BPD and SoD, trauma histories, dysfunctional affect regulation, dissociation, PTSD, and CPTSD were never assessed in unison in BPD and/or SoD. Method: BPD and/or SoD diagnoses were confirmed or ruled out in 472 psychiatric inpatients using clinical interviews. Dysfunctional under- and overregulation of affect and somatoform and psychoform dissociation, childhood trauma-by-primary-caretaker (TPC, PTSD, and CPTSD were all measured using self reports. Results: No disorder-specific form of dysfunctional affect regulation was found. Although both BPD and SoD can involve affect dysregulation and dissociation, there is a wide range of intensity of dysfunctional regulation phenomena in patients with these diagnoses. Evidence was found for the existence of three qualitatively different forms of experiencing states: inhibitory experiencing states (overregulation of affect and negative psychoform dissociation most commonly found in SoD, excitatory experiencing states (underregulation of affect and positive psychoform dissociation most commonly found in BPD, and

  12. Seasonal affective disorder, winter type: current insights and treatment options

    Directory of Open Access Journals (Sweden)

    Meesters Y

    2016-11-01

    Full Text Available Ybe Meesters,1 Marijke CM Gordijn,2,3 1University Center for Psychiatry, University Medical Center Groningen, 2Department of Chronobiology, GeLifes, University of Groningen, Groningen, the Netherlands; 3Chrono@Work B.V., Groningen, the Netherlands Abstract: Seasonal affective disorder (SAD, winter type, is a seasonal pattern of recurrent major depressive episodes most commonly occurring in autumn or winter and remitting in spring/summer. The syndrome has been well-known for more than three decades, with light treatment being the treatment of first choice. In this paper, an overview is presented of the present insights in SAD. Description of the syndrome, etiology, and treatment options are mentioned. Apart from light treatment, medication and psychotherapy are other treatment options. The predictable, repetitive nature of the syndrome makes it possible to discuss preventive treatment options. Furthermore, critical views on the concept of SAD as a distinct diagnosis are discussed. Keywords: seasonal affective disorder, review, light treatment, medication, psychotherapy, prevention

  13. Theory of mind deficits in bipolar affective disorder.

    Science.gov (United States)

    Kerr, Natalie; Dunbar, Robin I M; Bentall, Richard P

    2003-02-01

    Bipolar affective disorder patients often show cognitive deficits that are similar to those found in schizophrenia patients. Theory of mind (the ability to understand others' mental states) is compromised in currently ill schizophrenia patients. This study aimed to establish whether similar deficits are found in bipolar patients. We measured theory of mind ability in 20 bipolar-manic patients, 15 bipolar-depressed patients, 13 bipolar patients in remission and 15 normal controls. The task, which controlled for memory and comprehension, had previously been used in a study of schizophrenia patients. Impaired performance on theory of mind was found for both bipolar-depressed and bipolar-manic patients, even when memory was controlled for. No impairment was observed in the remitted patients. The manic patients scored lower than the remitted patients on a brief measure of intelligence; no other group differences in IQ were significant. Theory of mind deficits are found in currently symptomatic bipolar patients. These findings add to growing evidence that common mechanisms may contribute to bipolar affective disorder and schizophrenia.

  14. Schizophrenia and Bipolar Affective Disorder: a Dimensional Approach.

    Science.gov (United States)

    Aykut, Demet Sağlam; Arslan, Filiz Civil; Özkorumak, Evrim; Tiryaki, Ahmet

    2017-06-01

    Schizophrenia (SCH) and bipolar affective disorder (BAD) are currently classified separately according to the DSM (The Diagnostic and Statistical Manual of Mental Disorders) and ICD (International Statistical Classification of Diseases and Related Health Problems) standardized diagnostic guidelines. However, the validity of this categorical approach is controversial because psychotic symptoms may be observed in both diagnoses. The purpose of this study was to compare the clinical and social characteristics in a sample group consisting of patients diagnosed with SCH or BAD to help demonstrate the basic difficulty in the current classification of SCH and BAD as two etiologically distinct diseases. The study sample group consisted of 102 patients diagnosed with SCH and 92 patients diagnosed with BAD. All of the participants were evaluated by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition with regard to beginning symptoms of the disease, the symptoms and signs of active disease period within total disease duration, continuining residual symptoms in intermediate period. The patients were administered the Positive and Negative Syndrome Scale, the Quality of Life Enjoyment and Satisfaction Questionnaire and the Social Functioning Scale. The SCH and BAD groups in this study were statistically similar in terms of sex, length of education, age at disease onset, attempted suicide, quality of life and social functioning. Our study findings indicated that the course of disease in patients with BAD-1, in which psychotic features predominate and which exhibits a recurring course, shares various characteristics with SCH. It can be concluded that further phenomenological and neurobiological evaluations are required for intermediate cases with similiar clinical characteristics with schizophrenia and bipolar disorders.

  15. Reactivity of affect and self-esteem during remission in bipolar affective disorder: an experimental investigation.

    Science.gov (United States)

    Pavlova, Barbara; Uher, Rudolf; Dennington, Louis; Wright, Kim; Donaldson, Catherine

    2011-11-01

    Bipolar affective disorder (BPAD) is characterised by a lifelong vulnerability to develop episodes of depressed or elevated mood in response to stressful life events involving achievement or failure. We hypothesised that this latent vulnerability can manifest as reactivity of affect and self-esteem to experimentally induced experiences of success and failure and is shaped by history of childhood adversity. Twenty-four people with remitted BPAD and twenty-four healthy controls underwent anagram-solving tasks designed to generate experiences of success and failure in two separate sessions. Positive and negative affect and implicit and explicit self-esteem were measured before and after each task. Early adversity was measured by Childhood Trauma Questionnaire. People with BPAD showed larger reactivity of affect and explicit self-esteem in response to experimental success and failure than did healthy controls. There were no significant differences in reactivity of implicit self-esteem. History of childhood trauma predicted increased affective reactivity to failure but not to success. We used a convenience sample. The present experimental paradigm reveals reactivity of affect and self-esteem as features of BPAD, which are present even during good remission and thus are accessible as targets of interventions aiming at relapse prevention. Differential associations with childhood adversity indicate aetiological heterogeneity, with reactivity to failure influenced by early trauma and reactivity to success driven by other mechanisms. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Selenium, selenoproteins and neurodegenerative diseases.

    Science.gov (United States)

    Cardoso, Bárbara Rita; Roberts, Blaine R; Bush, Ashley I; Hare, Dominic J

    2015-08-01

    It is unsurprising that our understanding of the role of selenium in neurological function is somewhat immature, considering its relatively recent discovery as an essential element to human health. Selenocysteine, the 21st amino acid, is the defining feature of the 25 selenoprotein-encoding genes so far discovered within the human genome. The low abundance of these proteins in the brain belies the integral role they play in normal neurological function, from well-characterised antioxidant activity in the periphery to poorly understood mechanisms that modulate mitochondrial function and response to brain pathology. Selenium has been identified as playing a role in several neurodegenerative disorders, including Alzheimer's and Parkinson's disease, though its function as a 'cause or effect' of disease process remains unclear. This review discusses selenium metabolism in detail, specifically with regard to the role it plays within the central nervous system, and examines the most current literature investigating how selenium may be involved in chronic diseases of the central nervous system.

  17. Metals and neurodegenerative diseases. A systematic review.

    Science.gov (United States)

    Cicero, Calogero Edoardo; Mostile, Giovanni; Vasta, Rosario; Rapisarda, Venerando; Signorelli, Salvatore Santo; Ferrante, Margherita; Zappia, Mario; Nicoletti, Alessandra

    2017-11-01

    Neurodegenerative processes encompass a large variety of diseases with different pathological patterns and clinical presentation such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer Disease (AD) and Parkinson's disease (PD). Genetic mutations have a known causative role, but the majority of cases are likely to be probably caused by a complex gene-environment interaction. Exposure to metals has been hypothesized to increase oxidative stress in brain cells leading to cell death and neurodegeneration. Neurotoxicity of metals has been demonstrated by several in vitro and in vivo experimental studies and it is likely that each metal could be toxic through specific pathways. The possible pathogenic role of different metals has been supported by some epidemiological evidences coming from occupational and ecological studies. In order to assess the possible association between metals and neurodegenerative disorders, several case-control studies have also been carried out evaluating the metals concentration in different biological specimens such as blood/serum/plasma, cerebrospinal fluid (CSF), nail and hair, often reporting conflicting results. This review provides an overview of our current knowledge on the possible association between metals and ALS, AD and PD as main neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Negative Affect Instability among Individuals with Comorbid Borderline Personality Disorder and Posttraumatic Stress Disorder

    Science.gov (United States)

    Scheiderer, Emily M.; Wang, Ting; Tomko, Rachel L.; Wood, Phillip K.; Trull, Timothy J.

    2015-01-01

    Ecological momentary assessment (EMA; Stone & Shiffman, 1994) was utilized to examine affective instability (AI) in the daily lives of outpatients with borderline personality disorder (BPD; n=78) with and without posttraumatic stress disorder (PTSD). A psychiatric control group (n=50) composed of outpatients with major depressive disorder/dysthymia (MDD/DYS) was employed to compare across subgroups: BPD-only, BPD+PTSD, MDD/DYS-only, and MDD/DYS+PTSD. Compared to the BPD-only group, the BPD+PTSD group had significantly greater instability of fear and sadness, but did not significantly differ in instability of hostility or aggregate negative affect. This pattern of elevated instability of fear and sadness was not present—and, in fact, was reversed—in the MDD/DYS group. Results emphasize the importance of examining AI within the context of specific comorbidities and affect types. Treatment and research addressing AI in the context of BPD-PTSD comorbidity may benefit from a focus on fear and sadness as separate from hostility or general negative affect. PMID:26904388

  19. A longitudinal study of schizophrenia- and affective spectrum disorders in individuals diagnosed with a developmental language disorder as children

    DEFF Research Database (Denmark)

    Mouridsen, Svend Erik Birkebæk; Hauschild, K.M.

    2008-01-01

    The prevalence and types of schizophrenia- and affective spectrum disorders were studied in 469 individuals with a developmental language disorder (DLD), assessed in the same clinic during a period of 10 years, and 2,345 controls from the general population. All participants were screened through....... 1.8%; P language disorder was significantly associated with a schizophrenia spectrum disorder diagnosis in the DPCR. There was no significant increase in affective...

  20. A longitudinal study of schizophrenia- and affective spectrum disorders in individuals diagnosed with a developmental language disorder as children

    DEFF Research Database (Denmark)

    Mouridsen, Svend Erik; Hauschild, Karen-Marie

    2008-01-01

    The prevalence and types of schizophrenia- and affective spectrum disorders were studied in 469 individuals with a developmental language disorder (DLD), assessed in the same clinic during a period of 10 years, and 2,345 controls from the general population. All participants were screened through....... 1.8%; P language disorder was significantly associated with a schizophrenia spectrum disorder diagnosis in the DPCR. There was no significant increase in affective spectrum...

  1. Affective neural response to restricted interests in autism spectrum disorders.

    Science.gov (United States)

    Cascio, Carissa J; Foss-Feig, Jennifer H; Heacock, Jessica; Schauder, Kimberly B; Loring, Whitney A; Rogers, Baxter P; Pryweller, Jennifer R; Newsom, Cassandra R; Cockhren, Jurnell; Cao, Aize; Bolton, Scott

    2014-01-01

    Restricted interests are a class of repetitive behavior in autism spectrum disorders (ASD) whose intensity and narrow focus often contribute to significant interference with daily functioning. While numerous neuroimaging studies have investigated executive circuits as putative neural substrates of repetitive behavior, recent work implicates affective neural circuits in restricted interests. We sought to explore the role of affective neural circuits and determine how restricted interests are distinguished from hobbies or interests in typical development. We compared a group of children with ASD to a typically developing (TD) group of children with strong interests or hobbies, employing parent report, an operant behavioral task, and functional imaging with personalized stimuli based on individual interests. While performance on the operant task was similar between the two groups, parent report of intensity and interference of interests was significantly higher in the ASD group. Both the ASD and TD groups showed increased BOLD response in widespread affective neural regions to the pictures of their own interest. When viewing pictures of other children's interests, the TD group showed a similar pattern, whereas BOLD response in the ASD group was much more limited. Increased BOLD response in the insula and anterior cingulate cortex distinguished the ASD from the TD group, and parent report of the intensity and interference with daily life of the child's restricted interest predicted insula response. While affective neural network response and operant behavior are comparable in typical and restricted interests, the narrowness of focus that clinically distinguishes restricted interests in ASD is reflected in more interference in daily life and aberrantly enhanced insula and anterior cingulate response to individuals' own interests in the ASD group. These results further support the involvement of affective neural networks in repetitive behaviors in ASD. © 2013 The

  2. Age- and sex-dependent laterality of rat hippocampal cholinergic system in relation to animal models of neurodevelopmental and neurodegenerative disorders.

    Science.gov (United States)

    Kristofiková, Zdena; Stástný, Frantisek; Bubeniková, Vera; Druga, Rastislav; Klaschka, Jan; Spaniel, Filip

    2004-04-01

    symmetrical drop in the number of choline carriers of lesioned male rats but a asymmetrical decrease in the activity of remaing carriers, suggesting defects in processes of sexual brain differentiation, leading under normal conditions to the higher activity of carriers in the left hippocampus. The data demonstrate viral infection-mediated alterations in normal patterns of brain asymmetry and are discussed in relation to animal models of neurodevelopmental and neurodegenerative diseases.

  3. Tooth dentin defects reflect genetic disorders affecting bone mineralization

    Science.gov (United States)

    Vital, S. Opsahl; Gaucher, C.; Bardet, C.; Rowe, P.S.; George, A.; Linglart, A.; Chaussain, C.

    2012-01-01

    Several genetic disorders affecting bone mineralization may manifest during dentin mineralization. Dentin and bone are similar in several aspects, especially pertaining to the composition of the extracellular matrix (ECM) which is secreted by well-differentiated odontoblasts and osteoblasts, respectively. However, unlike bone, dentin is not remodelled and is not involved in the regulation of calcium and phosphate metabolism. In contrast to bone, teeth are accessible tissues with the shedding of deciduous teeth and the extractions of premolars and third molars for orthodontic treatment. The feasibility of obtaining dentin makes this a good model to study biomineralization in physiological and pathological conditions. In this review, we focus on two genetic diseases that disrupt both bone and dentin mineralization. Hypophosphatemic rickets is related to abnormal secretory proteins involved in the ECM organization of both bone and dentin, as well as in the calcium and phosphate metabolism. Osteogenesis imperfecta affects proteins involved in the local organization of the ECM. In addition, dentin examination permits evaluation of the effects of the systemic treatment prescribed to hypophosphatemic patients during growth. In conclusion, dentin constitutes a valuable tool for better understanding of the pathological processes affecting biomineralization. PMID:22296718

  4. Affective and cognitive empathy in adolescents with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Monica eMazza

    2014-10-01

    Full Text Available The broad construct of empathy incorporates both cognitive and affective dimensions. Recent evidence suggests that the subjects with Autistic Spectrum disorder (ASD show a significant impairment in empathic ability. The aim of this study was to evaluate the cognitive and affective components of empathy in adolescents with ASD compared to controls. Fifteen adolescents with ASD and fifteen controls underwent paper and pencil measures and a computerized Multifaceted Empathy Test. All measures were divided into Mentalizing and Experience sharing abilities. Adolescents with ASD compared to controls showed deficits in all mentalizing measures: they were incapable of interpreting and understanding the mental and emotional states of other people. Instead, in the sharing experience measures, the adolescents with ASD were able to empathize with the emotional experience of other people when they express emotions with positive valence, but were not able to do so when the emotional valence is negative. These results were confirmed by the computerized task. In conclusion, our results suggest that adolescents with ASD show a difficulty in cognitive empathy, whereas the deficit in affective empathy is specific for the negative emotional valence.

  5. Sensory modulation and affective disorders in children and adolescents with Asperger's disorder.

    Science.gov (United States)

    Pfeiffer, Beth; Kinnealey, Moya; Reed, Carol; Herzberg, Georgiana

    2005-01-01

    The purpose of the study was to determine if there were significant relationships between dysfunction in sensory modulation, symptoms of affective disorders, and adaptive behaviors in children and adolescents with Asperger's disorder between 6 and 17 years of age. Parents of 50 children and adolescents between 6 and 17 years of age diagnosed with Asperger's disorder based on the Diagnostic and Statistical Manual of Mental Disorders-IV criteria completed the (a) Sensory Profile for children 6 to 10 years of age or the Adolescent/Adult Sensory Profile for adolescents 11 to 17 years of age; (b) the Adaptive Behavior Assessment System: Parent Version; (c) Revised Children's Manifest Anxiety Scale Adapted Parent's Version; and (d) the Children's Depression Inventory Adapted Parent's Version. Descriptive statistics and the Pearson product-moment coefficient of correlation calculations were used for data analysis. The results indicated that there were significantly strong positive correlations between sensory defensiveness and anxiety (r = .476, p = .000) in children and adolescents with Asperger's disorder. There were also significant relationships between symptoms of depression and hyposensitivity in the total group (r = .214, p = .05) and the older group (r = .492, p = .027). There were no significant relationships between depression and overall adaptive behavior (r = -.243, p = .089) or anxiety and overall adaptive behavior (r = -.108, p = .455). Significantly strong inverse relationships were found between the specific adaptive behaviors of functional academics, leisure, social skills, and symptoms of depression. Functional academics were also significantly inversely related to anxiety. Specifically, sensory hyper- and hypersensitivity were significantly inversely related to community use and social skills. The data supports positive relationships between anxiety and sensory defensiveness in all age ranges and a relationship between depression and hyposensitivity in

  6. Affect recognition among adolescents in therapeutic schools: relationships with posttraumatic stress disorder and conduct disorder symptoms.

    Science.gov (United States)

    Javdani, Shabnam; Sadeh, Naomi; Donenberg, Geri R; Emerson, Erin; Houck, Christopher; Brown, Larry K

    2017-02-01

    Posttraumatic stress disorder (PTSD) and conduct disorder (CD) symptoms often co-occur in adolescence, but little is known about whether they show common or distinct emotional processing deficits. We examined the effects of PTSD and CD symptoms on facial affect processing in youth with emotional and behavior problems. Teens enrolled in therapeutic day schools (N = 371; ages 13-19) completed a structured diagnostic assessment and the Diagnostic Analysis of Nonverbal Accuracy-2 facial affect recognition task. PTSD symptoms were associated with deficits in the recognition of angry facial expressions, specifically the false identification of angry faces as fearful. CD symptoms were associated with greater difficulty correctly identifying sadness. Findings suggest specificity in the relationships of PTSD and CD symptoms with emotional processing.

  7. Bipolar affective disorder: A review of novel forms of therapy

    Directory of Open Access Journals (Sweden)

    Dziwota Ewelina

    2015-06-01

    Full Text Available Normothymic, antidepressant and antipsychotic pharmaceutics are, in accordance with international guidelines, employed both in the therapy and the prevention of bipolar disorder (BD. Long-term studies on the mechanisms of action of such medications, as well as on the pathogenetic background of BD, have led to the discovery of effective, albeit unconventional pharmacotherapeutic approaches. These methods have the potential to successfully treat mania and depression, as well as to counter affective episode relapse. Allopurinol - commonly used to treat gout, secondary hyperuricemia and Lesch-Nyhan syndrome, acts by inhibiting the synthesis of uric acid, levels of which are often increased in manic patients. Due to this, an evaluation of the potential effect of allopurinol on the reduction of mania symptoms seems to be reasonable. Additionally, the numerable research papers coming out of research regarding the role of purine neurotransmitters in mood alterations, indicate that adenosine agonists act analogously to dopamine antagonists.

  8. A cholinergic hypothesis of the unconscious in affective disorders.

    Directory of Open Access Journals (Sweden)

    Costa eVakalopoulos

    2013-11-01

    Full Text Available The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioural repertoires at the core of affective disorders and ADHD. Behavioural adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o and its modulation of m1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signalling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial. recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behaviour and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone.

  9. Altered resting-state activity in seasonal affective disorder.

    Science.gov (United States)

    Abou Elseoud, Ahmed; Nissilä, Juuso; Liettu, Anu; Remes, Jukka; Jokelainen, Jari; Takala, Timo; Aunio, Antti; Starck, Tuomo; Nikkinen, Juha; Koponen, Hannu; Zang, Yu-Feng; Tervonen, Osmo; Timonen, Markku; Kiviniemi, Vesa

    2014-01-01

    At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting-state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA-dual regression), and amplitude of low-frequency fluctuations (ALFF) were measured in 45 antidepressant-free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age-, gender- and ethnicity-matched healthy controls (HCs) using resting-state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter-RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD. Copyright © 2012 Wiley Periodicals, Inc.

  10. Abnormal hypothalamic response to light in Seasonal Affective Disorder

    Science.gov (United States)

    Gilles, Vandewalle; Marc, Hébert; Catherine, Beaulieu; Laurence, Richard; Véronique, Daneault; Marie-Lou, Garon; Jean, Leblanc; Didier, Grandjean; Pierre, Maquet; Sophie, Schwartz; Marie, Dumont; Julien, Doyon; Julie, Carrier

    2017-01-01

    Background Vulnerability to the reduction in natural light associated with fall/winter is generally accepted as the main trigger of Seasonal Affective Disorder (SAD), while light therapy is a treatment of choice of the disorder. However, the relationship between exposure to light and mood regulation remains unclear. As compared to green light, blue light was shown to acutely modulate emotion brain processing in healthy individuals. Here, we investigated the impact of light on emotion brain processing in patients with SAD and healthy controls and its relationship with retinal light sensitivity. Methods Fourteen symptomatic untreated patients with SAD (34.5 ± 8.2 y.o.; 9F) and sixteen healthy controls (32.3 ± 7.7 y.o.; 11F) performed an auditory emotional task in functional Magnetic Resonance Imaging (fMRI) during the fall/winter season, while being exposed to alternating blue and green monochromatic light. Scotopic and photopic retinal light sensitivities were then evaluated using electroretinography. Results Blue light enhanced responses to auditory emotional stimuli in the posterior hypothalamus in patients with SAD, while green light decreased these responses. These effects of blue and green light were not observed in healthy controls despite similar retinal sensitivity in SAD and control subjects. Conclusions; These results point to the posterior hypothalamus as the neurobiological substrate involved in specific aspects of SAD, including a distinctive response to light and altered emotional responses. PMID:21820647

  11. Prevalence and correlates of binge eating in seasonal affective disorder.

    Science.gov (United States)

    Donofry, Shannon D; Roecklein, Kathryn A; Rohan, Kelly J; Wildes, Jennifer E; Kamarck, Marissa L

    2014-06-30

    Eating pathology in Seasonal Affective Disorder (SAD) may be more severe than hyperphagia during winter. Although research has documented elevated rates of subclinical binge eating in women with SAD, the prevalence and correlates of binge eating disorder (BED) in SAD remain largely uncharacterized. We examined the prevalence and correlates of binge eating, weekly binge eating with distress, and BED as defined by the DSM-IV-TR in SAD. We also tested whether binge eating exhibits a seasonal pattern among individuals with BED. Two samples were combined to form a sample of individuals with SAD (N=112). A third sample included non-depressed adults with clinical (n=12) and subclinical (n=11) BED. All participants completed the Questionnaire of Eating and Weight Patterns-Revised (QEWP-R) and modified Seasonal Pattern Assessment Questionnaire (M-SPAQ). In the SAD sample, 26.5% reported binge eating, 11.6% met criteria for weekly binge eating with distress, and 8.9% met criteria for BED. Atypical symptom severity predicted binge eating and BED. In the BED sample, 30% endorsed seasonal worsening of mood, and 26% reported a winter pattern of binge eating. The spectrum of eating pathology in SAD includes symptoms of BED, which are associated with atypical depression symptoms, but typical depression symptoms. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Musculoskeletal Disorders among Dental Practitioners: Does It Affect Practice?

    Directory of Open Access Journals (Sweden)

    Dhanya Muralidharan

    2013-01-01

    Full Text Available Background. Literature reviews world over have shown a high prevalence of musculoskeletal disorders among dental practitioners. Prevalence of MSD among dental practitioners in India is not well documented. Aim. To determine the prevalence and distribution of MSD among dental practitioners in a city in the southern state of Andhra Pradesh, India. Material and Methods. A cross sectional descriptive study in which a self-administered questionnaire (the Standardized Nordic questionnaire was used to assess the musculoskeletal symptoms among dental practitioners. The recorded data was analyzed with SPSS 13. -value 0.05 was considered to statistically significant. Results. Seventy-three dental practitioners participated in the study of which seventy-eight percent had a prevalence of at least one MSD symptom over the past twelve months. Most common areas affected by MSD in order of magnitude were neck (52%, low back (41%, shoulders (29% and wrist (26%. One third of the practitioners (40% required sick leave from their practice during the preceding twelve months. Conclusions. High prevalence of MSD exists among our dental practitioners affecting the daily practice of more than one third. Further studies are needed to identify the specific risk factors for MSD so as to introduce effective remedial measures.

  13. The impact of metabotropic glutamate receptors into active neurodegenerative processes: A "dark side" in the development of new symptomatic treatments for neurologic and psychiatric disorders.

    Science.gov (United States)

    Bruno, Valeria; Caraci, Filippo; Copani, Agata; Matrisciano, Francesco; Nicoletti, Ferdinando; Battaglia, Giuseppe

    2017-03-15

    Metabotropic glutamate (mGlu) receptor ligands are under clinical development for the treatment of CNS disorders with high social and economic burden, such as schizophrenia, major depressive disorder (MDD), and Parkinson's disease (PD), and are promising drug candidates for the treatment of Alzheimer's disease (AD). So far, clinical studies have shown symptomatic effects of mGlu receptor ligands, but it is unknown whether these drugs act as disease modifiers or, at the opposite end, they accelerate disease progression by enhancing neurodegeneration. This is a fundamental issue in the treatment of PD and AD, and is also an emerging theme in the treatment of schizophrenia and MDD, in which neurodegeneration is also present and contribute to disease progression. Moving from in vitro data and preclinical studies, we discuss the potential impact of drugs targeting mGlu2, mGlu3, mGlu4 and mGlu5 receptor ligands on active neurodegeneration associated with AD, PD, schizophrenia, and MDD. We wish to highlight that our final comments on the best drug candidates are not influenced by commercial interests or by previous or ongoing collaborations with drug companies. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Psychosocial Functioning in Depressive Patients: A Comparative Study between Major Depressive Disorder and Bipolar Affective Disorder

    Directory of Open Access Journals (Sweden)

    Shubham Mehta

    2014-01-01

    Full Text Available Introduction. Major depressive disorder (MDD and bipolar affective disorder (BAD are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group were included in the study. Patients were recruited in depressive phase (moderate to severe depression. Patients having age outside 18–45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT. Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P=0.031 with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression.

  15. Psychosocial Functioning in Depressive Patients: A Comparative Study between Major Depressive Disorder and Bipolar Affective Disorder.

    Science.gov (United States)

    Mehta, Shubham; Mittal, Pankaj Kumar; Swami, Mukesh Kumar

    2014-01-01

    Introduction. Major depressive disorder (MDD) and bipolar affective disorder (BAD) are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group) were included in the study. Patients were recruited in depressive phase (moderate to severe depression). Patients having age outside 18-45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT). Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P = 0.031) with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression.

  16. Predictors of Suicide Attempts in 3.322 Patients with Affective Disorders and Schizophrenia Spectrum Disorders

    Science.gov (United States)

    Yuen, Eunice Y.; Fink, Sabina; Duque, Laura M.; Kane, John M.

    2015-01-01

    This study explores risk factors for suicide attempts using the electronic health records of 3,322 patients with either schizophrenia spectrum disorders or affective disorders who underwent a comprehensive psychiatric evaluation at the Emergency Department at the Long Island Jewish Medical Center or the Hillside Evaluation Center at The Zucker Hillside Hospital from August 3rd 2011 to July 5th 2012. Multivariate regression analyses showed, after adjusting for sex, that previous suicidal attempts and financial or relationship losses were significantly associated with a current suicidal attempt. Additionally, higher odds of having a suicidal attempt were also found in those subjects with a diagnosis of an affective disorder, compared to a schizophrenia spectrum diagnosis, and those patients in the children/adolescent group compared to those in the adult/elderly group. Our study results confirm and expand results from prior studies. Therefore, physicians should be alert for the presence of any or all of these factors upon evaluation of psychiatric patients, and if present, either psychiatric hospitalization or a close psychiatric follow up in collaboration with family and a therapist would be key in reducing the risk of potential suicidal behavior. PMID:26077849

  17. Retinoic acid and affective disorders: the evidence for an association.

    Science.gov (United States)

    Bremner, J Douglas; Shearer, Kirsty D; McCaffery, Peter J

    2012-01-01

    with suicide in a subgroup of vulnerable individuals. The relationship between isotretinoin and depression may have implications for a greater understanding of the neurobiology of affective disorders. © Copyright 2012 Physicians Postgraduate Press, Inc.

  18. Epidemiology and socioeconomic impact of seasonal affective disorder in Austria.

    Science.gov (United States)

    Pjrek, E; Baldinger-Melich, P; Spies, M; Papageorgiou, K; Kasper, S; Winkler, D

    2016-02-01

    Seasonal affective disorder (SAD) is a subtype of recurrent depressive or bipolar disorder that is characterized by regular onset and remission of affective episodes at the same time of the year. The aim of the present study was to provide epidemiological data and data on the socioeconomic impact of SAD in the general population of Austria. We conducted a computer-assisted telephone interview in 910 randomly selected subjects (577 females and 333 males) using the Seasonal Health Questionnaire (SHQ), the Seasonal Pattern Assessment Questionnaire (SPAQ), and the Sheehan Disability Scale (SDS). Telephone numbers were randomly drawn from all Austrian telephone books and transformed using the random last digits method. The last birthday method was employed to choose the target person for the interviews. Out of our subjects, 2.5% fulfilled criteria for the seasonal pattern specifier according to DSM-5 and 2.4% (95% CI=1.4-3.5%) were diagnosed with SAD. When applying the ICD-10 criteria 1.9% (95% CI=0.9-2.8%) fulfilled SAD diagnostic criteria. The prevalence of fall-winter depression according to the Kasper-Rosenthal criteria was determined to be 3.5%. The criteria was fulfilled by 15.1% for subsyndromal SAD (s-SAD). We did not find any statistically significant gender differences in prevalence rates. When using the DSM-5 as a gold standard for the diagnosis of SAD, diagnosis derived from the SPAQ yielded a sensitivity of 31.8% and a specificity of 97.2%. Subjects with SAD had significantly higher scores on the SDS and higher rates of sick leave and days with reduced productivity than healthy subjects. Prevalence estimates for SAD with the SHQ are lower than with the SPAQ. Our data are indicative of the substantial burden of disease and the socioeconomic impact of SAD. This epidemiological data shows a lack of gender differences in SAD prevalence. The higher rates of females in clinical SAD samples might, at least in part, be explained by lower help seeking behaviour in

  19. Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

    Science.gov (United States)

    Bhullar, Khushwant S.; Rupasinghe, H. P. Vasantha

    2013-01-01

    Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders. PMID:23840922

  20. Indian Herbs for the Treatment of Neurodegenerative Disease.

    Science.gov (United States)

    Mannangatti, Padmanabhan; Naidu, Kamalakkannan Narasimha

    2016-01-01

    Ayurveda, an ancient system of medicine that is indigenous to India, is believed to be the world's oldest comprehensive health-care system and is now one of the most recognized and widely practiced disciplines of alternative medicine in the world. Medicinal herbs have been in use for treating diseases since ancient times in India. Ayurvedic therapies with medicinal herbs and herbomineral products generally provide relief without much adverse effects even after prolonged administration. Neurodegenerative disorders are a major cause of mortality and disability, and increasing life spans represent one of the key challenges of medical research. Ayurvedic medicine describes most neurodegenerative diseases and has defined a number of plants with therapeutic benefits for the treatment of neurodegenerative diseases having antioxidant activities. In this chapter, the role of four important Ayurvedic medicinal plants, viz., Withania somnifera (ashwagandha), Bacopa monnieri (brahmi), Centella asiatica (gotu kola), and Mucuna pruriens (velvet bean), on neurodegenerative diseases are discussed.

  1. Comparative neuropsychiatry: white matter abnormalities in children and adolescents with schizophrenia, bipolar affective disorder, and obsessive-compulsive disorder.

    Science.gov (United States)

    White, T; Langen, C; Schmidt, M; Hough, M; James, A

    2015-02-01

    There is considerable evidence that white matter abnormalities play a key role in the pathogenesis of a number of major psychiatric disorders, including schizophrenia, bipolar affective disorder, and obsessive-compulsive disorder. Few studies, however, have compared white matter abnormalities early in the course of the illness. A total of 102 children and adolescents participated in the study, including 43 with early-onset schizophrenia, 13 with early-onset bipolar affective disorder, 17 with obsessive-compulsive disorder, and 29 healthy controls. Diffusion tensor imaging scans were obtained on all children and the images were assessed for the presence of non-spatially overlapping regions of white matter differences, a novel algorithm known as the pothole approach. Patients with early-onset schizophrenia and early-onset bipolar affective disorder had a significantly greater number of white matter potholes compared to controls, but the total number of potholes did not differ between the two groups. The volumes of the potholes were significantly larger in patients with early-onset bipolar affective disorder compared to the early-onset schizophrenia group. Children and adolescents with obsessive-compulsive disorder showed no differences in the total number of white matter potholes compared to controls. White matter abnormalities in early-onset schizophrenia and bipolar affective disorder are more global in nature, whereas children and adolescents with obsessive-compulsive disorder do not show widespread differences in FA. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Affect intensity measure in bipolar disorders: a multidimensional approach.

    Science.gov (United States)

    Mathieu, F; Etain, B; Daban, C; Raymond, R; Raust, A; Cochet, B; Gard, S; M'Bailara, K; Desage, A; Kahn, J P; Wajsbrot-Elgrabli, O; Cohen, R F; Azorin, J M; Leboyer, M; Bellivier, F; Scott, J; Henry, C

    2014-03-01

    Emotional dysregulation, characterized by high levels of both arousal and intensity of emotional responses, is a core feature of bipolar disorders (BDs). In non-clinical populations, the 40-item Affect Intensity Measure (AIM) can be used to assess the different dimensions of emotional reactivity. We analyzed the factor structure of the AIM in a sample of 310 euthymic patients with BD using Principal Component Analysis and examined associations between AIM sub-scale scores and demographic and illness characteristics. The French translation of the AIM demonstrated good reliability. A four-factor solution similar to that reported in non-clinical samples (Positive Affectivity, Unpeacefulness [lack of Serenity], Negative Reactivity, Negative Intensity), explained 47% of the total variance. Age and gender were associated with Unpeacefulness and Negative reactivity respectively. 'Unpeacefulness' was also positively associated with psychotic symptoms at onset (p=0.0006), but negatively associated with co-morbid substance misuse (p=0.008). Negative Intensity was positively associated with social phobia (p=0.0005). We cannot definitively exclude a lack of statistical power to classify all AIM items. Euthymia was carefully defined, but a degree of 'contamination' of the self-reported levels of emotion reactivity may occur because of subsyndromal BD symptoms. It was not feasible to control for the possible impact of on-going treatments. The AIM scale appears to be a useful measure of emotional reactivity and intensity in a clinical sample of patients with BD, suggesting it can be used in addition to other markers of BD characteristics and sub-types. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Bupropion for the treatment of seasonal affective disorder.

    Science.gov (United States)

    Niemegeers, Peter; Dumont, Glenn J H; Patteet, Lisbeth; Neels, Hugo; Sabbe, Bernard G C

    2013-09-01

    Seasonal affective disorder (SAD) is a psychiatric illness with recurring depressive episodes during particular seasons, mostly winter. Bupropion is effective in the preventive treatment of SAD and is probably also effective in the acute treatment of SAD. This review covers the pharmacokinetics and pharmacodynamics of bupropion. The authors also evaluate bupropion's clinical efficacy as well as its safety and tolerability. Bupropion is available in an immediate release formulation, as well as a sustained release formulation and an extended release (XR) formulation. The XR formulation is recommended for SAD due to its ease of use and is the only formulation currently used as a therapy. Due to the predictable nature of SAD, the use of bupropion XR is considered a relevant treatment option. Bupropion's efficacy is shown in three trials that started in autumn at a time when SAD symptoms were not yet present although treatment effects were relatively small compared with a placebo. Bupropion was also shown to have efficacy in an open-label study. That being said, in order to reach definitive conclusions about its efficacy with acute treatment of SAD, more placebo-controlled trials are needed.

  4. Lux vs. wavelength in light treatment of Seasonal Affective Disorder.

    Science.gov (United States)

    Anderson, J L; Glod, C A; Dai, J; Cao, Y; Lockley, S W

    2009-09-01

    Published dosing guidelines for treatment of Seasonal Affective Disorder (SAD) refer to photopic lux, which is not appropriate for short-wavelength light. Short wavelengths are most potent for many non-visual responses to light. If SAD therapy were similarly mediated, standards utilizing lux risk overestimating necessary dose. We investigated antidepressant responses to light using two light-emitting diode (LED) sources, each emitting substantial short-wavelength light, but <2500 lux. A randomized, double-blind trial investigated 3-week 45 min/day out-patient treatment with blue-appearing (goLITE) or blue-enriched white-appearing light in 18 moderately-depressed adults (12F, 49.1 +/- 9.5 years). Equivalent numbers of photons within the short-wavelength range were emitted, but the white source emitted twice as many photons overall and seven-fold more lux. Depression ratings (SIGH-ADS; http://www.cet.org) decrease averaged 82% (SD = 17%) from baseline (P < 0.0001) in both white- and blue-light groups. Both sources were well tolerated. Short-wavelength LED light sources may be effective in SAD treatment at fewer lux than traditional fluorescent sources.

  5. An overview of seasonal affective disorder and its treatment options.

    Science.gov (United States)

    Howland, Robert H

    2009-12-01

    Seasonal affective disorder (SAD) is defined as a history of major depressive episodes that recur regularly at a particular time of year. Depending on the diagnostic instruments and criteria available, the reported prevalence (1%-10%) varies. Neurotransmitter abnormalities have been implicated in the pathophysiology, but they do not necessarily explain the seasonal pattern or the known chronobiological abnormalities in SAD compared with nonseasonal depression. Circadian rhythm abnormalies have been hypothesized to account for these aspects of SAD, and they provide a rationale for the therapeutic use of light therapy. Family history, twin, and molecular genetics studies suggest that hereditary factors are also involved. Light therapy and antidepressant medication are effective treatment options, with limited evidence for the efficacy of psychotherapy. Some studies demonstrate that narrow-band short wavelength "blue" light, naturalistic dawn simulation, and high-density negative air ionization are effective. Patients should be informed of the benefits of diet and exercise. Light therapy should be clinically monitored in the same manner, as it is done for other antidepressant treatments.

  6. Prevalence and correlates of binge eating in seasonal affective disorder

    Science.gov (United States)

    Donofry, Shannon D.; Roecklein, Kathryn A.; Rohan, Kelly J.; Wildes, Jennifer E.; Kamarck, Marissa L.

    2014-01-01

    Eating pathology in Seasonal Affective Disorder (SAD) may be more severe than hyperphagia during winter. Although research has documented elevated rates of subclinical binge eating in women with SAD, the prevalence and correlates of BED in SAD remain largely uncharacterized. We examined the prevalence and correlates of binge eating, weekly binge eating with distress, and BED as defined by the DSM-IV-TR in SAD. We also tested whether binge eating exhibits a seasonal pattern among individuals with BED. Two samples were combined to form a sample of individuals with SAD (N = 112). A third sample included non-depressed adults with clinical (n=12) and subclinical (n=11) BED. All participants completed the Questionnaire of Eating and Weight Patterns-Revised (QEWP-R) and modified Seasonal Pattern Assessment Questionnaire (M-SPAQ). In the SAD sample, 26.5% reported binge eating, 11.6% met criteria for weekly binge eating with distress, and 8.9% met criteria for BED. Atypical symptom severity predicted binge eating and BED. In the BED sample, 30% endorsed seasonal worsening of mood, and 26% reported a winter pattern of binge eating. The spectrum of eating pathology in SAD includes symptoms of BED, which are associated with atypical depression symptoms, but typical depression symptoms. PMID:24680872

  7. Diagnostic issues affecting the epidemiology of fetal alcohol spectrum disorders.

    Science.gov (United States)

    Farag, Mena

    2014-01-01

    Epidemiological measures of the prevalence of fetal alcohol spectrum disorders (FASD) vary greatly in the literature. Irrespective of the methodology, the criteria to define a 'case' are set by the researchers. Hence, estimates of the prevalence of FASD primarily depend on the diagnostic criteria currently available. The problem lies therein - the aforementioned criteria are ill-defined. A critical analysis of the diagnostic criteria from the Institute of Medicine, Hoyme, 4-Digit Diagnostic Code and Canadian guidelines was performed, with particular attention focused on the inconsistencies in specificities of the fetal alcohol syndrome (FAS) facial phenotype. To date, the Canadian guidelines represent the only guidelines that have pushed for a uniform diagnostic capacity through harmonizing the IoM and 4-Digit Diagnostic Code criteria. In the absence of a reliable biochemical marker of effect to confirm maternal drinking during pregnancy, the importance and dependence on diagnostic guidelines for FASD is understated. With the availability of four published guidelines for diagnoses across the spectrum of FASD, there is a need to reach a set standard globally. There are profound implications of relaxed and strict diagnostic approaches on FAS prevalence reporting in the literature. This review exposes the clinical burden of diagnosing the range of FASD with disputing diagnostic criteria. Discrepancies in the criteria pose a danger to the validity of FASD diagnoses with respect to inaccurate estimates of incidence and prevalence. In turn, these discrepancies risk compromising the future healthcare of affected individuals with regards to intervention, counselling and treatment.

  8. Relationship of Myers Briggs type indicator personality characteristics to suicidality in affective disorder patients.

    Science.gov (United States)

    Janowsky, David S; Morter, Shirley; Hong, Liyi

    2002-01-01

    The current study characterized the Myers Briggs Type Indicator (MBTI) personality profiles of 64 suicidal and 30 non-suicidal psychiatric inpatients with affective disorder diagnoses. The MBTI divides individuals categorically into eight personality preferences (Extroverted and Introverted, Sensing and Intuitive, Thinking and Feeling, and Judging and Perceiving). Compared to the group of non-suicidal affective disorder patients, suicidal affective disorder patients were significantly more Introverted and Perceiving using ANCOVA analyses, and significantly more Introverted alone using Chi Square analyses.

  9. Occurrence of the Cys311 DRD2 variant in a pedigree multiply affected with panic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, F.; Hoyne, J.; Diaz, P. [Univ. of South Florida, Tampa, FL (United States)] [and others

    1995-08-14

    Following the detection of the rare DRD2 codon 311 variant (Ser{yields}Cys) in an affected member from a large, multiply affected panic disorder family, we investigated the occurrence of this variant in other family members. The variant occurred in both affected and unaffected individuals. Further screening in panic disorder sib pairs unrelated to this family failed to detect the Cys311 variant. Our data suggests that this variant has no pathogenic role in panic disorder. 18 refs., 1 fig.

  10. The Relationship between Sleep-Wake Cycle and Cognitive Functioning in Young People with Affective Disorders

    OpenAIRE

    Carpenter, Joanne S.; Rébecca Robillard; Lee, Rico S.C.; Hermens, Daniel F.; Naismith, Sharon L.; Django White; Bradley Whitwell; Scott, Elizabeth M.; Hickie, Ian B

    2015-01-01

    Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disord...

  11. Renin-angiotensin system gene expression and neurodegenerative diseases.

    Science.gov (United States)

    Goldstein, Benjamin; Speth, Robert C; Trivedi, Malav

    2016-07-01

    Single nucleotide polymorphisms and altered gene expression of components of the renin-angiotensin system (RAS) are associated with neurodegenerative diseases. Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease. A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis. No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with the five neurodegenerative diseases investigated. There was an inverse association between expression of ATP6AP2, which encodes the (pro)renin receptor, and multiple sclerosis, Alzheimer's disease and Parkinson's disease. An association of AGTR, which encodes the AT1 angiotensin II receptor, and Parkinson's disease and Alzheimer's disease was also observed. To date, no single nucleotide polymorphisms in components of the RAS can be definitively linked to the neurodegenerative diseases evaluated in this study. However, altered gene expression of several components of the RAS is associated with several neurodegenerative diseases, which may indicate that the RAS contributes to the pathology of these diseases. © The Author(s) 2016.

  12. Seasonal affective disorder and alcohol abuse disorder in a population-based study.

    Science.gov (United States)

    Morales-Muñoz, Isabel; Koskinen, Seppo; Partonen, Timo

    2017-07-01

    Seasonal affective disorder (SAD) is a recurrent major depressive disorder with a seasonal pattern, which is characterized by sad mood, low energy, longer sleep duration and carbohydrate craving. Furthermore, seasonal changes in mood and behavior may be closely related to alcohol use disorder (AUD). Nevertheless, there is scarce research on the study of cognitive impairments in SAD and AUD. We aimed to examine the relationship between the prevalence between SAD and AUD patients, and how cognitive functioning might be related to these variables. To do this, a sample of 8135 Finnish subjects was invited to take part in the population-based Health 2011 Survey, of whom 5903 did participate and 4554 were interviewed for mental health status with the Munich version of Composite International Diagnostic Interview. They also completed the modified Seasonal Pattern Assessment Questionnaire, the Mini-Mental State Examination, the category (animals) verbal fluency test, and the Rey Auditory Verbal Learning Test. Our results reveal the existence of a strong link between SAD and AUD in a large sample of Finnish population, as well as association between SAD and short-term memory problems. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  13. Baseline characteristics of depressive disorders in Thai outpatients: findings from the Thai Study of Affective Disorders

    Directory of Open Access Journals (Sweden)

    Wongpakaran T

    2014-01-01

    Full Text Available Tinakon Wongpakaran,1 Nahathai Wongpakaran,1 Manee Pinyopornpanish,1 Usaree Srisutasanavong,1 Peeraphon Lueboonthavatchai,2 Raviwan Nivataphand,2 Nattaporn Apisiridej,3 Donruedee Petchsuwan,3 Nattha Saisavoey,4 Kamonporn Wannarit,4 Ruk Ruktrakul,5 Thawanrat Srichan,5 Sirina Satthapisit,6 Daochompu Nakawiro,7 Thanita Hiranyatheb,7 Anakevich Temboonkiat,8 Namtip Tubtimtong,9 Sukanya Rakkhajeekul,9 Boonsanong Wongtanoi,10 Sitthinant Tanchakvaranont,11 Putipong Bookkamana121Faculty of Medicine, Chiang Mai University, Chiang Mai, 2Faculty of Medicine, Chulalongkorn University, Bangkok, 3Trang Hospital, Trang, 4Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, 5Lampang Hospital, Lampang, 6KhonKaen Hospital, Khon Kaen, 7Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 8Phramongkutklao Hospital, Bangkok, 9Faculty of Medicine Naresuan University, Pitsanulok, 10Srisangwal Hospital, Mae Hong Son, 11Queen Savang Vadhana Memorial Hospital, Chonburi, 12Faculty of Science, Chiang Mai University, Chiang Mai Kingdom of ThailandBackground: The Thai Study of Affective Disorders was a tertiary hospital-based cohort study developed to identify treatment outcomes among depressed patients and the variables involved. In this study, we examined the baseline characteristics of these depressed patients.Methods: Patients were investigated at eleven psychiatric outpatient clinics at tertiary hospitals for the presence of unipolar depressive disorders, as diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The severity of any depression found was measured using the Clinical Global Impression and 17-item Hamilton Depression Rating Scale (HAMD clinician-rated tools, with the Thai Depression Inventory (a self-rated instrument administered alongside them. Sociodemographic and psychosocial variables were collected, and quality of life was also captured using the health-related quality of life (SF-36v2

  14. Composition, Standardization and Chemical Profiling of Banisteriopsis caapi, a Plant for the Treatment of Neurodegenerative Disorders Relevant to Parkinson’s Disease†

    Science.gov (United States)

    Wang, Yan-Hong; Samoylenko, Volodymyr; Tekwani, Babu L.; Khan, Ikhlas A.; Miller, Loren S.; Chaurasiya, Narayan D.; Rahman, Md. Mostafizur; Tripathi, Lalit M.; Khan, Shabana I.; Joshi, Vaishali C.; Wigger, Frank T.; Muhammad, Ilias

    2010-01-01

    Ethnopharmacological relevance Banisteriopsis caapi, a woody vine from the Amazonian basin, is popularly known as an ingredient of a sacred drink ayahuasca, widely used throughout the Amazon as a medicinal tea for healing and spiritual exploration. The usefulness of B. caapi has been established for alleviating symptoms of neurological disorders including Parkinson’s disease. Aim of the study Primary objective of this study was to develop the process for preparing standardized extracts of B. caapi to achieve high potency for inhibition of human monoamine oxidases (MAO) and antioxidant properties. The aqueous extracts prepared from different parts of the plant collected from different geographical locations and seasons were analyzed by HPLC for principal bioactive markers. The extracts were simultaneously tested in vitro for inhibition of human MAOs and antioxidant activity for analysis of correlation between phytochemical composition of the extracts and bioactivities. Materials and methods Reversed-phase HPLC with photodiode array detection was employed to profile the alkaloidal and non-alkaloidal components of the aqueous extract of B. caapi. The B. caapi extracts and standardized compositions were tested in vitro for inhibition of recombinant preparations of human MAO-A and MAO-B. In vitro cell-based assays were employed for evaluation of antioxidant property and mammalian cell cytotoxicity of these preparations. Results Among the different aerial parts, leaves, stems/large branches and stem bark of B. caapi, HPLC analysis revealed that most of the dominant chemical and bioactive markers (1, 2, 5, 7-9) were present in high concentrations in dried bark of large branch. A library of HPLC chromatograms has also been generated as a tool for fingerprinting and authentication of the studied B. caapi species. The correlation between potency of MAO inhibition and antioxidant activity with the content of the main active constituents of the aqueous B. caapi extracts and

  15. Risk. Impact of having a first-degree relative with affective disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj

    2016-01-01

    This study investigated a high-risk sample in order to elucidate risk factors for affective disorder. Healthy monozygotic (MZ) and dizygotic (DZ) twins with and without a co-twin with a history of affective disorder were identified through nationwide registers. Two risk groups were identified......: the high-risk group comprised twins at risk of developing affective disorder (DZ or MZ twin; index co-twin affected); the low risk group (control group) comprised twins at low risk of developing affective disorder (DZ or MZ twin; index co-twin not affected). At baseline 234 participants were divided...... into groups according to their risk for affective disorder; they were followed up at 6-month intervals with posted questionnaires assessing depression. After a mean follow-up period of 7 years, the participants were invited to participate in an individual interview. A total of 36 participants (31 high...

  16. Allostatic load in parents of children with developmental disorders: moderating influence of positive affect.

    Science.gov (United States)

    Song, Jieun; Mailick, Marsha R; Ryff, Carol D; Coe, Christopher L; Greenberg, Jan S; Hong, Jinkuk

    2014-02-01

    This study examines whether parents of children with developmental disorders are at risk of elevated allostatic load relative to control parents and whether positive affect moderates difference in risk. In all, 38 parents of children with developmental disorders and 38 matched comparison parents were analyzed. Regression analyses revealed a significant interaction between parent status and positive affect: parents of children with developmental disorders had lower allostatic load when they had higher positive affect, whereas no such association was evident for comparison parents. The findings suggest that promoting greater positive affect may lower health risks among parents of children with developmental disorders.

  17. Bipolar disorder dynamics: affective instabilities, relaxation oscillations and noise

    Science.gov (United States)

    Geddes, John R.; Goodwin, Guy M.; Holmes, Emily A.

    2015-01-01

    Bipolar disorder is a chronic, recurrent mental illness characterized by extreme episodes of depressed and manic mood, interspersed with less severe but highly variable mood fluctuations. Here, we develop a novel mathematical approach for exploring the dynamics of bipolar disorder. We investigate how the dynamics of subjective experience of mood in bipolar disorder can be understood using a relaxation oscillator (RO) framework and test the model against mood time-series fluctuations from a set of individuals with bipolar disorder. We show that variable mood fluctuations in individuals diagnosed with bipolar disorder can be driven by the coupled effects of deterministic dynamics (captured by ROs) and noise. Using a statistical likelihood-based approach, we show that, in general, mood dynamics are described by two independent ROs with differing levels of endogenous variability among individuals. We suggest that this sort of nonlinear approach to bipolar disorder has neurobiological, cognitive and clinical implications for understanding this mental illness through a mechacognitive framework. PMID:26577592

  18. [Cortical Release Signs in Patients with Schizophrenia, Depressive Disorders, and Bipolar Affective Disorder].

    Science.gov (United States)

    de la Espriella, Ricardo Andrés; Hernández, José Fernando; Espejo, Lina María

    2013-12-01

    Determining the presence of cortical release signs associated with white matter damage, is a clinically easy method to perform. The objective of this study is to determine the presence of cortical release signs in patients with mental illnesses and cerebrovascular disease, as well as its clinical usefulness, given that it indicates cortical damage. A review was made of cortical release signs in patients hospitalized in clinical psychiatry and general hospitals with bipolar affective disorder (40), depression (37), schizophrenia (33), cardiovascular disease (33) and dementia (37). The signs of cortical release do not have the same importance as cortical damage. For example, the glabellar reflex was found in all the groups, that of paratonia, particularly in the group with schizophrenia, and others signs in the group of patients with dementia. It is suggested that these signs imply subcortical white matter damage. The appearance of these signs shows the need for a follow up of patients diagnosed with bipolar affective disorder, depression and schizophrenia. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  19. Hypothyroidism and Bipolar Affective Disorder: Is There a Connection?

    OpenAIRE

    Menon, Bindu

    2014-01-01

    Context: Hypothalamic-pituitary-thyroid axis dysfunction in the pathophysiology of bipolar disorder has received less attention as compared with that in depressive disorder. Aims: To study the prevalence of hypothyroidism in patients diagnosed with bipolar disorder and compare it with a population norm. Settings and Design: The setting was the psychiatry inpatient unit of a tertiary care hospital. The design was retrospective and observational. Subjects and Methods: A retrospective observatio...

  20. Disorder affects judgements about a neighbourhood: police presence does not

    Directory of Open Access Journals (Sweden)

    Jessica Hill

    2014-03-01

    Full Text Available Many police forces operate a policy of high visibility in disordered neighbourhoods with high crime. However, little is known about whether increased police presence influences people’s beliefs about a neighbourhood’s social environment or their fear of crime. Three experimental studies compared people’s perceptions of social capital and fear of crime in disordered and ordered neighbourhoods, either with a police presence or no police presence. In all studies, neighbourhood disorder lowered perceptions of social capital, resulting in a higher fear of crime. Police presence or absence had no significant effect. The pervasive effects of disorder above other environmental cues are discussed.

  1. Platelet serotonergic functions and light therapy in seasonal affective disorder.

    Science.gov (United States)

    Stain-Malmgren, R; Kjellman, B F; Aberg-Wistedt, A

    1998-05-08

    We investigated platelet 14C-serotonin uptake and platelet [3H]LSD and [3H]paroxetine binding in 11 patients with seasonal affective disorder (SAD). Patients were reinvestigated after light therapy, applied at 07.00-09.00 h for 10 consecutive days. The degree of depression was rated before and after light therapy using the Comprehensive Psychopathological Rating Scale (CPRS). Baseline data in patients were compared with data from a control group consisting of 11 age- and sex-matched healthy volunteers. Seven patients responded to light therapy with a > 50% reduction in CPRS scores. In non-responders, the reduction in CPRS was 24.7 +/- 5.5%. There was a significant inverse correlation (P = 0.014) between Km for platelet 14C-serotonin uptake and CPRS scores. Patients had significantly higher Bmax for platelet [3H]LSD binding (P = 0.04) and significantly lower Bmax for platelet [3H]paroxetine binding (P = 0.016). There was a strong, multiple correlation between Bmax for [3H]LSD, as the dependent variable, and Km, Vmax and Bmax for [3H]paroxetine binding in patients (P < 0.0001) but not in controls. Responders to light therapy had significantly higher Km (P = 0.023) and significantly lower Bmax for [3H]paroxetine binding (P = 0.028) than non-responders. Bmax for [3H]paroxetine binding increased significantly to normal levels after light therapy. The results indicate that SAD is associated with aberrations in the serotonin uptake mechanism. The enhanced 5-HT2-receptor density may reflect a consequential up-regulation.

  2. Delayed sleep phase syndrome is related to seasonal affective disorder.

    Science.gov (United States)

    Lee, Heon-Jeong; Rex, Katharine M; Nievergelt, Caroline M; Kelsoe, John R; Kripke, Daniel F

    2011-10-01

    Both delayed sleep phase syndrome (DSPS) and seasonal affective disorder (SAD) may manifest similar delayed circadian phase problems. However, the relationships and co-morbidity between the two conditions have not been fully studied. The authors examined the comorbidity between DSPS and SAD. We recruited a case series of 327 DSPS and 331 controls with normal sleep, roughly matched for age, gender, and ancestry. Both DSPS and controls completed extensive questionnaires about sleep, the morningness-eveningness trait, depression, mania, seasonality of symptoms, etc. The prevalences of SAD and subsyndromal SAD (S-SAD) were higher in DSPS compared to controls (χ(2)=12.65, p=0.002). DSPS were 3.3 times more likely to report SAD (odds ratio, 3.34; 95% CI, 1.41-7.93) compared to controls as defined by the Seasonal Pattern Assessment Questionnaire (SPAQ). Correspondingly, DSPS showed significantly higher seasonality scores compared to controls in mood, appetite, and energy level subscores and the global seasonality score (t=3.12, t=0.002; t=2.04, p=0.041; t=2.64, p=0.008; and t=2.15, p=0.032, respectively). Weight fluctuation during seasons and winter-summer sleep length differences were also significantly higher in DSPS than controls (t=5.16, pseasonal subjects regardless of whether they were DSPS or controls. These cases suggested that DSPS is partially comorbid with SAD. These data support the hypothesis that DSPS and SAD may share a pathophysiological mechanism causing delayed circadian phase. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Cyclothymia reloaded: A reappraisal of the most misconceived affective disorder.

    Science.gov (United States)

    Perugi, Giulio; Hantouche, Elie; Vannucchi, Giulia; Pinto, Olavo

    2015-09-01

    Data emerging from both academic centers and from public and private outpatient facilities indicate that from 20% to 50% of all subjects that seek help for mood, anxiety, impulsive and addictive disorders turn out, after careful screening, to be affected by cyclothymia. The proportion of patients who can be classified as cyclothymic rises significantly if the diagnostic rules proposed by the DSM-5 are reconsidered and a broader approach is adopted. Unlike the DSM-5 definition based on the recurrence of low-grade hypomanic and depressive symptoms, cyclothymia is best identified as an exaggeration of cyclothymic temperament (basic mood and emotional instability) with early onset and extreme mood reactivity linked with interpersonal and separation sensitivity, frequent mixed features during depressive states, the dark side of hypomanic symptoms, multiple comorbidities, and a high risk of impulsive and suicidal behavior. Epidemiological and clinical research have shown the high prevalence of cyclothymia and the validity of the concept that it should be seen as a distinct form of bipolarity, not simply as a softer form. Misdiagnosis and consequent mistreatment are associated with a high risk of transforming cyclothymia into severe complex borderline-like bipolarity, especially with chronic and repetitive exposure to antidepressants and sedatives. The early detection and treatment of cyclothymia can guarantee a significant change in the long-term prognosis, when appropriate mood-stabilizing pharmacotherapy and specific psychological approaches and psychoeducation are adopted. The authors present and discuss clinical research in the field and their own expertise in the understanding and medical management of cyclothymia and its complex comorbidities. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Chronic sleep disturbance and neural injury: links to neurodegenerative disease.

    Science.gov (United States)

    Abbott, Sabra M; Videnovic, Aleksandar

    2016-01-01

    Sleep-wake disruption is frequently observed and often one of the earliest reported symptoms of many neurodegenerative disorders. This provides insight into the underlying pathophysiology of these disorders, as sleep-wake abnormalities are often accompanied by neurodegenerative or neurotransmitter changes. However, in addition to being a symptom of the underlying neurodegenerative condition, there is also emerging evidence that sleep disturbance itself may contribute to the development and facilitate the progression of several of these disorders. Due to its impact both as an early symptom and as a potential factor contributing to ongoing neurodegeneration, the sleep-wake cycle is an ideal target for further study for potential interventions not only to lessen the burden of these diseases but also to slow their progression. In this review, we will highlight the sleep phenotypes associated with some of the major neurodegenerative disorders, focusing on the circadian disruption associated with Alzheimer's disease, the rapid eye movement behavior disorder and sleep fragmentation associated with Parkinson's disease, and the insomnia and circadian dysregulation associated with Huntington's disease.

  5. Chronic sleep disturbance and neural injury: links to neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Abbott SM

    2016-01-01

    Full Text Available Sabra M Abbott,1 Aleksandar Videnovic21Department of Neurology, Northwestern Feinberg School of Medicine, Chicago, IL, USA; 2Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Abstract: Sleep–wake disruption is frequently observed and often one of the earliest reported symptoms of many neurodegenerative disorders. This provides insight into the underlying pathophysiology of these disorders, as sleep–wake abnormalities are often accompanied by neurodegenerative or neurotransmitter changes. However, in addition to being a symptom of the underlying neurodegenerative condition, there is also emerging evidence that sleep disturbance itself may contribute to the development and facilitate the progression of several of these disorders. Due to its impact both as an early symptom and as a potential factor contributing to ongoing neurodegeneration, the sleep–wake cycle is an ideal target for further study for potential interventions not only to lessen the burden of these diseases but also to slow their progression. In this review, we will highlight the sleep phenotypes associated with some of the major neurodegenerative disorders, focusing on the circadian disruption associated with Alzheimer’s disease, the rapid eye movement behavior disorder and sleep fragmentation associated with Parkinson’s disease, and the insomnia and circadian dysregulation associated with Huntington’s disease. Keywords: sleep, neurodegeneration, Alzheimer's disease, Parkinson's disease, Huntington's disease

  6. Major affective disorders in chronic obstructive pulmonary disease compared with other chronic respiratory diseases.

    Science.gov (United States)

    Pothirat, Chaicharn; Chaiwong, Warawut; Phetsuk, Nittaya; Pisalthanapuna, Sangnual; Chetsadaphan, Nonglak; Inchai, Juthamas

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) and other chronic respiratory diseases (CRDs) have significant impacts on quality of life including psychomotor domain. To evaluate three major affective disorders in subjects with COPD compared with other CRDs and nonill population. The Thai version of Mini International Neuropsychiatric Interview (MINI) was used as a diagnostic instrument for three major affective disorders (generalized anxiety disorder, major depressive disorder, and panic disorder) by face-to-face interview in assessing patients with CRDs [COPD, asthma, rhinasthma, all asthma (asthma and rhinasthma), and chronic rhinitis], and nonill subjects. Logistic regression analyses were used to determine the relation between major affective disorders and CRDs adjusting for age, sex, and disease severity. Major affective disorders were more prevalent in CRDs than nonill groups (adjusted OR =2.6 [95% CI, 1.8-3.9], Pdisorder (adjusted OR =4.0 [95% CI, 1.4-11.9], P=0.011, and 4.4 [95% CI, 1.1-18.1], P=0.038, respectively) but not major depressive disorder (adjusted OR =2.7 [95% CI, 0.8-9.0, P=0.105]) than nonill group. Comparing with all asthma, COPD patients had lower occurrence of major depressive and panic disorders (adjusted OR =0.1 [95% CI, 0.0-0.4], P=0.002, and 0.1 [95% CI, 0.0-0.9], P=0.043, respectively). There was no difference in major mood disorders in COPD, rhinasthma, and chronic rhinitis patients. Major affective disorders were not increased by disease severity in COPD. Major affective disorders were significantly higher in CRDs than nonill population. Generalized anxiety and panic disorders were significantly high in COPD patients. Moreover, major depressive and panic disorders in COPD were significantly lower than all asthma. The prevalence of major affective disorders may not be related to severity of COPD.

  7. Long-lasting effects of affective disorders and childhood trauma on dispositional optimism

    NARCIS (Netherlands)

    Broekhof, Rosalie; Rius-Ottenheim, Nathaly; Spinhoven, Philip; van der Mast, Roos C.; Penninx, Brenda W. J. H.; Zitman, Frans G.; Giltay, Erik J.

    2015-01-01

    Background: Dispositional optimism, a personality trait characterized by generalized positive expectations towards the future, is thought to remain rather stable over time. It is however largely unknown to what extent affective disorders and its risk factors affect dispositional optimism. Methods:

  8. Risk. Impact of having a first-degree relative with affective disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj

    2016-01-01

    : the high-risk group comprised twins at risk of developing affective disorder (DZ or MZ twin; index co-twin affected); the low risk group (control group) comprised twins at low risk of developing affective disorder (DZ or MZ twin; index co-twin not affected). At baseline 234 participants were divided...... enhanced risk and thus accelerate the onset of illness. Low-risk individuals seem to experience fewer life events and may exhibit resilience to their adverse psychological effects. Overall, having a 1st-degree relative with affective disorder matters. This thesis demonstrates that high-risk studies...

  9. Subclinical psychopathology and socio-economic status in unaffected twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Vinberg Christensen, Maj; Kyvik, Kirsten Ohm; Vedel Kessing, Lars

    2006-01-01

    .g.: a study of the healthy relatives of patients with affective disorders. AIM: To compare psychopathology and socio-economic status between twins with a co-twin history of affective disorder and twins without. METHODS: In a cross-sectional high-risk case-control study, healthy monozygotic and dizygotic twins...... to affective disorder seem to present lower socio-economic status, higher rates of subclinical affective symptoms and more often experience a minor psychiatric diagnosis than twins with no familial history of affective disorder. It is not possible from the present cross-sectional data to determine...... the causality of these findings, thus genetic liability to affective disorder, socio-economic status and minor psychopathology seem to have a complex interrelation....

  10. Melatonin and agomelatine for preventing seasonal affective disorder.

    Science.gov (United States)

    Kaminski-Hartenthaler, Angela; Nussbaumer, Barbara; Forneris, Catherine A; Morgan, Laura C; Gaynes, Bradley N; Sonis, Jeffrey H; Greenblatt, Amy; Wipplinger, Jörg; Lux, Linda J; Winkler, Dietmar; Van Noord, Megan G; Hofmann, Julia; Gartlehner, Gerald

    2015-11-11

    Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD in the United States ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on agomelatine and melatonin as preventive interventions. To assess the efficacy and safety of agomelatine and melatonin (in comparison with each other, placebo, second-generation antidepressants, light therapy, psychological therapy or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. We conducted a search of the Specialised Register of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDANCTR) to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We conducted a grey literature search (e.g. in clinical trial registries) and handsearched the reference lists of all included studies and pertinent review articles. To examine efficacy, we planned to include randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. To examine adverse events, we intended to include non-randomised studies. We planned to include studies that compared agomelatine versus melatonin, or agomelatine or melatonin versus placebo, any second-generation antidepressant (SGA), light therapy, psychological therapies or lifestyle

  11. DSM-III-R SCHIZOTYPAL PERSONALITY TRAITS IN OFFSPRING OF SCHIZOPHRENIC DISORDER, AFFECTIVE DISORDER, AND NORMAL CONTROL PARENTS

    Science.gov (United States)

    Squires-Wheeler, Elizabeth; Skodol, Andrew E.; Bassett, Anne; Erlenmeyer-Kimling, L.

    2011-01-01

    Summary The aggregation of disorder in families identified by a schizophrenic disorder proband (index case) has provided indirect clues to the question of diagnostic boundaries of schizophrenic spectrum categories. The Danish Adoption Studies provided quasi-experimental evidence for the range of expression of a putative schizophrenic spectrum disorder which was subsequently denoted schizotypal personality disorder (STPD) in DSM-III-R. It has been hypothesized that such schizophrenic spectrum categories bear a genetic relationship to schizophrenic disorder and thus are continuous with schizophrenia in terms of etiology and pathogenesis. For meaningful use of such spectrum categories in genetic analyses, e.g., linkage analysis, it is important that rates of spectrum traits and disorder in normal control and in psychiatric control populations are known. The rate of DSM-III-R schizotypal traits and disorder was assessed in three offspring groups (ages 18–29) defined by parental diagnoses, including schizophrenic disorder (N = 90), affective disorder (N = 79), and no parental disorder (N = 161). The assessment was conducted by trained social workers and psychologists by means of a direct interview (Personality Disorder Examination). The interviewers were blind to the parental status and to previous psychiatric assessments of these offspring. The rates of three, four and five schizotypal features were elevated in the offspring with parental psychiatric disorder in contrast to the offspring with no parental psychiatric disorder. However, the rates between the offspring of the schizophrenic disorder parental group and the offspring of the affective disorder parental group did not differ significantly, thus failing to support the assumption of diagnostic specificity. PMID:2635220

  12. Qui non proficit, deficit: experimental models for 'integrative' research of affective disorders.

    Science.gov (United States)

    LaPorte, Justin L; Egan, Rupert J; Hart, Peter C; Bergner, Carisa L; Cachat, Jonathan M; Canavello, Peter R; Kalueff, Allan V

    2010-02-01

    Experimental models are an important tool for the study of biological mechanisms of psychiatric disorders. Although encouraging progress has been made in biological psychiatry of affective disorders, there remain numerous methodological, conceptual, and translational challenges in this field. Mounting clinical data support the view that psychiatric disorders as spectra, rather than as discrete or isolated illnesses. This requires new theories as well as new animal paradigms for "integrative" modeling of psychiatric disorders and their spectra. Here we discuss recent "integrative" experimental models and concepts that promise to advance translational research of affective disorders. 2009 Elsevier B.V. All rights reserved.

  13. Chronotype and personality factors of predisposition to seasonal affective disorder.

    Science.gov (United States)

    Oginska, Halszka; Oginska-Bruchal, Katarzyna

    2014-05-01

    The study aimed to recognize the personality factors of a predisposition to seasonal mood fluctuations in a non-clinical sample. A group of 101 subjects (57 women, 44 men; mean age 26.4 ± 6.5 years) completed a battery of tests comprising a Seasonal Pattern Assessment Questionnaire (SPAQ), Chronotype Questionnaire (ChQ), a NEO-Five Factor Inventory and a Coping Inventory for Stressful Situations (CISS). A smaller sample (n = 44) completed a Winter Blues Scale (WBS). Women scored significantly higher than men in seasonality (p = 0.014), neuroticism (p = 0.049), agreeableness (p = 0.010), and avoidance-oriented coping style (p = 0.041). Subjects with seasonal affective disorder (SAD) (n = 41) or sub-SAD (n = 33), as diagnosed with SPAQ, exhibited higher levels of neuroticism (p = 0.017) and openness (p = 0.016) in comparison to non-SAD individuals. The latter declared a less frequent avoidance coping style. Both measures of seasonality, i.e. the SPAQ Global Seasonality Score and WBS, correlated significantly (r = 0.28 and 0.44, respectively) with the subjective amplitude of the circadian rhythm, as described with the "distinctness" scale of ChQ. Female gender, neuroticism and openness were confirmed as factors linked to seasonal mood variability. Additionally, the study revealed an association between susceptibility to mild winter depression and an avoidance-oriented coping style. The avoidance coping style was correlated positively with all the aspects of seasonality described by SPAQ (correlation coefficients from 0.21 to 0.34). Both sub-types of avoidance-oriented style, i.e. distraction and social diversion, were associated with marked subjective seasonal changes in sleep length, mood and the energy level. While the subjective amplitude of circadian rhythm proved to be connected with seasonality, the subjective acrophase of the rhythm (morningness-eveningness preference) did not. It may be hypothesized that sensitivity

  14. Disordered eating behavior and obsessive compulsive symptoms in college students: cognitive and affective similarities.

    Science.gov (United States)

    Humphreys, Joy D; Clopton, James R; Reich, Darcy A

    2007-01-01

    Few studies have examined the psychological similarities between disordered eating behavior and obsessive-compulsive (OC) symptoms. The present study examined relationships among disordered eating, OC symptoms, and three cognitive and affective variables (perfectionism, obsessive beliefs, and negative affect). The cognitive and affective variables were significantly associated with disordered eating and with OC symptoms in a sample of 160 college women. Results also indicated that perfectionism is an important link between disordered eating behavior and OC symptoms, although the nature of perfectionism differs somewhat for the two types of behavior. Implications of the current results and directions for future research are discussed.

  15. Impaired Neurocognitive Functions Affect Social Learning Processes in Oppositional Defiant Disorder and Conduct Disorder: Implications for Intervention

    NARCIS (Netherlands)

    Matthys, W.C.H.J.; Vanderschuren, L.J.M.J.; Schutter, D.J.L.G.; Lochman, J.E.

    2012-01-01

    In this review, a conceptualization of oppositional defiant (ODD) and conduct disorder (CD) is presented according to which social learning processes in these disorders are affected by neurocognitive dysfunctions. Neurobiological studies in ODD and CD suggest that the ability to make associations

  16. Female hormones affect symptom severity in obsessive-compulsive disorder

    NARCIS (Netherlands)

    Vulink, Nienke C. C.; Denys, Damiaan; Bus, Léonie; Westenberg, Herman G. M.

    2006-01-01

    There is circumstantial evidence that reproductive events can influence symptom severity of obsessive-compulsive disorder (OCD). We sent self-report questionnaires to 350 female outpatients with OCD to examine the relationship between the menstrual cycle, pregnancy, menopause, hormonal

  17. Reproductive Affective Disorders: a Review of the Genetic Evidence for Premenstrual Dysphoric Disorder and Postpartum Depression.

    Science.gov (United States)

    McEvoy, Katherine; Osborne, Lauren M; Nanavati, Julie; Payne, Jennifer L

    2017-10-30

    The purpose of this study is to review and summarize the literature exploring the genetic basis for premenstrual dysphoric disorder (PMDD) and postpartum depression (PPD). There is more evidence for a genetic basis for PPD than for PMDD, but only when PPD is defined as beginning in the immediate postpartum time period. Familial, genome-wide linkage and association studies, and candidate gene studies, most in the past 10 years, have examined the genetic etiology of reproductive affective disorders, including PMDD and PPD. The most commonly studied genes include SERT, COMT, MAOA, BDNF, and ESR1 and 2. This qualitative review of the recent literature finds limited evidence so far for the genetic basis for PMDD, with both familial and candidate gene studies having negative or conflicting results. Evidence is stronger for the genetic basis for PPD, with positive associations found in family studies and in several genes associated with major depression as well as genes involved in estrogen signaling but only when PPD onset is shortly after delivery. Epigenetic biomarkers on genes responsive to estrogen have also been found to predict PPD. Our findings underscore the need for additional studies with larger samples, as well as the crucial importance of timing in the definition of PPD for genetic studies.

  18. Deficits in Degraded Facial Affect Labeling in Schizophrenia and Borderline Personality Disorder

    NARCIS (Netherlands)

    van Dijke, Annemiek; van 't Wout, Mascha; Ford, Julian D.; Aleman, Andre

    2016-01-01

    Although deficits in facial affect processing have been reported in schizophrenia as well as in borderline personality disorder (BPD), these disorders have not yet been directly compared on facial affect labeling. Using degraded stimuli portraying neutral, angry, fearful and angry facial

  19. Reliability of clinical ICD-10 diagnoses among electroconvulsive therapy patients with chronic affective disorders

    DEFF Research Database (Denmark)

    Jakobsen, Klaus Damgaard; Hansen, Thomas Folkmann; Dam, Henrik

    2008-01-01

    Background and Objectives: Diagnostic reliability is of major concern both to clinicians and researchers. The aim has been to investigate the trustworthiness of clinical ICD-10 affective disorder diagnoses for research purpose. Methods: 150 ECT patients with chronic affective disorders were inves...

  20. Effect of affect on social cost bias in social anxiety disorder

    NARCIS (Netherlands)

    Bitran, S.; Hofmann, S.G.

    2010-01-01

    The cognitive model of social anxiety disorder (SAD) assumes that cognitive biases are important maintaining factors of the disorder. Research and theory have highlighted the impact of cognitive self-regulatory processes on affect, but have not sufficiently focused on the influence of affect on

  1. Variations in 5-HTTLPR: relation to familiar risk of affective disorder, life events, neuroticism and cortisol

    DEFF Research Database (Denmark)

    Vinberg, Maj; Mellerup, Erling; Andersen, Per Kragh

    2009-01-01

    BACKGROUND: Variations in the serotonin transporter gene (5-HTTLPR) and stressful life events are associated with affective disorders. AIM: To investigate whether the distribution of the alleles of the 5-HTTLPR is associated with a genetic predisposition to affective disorder and whether...

  2. Support for a bipolar affective disorder susceptibility locus on chromosome 12q24.3

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Foldager, Leslie; Zacharov, Tracey Flint

    2010-01-01

    Linkage and association studies of bipolar affective disorder (BAD) point out chromosome 12q24 as a region of interest.......Linkage and association studies of bipolar affective disorder (BAD) point out chromosome 12q24 as a region of interest....

  3. DNA triplex structures in neurodegenerative disorder, Friedreich's ...

    Indian Academy of Sciences (India)

    The unusual DNA structures like DNA-hairpin, cruciform, Z-DNA, triplex and tetraplex are represented as hotspots of chromosomal breaks, homologous recombination and gross chromosomal rearrangements since they are prone to the structural alterations. Friedreich's ataxia (FRDA), the autosomal recessive degenerative ...

  4. Diabetic retinopathy is a neurodegenerative disorder.

    Science.gov (United States)

    Lynch, Stephanie K; Abràmoff, Michael D

    2017-10-01

    Since 1875, controversy has ensued over whether ocular diabetic complications are primarily vasculopathic or neuropathic in nature. Here, we discuss the historical context by which diabetic retinopathy (DR) came to be considered a primary vasculopathy, in contrast to more recent data suggesting the importance of diabetic retinal neurodegeneration (DRN) as the primary manifestation of ocular diabetic damage. Unsurprisingly, DRN parallels other diabetic complications related to neuropathy. In general, there are three possible relationships between microvascular DR and DRN: i) microvasculopathy causes neurodegeneration; ii) neurodegeneration causes microvasculopathy or iii) they are mutually independent. The authors' group has recently produced experimental data showing that DRN precedes even the earliest manifestations of DR microvasculopathy. In combination with earlier studies showing that focal implicit time delays predicted future development of DR microvasculopathy in the same location, relationships i) and iii) are unlikely. As such, ii) is the most likely relationship: DRN is a cause of DR. Granted, additional studies are needed to confirm this hypothesis and elucidate the mechanism of diabetes-induced neurodegeneration. We conclude this review by proposing experimental approaches to test the hypothesis that DRN causes DR. If confirmed, this new paradigm may lead to earlier detection of ocular diabetic damage and earlier treatment of early DR, thereby preventing visual loss in people with diabetes. Published by Elsevier Ltd.

  5. NSAIDs and cardiovascular drugs in neurodegenerative and cerebrovascular diseases

    NARCIS (Netherlands)

    M.D.M. Haag (Mendel)

    2009-01-01

    textabstractNeurodegenerative and cerebrovascular diseases are frequent in elderly populations and comprise primarily of dementia (mainly Alzheimer disease (AD)), Parkinson disease (PD) and stroke. The prevalence of these neurological disorders rises with older age. From 55 years to 90 years and

  6. The dopamine D3 receptor gene: no association with bipolar affective disorder.

    OpenAIRE

    Shaikh, S; Ball, D; Craddock, N; Castle, D; Hunt, N; Mant, R; Owen, M; Collier, D; Gill, M

    1993-01-01

    Bipolar affective disorder and schizophrenia share many clinical and genetic characteristics, and are thought by some to be different expressions of the same underlying disorder. A recent study showed an excess of homozygosity at a BalI polymorphism in the dopamine D3 receptor gene in schizophrenic patients compared with controls, from two independent centres. We have found no evidence of such an excess in a comparable sample of patients with bipolar affective disorder compared with matched c...

  7. Childhood traumatization by primary caretaker and affect dysregulation in patients with borderline personality disorder and somatoform disorder

    Directory of Open Access Journals (Sweden)

    Annemiek van Dijke

    2011-03-01

    Full Text Available Affect regulation is often compromised as a result of early life interpersonal traumatization and disruption in caregiving relationships like in situations where the caretaker is emotionally, sexually or physically abusing the child. Prior studies suggest a clear relationship between early childhood attachment-related psychological trauma and affect dysregulation. We evaluated the relationship of retrospectively recalled childhood traumatization by primary caretaker(s (TPC and affect dysregulation in 472 adult psychiatric patients diagnosed with borderline personality disorder (BPD, somatoform disorder (SoD, both BPD and SoD, or disorders other than BPD or SoD, using the Bermond-Vorst Alexithymia Questionnaire, the self-report version of the Structured Interview for Disorders of Extreme Stress, the Self-rating Inventory for Posttraumatic Stress Disorder (SRIP and the Traumatic Experiences Checklist. Almost two-thirds of participants reported having experienced childhood TPC, ranging from approximately 50% of patients with SoD or other psychiatric disorders to more than 75% of patients with comorbid BPD + SoD. Underregulation of affect was associated with emotional TPC and TPC occurring in developmental epoch 0–6 years. Over-regulation of affect was associated with physical TPC. Childhood trauma by a primary caretaker is prevalent among psychiatric patients, particularly those with BPD, and differentially associated with underand over-regulation of affect depending on the type of traumatic exposure.For the abstract or full text in other languages, please see Supplementary files under Reading Tools online

  8. Neural systems supporting cognitive-affective interactions in adolescence: The role of puberty and implications for affective disorders

    Directory of Open Access Journals (Sweden)

    Cecile D. Ladouceur

    2012-08-01

    Full Text Available Evidence from longitudinal studies suggests that adolescence may represent a period of vulnerability that, in the context of adverse events, could contribute to developmental trajectories toward behavioral and emotional health problems, including affective disorders. Adolescence is also a sensitive period for the development of neural systems supporting cognitive-affective processes, which have been implicated in the pathophysiology of affective disorders such as anxiety and mood disorders. In particular, the onset of puberty brings about a cascade of physical, hormonal, psychological, and social changes that contribute in complex ways to the development of these systems. This article provides a brief overview of neuroimaging research pertaining to the development of cognitive-affective processes in adolescence. It also includes a brief review of evidence from animal and human neuroimaging studies suggesting that sex steroids influence the connectivity between prefrontal cortical and subcortical limbic regions in ways that contribute to increased reactivity to emotionally salient stimuli. We integrate these findings in the context of a developmental affective neuroscience framework suggesting that the impact of rising levels of sex steroids during puberty on fronto-limbic connectivity may be even greater in the context of protracted development of prefrontal cortical regions in adolescence. We conclude by discussing the implications of these findings for future research aimed at identifying neurodevelopmental markers of risk for future onset of affective disorders.

  9. Neuronal migration and its disorders affecting the CA3 region

    Directory of Open Access Journals (Sweden)

    Richard eBelvindrah

    2014-03-01

    Full Text Available In this review, we focus on CA3 neuronal migration disorders in the rodent. We begin by introducing the main steps of hippocampal development, and we summarize characteristic hippocampal malformations in human. We then describe various mouse mutants showing structural hippocampal defects. Notably, genes identified in human cortical neuronal migration disorders consistently give rise to a CA3 phenotype when mutated in the mouse. We successively describe their molecular, physiological and behavioral phenotypes that together contribute to a better understanding of CA3-dependent functions. We finally discuss potential factors underlying the CA3 vulnerability revealed by these mouse mutants and that may also contribute to other human neurological and psychiatric disorders.

  10. No association between serum cholesterol and death by suicide in patients with schizophrenia, bipolar affective disorder, or major depressive disorder.

    Science.gov (United States)

    Park, Subin; Yi, Ki Kyoung; Na, Riji; Lim, Ahyoung; Hong, Jin Pyo

    2013-12-05

    Previous research on serum total cholesterol and suicidality has yielded conflicting results. Several studies have reported a link between low serum total cholesterol and suicidality, whereas others have failed to replicate these findings, particularly in patients with major affective disorders. These discordant findings may reflect the fact that studies often do not distinguish between patients with bipolar and unipolar depression; moreover, definitions and classification schemes for suicide attempts in the literature vary widely. Subjects were patients with one of the three major psychiatric disorders commonly associated with suicide: schizophrenia, bipolar affective disorder, and major depressive disorder (MDD). We compared serum lipid levels in patients who died by suicide (82 schizophrenia, 23 bipolar affective disorder, and 67 MDD) and non-suicide controls (200 schizophrenia, 49 bipolar affective disorder, and 175 MDD). Serum lipid profiles did not differ between patients who died by suicide and control patients in any diagnostic group. Our results do not support the use of biological indicators such as serum total cholesterol to predict suicide risk among patients with a major psychiatric disorder.

  11. Diabulimia: how eating disorders can affect adolescents with diabetes.

    Science.gov (United States)

    Davidson, Jennifer

    2014-09-16

    Adherence to self-management and medication regimens is required to achieve optimal blood glucose control in adolescents with type 1 diabetes mellitus. Non-adherence places adolescents at serious risk of short and long-term health complications. Adherence difficulties may be exacerbated by concurrent eating disorders. Diabulimia is a term used to describe the deliberate administration of insufficient insulin to maintain glycaemic control for the purpose of causing weight loss. This article explores the concept of diabulimia and the compounding complications of an eating disorder on maintaining self-management regimens in adolescents with diabetes.

  12. Chronic sleep disturbance and neural injury: links to neurodegenerative disease

    OpenAIRE

    Abbott SM; Videnovic A

    2016-01-01

    Sabra M Abbott,1 Aleksandar Videnovic21Department of Neurology, Northwestern Feinberg School of Medicine, Chicago, IL, USA; 2Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Abstract: Sleep–wake disruption is frequently observed and often one of the earliest reported symptoms of many neurodegenerative disorders. This provides insight into the underlying pathophysiology of these disorders, as sleep–wake abnormalities are ofte...

  13. Second-generation antidepressants for seasonal affective disorder.

    Science.gov (United States)

    Thaler, Kylie; Delivuk, Marlene; Chapman, Andrea; Gaynes, Bradley N; Kaminski, Angela; Gartlehner, Gerald

    2011-12-07

    Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light therapy or psychotherapy. To assess the efficacy and safety of SGAs for the treatment of SAD in adults in comparison with placebo, light therapy, other SGAs or psychotherapy. We searched the Cochrane Depression, Anxiety and Neuorosis Review Group's specialised register (CCDANCTR) on the 26 August 2011. The CCDANCTR contains reports of relevant randomised controlled trials from The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). In addition, we searched pharmaceutical industry trials registers via the Internet to identify unpublished trial data. Furthermore, we searched OVID MEDLINE, MEDLINE In-process, EMBASE and PsycINFO to 27July 2011 for publications on adverse effects (including non-randomised studies). For efficacy we included randomised trials of SGAs compared with other SGAs, placebo, light therapy or psychotherapy in adult participants with SAD. For adverse effects we also included non-randomised studies. Two review authors screened abstracts and full-text publications against the inclusion criteria. Data abstraction and risk of bias assessment were conducted by one reviewer and checked for accuracy and completeness by a second. We pooled data for meta-analysis where the participant groups were similar and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment. For efficacy we included three randomised trials of between five and eight weeks duration with a total of 204 participants. For adverse effects we included two randomised trials and three observational (non-randomised) studies of five to eight weeks duration with a total of 225 participants. Overall, the randomised trials had low-to-moderate risk of bias, and the observational studies had

  14. Engineering enhanced protein disaggregases for neurodegenerative disease.

    Science.gov (United States)

    Jackrel, Meredith E; Shorter, James

    2015-01-01

    Protein misfolding and aggregation underpin several fatal neurodegenerative diseases, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). There are no treatments that directly antagonize the protein-misfolding events that cause these disorders. Agents that reverse protein misfolding and restore proteins to native form and function could simultaneously eliminate any deleterious loss-of-function or toxic gain-of-function caused by misfolded conformers. Moreover, a disruptive technology of this nature would eliminate self-templating conformers that spread pathology and catalyze formation of toxic, soluble oligomers. Here, we highlight our efforts to engineer Hsp104, a protein disaggregase from yeast, to more effectively disaggregate misfolded proteins connected with PD, ALS, and FTD. Remarkably subtle modifications of Hsp104 primary sequence yielded large gains in protective activity against deleterious α-synuclein, TDP-43, FUS, and TAF15 misfolding. Unusually, in many cases loss of amino acid identity at select positions in Hsp104 rather than specific mutation conferred a robust therapeutic gain-of-function. Nevertheless, the misfolding and toxicity of EWSR1, an RNA-binding protein with a prion-like domain linked to ALS and FTD, could not be buffered by potentiated Hsp104 variants, indicating that further amelioration of disaggregase activity or sharpening of substrate specificity is warranted. We suggest that neuroprotection is achievable for diverse neurodegenerative conditions via surprisingly subtle structural modifications of existing chaperones.

  15. Affective cognition and its disruption in mood disorders

    OpenAIRE

    Elliott, Rebecca; Zahn, Roland; Deakin, J. F. William; Anderson, Ian M.

    2011-01-01

    In this review, we consider affective cognition, responses to emotional stimuli occurring in the context of cognitive evaluation. In particular, we discuss emotion categorization, biasing of memory and attention, as well as social/moral emotion. We discuss limited neuropsychological evidence suggesting that affective cognition depends critically on the amygdala, ventromedial frontal cortex, and the connections between them. We then consider neuroimaging studies of affective cognition in healt...

  16. Comparison of psychopathological dimensions between major depressive disorder and schizophrenia spectrum disorders focusing on language, affectivity and motor behavior.

    Science.gov (United States)

    Steinau, Sarah; Stegmayer, Katharina; Lang, Fabian U; Jäger, Markus; Strik, Werner; Walther, Sebastian

    2017-04-01

    This study tested whether patients with major depressive disorder (MDD) and schizophrenia spectrum disorders would differ in three dimensions of psychopathology (language, affectivity and motor behavior) as assessed by the Bern Psychopathology Scale (BPS) in a cohort of 58 patients with MDD and 146 patients with schizophrenia spectrum disorders. The overall estimation of severity of each of the three dimensions was rated on a seven-point Likert scale from severely inhibited to severely disinhibited. Here, more than half of the patients endorsed ratings that showed normal or mildly (dis-)inhibited behavior. At group level more pronounced negative ratings of affect were seen in MDD. Group comparisons of the severity ratings on language or motor behavior yielded no differences between schizophrenia spectrum disorders and MDD. At the individuals' levels, extreme ratings in the language and motor dimensions were more frequent in schizophrenia spectrum disorders and in the affectivity dimension more frequent in MDD. Shared psychopathological features could be seen across diagnoses, supporting a dimensional approach to psychopathology in endogenous psychoses. However, the groups differ in the severity of affect ratings as well as in the distribution of language, affectivity and motor ratings with more variance among the group of schizophrenia spectrum disorders. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Social-affective behaviour in autistic disorder: description and psychoeducational intervention

    OpenAIRE

    López Gómez, Santiago; García, Consuelo

    2010-01-01

    Autistic disorder refers to a neuropsychological disorder with serious and heterogeneous manifestations that include three main areas of development, namely: social and affective alterations, alterations in the linguistic and communicative behaviour and the presence of behavioural patterns, interests or restricted and stereotyped activities. The failure that affects the maintenance and development of social and affective bonds, characterized by social isolation and the presence of inadequate ...

  18. Reward processing in neurodegenerative disease

    Science.gov (United States)

    Perry, David C.; Kramer, Joel H.

    2015-01-01

    Representation of reward value involves a distributed network including cortical and subcortical structures. Because neurodegenerative illnesses target specific anatomic networks that partially overlap with the reward circuit they would be predicted to have distinct impairments in reward processing. This review presents the existing evidence of reward processing changes in neurodegenerative diseases including mild cognitive impairment, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease, as well as in healthy aging. Carefully distinguishing the different aspects of reward processing (primary rewards, secondary rewards, reward-based learning, and reward-based decision-making) and using tasks that differentiate the stages of processing reward will lead to improved understanding of this fundamental process and clarify a contributing cause of behavioral change in these illnesses. PMID:24417286

  19. Factors affecting the management of substance use disorders ...

    African Journals Online (AJOL)

    Findings of the study highlighted the need for adequate substance abuse management facilities to be put in the state. More professionals, especially psychiatrists and ... to ensure greater effectiveness of interventions. Keywords: Substance use disorders, Nigeria, Bayelsa State, barriers to drug treatment, treatment policy ...

  20. Disorder affects judgements about a neighbourhood: police presence does not

    NARCIS (Netherlands)

    Hill, J.; Pollet, T.V.; Nettle, D.

    2014-01-01

    Many police forces operate a policy of high visibility in disordered neighbourhoods with high crime. However, little is known about whether increased police presence influences people's beliefs about a neighbourhood's social environment or their fear of crime. Three experimental studies compared

  1. Metal imaging in neurodegenerative diseases

    Science.gov (United States)

    Bourassa, Megan W.

    2014-01-01

    Metal ions are known to play an important role in many neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and prion diseases. In these diseases, aberrant metal binding or improper regulation of redox active metal ions can induce oxidative stress by producing cytotoxic reactive oxygen species (ROS). Altered metal homeostasis is also frequently seen in the diseased state. As a result, the imaging of metals in intact biological cells and tissues has been very important for understanding the role of metals in neurodegenerative diseases. A wide range of imaging techniques have been utilized, including X-ray fluorescence microscopy (XFM), particle induced X-ray emission (PIXE), energy dispersive X-ray spectroscopy (EDS), laser ablation inductively coupled mass spectrometry (LA-ICP-MS), and secondary ion mass spectrometry (SIMS), all of which allow for the imaging of metals in biological specimens with high spatial resolution and detection sensitivity. These techniques represent unique tools for advancing the understanding of the disease mechanisms and for identifying possible targets for developing treatments. In this review, we will highlight the advances in neurodegenerative disease research facilitated by metal imaging techniques. PMID:22797194

  2. Automatic processing of facial affects in patients with borderline personality disorder: associations with symptomatology and comorbid disorders.

    Science.gov (United States)

    Donges, Uta-Susan; Dukalski, Bibiana; Kersting, Anette; Suslow, Thomas

    2015-01-01

    Instability of affects and interpersonal relations are important features of borderline personality disorder (BPD). Interpersonal problems of individuals suffering from BPD might develop based on abnormalities in the processing of facial affects and high sensitivity to negative affective expressions. The aims of the present study were to examine automatic evaluative shifts and latencies as a function of masked facial affects in patients with BPD compared to healthy individuals. As BPD comorbidity rates for mental and personality disorders are high, we investigated also the relationships of affective processing characteristics with specific borderline symptoms and comorbidity. Twenty-nine women with BPD and 38 healthy women participated in the study. The majority of patients suffered from additional Axis I disorders and/or additional personality disorders. In the priming experiment, angry, happy, neutral, or no facial expression was briefly presented (for 33 ms) and masked by neutral faces that had to be evaluated. Evaluative decisions and response latencies were registered. Borderline-typical symptomatology was assessed with the Borderline Symptom List. In the total sample, valence-congruent evaluative shifts and delays of evaluative decision due to facial affect were observed. No between-group differences were obtained for evaluative decisions and latencies. The presence of comorbid anxiety disorders was found to be positively correlated with evaluative shifting owing to masked happy primes, regardless of baseline-neutral or no facial expression condition. The presence of comorbid depressive disorder, paranoid personality disorder, and symptoms of social isolation and self-aggression were significantly correlated with response delay due to masked angry faces, regardless of baseline. In the present affective priming study, no abnormalities in the automatic recognition and processing of facial affects were observed in BPD patients compared to healthy individuals

  3. [Influence of consanguinity on clinical characteristics and affective disorders frequency in relatives of bipolar I patients].

    Science.gov (United States)

    Mechri, Anwar; Rouissi, Khadija; Mehdi, Boutheina; Khiari, Geneviève; Abdelhak, Sonia; Gaha, Lotfi

    2007-11-01

    The genetic transmission of bipolar disorder remained undetermined up to now, partly due to clinical and genetically heterogeneity. In Tunisia, genetic study will profit from the existence of high rates of consanguinity. To determine the rate of consanguinity in bipolar I disorders sample and to compare the clinical characteristics and the frequency of affective disorders in first and second degree relatives of probands with and without consanguinity. One hundred thirty subjects met DSM-IV criteria for a bipolar I disorder were recruited. Available Information was obtained from a structured clinical interview, collateral history and medical records. The family investigation allowed completion of genealogies over three generations. The comparison was based on the clinical characteristics (age of onset, numbers of affective episodes, nature and severity of the last affective episode) and the frequency of affective disorders in first and second degree relatives of probands with and without consanguinity. the rate of consanguinity was estimated to 28,5% It was higher in patients with family history of affective disorders : 34,2% versus 20,4% (p=0,08). Bipolar I patients with consanguinity were characterised by a high frequency of affective episodes and a more severe of the last affective episode, but theses differences were not significantly. However, the frequency of affective disorders was significantly increased in first degree relatives of probands with consanguinity: 10,5% versus 6,1% (p=0,01), and in first and second degree relatives of probands with consanguinity : 4,5% versus 29% (p=0,02). The influence of consanguinity on the clinical characteristics and the frequency of affective disorders in first and second degree relatives of bipolar patients is en favour the recessive polygenetic transmission of bipolar disorders.

  4. Redox Imbalance and Viral Infections in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Dolores Limongi

    2016-01-01

    Full Text Available Reactive oxygen species (ROS are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson’s disease (PD, Alzheimer’s disease (AD, and amyotrophic lateral sclerosis (ALS.

  5. Stem Cells for the Treatment of Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    2010-09-01

    Full Text Available Neurodegenerative diseases are characterized by neurodegenerative changes or apoptosis of neurons involved in networks, leading to permanent paralysis and loss of sensation below the site of the injury. Cell replacement therapy has provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. In recent years, neurons and glial cells have successfully been generated from stem cells, and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. We review here notable previously published experimental and preclinical studies involving stem cell-based cell for neurodegenerative diseases and discuss the future prospects for stem cell therapy of neurological disorders in the clinical setting. Steady and solid progress in stem cell research in both basic and preclinical settings should support the hope for development of stem cell-based cell therapies for neurological diseases.

  6. The effect of erythropoietin on cognition in affective disorders

    DEFF Research Database (Denmark)

    Ott, Caroline Vintergaard; Vinberg, Maj; Kessing, Lars V

    2016-01-01

    This is a secondary data analysis from our erythropoietin (EPO) trials. We examine (I) whether EPO improves speed of complex cognitive processing across bipolar and unipolar disorder, (II) if objective and subjective baseline cognitive impairment increases patients׳ chances of treatment......-efficacy and (III) if cognitive improvement correlates with better subjective cognitive function, quality of life and socio-occupational capacity. Patients with unipolar or bipolar disorder were randomized to eight weekly EPO (N=40) or saline (N=39) infusions. Cognition, mood, quality of life and socio......-occupational capacity were assessed at baseline (week 1), after treatment completion (week 9) and at follow-up (week 14). We used repeated measures analysis of covariance to investigate the effect of EPO on speed of complex cognitive processing. With logistic regression, we examined whether baseline cognitive...

  7. Brain Mechanisms of Affective Language Comprehension in Autism Spectrum Disorders

    Science.gov (United States)

    2015-10-01

    with Asperger syndrome and conduct disorder. Journal of Child Psychology and Psychiatry and Allied Disciplines, 43(5), 679–690. doi:10.1111/1469...social brain” during fearful face-processing in Asperger Syndrome. Neuropsychologia, 45(1), 2–14. doi:10.1016/j.neuropsychologia.2006.04.014 202...Wheelwright, S. (2004). The empathy quotient: an investigation of adults with Asperger syndrome or high functioning autism, and normal sex

  8. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Antonio Paoli

    2014-01-01

    Full Text Available An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson’s disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review.

  9. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

    Science.gov (United States)

    Damiani, Ernesto; Bosco, Gerardo

    2014-01-01

    An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson's disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review. PMID:25101284

  10. Winter is coming: nightmares and sleep problems during seasonal affective disorder.

    Science.gov (United States)

    Sandman, Nils; Merikanto, Ilona; Määttänen, Hanna; Valli, Katja; Kronholm, Erkki; Laatikainen, Tiina; Partonen, Timo; Paunio, Tiina

    2016-10-01

    Sleep problems, especially nightmares and insomnia, often accompany depression. This study investigated how nightmares, symptoms of insomnia, chronotype and sleep duration associate with seasonal affective disorder, a special form of depression. Additionally, it was noted how latitude, a proxy for photoperiod, and characteristics of the place of residence affect the prevalence of seasonal affective disorder and sleep problems. To study these questions, data from FINRISK 2012 study were used. FINRISK 2012 consists of a random population sample of Finnish adults aged 25-74 years (n = 4905) collected during winter from Finnish urban and rural areas spanning the latitudes of 60°N to 66°N. The Seasonal Pattern Assessment Questionnaire was used to assess symptoms of seasonal affective disorder. Participants with symptoms of seasonal affective disorder had significantly increased odds of experiencing frequent nightmares and symptoms of insomnia, and they were more often evening chronotypes. Associations between latitude, population size and urbanicity with seasonal affective disorder symptoms and sleep disturbances were generally not significant, although participants living in areas bordering urban centres had less sleep problems than participants from other regions. These data show that the prevalence of seasonal affective disorder was not affected by latitude. © 2016 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

  11. Affect regulation and psychopathology in women with borderline personality disorder

    DEFF Research Database (Denmark)

    Andersen, Rune; Timmerby, Nina; Simonsen, Erik

    2012-01-01

    subjects (n = 29) who reported psychopathology and levels of affective instability, aggression, impulsivity and alexithymia by self-report measures. RESULTS: Our results demonstrated that women with BPD have significant psychopathology and report significantly higher levels of dysfunction in separate...

  12. Marital adjustment of patients with substance dependence, schizophrenia and bipolar affective disorder

    Directory of Open Access Journals (Sweden)

    Shital S Muke

    2014-01-01

    Full Text Available Background: Marital adjustment is considered as a part of social well-being. Disturbed marital relationship can directly affect the disease adjustment and the way they face disease outcomes and complications. It may adversely affect physical health, mental health, the quality-of-life and even economic status of individuals. Aim: The aim of this study was to compare the marital adjustment among patients with substance dependence, schizophrenia and bipolar affective disorder. Materials and Methods: The sample consisted of each 30 patients with substance dependence, bipolar affective disorder and schizophrenia, diagnosed as per international classification of diseases-10 diagnostic criteria for research with a minimum duration of illness of 1 year were evaluated using marital adjustment questionnaire. The data was analyzed using parametric and non-parametric statistics. Results: Prevalence of poor marital adjustment in patients with schizophrenia, bipolar affective disorder and substance dependence was 60%, 70% and 50% respectively. There was a significant difference on overall marital adjustment among substance dependence and bipolar affective disorder patients. There was no significant difference on overall marital adjustment among patients with substance dependence and schizophrenia as well as among patients with schizophrenia and bipolar affective disorder. On marital adjustment domains, schizophrenia patients had significantly poor sexual adjustment than substance dependence patients while bipolar affective disorder patients had significantly poor sexual and social adjustment compared with substance dependence patients. Conclusion: Patients with substance dependence have significant better overall marital adjustment compared with bipolar affective disorder patients. Patients with substance dependence have significantly better social and sexual adjustment than patients with bipolar affective disorder as well as significantly better sexual

  13. Factors Affecting the Risk of Mental Disorders in Patients With Bipolar Disorder in the West of Iran

    Directory of Open Access Journals (Sweden)

    Najafi Vosough

    2016-02-01

    Full Text Available Background Drug addiction, obsessive compulsive disorders (OCD, and other anxiety disorders are the disorders most commonly found in patients with bipolar disorder. Objectives The purpose of this study was to identify the factors affecting the risk of drug addiction, obsessive compulsive disorders, and other anxiety disorders in patients with bipolar disorder. Patients and Methods In this retrospective cohort study, the medical records of 400 patients with bipolar disorder hospitalized in Hamadan, Iran, between 2008 and 2014 were examined. Patient information, including demographic characteristics and comorbidity, was collected. A data analysis was performed using a separate logistic regression for each disorder. The statistical package used was STATA software version 11. A P-value of less than 0.05 was considered statistically significant. Results The mean (SD age of the patients with bipolar disorder was 34.62 (1.68 years. Of the 400 patients with bipolar disorder, 135 (33.75% patients had anxiety disorders, 67 (16.8% patients suffered from drug addiction, and 45 (11% patients had OCD. An association was established between drug addiction and OCD, and gender (P ≤ 0.05. The ORs of anxiety disorders, drug addiction, and OCD were 1.05 (95% CI = 0.65 - 1.68, 0.26 (95% CI = 0.10 - 0.63, and 2.33 (95% CI = 1.21 - 4.48 for women, and 0.92 (95% CI = 0.52 - 2.13, 3.01 (95% CI = 1.64 - 5.55, and 0.64 (95% CI = 0.25 - 1.62 for the patients who smoked, respectively. In addition, there was no significant association between the different disorders and age, marital status, history of relapse, and history of suicide. Conclusions The results showed that there was a greater risk of anxiety disorders with bipolar disorder than other disorders. While women with bipolar disorder were at higher risk of anxiety disorders and OCD, men were at greater risk of drug addiction.

  14. Transgenic nonhuman primates for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Chan Anthony WS

    2004-06-01

    Full Text Available Abstract Animal models that represent human diseases constitute an important tool in understanding the pathogenesis of the diseases, and in developing effective therapies. Neurodegenerative diseases are complex disorders involving neuropathologic and psychiatric alterations. Although transgenic and knock-in mouse models of Alzheimer's disease, (AD, Parkinson's disease (PD and Huntington's disease (HD have been created, limited representation in clinical aspects has been recognized and the rodent models lack true neurodegeneration. Chemical induction of HD and PD in nonhuman primates (NHP has been reported, however, the role of intrinsic genetic factors in the development of the diseases is indeterminable. Nonhuman primates closely parallel humans with regard to genetic, neuroanatomic, and cognitive/behavioral characteristics. Accordingly, the development of NHP models for neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Therefore, a transgenic NHP carrying a mutant gene similar to that of patients will help to clarify our understanding of disease onset and progression. Additionally, monitoring disease onset and development in the transgenic NHP by high resolution brain imaging technology such as MRI, and behavioral and cognitive testing can all be carried out simultaneously in the NHP but not in other animal models. Moreover, because of the similarity in motor repertoire between NHPs and humans, it will also be possible to compare the neurologic syndrome observed in the NHP model to that in patients. Understanding the correlation between genetic defects and physiologic changes (e.g. oxidative damage will lead to a better understanding of disease progression and the development of patient treatments, medications and preventive approaches for high risk individuals. The impact of the transgenic NHP model in understanding the role which

  15. Association between environmental exposure to pesticides and neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Parron, Tesifon [University of Almeria, Department of Neurosciences and Health Sciences, Almeria (Spain); Andalusian Council of Health at Almeria province, Almeria (Spain); Requena, Mar [Andalusian Council of Health at Almeria province, Almeria (Spain); Hernandez, Antonio F., E-mail: ajerez@ugr.es [University of Granada School of Medicine, Granada (Spain); Alarcon, Raquel [Andalusian Council of Health at Almeria province, Almeria (Spain)

    2011-11-15

    Preliminary studies have shown associations between chronic pesticide exposure in occupational settings and neurological disorders. However, data on the effects of long-term non-occupational exposures are too sparse to allow any conclusions. This study examines the influence of environmental pesticide exposure on a number of neuropsychiatric conditions and discusses their underlying pathologic mechanisms. An ecological study was conducted using averaged prevalence rates of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral degeneration, polyneuropathies, affective psychosis and suicide attempts in selected Andalusian health districts categorized into areas of high and low environmental pesticide exposure based on the number of hectares devoted to intensive agriculture and pesticide sales per capita. A total of 17,429 cases were collected from computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of having Alzheimer's disease, Parkinson's disease, multiple sclerosis and suicide were significantly higher in districts with greater pesticide use as compared to those with lower pesticide use. The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. In conclusion, this study supports and extends previous findings and provides an indication that environmental exposure to pesticides may affect the human health by increasing the incidence of certain neurological disorders at the level of the general population. -- Highlights: Black-Right-Pointing-Pointer Environmental exposure to pesticides and neurodegenerative-psychiatric disorders. Black-Right-Pointing-Pointer Increased risk for Alzheimer's disease and suicide attempts in high exposure areas. Black

  16. Predominant polarity and temperament in bipolar and unipolar affective disorders.

    Science.gov (United States)

    Mazzarini, Lorenzo; Pacchiarotti, Isabella; Colom, Francesc; Sani, Gabriele; Kotzalidis, Giorgio D; Rosa, Adriane R; Sanna, Livia; De Rossi, Pietro; Girardi, Nicoletta; Bonnin, C Mar; Sanchez-Moreno, Jose; Vazquez, Gustavo H; Gasto, Cristobal; Tatarelli, Roberto; Vieta, Eduard

    2009-12-01

    Recently, the concept of predominant polarity (two-thirds of episodes belonging to a single pole of the illness) has been introduced to further characterise subtypes of bipolar disorders. This concept has been proven to have diagnostic and therapeutic implications, but little is known on the underlying psychopathology and temperaments. With this study, we aimed to further validate the concept and explore its relationships with temperament. This study enrolled 143 patients with bipolar or unipolar disorder. We analysed predominant polarity in the sample of bipolar I patients (N=124), focussing on those who showed a clear predominance for one or the other polarity, and distinguishing manic/hypomanic (MP) from depressive polarity (DP), and a unipolar major depression (UP) group (N=19),. We also assessed temperament by means of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). Over 55% of the bipolar I sample fulfilled predominant polarity criteria, with two-thirds of those meeting criteria for MP and one third for DP. MP and DP were similar in scoring higher than UP on the hyperthymic/cyclothymic scales of the TEMPS-A; the UP group scored higher on the anxious/depressive scales. Our results show that both bipolar I MP and DP subgroups are temperamentally similar and different from UP. Depression in DP bipolar I patients should be viewed as the overlap of depression on a hyperthymic/cyclothymic temperament. These findings confirm the value of the predominant polarity concept as well as the importance of temperaments to separate bipolar from unipolar disorders.

  17. Religious convictions in patients with epilepsy-associated affective disorders

    DEFF Research Database (Denmark)

    Vaaler, Arne E; Kondziella, Daniel; Morken, Gunnar

    2015-01-01

    Patients with epilepsy often have different mood symptoms and behavioral trait characteristics compared to the non-epileptic population. In the present prospective study, we aimed to assess differences in behavioral trait characteristics between acutely admitted, psychiatric in-patients with epil......Patients with epilepsy often have different mood symptoms and behavioral trait characteristics compared to the non-epileptic population. In the present prospective study, we aimed to assess differences in behavioral trait characteristics between acutely admitted, psychiatric in...... characteristics at admission or in clinical history should alert the psychiatrist and lead to closer examination for a possible convulsive disorder....

  18. Personality and social cognition in neurodegenerative disease.

    Science.gov (United States)

    Shany-Ur, Tal; Rankin, Katherine P

    2011-12-01

    Neurodegenerative diseases often cause focal damage to brain structures mediating social cognition and personality, resulting in altered interpersonal communication and behavior. We review recent research describing this phenomenon in various aspects of social cognition. Corresponding to their pervasive socioemotional deficits, patients with frontotemporal dementia perform poorly on laboratory-based tasks including recognizing emotions, attending to salient information that guides social behavior, representing social knowledge, comprehending others' mental states, and maintaining insight to their own difficulties. Together with poor executive and regulation mechanisms, these social cognition deficits ultimately impact behavior. Patients with logopenic and nonfluent primary progressive aphasia have some deficits recognizing emotional prosody, whereas those with the semantic variant show more widespread deficits in social comprehension. Although Alzheimer's disease patients perform poorly on some social cognition tasks, this typically reflects general cognitive impairment, and their real-life social functioning is less affected than in diseases targeting frontotemporal structures. Studies in motor diseases such as Parkinson's suggest some degradation of emotion recognition and social comprehension, which should be investigated further. We summarize recent findings concerning perception and evaluation of socioemotional information, social knowledge storage and access, advanced information processing mechanisms, and behavioral response selection and regulation across various neurodegenerative diseases.

  19. Affective spectrum disorders and role of serotonergic system of the brain

    Directory of Open Access Journals (Sweden)

    Timotijević Ivana P.

    2014-01-01

    Full Text Available Affective spectrum disorders include mood and anxiety disorders, whereas the term functional somatic syndromes describes disorders in which the main symptom is chronic pain, with no pathognomonic tissue damage, such as fibromyalgia, irritable colon, tension headache. Pain as a symptom is often present in patients with depression and anxiety, and similarly, depressed mood, anxiety and other psychiatric symptoms are common in patients with functional somatic syndromes. This explains attitudes that affective disorders and functional somatic syndromes should be found along the same spectrum, due to a similar neurobiochemicalmehanism and dysfunction of these CNS structures and neurotransmitter systems, which lead to similar symptoms in both groups. The symptoms of affective disorders, including somatic are associated with serotonin and serotonergic transmission in the CNS. The existence of depressive and anxiety disorders, such as fatigue, sleep disorders, cognitive disorders, depressed mood, anxiety, and functional somatic syndromes code indicate a similar mechanism of origin. Hypothesis of central neuropathic pain explains the possibility of the descending inhibitory pain mechanisms, including serotonergic and noradrenergic projections and their receptors. Central suprasegmental senzitization in nociceptive pathways, also at the level of the thalamus and the sensory cortex, trigered by an emotional stressors can cause painful symptoms in both groups of disorders. Serotonergic and noradrenergic pathways and voltage sensitive channels of their receptors are included in the mechanism. Modern psychopharmacology can no longer ignore the existence of painful symptoms in affective disorder or depressive and anxiety symptoms in functional somatic syndromes and their treatment can improve. Therapeutic effects of SSRI and SNRI antidepressants and alpha 2 delta ligands for all kinds of painful symptoms in affective disorders - serotonergic spectrum is

  20. Effects of childhood trauma on working memory in affective and non-affective psychotic disorders.

    Science.gov (United States)

    Quidé, Yann; O'Reilly, Nicole; Rowland, Jesseca E; Carr, Vaughan J; Elzinga, Bernet M; Green, Melissa J

    2017-06-01

    Childhood trauma is a significant risk factor for the development of psychotic disorders, and may influence executive brain functions. We thus set out to investigate the long-term effects of childhood trauma exposure on brain function of adult chronic patients diagnosed with schizophrenia, schizoaffective disorder and (psychotic) bipolar-I disorder while performing a standard 2/0-back working memory task. Participants were 50 cases diagnosed with schizophrenia/schizoaffective disorder (SCZ), 42 cases with bipolar-I disorder (BD), and 47 healthy controls (HC). Among this sample, 56 clinical cases (SCZ = 32; BD = 24) and 17 HC reported significant levels of childhood trauma, while 36 clinical cases (SCZ = 18; BD = 18) and 30 HC did not. Effects of childhood trauma on working memory-related brain activation were examined in combined samples of clinical cases (independently of diagnosis) relative to HCs, as well as within each diagnostic category. Case-control analyses revealed increased activation of the left inferior parietal lobule as a main effect of trauma exposure. In addition, trauma exposure interacted with a diagnosis of SCZ or BD to reveal trauma-related increased activation in the cuneus in clinical cases and decreased activation in this region in controls. Disorder-specific functional alterations were also evident in the SCZ sample, but not BD. Childhood trauma exposure elicits aberrant function of parietal regions involved in working memory performance regardless of clinical status, as well as task-relevant visual regions that participates to attentional processes. Childhood trauma may therefore contribute to alterations in attention in SCZ and BD while performing an n-back working memory task.

  1. Social adjustment based on reported behaviour in bipolar affective disorder.

    Science.gov (United States)

    Morriss, Richard; Scott, Jan; Paykel, Eugene; Bentall, Richard; Hayhurst, Hazel; Johnson, Tony

    2007-01-01

    To determine the effects of mood and additional clinical variables on different domains of current interviewer-rated social adjustment reflecting the reported behaviour of patients with bipolar disorder (BD). Multi-center cross-sectional study employing multiple linear regression to investigate whether mood and other clinical features, previously linked to self-rated social adjustment, were associated with eight domains of interviewer-rated social adjustment in 253 BD patients. Baseline variables were entered sequentially in blocks representing current mood, demographic, current other psychiatric, past psychiatric and current treatment variables. Mood episode or symptoms together with five other variables (borderline/antisocial personality disorder, male gender, living alone, hypnotic drug and drugs for physical illness) were associated with impairment on two or more domains of interviewer-rated social adjustment. They explained up to 31% of the variance in social adjustment, although friction, dependence and overactivity were associated with a different pattern of variables. Hypomanic symptoms were associated with increased friction and worse social adjustment with the extended family in the whole sample but improved performance and social and leisure activities in patients who were not in acute bipolar episode. Clinicians may determine up to about 30% of outcome in current social adjustment in BD patients from the patient's current mood episode or symptoms and a small number of other clinical or demographic variables. Hypomanic episodes and symptoms usually worsen friction and overall social adjustment, but in patients who are not in acute episode, hypomanic symptoms can increase performance and social and leisure activities.

  2. Genetic studies in narcolepsy, a disorder affecting REM sleep.

    Science.gov (United States)

    Faraco, J; Lin, X; Li, R; Hinton, L; Lin, L; Mignot, E

    1999-01-01

    Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal manifestations of rapid eye movement (REM) sleep including cataplexy, sleep paralysis, and hypnagogic hallucinations. It is known to be a complex disorder, with both genetic predisposition and environmental factors playing a role. In humans, susceptibility to narcolepsy is tightly associated with a specific HLA allele, DQB1*0602. In humans and canines, most cases are sporadic. In Doberman pinschers and Labrador retrievers, however, the disease is transmitted as an autosomal recessive gene canarc-1 with full penetrance. This gene is not linked with the dog leukocyte antigen complex, but is tightly linked with a marker with high homology to the human mu-switch immunoglobulin gene. We have isolated several genomic clones encompassing the canarc-1 marker and the variable heavy chain immunoglobulin region in canines. These have been partially sequenced and have been mapped onto specific dog chromosomes by fluorescence in situ hybridization (FISH). Our results indicate that the mu-switch-like marker is not part of the canine immunoglobulin machinery. We are continuing to extend the genomic contig using a newly developed canine BAC library and attempting to identify the corresponding human region of conserved synteny.

  3. Imprinting Disorders: Non-Mendelian Mechanisms Affecting Growth

    Science.gov (United States)

    Butler, Merlin G.

    2016-01-01

    Most autosomal genes are expressed from both maternal and paternal alleles. However, imprinted genes are an example of non-Mendelian genetics, in which only one member of the gene pair is expressed and expression is determined by the parent of origin. Imprinted genes may account for 0.1–1% of all mammalian genes. At least 50 imprinted genes have been identified in humans, and imprinted genes frequently cluster under the control of an imprinting center. Many imprinted genes contribute to growth, either as growth factors, such as insulin-like growth factors (IGF2 in Beckwith-Wiedemann syndrome), or as growth inhibitors, such as the GRB10 gene in Russell-Silver syndrome. Imprinted genes have evolved over time in mammals to fine-tune the growth of the fetus. Paternally expressed genes generally enhance growth, whereas maternally expressed genes appear to suppress growth. In addition, normal and abnormal genomic imprinting and loss of heterozygosity contribute to a wide range of malignancies. A common process for controlling gene activity is methylation, which can be changed during male or female gametogenesis. Examples of classic human disorders related to genomic imprinting are Beckwith-Wiedemann syndrome (chromosome 11), Prader-Willi/Angelman syndromes (chromosome 15), Russell-Silver syndrome (chromosome 7), and Albright hereditary osteodystrophy (chromosome 20). Several of these disorders are discussed and illustrated. PMID:12510981

  4. Profile and Correlates of Disability Among Bipolar Affective Disorder ...

    African Journals Online (AJOL)

    Background: Individuals with Bipolar Affective Disordere unpredictable. This study is aimed at investigating the profile of disability among individuals with BAD and the associated factors. Methods: A total of one hundred consecutively enrolled study participants, made up of adult outpatients with BAD attending a Lagos ...

  5. Can Psychological, Social and Demographical Factors Predict Clinical Characteristics Symptomatology of Bipolar Affective Disorder and Schizophrenia?

    Science.gov (United States)

    Maciukiewicz, Malgorzata; Pawlak, Joanna; Kapelski, Pawel; Łabędzka, Magdalena; Skibinska, Maria; Zaremba, Dorota; Leszczynska-Rodziewicz, Anna; Dmitrzak-Weglarz, Monika; Hauser, Joanna

    2016-09-01

    Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5-1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder.

  6. Negative Affect Shares Genetic and Environmental Influences with Symptoms of Childhood Internalizing and Externalizing Disorders

    Science.gov (United States)

    Mikolajewski, Amy J.; Allan, Nicholas P.; Hart, Sara A.; Lonigan, Christopher J.; Taylor, Jeanette

    2013-01-01

    The co-occurrence of internalizing and externalizing disorders suggests that they may have common underlying vulnerability factors. Research has shown that negative affect is moderately positively correlated with both internalizing and externalizing disorders in children. The present study is the first to provide an examination of negative affect…

  7. Comparing a Cognitive Model and Phototherapy in the Treatment of Seasonal Affective Disorder.

    Science.gov (United States)

    Krantz, Sandra

    Seasonal affective disorder (SAD) is characterized by recurrent major depression or bipolar disorder that occurs annually, usually later in fall as the daylight hours decrease, and that alternates with euthymic or hypomanic moods in the spring and summer. Pioneering research by Dr. Norman Rosenthal and associates has found phototherapy to be…

  8. Delusion of pregnancy in a patient with bipolar affective disorder: A ...

    African Journals Online (AJOL)

    ... seen in a patient with bipolar affective disorder. Early diagnosis and treatment of delusions of pregnancy are important in order to prevent the attendant psychological and social consequences as evident in this case report. Attention of clinicians was drawn to this disorder that was once thought to be rare in this society.

  9. Associations Between Self-Report of Emotional State and the EEG Patterns in Affective Disorders Patients

    NARCIS (Netherlands)

    Wyczesany, M.; Kaiser, J.; Coenen, A.M.L.

    2010-01-01

    The study determines the associations between self-report of ongoing emotional state and EEG patterns. A group of 31 hospitalized patients were enrolled with three types of diagnosis: major depressive disorder, manic episode of bipolar affective disorder, and nonaffective patients. The Thayer ADACL

  10. Impairment of executive function and attention predicts onset of affective disorder in healthy high-risk twins

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla W; Kessing, Lars Vedel

    2013-01-01

    To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk.......To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk....

  11. The temperament and character traits in patients with major depressive disorder and bipolar affective disorder with and without suicide attempt.

    Science.gov (United States)

    Erić, Anamarija Petek; Erić, Ivan; Ćurković, Mario; Dodig-Ćurković, Katarina; Kralik, Kristina; Kovač, Vlatka; Filaković, Pavo

    2017-06-01

    Suicide and mood disorders (especially major depressive disorder (MDD) and bipolar affective disorder (BD)) represent a significant global health burden. Major depressive disorder and bipolar affective disorder have been associated with increased risk for suicide. Some specific suicide risk factors might be found in underlying individual personality traits. Specific personality features may predispose an individual to mood disorders (MDD or BD) hence increased suicide risk. The specificity of this research is in the assessment of personality features during the acute phase of illness immediately after suicide attempt which resulted in psychiatric inpatient treatment. The study included 119 unrelated Caucasian participants with MDD-severe depressive episode without psychotic symptoms (MDD) and BD-severe depressive episode without psychotic symptoms (BD-sDE). Both groups of patients with MDD and BD-sDE were divided into the suicide attempters and non-suicidal group. The diagnoses of the severe depressive episode without psychotic symptoms in major depressive disorder (MDD; F32.2) and bipolar disorder (BD-sDE; F31.4) were made according to ICD-10 (WHO 1992) diagnostic criteria. Methods of suicide attempts were also assessed according to ICD-10 and a self-report questionnaire, the Temperament and Character Inventory (TCI) was applied. The participants who exhibited suicide attempt had significantly higher scores on harm-avoidance (HA) (psuicidal attempt had significantly lower scores on self-directedness (SD) (psuicide attempt may have some significantly different personality traits than non-suicidal patients with mood disorders. The combination of high harm-avoidance (HA) and low self-directedness (SD) may be specific for depressive episode while the combination of high HA, novelty-seeking (NS), and self-transcendence (ST) with low SD may be related to suicide attempts during the depressive episode in bipolar disorder. The novelty-seeking (NS), self-transcendence (ST

  12. Cognition in schizophrenia and schizo-affective disorder: impairments that are more similar than different

    Science.gov (United States)

    Owoso, A.; Carter, C. S.; Gold, J.M.; MacDonald, A.W.; Ragland, J.D.; Silverstein, S.M.; Strauss, M. E.; Barch, D. M.

    2014-01-01

    Background Cognition is increasingly being recognized as an important aspect of psychotic disorders and a key contributor to functional outcome. In the past, comparative studies have been performed in schizophrenia and schizo-affective disorder with regard to cognitive performance, but the results have been mixed and the cognitive measures used have not always assessed the cognitive deficits found to be specific to psychosis. A set of optimized cognitive paradigms designed by the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) Consortium to assess deficits specific to schizophrenia was used to measure cognition in a large group of individuals with schizophrenia and schizo-affective disorder. Method A total of 519 participants (188 with schizophrenia, 63 with schizo-affective disorder and 268 controls) were administered three cognitive paradigms assessing the domains of goal maintenance in working memory, relational encoding and retrieval in episodic memory and visual integration. Results Across the three domains, the results showed no major quantitative differences between patient groups, with both groups uniformly performing worse than healthy subjects. Conclusions The findings of this study suggests that, with regard to deficits in cognition, considered a major aspect of psychotic disorder, schizophrenia and schizo-affective disorder do not demonstrate major significant distinctions. These results have important implications for our understanding of the nosological structure of major psychopathology, providing evidence consistent with the hypothesis that there is no natural distinction between cognitive functioning in schizophrenia and schizo-affective disorder. PMID:23522057

  13. Autonomous motivation is associated with the maintenance stage of behaviour change in people with affective disorders.

    Science.gov (United States)

    Vancampfort, Davy; Moens, Herman; Madou, Tomas; De Backer, Tanja; Vallons, Veerle; Bruyninx, Peter; Vanheuverzwijn, Sarah; Mota, Cindy Teixeira; Soundy, Andy; Probst, Michel

    2016-06-30

    The present study examined whether in people with affective disorders motives for adopting and maintaining physical activity recommendations (as formulated by the self-determination theory) differed across the stages of behaviour change (identified by the transtheoretical model). A total of 165 (105♀) persons (45.6±14.2years) with affective disorders [major depressive disorder (n=96) or bipolar disorder (n=69)] completed the Behavioural Regulation in Exercise Questionnaire-2 and the Patient-centred Assessment and Counselling for Exercise questionnaire. Discriminant and multivariate analyses demonstrated that persons with affective disorders at the early stages of change have less autonomous and more controlled physical activity motives than those at the later stages. Our results suggest that autonomous motivation may have an important role to play in the maintenance of health recommendations in persons with affective disorders. Longitudinal and intervention studies should be designed in people with affective disorders to identify the causal pathways between motives for maintaining health recommendations, effective changes in health behaviour and physical and mental health outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Early parental death and risk of hospitalization for affective disorder in adulthood

    DEFF Research Database (Denmark)

    Appel, Charlotte Welling; Johansen, Christoffer; Deltour, Isabelle

    2013-01-01

    Early parental death is one of the most stressful childhood life events and may influence subsequent psychological health. We investigated the association between early parental loss and risk of hospitalization for an affective disorder in adulthood.......Early parental death is one of the most stressful childhood life events and may influence subsequent psychological health. We investigated the association between early parental loss and risk of hospitalization for an affective disorder in adulthood....

  15. Binder phenotype in mothers affected with autoimmune disorders.

    Science.gov (United States)

    Colin, E; Touraine, R; Levaillant, J M; Pasquier, L; Boussion, F; Ferry, M; Guichet, A; Barth, M; Mercier, A; Gérard-Blanluet, M; Odent, S; Bonneau, D

    2012-08-01

    To report four foetal cases of the Binder phenotype associated with maternal autoimmune disorders. In three mothers with autoimmune diseases, 2D and 3D ultrasonographic measurements were made on four foetuses with the Binder profile, and were compared with postnatal phenotypes. The Binder phenotype can be detected in early pregnancy (14.5 WG). All foetuses had verticalized nasal bones and midfacial hypoplasia. Punctuate calcifications were found in almost all the cases. No specific maternal auto-antibody has been associated with foetal Binder phenotype. Since the Binder phenotype can be diagnosed at ultrasound examination during pregnancy, it is important to establish the underlying cause so as to assess the foetal prognosis. This study stresses the importance of systematic checks for maternal autoimmune disease in cases of prenatally diagnosed Binder phenotypes.

  16. Dandy-Walker variant associated with bipolar affective disorder.

    Science.gov (United States)

    Lingeswaran, Anand; Barathi, Deepak; Sharma, Gyaneswahr

    2009-07-01

    The Dandy-Walker malformation is a congenital brain malformation, typically involving the fourth ventricle and the cerebellum. To date, the Dandy-Walker syndrome has not been described in association with bipolar disorder type I mania, and therefore we briefly report the case of a Dandy-Walker variant associated with acute mania. A 10-year-old boy was brought by his mother to the outpatient clinic of the Department of Psychiatry of a tertiary care hospital, with symptoms of mania. The MRI brain of the patient showed a posterior fossa cystic lesion, a giant cisterna magna communicating with the fourth ventricle and mild hypoplasia of the cerebellar vermis, with the rest of the structures being normal and no signs of hydrocephalus. These findings showed that the patient had a Dandy-Walker variant. He responded partially to valproate and olanzepine, which controlled the acute manic symptoms in the ward.

  17. The relationship between activating affects, inhibitory affects, and self-compassion in patients with Cluster C personality disorders.

    Science.gov (United States)

    Schanche, Elisabeth; Stiles, Tore C; McCullough, Leigh; Svartberg, Martin; Nielsen, Geir Høstmark

    2011-09-01

    In the short-term dynamic psychotherapy model termed "Affect Phobia Treatment," it is assumed that increase in patients' defense recognition, decrease in inhibitory affects (e.g., anxiety, shame, guilt), and increase in the experience of activating affects (e.g., sadness, anger, closeness) are related to enhanced self-compassion across therapeutic approaches. The present study aimed to test this assumption on the basis of data from a randomized controlled trial, which compared a 40-session short-term dynamic psychotherapy (N = 25) with 40-session cognitive treatment (N = 25) for outpatients with Cluster C personality disorders. Patients' defense recognition, inhibitory affects, activating affects, and self-compassion were rated with the Achievement of Therapeutic Objectives Scale (McCullough et al., 2003b) in Sessions 6 and 36. Results showed that increase in self-compassion from early to late in therapy significantly predicted pre- to post-decrease in psychiatric symptoms, interpersonal problems, and personality pathology. Decrease in levels of inhibitory affects and increase in levels of activating affects during therapy were significantly associated with higher self-compassion toward the end of treatment. Increased levels of defense recognition did not predict higher self-compassion when changes in inhibitory and activating affects were statistically controlled for. There were no significant interaction effects with type of treatment. These findings support self-compassion as an important goal of psychotherapy and indicate that increase in the experience of activating affects and decrease in inhibitory affects seem to be worthwhile therapeutic targets when working to enhance self-compassion in patients with Cluster C personality disorders. (c) 2011 APA, all rights reserved.

  18. Online social networking addiction among college students in Singapore: Comorbidity with behavioral addiction and affective disorder.

    Science.gov (United States)

    Tang, Catherine So-Kum; Koh, Yvaine Yee Woen

    2017-02-01

    This study aimed to determine the prevalence of addiction to social networking sites/platforms (SNS) and its comorbidity with other behavioral addiction and affective disorder among college students in Singapore. 1110 college students (age: M=21.46, SD=1.80) in Singapore completed measures assessing online social networking, unhealthy food intake and shopping addiction as well as depression, anxiety and mania. Descriptive analyses were conducted to investigate the prevalence and comorbidity of behavioral addiction and affective disorder. Chi-square tests were used to examine gender differences. The prevalence rates of SNS, food and shopping addiction were 29.5%, 4.7% and 9.3% respectively for the total sample. SNS addiction was found to co-occur with food addiction (3%), shopping addiction (5%), and both food and shopping addiction (1%). The comorbidity rates of SNS addiction and affective disorder were 21% for depression, 27.7% for anxiety, and 26.1% for mania. Compared with the total sample, students with SNS addiction reported higher comorbidity rates with other behavioral addiction and affective disorder. In general, females as compared to males reported higher comorbidity rates of SNS addiction and affective disorder. SNS addiction has a high prevalence rate among college students in Singapore. Students with SNS addiction were vulnerable to experience other behavior addiction as well as affective disorder, especially among females. Copyright © 2016. Published by Elsevier B.V.

  19. Behavioral family treatment for patients with bipolar affective disorder.

    Science.gov (United States)

    Miklowitz, D J; Goldstein, M J

    1990-10-01

    Techniques of behavioral family management (BFM), which have been found to be highly effective in delaying relapse for schizophrenic patients when used as adjuncts to medication maintenance, are also applicable in the outpatient treatment of recently hospitalized bipolar, manic patients. The authors describe their adaptation of the educational, communication skills training, and problem-solving skills training modules of BFM to families containing a bipolar member. The observations that families of bipolar patients are often high functioning, and that these families seem to enjoy interchanges that are highly affective and spontaneous, led to certain modifications in the original BFM approach. The authors found it necessary to be (a) more flexible and less didactic, (b) more oriented toward dealing with affect and resistance to change, and (c) more focused on the patient's and family members' feelings about labeling, stigmatization, and medication usage. Research issues relevant to testing the efficacy of this approach are also discussed.

  20. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases.

    Science.gov (United States)

    Vanni, Silvia; Zattoni, Marco; Moda, Fabio; Giaccone, Giorgio; Tagliavini, Fabrizio; Haïk, Stéphane; Deslys, Jean-Philippe; Zanusso, Gianluigi; Ironside, James W; Carmona, Margarita; Ferrer, Isidre; Kovacs, Gabor G; Legname, Giuseppe

    2018-01-01

    Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively) and in different genetic forms of prion diseases (gPrD) in comparison to Alzheimer's disease (AD) subjects and age-matched controls. Methods: Total RNA was obtained from the frontal cortex of vCJD ( n = 20), iCJD ( n = 11), sCJD ( n = 23), gPrD ( n = 30), and AD ( n = 14) patients and age-matched controls ( n = 30). RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis. Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level. Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue)-together with specific molecular and conformational features of the pathological agent of the disease-seem to dictate the peculiar hemoglobin

  1. Perspectives on Individual Differences Affecting Therapeutic Change in Communication Disorders. New Directions in Communication Disorders Research

    Science.gov (United States)

    Weiss, Amy L., Ed.

    2009-01-01

    This volume examines the ramifications of individual differences in therapy outcomes for a wide variety of communication disorders. In an era where evidence-based practice is the clinical profession's watchword, each chapter attacks this highly relevant issue from a somewhat different perspective. In some areas of communication disorders,…

  2. [Psychiatric disorders in intensive care--part three: psychic reactions, affective and anxiety disorders].

    Science.gov (United States)

    Krauseneck, Till; Krähenmann, Olivia; Heimendahl, Jenny von; Schelling, Gustav; Padberg, Frank

    2007-03-01

    Perpetual noise, pain, disturbed day-night-cycle, the inability to talk and the difficulty, especially during weaning, to differentiate alertness from sleep and dream from reality are some of the burdens ICU patients are suffering from. Additional sedation and potential sedation gaps plus the medical treatment itself put strain on critically ill humans. Those external stimuli partly cannot be handled well by the patients. Some of these factors or a combination of them, combined with a predisposition and/or insufficient coping mechanisms can result in a wide range of psychiatric disorders. Often psychiatric symptoms appear unspecific and difficult to categorize. Firstly some psychopathological cardinal symptoms are described and potential differential diagnoses are mentioned. After that the following article focuses on sleep, adjustment, depressive and the spectrum of anxiety disorders (especially generalized anxiety disorders, panic disorders, acute stress disorder (ASD) and posttraumatic stress disorder (PTSD)). The article provides prevalences, etiology and risk factors as well as symptomatology, diagnostics and therapeutic options. Those disorders can be diagnosed in ICU but also after transferring to general ward. In our own experience the transfer period is a vulnerable phase for psychopathologic symptoms. As apart from the individual suffering the course of the somatic disease as well as the rehabilitation process are impaired and the disorders have a tendency to have a chronic course, close and early collaboration of ICU physicians and psychiatrists is mandatory.

  3. Apocynin, a Low Molecular Oral Treatment for Neurodegenerative Disease

    Directory of Open Access Journals (Sweden)

    Bert A. ‘t Hart

    2014-01-01

    Full Text Available Accumulating evidence suggests that inflammatory mediators secreted by activated resident or infiltrated innate immune cells have a significant impact on the pathogenesis of neurodegenerative diseases. This may imply that patients affected by a neurodegenerative disease may benefit from treatment with selective inhibitors of innate immune activity. Here we review the therapeutic potential of apocynin, an essentially nontoxic phenolic compound isolated from the medicinal plant Jatropha multifida. Apocynin is a selective inhibitor of the phagocyte NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low dose.

  4. Chameleon sequences in neurodegenerative diseases.

    Science.gov (United States)

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Salari, Ali

    2016-03-25

    Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to "helix to strand (HE)", "helix to coil (HC)" and "strand to coil (CE)" alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Chameleon sequences in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Bahramali, Golnaz [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Goliaei, Bahram, E-mail: goliaei@ut.ac.ir [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Minuchehr, Zarrin, E-mail: minuchehr@nigeb.ac.ir [Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology, (NIGEB), Tehran (Iran, Islamic Republic of); Salari, Ali [Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology, (NIGEB), Tehran (Iran, Islamic Republic of)

    2016-03-25

    Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to “helix to strand (HE)”, “helix to coil (HC)” and “strand to coil (CE)” alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

  6. Tau imaging in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Dani, M.; Edison, P. [Imperial College London, Neurology Imaging Unit, Division of Neuroscience, London (United Kingdom); Brooks, D.J. [Imperial College London, Neurology Imaging Unit, Division of Neuroscience, London (United Kingdom); Aarhus University, Institute of Clinical Medicine, Aarhus (Denmark)

    2016-06-15

    Aggregated tau protein is a major neuropathological substrate central to the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration and chronic traumatic encephalopathy. In AD, it has been shown that the density of hyperphosphorylated tau tangles correlates closely with neuronal dysfunction and cell death, unlike β-amyloid. Until now, diagnostic and pathologic information about tau deposition has only been available from invasive techniques such as brain biopsy or autopsy. The recent development of selective in-vivo tau PET imaging ligands including [{sup 18}F]THK523, [{sup 18}F]THK5117, [{sup 18}F]THK5105 and [{sup 18}F]THK5351, [{sup 18}F]AV1451(T807) and [{sup 11}C]PBB3 has provided information about the role of tau in the early phases of neurodegenerative diseases, and provided support for diagnosis, prognosis, and imaging biomarkers to track disease progression. Moreover, the spatial and longitudinal relationship of tau distribution compared with β - amyloid and other pathologies in these diseases can be mapped. In this review, we discuss the role of aggregated tau in tauopathies, the challenges posed in developing selective tau ligands as biomarkers, the state of development in tau tracers, and the new clinical information that has been uncovered, as well as the opportunities for improving diagnosis and designing clinical trials in the future. (orig.)

  7. The Effects of Dietary Tryptophan on Affective Disorders

    Science.gov (United States)

    Lindseth, Glenda; Helland, Brian; Caspers, Julie

    2014-01-01

    Using a randomized crossover study design, 25 healthy young adults were examined for differences in anxiety, depression, and mood after consuming a high tryptophan and a low tryptophan diet for four days each. There was a two week washout between the diets. A within-subjects analysis of the participants’ mood indicated significantly (p tryptophan diet as compared to a low tryptophan diet. Negative affect differences between the diets were not statistically significant (p > .05). Also, consuming more dietary tryptophan resulted in (p < .05) less depressive symptoms and decreased anxiety. PMID:25858202

  8. Body dysmorphic disorder: A complex and polymorphic affection

    Directory of Open Access Journals (Sweden)

    Patrizia Fiori

    2009-09-01

    Full Text Available Patrizia Fiori1,2, Luigi Maria Giannetti1,31II University of Naples, 2Neurologist, 3Director of Infantile Neuropsychiatry, Civil Hospital of Ariano Irpino, ASL AV, II University of Naples, Naples, Italy; 3La Crisalide, Aesthetical Medical Center, Naples, ItalyBackground: Body dysmorphic disorder (BDD is defined as a syndrome characterized by an excessive preoccupation because of a presumed or minimal physical flaw in appearance that polarizes the energies of the subject. So far, its specular aspect, represented by the presence of an evident physical defect that is not recognized or is even denied and neglected, has been disregarded. The aim of our study was to examine the individual and relational meaning of BDD and to evaluate the efficacy of cognitive-behavioral and medical–aesthetical treatments.Methods and results: We describe two subjects with BDD, diagnosed by clinical interviews and test. Both patients were compliant to cognitive-behavioral approach. One out of two subjects underwent aesthetical treatments.Conclusions: Cognitive-behavioral therapy stimulates self-consciousness, rebuilds the body image, promotes health care, and improves relational capacity. Moreover, it ensures the success of any medical and/or surgical procedures by preventing unrealistic expectations. Lastly, it contributes to the definition of worldwide shared behavioral models.Keywords: diagnostic criteria, body image, cognition, aesthetical treatments

  9. Bipolar disorder affects behavior and social skills on the Internet.

    Science.gov (United States)

    Martini, Thaís; Czepielewski, Letícia Sanguinetti; Fijtman, Adam; Sodré, Leonardo; Wollenhaupt-Aguiar, Bianca; Pereira, Caroline Silveira; Vianna-Sulzbach, Mireia; Goi, Pedro D; Rosa, Adriane Ribeiro; Kapczinski, Flavio; Kunz, Maurício; Kauer-Sant'anna, Marcia

    2013-01-01

    Bipolar disorder (BD) is a significant cause of functional, cognitive, and social impairment. However, classic studies of functioning and social skills have not investigated how BD may impact behavior on the Internet. Given that the digital age has been changing the way people communicate, this study aims to investigate the pattern of Internet use in patients with BD. This cross-sectional study assessed 30 patients with BD I or II and 30 matched controls. Patients were not in an acute mood episode, according to DSM-IV. A standard protocol examined sociodemographic variables and social behavior on the Internet, assessed by Facebook number of friends (FBN) and lifetime estimated number of offline contacts (social network number, SNN). SNN (psocial networking sites (p = 0.042). Also, patients showed lower rates of the expected pattern of Internet use (based on their age generation), including a poorer knowledge of SNS (p = 0.018) and a lower frequency of Internet use (p = 0.010). This study suggests that patients with BD show smaller social networks both in real-world settings and on the Internet. Also, patients tend to use the Internet and social networking sites less frequently and show a poorer knowledge of Internet and social media than healthy controls, below the expected for their generation. These significant differences between patients and controls suggest that the effects of BD on social relationships and functioning extend to electronic media.

  10. Affective Reactivity in Response to Criticism in Remitted Bipolar Disorder: A Laboratory Analog of Expressed Emotion

    Science.gov (United States)

    Cuellar, Amy K.; Johnson, Sheri L.; Ruggero, Camilo J.

    2010-01-01

    Potential mechanisms to explain the relationship between Expressed Emotion (EE) and poor outcome within bipolar disorder are poorly understood. One possibility is that people with bipolar disorder have difficulty regulating their affect in response to criticism. The present study examined whether participants with bipolar disorder were more affectively dysregulated than control participants when presented with a criticism by a confederate. There was a trend for people with bipolar disorder to react more negatively to the criticism, but there was also evidence that they recovered as quickly as controls. Exploratory analyses found that female gender, the perception of the criticism as more negative, being disabled, and having fewer positive relationships predicted greater reactivity to criticism among people with bipolar disorder. PMID:19459195

  11. Cognitive, affective, and behavioral characteristics of mothers with anxiety disorders in the context of child anxiety disorder.

    Science.gov (United States)

    Creswell, Cathy; Apetroaia, Adela; Murray, Lynne; Cooper, Peter

    2013-02-01

    Parental emotional distress, particularly high maternal anxiety, is one of the most consistent predictors of child anxiety treatment outcome. In order to identify the cognitive, affective, and behavioral parenting characteristics of mothers of children with anxiety disorders who themselves have an anxiety disorder, we assessed the expectations, appraisals, and behaviors of 88 mothers of anxious children (44 mothers who were not anxious [NONANX] and 44 mothers with a current anxiety disorder [ANX]) when interacting with their 7-12-year-old children. There were no observed differences in anxiety and avoidance among children of ANX and NONANX mothers, but, compared with NONANX mothers, ANX mothers held more negative expectations, and they differed on observations of intrusiveness, expressed anxiety, warmth, and the quality of the relationship. Associations were moderated by the degree to which children expressed anxiety during the tasks. Maternal-reported negative emotions during the task significantly mediated the association between maternal anxiety status and the observed quality of the relationship. These findings suggest that maternal anxiety disorder is associated with reduced tolerance of children's negative emotions. This may interfere with the maintenance of a positive, supportive mother-child interaction under conditions of stress and, as such, this may impede optimum treatment outcomes. The findings identify potential cognitive, affective, and behavioral targets to improve treatment outcomes for children with anxiety disorders in the context of a current maternal anxiety disorder. 2013 APA, all rights reserved

  12. Unaffected twins discordant for affective disorders show changes in anterior callosal white matter microstructure

    DEFF Research Database (Denmark)

    Macoveanu, J; Vinberg, M; Madsen, K.

    2016-01-01

    tracts, that is, cingulum bundle, uncinate fasciculus, anterior limb of the internal capsule, and corpus callosum, that facilitate the communication between brain regions implicated in affective disorders. METHOD: Eighty-nine healthy mono- or dizygotic twins with a co-twin diagnosed with MDD or BD (high...... communication between left and right frontal regions critically involved in mood regulation. Reduced anterior callosal FA may act as a vulnerability marker for affective disorders in individuals at familial risk.......OBJECTIVE: The neurobiological mechanisms mediating an increased risk to develop affective disorders remain poorly understood. In a group of individuals with a family history of major depressive (MDD) or bipolar disorder (BD), we investigated the microstructural properties of white matter fiber...

  13. Suicide attempts and psychological risk factors in patients with bipolar and unipolar affective disorder.

    Science.gov (United States)

    Pawlak, Joanna; Dmitrzak-Węglarz, Monika; Skibińska, Maria; Szczepankiewicz, Aleksandra; Leszczyńska-Rodziewicz, Anna; Rajewska-Rager, Aleksandra; Maciukiewicz, Małgorzata; Czerski, Piotr; Hauser, Joanna

    2013-01-01

    Suicide is an important clinical problem in psychiatric patients. The highest risk of suicide attempts is noted in affective disorders. The aim of the study was looking for suicide risk factors among personality dimensions and value system in patients with diagnosis of unipolar and bipolar affective disorder (n=189 patients, n=101 controls). To establish the diagnosis, we used SCID (Structured clinical interview for diagnostic and statistical manual of mental disorders, fourth edition) questionnaire, TCI (Temperament and Character Inventory) questionnaire and Value Survey--to assess the personality. The main limitations of the study are number of participants, lack of data about stressful life events and treatment with lithium. Novelty seeking and harm avoidance dimensions constituted suicide attempt risk factors in the group of patients with affective disorders. Protective role of cooperativeness was discovered. Patients with and without suicide attempt in lifetime history varied in self-esteem position in Value Survey. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Recruiting for research studies using online public advertisements: examples from research in affective disorders

    Science.gov (United States)

    Wise, Toby; Arnone, Danilo; Marwood, Lindsey; Zahn, Roland; Lythe, Karen E; Young, Allan H

    2016-01-01

    Successful recruitment is vital for any research study. Difficulties in recruitment are not uncommon and can have important implications. This is particularly relevant to research conducted in affective disorders due to the nature of the conditions and the clinical services that serve these patients. Recently, online public advertisements have become more generally accessible and may provide an effective way to recruit patient populations. However, there is paucity of evidence on their viability as a method of recruiting patients into studies of disease mechanisms in these disorders. Public advertisement methods can be useful when researchers require specific populations, such as those not receiving pharmacological treatment. This work describes our experience in successfully recruiting participants into neuroimaging research studies in affective disorders using online public advertisements. Results suggest that these online public advertisements are an effective method for successfully recruiting participants with affective disorders into research studies, particularly for research focusing on disease mechanisms in specific populations. PMID:26917961

  15. Recruiting for research studies using online public advertisements: examples from research in affective disorders.

    Science.gov (United States)

    Wise, Toby; Arnone, Danilo; Marwood, Lindsey; Zahn, Roland; Lythe, Karen E; Young, Allan H

    2016-01-01

    Successful recruitment is vital for any research study. Difficulties in recruitment are not uncommon and can have important implications. This is particularly relevant to research conducted in affective disorders due to the nature of the conditions and the clinical services that serve these patients. Recently, online public advertisements have become more generally accessible and may provide an effective way to recruit patient populations. However, there is paucity of evidence on their viability as a method of recruiting patients into studies of disease mechanisms in these disorders. Public advertisement methods can be useful when researchers require specific populations, such as those not receiving pharmacological treatment. This work describes our experience in successfully recruiting participants into neuroimaging research studies in affective disorders using online public advertisements. Results suggest that these online public advertisements are an effective method for successfully recruiting participants with affective disorders into research studies, particularly for research focusing on disease mechanisms in specific populations.

  16. Recruiting for research studies using online public advertisements examples from research in affective disorders

    Directory of Open Access Journals (Sweden)

    Wise T

    2016-02-01

    Full Text Available Toby Wise,1 Danilo Arnone,1 Lindsey Marwood,1 Roland Zahn,1–3 Karen E Lythe,2,3 Allan H Young1 1Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, King’s College London, London, 2Neuroscience and Aphasia Research Unit, School of Psychological Sciences, 3Manchester Academic Health Science Centre, University of Manchester, Manchester, UK Abstract: Successful recruitment is vital for any research study. Difficulties in recruitment are not uncommon and can have important implications. This is particularly relevant to research conducted in affective disorders due to the nature of the conditions and the clinical services that serve these patients. Recently, online public advertisements have become more generally accessible and may provide an effective way to recruit patient populations. However, there is paucity of evidence on their viability as a method of recruiting patients into studies of disease mechanisms in these disorders. Public advertisement methods can be useful when researchers require specific populations, such as those not receiving pharmacological treatment. This work describes our experience in successfully recruiting participants into neuroimaging research studies in affective disorders using online public advertisements. Results suggest that these online public advertisements are an effective method for successfully recruiting participants with affective disorders into research studies, particularly for research focusing on disease mechanisms in specific populations. Keywords: recruitment, affective disorders, advertising, depression, anxiety, bipolar

  17. Autophagy and ageing: implications for age-related neurodegenerative diseases.

    Science.gov (United States)

    Carroll, Bernadette; Hewitt, Graeme; Korolchuk, Viktor I

    2013-01-01

    Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our 'ageing' world.

  18. PENN neurodegenerative disease research - in the spirit of Benjamin Franklin.

    Science.gov (United States)

    Trojanowski, John Q

    2008-01-01

    Benjamin Franklin (1706-1790) was entrepreneur, statesman, supporter of the public good as well as inventor, and his most significant invention was the University of Pennsylvania (PENN). Franklin outlined his plans for a college providing practical and classical instruction to prepare youth for real-world pursuits in his 'Proposals Relating to the Education of Youth in Pensilvania' (1749), and Franklin's spirit of learning to serve society guides PENN to the present day. This is evidenced by the series of articles in this special issue of Neurosignals, describing research conducted by seasoned and newly recruited PENN faculty, addressing consequences of the longevity revolution which defines our epoch at the dawn of this millennium. While aging affects all organ systems, the nervous system is most critical to successful aging. Thus, the articles in this special issue of Neurosignals focus on research at PENN that is designed to prevent or ameliorate aging-related neurodegenerative disorders such as Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis and frontotemporal dementia. This research could enhance our chances of aging successfully in the continuing longevity revolution, and the essay here provides context and background on this research.

  19. The Unique Effects of Parental Alcohol and Affective Disorders, Parenting, and Parental Negative Affect on Adolescent Maladjustment.

    Science.gov (United States)

    Haller, Moira; Chassin, Laurie

    2011-07-01

    Using a high-risk community sample, multiple regression analyses were conducted separately for mothers ( N =416) and fathers ( N = 346) to test the unique, prospective influence of parental negative affect on adolescent maladjustment (internalizing symptoms, externalizing symptoms, and negative emotionality) two years later over and above parental alcohol and affective disorders, major disruption in the family environment, and parenting. Adolescent sex was tested as a moderator. Results indicated that maternal (but not paternal) negative affect had a unique, prospective effect on adolescent internalizing symptoms in girls and negative emotionality in both sexes, but did not predict adolescent externalizing symptoms. Findings demonstrate that mothers' negative affect may have unique effects on adolescent adjustment, separate from the effects of clinically significant parental psychopathology, parenting, and disruption in the family environment.

  20. COMT genetic variation confers risk for psychotic and affective disorders: a case control study

    Directory of Open Access Journals (Sweden)

    Lencz Todd

    2005-10-01

    Full Text Available Abstract Background Variation in the COMT gene has been implicated in a number of psychiatric disorders, including psychotic, affective and anxiety disorders. The majority of these studies have focused on the functional Val108/158Met polymorphism and yielded conflicting results, with limited studies examining the relationship between other polymorphisms, or haplotypes, and psychiatric illness. We hypothesized that COMT variation may confer a general risk for psychiatric disorders and have genotyped four COMT variants (Val158Met, rs737865, rs165599, and a SNP in the P2 promoter [-278A/G; rs2097603] in 394 Caucasian cases and 467 controls. Cases included patients with schizophrenia (n = 196, schizoaffective disorder (n = 62, bipolar disorder (n = 82, major depression (n = 30, and patients diagnosed with either psychotic disorder NOS or depressive disorder NOS (n = 24. Results SNP rs2097603, the Val/Met variant and SNP rs165599 were significantly associated (p = 0.004; p = 0.05; p = 0.035 with a broad "all affected" diagnosis. Haplotype analysis revealed a potentially protective G-A-A-A haplotype haplotype (-278A/G; rs737865; Val108/158Met; rs165599, which was significantly underrepresented in this group (p = 0.0033 and contained the opposite alleles of the risk haplotype previously described by Shifman et al. Analysis of diagnostic subgroups within the "all affecteds group" showed an association of COMT in patients with psychotic disorders as well as in cases with affective illness although the associated variants differed. The protective haplotype remained significantly underrepresented in most of these subgroups. Conclusion Our results support the view that COMT variation provides a weak general predisposition to neuropsychiatric disease including psychotic and affective disorders.

  1. Bipolar disorder affects behavior and social skills on the Internet.

    Directory of Open Access Journals (Sweden)

    Thaís Martini

    Full Text Available BACKGROUND: Bipolar disorder (BD is a significant cause of functional, cognitive, and social impairment. However, classic studies of functioning and social skills have not investigated how BD may impact behavior on the Internet. Given that the digital age has been changing the way people communicate, this study aims to investigate the pattern of Internet use in patients with BD. METHODS: This cross-sectional study assessed 30 patients with BD I or II and 30 matched controls. Patients were not in an acute mood episode, according to DSM-IV. A standard protocol examined sociodemographic variables and social behavior on the Internet, assessed by Facebook number of friends (FBN and lifetime estimated number of offline contacts (social network number, SNN. RESULTS: SNN (p<0.001 and FBN (p = 0.036 of patients with BD were significantly lower than those of controls. Also, variables related with Internet use were significantly lower in patients, e.g., close contacts on Facebook (p = 0.021, Internet experience (p = 0.020, and knowledge of terms associated with social networking sites (p = 0.042. Also, patients showed lower rates of the expected pattern of Internet use (based on their age generation, including a poorer knowledge of SNS (p = 0.018 and a lower frequency of Internet use (p = 0.010. DISCUSSION: This study suggests that patients with BD show smaller social networks both in real-world settings and on the Internet. Also, patients tend to use the Internet and social networking sites less frequently and show a poorer knowledge of Internet and social media than healthy controls, below the expected for their generation. These significant differences between patients and controls suggest that the effects of BD on social relationships and functioning extend to electronic media.

  2. Long-lasting effects of affective disorders and childhood trauma on dispositional optimism

    NARCIS (Netherlands)

    Broekhof, R.; Rius-Ottenheim, N.; Spinhoven, P.; van der Mast, R.C.; Penninx, B.W.; Zitman, F. G.; Giltay, E.J.

    2015-01-01

    Background Dispositional optimism, a personality trait characterized by generalized positive expectations towards the future, is thought to remain rather stable over time. It is however largely unknown to what extent affective disorders and its risk factors affect dispositional optimism. Methods We

  3. Affective Modulation of the Startle Eyeblink and Postauricular Reflexes in Autism Spectrum Disorder

    Science.gov (United States)

    Dichter, Gabriel S.; Benning, Stephen D.; Holtzclaw, Tia N.; Bodfish, James W.

    2010-01-01

    Eyeblink and postauricular reflexes to standardized affective images were examined in individuals without (n = 37) and with (n = 20) autism spectrum disorders (ASDs). Affective reflex modulation in control participants replicated previous findings. The ASD group, however, showed anomalous reflex modulation patterns, despite similar self-report…

  4. Meteorological analysis of symptom data for people with seasonal affective disorder

    NARCIS (Netherlands)

    Sarran, Christophe; Albers, Casper; Sachon, Patrick; Meesters, Ybe

    2017-01-01

    It is thought that variation in natural light levels affect people with Seasonal Affective Disorder (SAD). Several meteorological factors related to luminance can be forecast but little is known about which factors are most indicative of worsening SAD symptoms. The aim of this meteorological

  5. Relationship between affective temperaments and aggression in euthymic patients with bipolar mood disorder and major depressive disorder.

    Science.gov (United States)

    Dolenc, B; Dernovšek, M Z; Sprah, L; Tavcar, R; Perugi, G; Akiskal, H S

    2015-03-15

    So far there is a scarce of studies dealing with the relationship between different aspects of aggressive behaviour and affective temperaments among various mood disorders. The aim of the present study was to explore in a group of patients with affective mood disorders the relationship between affective temperaments and aggression. 100 consecutive outpatients in euthymic phase of mood disorders (46 with bipolar disorder-type I, 18 with bipolar disorder-type II and 36 with major depressive disorder) were self-assessed with the Aggression Questionnaire and the short version of Slovenian Temperament Evaluation of Memphis, Pisa, Paris and San Diego - Autoquestionnaire (TEMPS-A). The factorial analysis of the TEMPS-A subscales revealed 2 main factors: Factor 1 (prominent cyclothymic profile) consisted of cyclothymic, depressive, irritable, and anxious temperaments and Factor 2 (prominent hyperthymic profile) which was represented by the hyperthymic temperament, and by depressive and anxious temperaments as negative components. Patients with prominent cyclothymic profile got their diagnosis later in their life and had significantly higher mean scores on anger and hostility (non-motor aggressive behaviour) compared with patients with prominent hyperthymic profile. We included patients with different mood disorders, therefore the sample selection may influence temperamental and aggression profiles. We used self-report questionnaires which can elicit sociable desirable answers. Anger and hostility could represent stable personality characteristics of prominent cyclothymic profile that endure even in remission. It seems that distinct temperamental profile could serve as a good diagnostic and prognostic value for non-motor aspects of aggressive behaviour. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. A preliminary study of lamotrigine in the treatment of affective instability in borderline personality disorder.

    Science.gov (United States)

    Reich, Donald Bradford; Zanarini, Mary C; Bieri, Katheryn A

    2009-09-01

    The objective of this study was to evaluate the effectiveness of lamotrigine in reducing affective instability in borderline personality disorder (BPD). We conducted a 12-week, double-blind, placebo-controlled study of 28 patients who met Revised Diagnostic Interview for Borderlines and Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for BPD. Patients could not meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for bipolar disorder. Patients could be taking one antidepressant during the study. Patients were randomly assigned to treatment with flexible-dose lamotrigine or placebo in a 1 : 1 manner. The primary outcome measures were: (i) the Affective Lability Scale total score; and (ii) the Affective Instability Item of the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). The study randomized 15 patients to receive lamotrigine and 13 patients to receive placebo. Patients in the lamotrigine group had significantly greater reductions in the total Affective Lability Scale scores (P<0.05) and significantly greater reductions in scores on the affective instability item of the ZAN-BPD (P<0.05). A secondary finding was that patients in the lamotrigine group had significantly greater reductions in scores on the ZAN-BPD impulsivity item (P = 0.001). Results from the study suggest that lamotrigine is an effective treatment for affective instability and for the general impulsivity characteristic of BPD.

  7. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease.

    Science.gov (United States)

    Wulff, Katharina; Gatti, Silvia; Wettstein, Joseph G; Foster, Russell G

    2010-08-01

    Sleep and circadian rhythm disruption are frequently observed in patients with psychiatric disorders and neurodegenerative disease. The abnormal sleep that is experienced by these patients is largely assumed to be the product of medication or some other influence that is not well defined. However, normal brain function and the generation of sleep are linked by common neurotransmitter systems and regulatory pathways. Disruption of sleep alters sleep-wake timing, destabilizes physiology and promotes a range of pathologies (from cognitive to metabolic defects) that are rarely considered to be associated with abnormal sleep. We propose that brain disorders and abnormal sleep have a common mechanistic origin and that many co-morbid pathologies that are found in brain disease arise from a destabilization of sleep mechanisms. The stabilization of sleep may be a means by which to reduce the symptoms of--and permit early intervention of--psychiatric and neurodegenerative disease.

  8. Exploring mitochondrial system properties of neurodegenerative diseases through interactome mapping.

    Science.gov (United States)

    Vlasblom, James; Jin, Ke; Kassir, Sandy; Babu, Mohan

    2014-04-04

    Mitochondria are double membraned, dynamic organelles that are required for a large number of cellular processes, and defects in their function have emerged as causative factors for a growing number of human disorders and are highly associated with cancer, metabolic, and neurodegenerative (ND) diseases. Biochemical and genetic investigations have uncovered small numbers of candidate mitochondrial proteins (MPs) involved in ND disease, but given the diversity of processes affected by MP function and the difficulty of detecting interactions involving these proteins, many more likely remain unknown. However, high-throughput proteomic and genomic approaches developed in genetically tractable model prokaryotes and lower eukaryotes have proven to be effective tools for querying the physical (protein-protein) and functional (gene-gene) relationships between diverse types of proteins, including cytosolic and membrane proteins. In this review, we highlight how experimental and computational approaches developed recently by our group and others can be effectively used towards elucidating the mitochondrial interactome in an unbiased and systematic manner to uncover network-based connections. We discuss how the knowledge from the resulting interaction networks can effectively contribute towards the identification of new mitochondrial disease gene candidates, and thus further clarify the role of mitochondrial biology and the complex etiologies of ND disease. Biochemical and genetic investigations have uncovered small numbers of candidate mitochondrial proteins (MPs) involved in neurodegenerative (ND) diseases, but given the diversity of processes affected by MP function and the difficulty of detecting interactions involving these proteins, many more likely remain unknown. Large-scale proteomic and genomic approaches developed in model prokaryotes and lower eukaryotes have proven to be effective tools for querying the physical (protein-protein) and functional (gene

  9. Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder.

    Science.gov (United States)

    Mc Mahon, Brenda; Andersen, Sofie B; Madsen, Martin K; Hjordt, Liv V; Hageman, Ida; Dam, Henrik; Svarer, Claus; da Cunha-Bang, Sofi; Baaré, William; Madsen, Jacob; Hasholt, Lis; Holst, Klaus; Frokjaer, Vibe G; Knudsen, Gitte M

    2016-05-01

    Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions

  10. Negative Affective Experiences in Relation to Stages of Eating Disorder Recovery

    Science.gov (United States)

    Harney, Megan B.; Fitzsimmons-Crafr, Ellen E.; Maldonado, Christine R.; Bardone-Cone, Anna M.

    2013-01-01

    The purpose of this study was to examine a collection of negative affect symptoms in relation to stages of eating disorder recovery. Depressive symptoms, anxiety symptoms, loneliness, and perceived stress are known to be present in individuals with eating disorders; however, less is known about the presence of such constructs throughout the recovery process. Does this negative affect fog continue to linger in individuals who have recovered from an eating disorder? Female participants seen at some point for an eating disorder at a primary care clinic were categorized into one of three groups using a stringent definition of eating disorder recovery based on physical, behavioral, and psychological criteria: active eating disorder (n =53), partially recovered (n =15; psychological criteria not met), and fully recovered (n =20; all recovery criteria met). Additionally, data were obtained from 67 female controls who had no history of an eating disorder. Self-report data indicated that controls and women fully recovered from an eating disorder scored significantly lower than partially recovered and active eating disorder groups in perceived stress, depression, and anxiety. Controls and the fully recovered group were statistically indistinguishable from each other in these domains, as were the partially recovered and active eating disorder groups, suggesting an interesting divide depending on whether psychological criteria (e.g., normative levels of weight/shape concern) were met. In contrast, controls and fully recovered and partially recovered groups all reported feeling significantly less lonely relative to those with an active eating disorder suggesting that improved perceptions of interpersonal, social support may act as a stepping stone toward more comprehensive eating disorder recovery. Future research may want to longitudinally determine if an increase in actual or perceived social support facilitates the movement toward full recovery and whether this, in turn, has

  11. Negative affective experiences in relation to stages of eating disorder recovery.

    Science.gov (United States)

    Harney, Megan B; Fitzsimmons-Craft, Ellen E; Maldonado, Christine R; Bardone-Cone, Anna M

    2014-01-01

    The purpose of this study was to examine a collection of negative affect symptoms in relation to stages of eating disorder recovery. Depressive symptoms, anxiety symptoms, loneliness, and perceived stress are known to be present in individuals with eating disorders; however, less is known about the presence of such constructs throughout the recovery process. Does this negative affect fog continue to linger in individuals who have recovered from an eating disorder? Female participants seen at some point for an eating disorder at a primary care clinic were categorized into one of three groups using a stringent definition of eating disorder recovery based on physical, behavioral, and psychological criteria: active eating disorder (n=53), partially recovered (n=15; psychological criteria not met), and fully recovered (n=20; all recovery criteria met). Additionally, data were obtained from 67 female controls who had no history of an eating disorder. Self-report data indicated that controls and women fully recovered from an eating disorder scored significantly lower than partially recovered and active eating disorder groups in perceived stress, depression, and anxiety. Controls and the fully recovered group were statistically indistinguishable from each other in these domains, as were the partially recovered and active eating disorder groups, suggesting an interesting divide depending on whether psychological criteria (e.g., normative levels of weight/shape concern) were met. In contrast, controls and fully recovered and partially recovered groups all reported feeling significantly less lonely relative to those with an active eating disorder suggesting that improved perceptions of interpersonal functioning and social support may act as a stepping stone toward more comprehensive eating disorder recovery. Future research may want to longitudinally determine if an increase in actual or perceived social support facilitates the movement toward full recovery and whether this

  12. Spatial affect learning restricted in major depression relative to anxiety disorders and healthy controls.

    Science.gov (United States)

    Gollan, Jackie K; Norris, Catherine J; Hoxha, Denada; Irick, John Stockton; Hawkley, Louise C; Cacioppo, John T

    2014-01-01

    Detecting and learning the location of unpleasant or pleasant scenarios, or spatial affect learning, is an essential skill that safeguards well-being (Crawford & Cacioppo, 2002). Potentially altered by psychiatric illness, this skill has yet to be measured in adults with and without major depressive disorder (MDD) and anxiety disorders (AD). This study enrolled 199 adults diagnosed with MDD and AD (n=53), MDD (n=47), AD (n=54), and no disorders (n=45). Measures included clinical interviews, self-reports, and a validated spatial affect task using affective pictures (IAPS; Lang, Bradley, & Cuthbert, 2005). Participants with MDD showed impaired spatial affect learning of negative stimuli and irrelevant learning of pleasant pictures compared with non-depressed adults. Adults with MDD may use a "GOOD is UP" heuristic reflected by their impaired learning of the opposite correlation (i.e., "BAD is UP") and performance in the pleasant version of the task.

  13. [Changes in olfaction during ageing and in certain neurodegenerative diseases: up-to-date].

    Science.gov (United States)

    Bianchi, A-J; Guépet-Sordet, H; Manckoundia, P

    2015-01-01

    Olfaction is a complex sensory system, and increasing interest is being shown in the link between olfaction and cognition, notably in the elderly. In this literature review, we revisit the specific neurophysiological features of the olfactory system and odorants that lead to a durable olfactory memory and an emotional memory, for which the implicit component produces subconscious olfactory conditioning. Olfaction is known to affect cognitive abilities and mood. We also consider the impairment of olfactory function due to ageing and to neurodegenerative diseases, in particular Alzheimer's disease and Parkinson's disease, through anatomopathological changes in the peripheral and central olfactory structures. The high frequency of these olfactory disorders as well as their early occurrence in Alzheimer disease and Parkinson disease are in favour of their clinical detection in subjects suffering from these two neurodegenerative diseases. Finally, we analyse the impact of olfactory stimulation on cognitive performance and attention. Current observational data from studies in elderly patients with Alzheimer-type dementia are limited to multiple sensory stimulation methods, such as the Snoezelen method, and aromatherapy. These therapies have shown benefits for dementia-related mood and behaviour disorders in the short term, with few side effects. Since olfactory chemosensory stimulation may be beneficial, it may be proposed in patients with dementia, especially Alzheimer-type dementia, as a complementary or even alternative therapy to existing medical strategies. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  14. The role of affective instability and UPPS impulsivity in borderline personality disorder features.

    Science.gov (United States)

    Tragesser, Sarah L; Robinson, R Joe

    2009-08-01

    Current theories of borderline personality disorder (BPD) suggest that extreme levels of affective instability/emotional dysregulation, impulsivity, or a combination of these traits account for the symptoms of BPD. The present study tested the extent to which personality measures of affective instability and impulsivity could account for BPD features in a nonclinical sample. One hundred forty-one undergraduates completed the Affective Lability Scale, the UPPS Impulsive Behavior Scale, and the Personality Assessment Inventory for Borderlines. Both affective instability and impulsivity were uniquely associated with BPD features. Shifts between euthymia and anger, and between anxiety and depression, were associated with BPD features, as were the urgency and (lack of) premeditation scales. Results indicated that specific BPD features may be differentially accounted for by affective instability vs. impulsivity, consistent with perspectives on BPD emphasizing combinations of affective instability and impulsivity as underlying dimensions of the disorder.

  15. Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech

    OpenAIRE

    Josephs, Keith A.; Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Matthew L. Senjem; Master, Ankit V.; Lowe, Val J.; Jack, Clifford R.; Jennifer L. Whitwell

    2012-01-01

    Apraxia of speech is a disorder of speech motor planning and/or programming that is distinguishable from aphasia and dysarthria. It most commonly results from vascular insults but can occur in degenerative diseases where it has typically been subsumed under aphasia, or it occurs in the context of more widespread neurodegeneration. The aim of this study was to determine whether apraxia of speech can present as an isolated sign of neurodegenerative disease. Between July 2010 and July 2011, 37 s...

  16. High prevalence of affective disorders among adolescents living in Rural Zimbabwe.

    Science.gov (United States)

    Langhaug, Lisa F; Pascoe, Sophie J; Mavhu, Webster; Woelk, Godfrey; Sherr, Lorraine; Hayes, Richard J; Cowan, Frances M

    2010-08-01

    Poor mental health accounts for considerable disease burden among young people globally. We investigated the prevalence and determinants of affective disorders among rural Zimbabwean youth in 2006. We undertook a cross-sectional survey among 1495 Zimbabwean youth aged 15-23 (median 18) from 12 rural communities in three provinces in south-eastern Zimbabwe. Mental health was assessed using the Shona Symptom Questionnaire (SSQ), a locally validated 14-item indigenous screening tool for affective disorders, notably depression and anxiety disorders. Participants scoring >or=8/14 were considered at risk of being affected and >or=11 as at risk of being severely affected. Most participants (93.1%) completed the SSQ. Of these, 51.7% (95%CI:49.0-54.3%) scored >or=8/14 and 23.8% (95%CI:21.5-26.0%) scored >or=11. Affective disorders were independently associated with household poverty (adjusted odds ratio (AOR) 1.9, 95%CI:1.4-2.7), living in a female-headed household (AOR 1.3, 95%CI:1.0-1.7), having moved home within last 5 years (AOR 1.4, 95%CI:1.0-1.9) and feeling stigmatized (AOR being shunned by others 3.7, 95%CI:2.5-5.7). There was a strong linear association between risk of affective disorders and sexual risk taking (ever sex AOR 1.5, 95%CI:1.0-2.4, and 2.8, 95%CI:1.9-4.2 for affected and severely affected, respectively, test for trend P or=2 lifetime partners AOR 2.3, 95%CI:1.1-4.8 and 5.4, 95%CI:2.7-10.7, test for trend P mental health disorders in this vulnerable population are urgently required. In HIV-endemic countries, such interventions may also help reduce HIV transmission.

  17. Marital adjustment of patients with substance dependence, schizophrenia and bipolar affective disorder

    OpenAIRE

    Shital S Muke; Girish M Ghanawat; Suprakash Chaudhury; Sujit K Mishra; Verma, A. N.; Singh, Amool R.

    2014-01-01

    Background: Marital adjustment is considered as a part of social well-being. Disturbed marital relationship can directly affect the disease adjustment and the way they face disease outcomes and complications. It may adversely affect physical health, mental health, the quality-of-life and even economic status of individuals. Aim: The aim of this study was to compare the marital adjustment among patients with substance dependence, schizophrenia and bipolar affective disorder. Materials and Meth...

  18. Escitalopram tolerability as mono- versus augmentative therapy in patients with affective disorders: a naturalistic study

    Directory of Open Access Journals (Sweden)

    Dell'Osso B

    2013-02-01

    Full Text Available Bernardo Dell’Osso, Chiara Arici, Cristina Dobrea, Giulia Camuri, Beatrice Benatti, A Carlo AltamuraUniversity of Milan, Department of Psychiatry, Fondazione IRCSS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, ItalyBackground: Escitalopram is a selective serotonin reuptake inhibitor, widely used in the treatment of affective disorders. The purpose of this study was to examine its safety and tolerability, as mono- versus augmentative therapy, in a group of patients with affective disorders.Materials and methods: The sample consisted of 131 patients suffering from different affective disorders, including major depressive disorder, bipolar disorder, and generalized anxiety disorder, who received escitalopram for at least 4 weeks. Data were analyzed on the basis of mono- versus augmentative therapy, as well as age, gender, mean daily dosage, and patterns of combination therapy.Results: Sixty-seven (51.1% patients were treated with monotherapy (mean dose of 11.76 mg/day and 64 (48.9% with augmentative escitalopram (mean dose of 12.81 mg/day. The mean duration of escitalopram treatment was 14 months. The most frequently combined compounds were: other antidepressants (36.5%, mood stabilizers (33.4%, and atypical antipsychotics (30.1%. Side effects were reported in 5.3% of the total sample and the most common were insomnia (2.3%, nausea (2.3%, and dizziness (0.8%. No significant difference, in terms of tolerability, in mono- versus augmentative therapy groups was found. In addition, neither age nor gender was significantly correlated with a greater presence of side effects. Finally, no significant correlation between dosage and side effects was observed.Conclusion: Over a 14-month observation period, escitalopram, either as monotherapy or an augmentative treatment, was found to be well tolerated in a large sample of patients with affective disorders, with an overall low rate of side effects.Keywords: affective disorders, escitalopram

  19. Pain in Neurodegenerative Disease: Current Knowledge and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Marina de Tommaso

    2016-01-01

    Full Text Available Neurodegenerative diseases are going to increase as the life expectancy is getting longer. The management of neurodegenerative diseases such as Alzheimer’s disease (AD and other dementias, Parkinson’s disease (PD and PD related disorders, motor neuron diseases (MND, Huntington’s disease (HD, spinocerebellar ataxia (SCA, and spinal muscular atrophy (SMA, is mainly addressed to motor and cognitive impairment, with special care to vital functions as breathing and feeding. Many of these patients complain of painful symptoms though their origin is variable, and their presence is frequently not considered in the treatment guidelines, leaving their management to the decision of the clinicians alone. However, studies focusing on pain frequency in such disorders suggest a high prevalence of pain in selected populations from 38 to 75% in AD, 40% to 86% in PD, and 19 to 85% in MND. The methods of pain assessment vary between studies so the type of pain has been rarely reported. However, a prevalent nonneuropathic origin of pain emerged for MND and PD. In AD, no data on pain features are available. No controlled therapeutic trials and guidelines are currently available. Given the relevance of pain in neurodegenerative disorders, the comprehensive understanding of mechanisms and predisposing factors, the application and validation of specific scales, and new specific therapeutic trials are needed.

  20. Recommendations for the Use of ICT in Elderly Populations with Affective Disorders.

    Science.gov (United States)

    Gros, Auriane; Bensamoun, David; Manera, Valeria; Fabre, Roxane; Zacconi-Cauvin, Anne-Marie; Thummler, Susanne; Benoit, Michel; Robert, Philippe; David, Renaud

    2016-01-01

    Objective : Affective disorders are frequently encountered among elderly populations, and the use of information and communication technologies (ICT) could provide an added value for their recognition and assessment in addition to current clinical methods. The diversity and lack of consensus in the emerging field of ICTs is however a strong limitation for their global use in daily practice. The aim of the present article is to provide recommendations for the use of ICTs for the assessment and management of affective disorders among elderly populations with or without dementia. Methods : A Delphi panel was organized to gather recommendations from experts in the domain. A set of initial general questions for the use of ICT in affective disorders was used to guide the discussion of the expert panel and to analyze the Strengths, Weaknesses, Opportunities, and Threats (SWOT) of employing ICT in elderly populations with affective disorders. Based on the results collected from this first round, a web survey was sent to local general practitioners (GPs) and to all interns in psychiatry in France. Results : The results of the first round revealed that ICT may offer very useful tools for practitioners involved in the diagnosis and management of affective disorders. However, the results of the web survey showed the interest to explain better to current and upcoming practitioners the utility of ICT especially for people living with dementia.

  1. Long-lasting effects of affective disorders and childhood trauma on dispositional optimism.

    Science.gov (United States)

    Broekhof, Rosalie; Rius-Ottenheim, Nathaly; Spinhoven, Philip; van der Mast, Roos C; Penninx, Brenda W J H; Zitman, Frans G; Giltay, Erik J

    2015-04-01

    Dispositional optimism, a personality trait characterized by generalized positive expectations towards the future, is thought to remain rather stable over time. It is however largely unknown to what extent affective disorders and its risk factors affect dispositional optimism. We examined the association between (lifetime) affective disorders and childhood trauma with dispositional optimism in a sample of 2104 subjects (aged 18-65 years) from the Netherlands Study of Depression and Anxiety (NESDA). Dispositional optimism was measured with the Life Orientation Test Revised (LOT-R). Diagnoses of depressive and anxiety disorders were based on the Composite Interview diagnostic Instrument (CIDI).Childhood trauma was assessed using the Childhood Trauma Interview (CTI) and life-events with the List of Threatening Events Questionnaire (LTQ). The 2104 participants were on average 46.0 (SD 13.1) years old and 65.8% were female. Multivariate analyses showed that dispositional optimism was inversely associated with current affective disorders (depression: B=-1.089 and anxiety: B=-1.066, both poptimism, whilst positive life-events were associated with higher levels of optimism (B=0.235, p>0.001). The cross-sectional design hampers inferences about causality. Lower levels of dispositional optimism are associated with stage of affective disorders, even after remission, and a history of childhood emotional maltreatment. Identification of the risk factors contributes to understand fluctuations in dispositional optimism. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Recommendations for the use of ICT in elderly populations with affective disorders

    Directory of Open Access Journals (Sweden)

    Auriane Gros

    2016-11-01

    Full Text Available Objective: Affective disorders are frequently encountered among elderly populations, and the use of Information and Communication Technologies (ICT could provide an added value for their recognition and assessment in addition to current clinical methods. The diversity and lack of consensus in the emerging field of ICTs is however a strong limitation for their global use in daily practice. The aim of the present article is to provide recommendations for the use of ICTs for the assessment and management of affective disorders among elderly populations with or without dementia.Methods: A Delphi panel was organized to gather recommendations from experts in the domain. A set of initial general questions for the use of ICT in affective disorders was used to guide the discussion of the expert panel and to analyze the Strengths, Weaknesses, Opportunities, and Threats (SWOT of employing ICT in elderly populations with affective disorders. Based on the results collected from this first round, a web survey was sent to local general practitioners (GPs and to all interns in psychiatry in France. Results: The results of the first round revealed that ICT may offer very useful tools for practitioners involved in the diagnosis and management of affective disorders. However, the results of the web survey showed the interest to better explain to current and coming practitioners the utility of ICT especially for AD patients.

  3. Affect and alcohol use: an ecological momentary assessment study of outpatients with borderline personality disorder.

    Science.gov (United States)

    Jahng, Seungmin; Solhan, Marika B; Tomko, Rachel L; Wood, Phillip K; Piasecki, Thomas M; Trull, Timothy J

    2011-08-01

    Alcohol use may be viewed as an attempt (albeit maladaptive) to regulate negative emotional states. We examined associations between both negative and positive affects and alcohol use in outpatient women diagnosed with borderline personality disorder (BPD; n=74), a prototype of emotional dysregulation, as well as a psychiatric control group of women with current depressive disorder (major depressive disorder/dysthymic disorder [MDD\\DYS]; n=50). Participants completed randomly prompted reports of mood and alcohol use up to six times a day over a 28-day period using electronic diaries. Mean levels of either positive or negative affects did not distinguish between drinkers and nondrinkers in either diagnostic group. However, levels of both negative and positive affects were positively associated with alcohol use at the momentary level in BPD drinkers. More robust findings were obtained with respect to within-person affective variability, which was related to alcohol use in multiple ways. BPD drinkers showed higher within-person variability for most negative affects than BPD nondrinkers; MDD\\DYS drinkers in general showed less within-person variability than MDD\\DYS nondrinkers for negative affects. Multilevel lagged analyses for BPD drinkers indicated that alcohol use was positively related to variability in all affects, concurrently, but fewer significant effects of affect variability on the next day's drinking or significant effects of alcohol use on the next day's affect variability were observed. Among MDD\\DYS drinkers, we observed more significant associations between affect variability on next day's alcohol use and of alcohol use on next day's affect variability. We discuss theoretical and methodological issues relevant to these findings as well as implications for future research. © 2011 American Psychological Association

  4. Affective disorder and homicide: a case of familial filicide theoretical and clinical considerations.

    Science.gov (United States)

    Bourget, D; Bradford, J M

    1987-04-01

    This paper discusses a case of maternal homicide which occurred in the course of a major affective disorder. The relationship between mental illness and criminality is reviewed with a particular emphasis on affective disorder in relation to filicide. A number of significant issues are dealt with including consequences of failure to elicit positive family history of affective disorder, suicide and filicide. Indeed, a history of familial double filicide raises the question of possible hereditary influences. The significance of hypochondriacal symptomatology in the course of the illness and the role of steroids in precipitating or aggravating a psychotic depression also need to be explored. It primarily addresses the importance of prevention and recognition of risk factors associated with child murder committed by depressed parents.

  5. Subjective and objective binge eating in relation to eating disorder symptomatology, negative affect, and personality dimensions.

    Science.gov (United States)

    Brownstone, Lisa M; Bardone-Cone, Anna M; Fitzsimmons-Craft, Ellen E; Printz, Katherine S; Le Grange, Daniel; Mitchell, James E; Crow, Scott J; Peterson, Carol B; Crosby, Ross D; Klein, Marjorie H; Wonderlich, Stephen A; Joiner, Thomas E

    2013-01-01

    The current study explored the clinical meaningfulness of distinguishing subjective (SBE) from objective binge eating (OBE) among individuals with threshold/subthreshold bulimia nervosa (BN). We examined relations between OBEs and SBEs and eating disorder symptoms, negative affect, and personality dimensions using both a group comparison and a continuous approach. Participants were 204 adult females meeting criteria for threshold/subthreshold BN who completed questionnaires related to disordered eating, affect, and personality. Group comparisons indicated that SBE and OBE groups did not significantly differ on eating disorder pathology or negative affect, but did differ on two personality dimensions (cognitive distortion and attentional impulsivity). Using the continuous approach, we found that frequencies of SBEs (not OBEs) accounted for unique variance in weight/shape concern, diuretic use frequency, depressive symptoms, anxiety, social avoidance, insecure attachment, and cognitive distortion. SBEs in the context of BN may indicate broader areas of psychopathology. Copyright © 2012 Wiley Periodicals, Inc.

  6. Identification of rare high-risk copy number variants affecting the dopamine transporter gene in mental disorders

    DEFF Research Database (Denmark)

    Hoeffding, Louise Kristine Enggaard; Duong, Linh T T; Ingason, Andres

    2016-01-01

    rare high-risk variants of psychiatric disorders. METHODS: We performed a systematic screening for CNVs affecting SLC6A3 in 761 healthy controls, 672 schizophrenia patients, and 194 patients with bipolar disorder in addition to 253 family members from six large pedigrees affected by mental disorders...

  7. Gait unsteadiness and fall risk in two affective disorders: a preliminary study

    Directory of Open Access Journals (Sweden)

    Peng Chung-Kang

    2004-11-01

    Full Text Available Abstract Background In older adults, depression has been associated with increased fall risk, but the reasons for this link are not fully clear. Given parallels between major depression and Parkinson's disease, we hypothesized that major depression and related affective disorders would be associated with impairment in the ability to regulate the stride-to-stride fluctuations in gait cycle timing. Methods We measured stride-to-stride fluctuations of patients with two forms of mood disorders, unipolar major depressive disorder (MDD and bipolar disorder, and compared their gait to that of a healthy control group. The primary outcomes were two measures of gait unsteadiness that have been associated with fall risk: stride time variability and swing time variability. Results Compared to the control group, the two patient groups tended to walk more slowly and with decreased swing time and increased stride time. However, none of these differences was statistically significant. Compared to the control group, swing time variability was significantly larger in the subjects with bipolar disorder (p Conclusions Patients with MDD and patients with bipolar disorder display gait unsteadiness. This perturbation in gait may provide a mechanistic link connecting depression and falls. The present findings also suggest the possibility that measurement of variability of gait may provide a readily quantifiable objective approach to monitoring depression and related affective disorders.

  8. The joint structure of major depression, anxiety disorders, and trait negative affect

    Directory of Open Access Journals (Sweden)

    Hudson W. de Carvalho

    2014-12-01

    Full Text Available Background: Dimensional models of psychopathology demonstrate that two correlated factors of fear and distress account for the covariation among depressive and anxiety disorders. Nevertheless, these models tend to exclude variables relevant to psychopathology, such as temperament traits. This study examined the joint structure of DSM-IV-based major depression and anxiety disorders along with trait negative affect in a representative sample of adult individuals residing in the cities of São Paulo and Rio de Janeiro, Brazil. Methods: The sample consisted of 3,728 individuals who were administered sections D (phobic, anxiety and panic disorders and E (depressive disorders of the Composite International Diagnostic Interview (CIDI 2.1 and a validated version of the Positive and Negative Affect Schedule. Data were analyzed using correlational and structural equation modeling. Results: Lifetime prevalence ranged from 2.4% for panic disorder to 23.2% for major depression. Most target variables were moderately correlated. A two-factor model specifying correlated fear and distress factors was retained and confirmed for models including only diagnostic variables and diagnostic variables along with trait negative affect. Conclusions: This study provides support for characterization of internalizing psychopathology and trait negative affect in terms of correlated dimensions of distress and fear. These results have potential implications for psychiatric taxonomy and for understanding the relationship between temperament and psychopathology.

  9. Functional connectivity of pain-mediated affect regulation in Borderline Personality Disorder.

    Directory of Open Access Journals (Sweden)

    Inga Niedtfeld

    Full Text Available Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD.We used psychophysiological interactions to analyze functional connectivity of (para- limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral affect and subsequently applying heat pain (versus warmth perception.Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen, as well areas involved in self-referential processing (precuneus and posterior cingulate.We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia.

  10. Comparative clinical characteristics of depression in bipolar affective disorders