Kocerha, Jannet; Kauppinen, Sakari; Wahlestedt, Claes
RNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact...
Neis, Vivian B; Rosa, Priscila B; Olescowicz, Gislaine; Rodrigues, Ana Lúcia S
Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.
Verberne, Lisa M; Maurice-Stam, Heleen; Grootenhuis, Martha A; Van Santen, Hanneke M; Schouten-Van Meeteren, Antoinette Y N
The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with clinical characteristics and daily performance (fatigue and psychosocial functioning). In a cross-sectional study at the outpatient clinic of the Emma Children's Hospital AMC (February-June 2010), sleep, fatigue and psychosocial functioning were analysed in 31 CNS tumour patients (mean age: 11.8years; 20 boys) and compared with 78 patients treated for a non-CNS malignancy (mean age: 9.7years; 41 boys) and norm data. Questionnaires applied were the Sleep Disorder Scale for Children, the Epworth Sleepiness Scale, the Pediatric Quality of Life Inventory, and the Strengths and Difficulties Questionnaire. Sleeping habits and endocrine deficiencies were assessed with a self-developed questionnaire. Increased somnolence was found in CNS tumour patients compared with those with a non-CNS malignancy (8.8±2.8 versus 7.5±2.7; Psleep. No specific risk factors were identified for a sleep disorder in CNS tumour patients, but their excessive somnolence was correlated with lower fatigue related quality of life (QoL) (r=-0.78, Psleep quality and diminish fatigue. © 2011 European Sleep Research Society.
Verberne, Lisa M.; Maurice-Stam, Heleen; Grootenhuis, Martha A.; van Santen, Hanneke M.; Schouten-van Meeteren, Antoinette Y. N.
The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with
Starzyk, Jerzy; Kwiatkowski, Stanisław; Kaciński, Marek; Kroczka, Sławomir; Wójcik, Małgorzata
suprasellar arachnoid cyst (7 patients), septo-optic dysplasia (8 patients), craniopharyngioma (15 patients), glioma of the optic chiasm in neurofibromatosis type 1 (NF-1) (12 patients). There were no endocrine disorders in any of the ten patients with hamartoma of the hypothalamus and CPP. Endocrine and/ or neurological disorders did not resolve or were progressive after neurosurgery. Of 42 patients, a group of seven children representative for individual disorders was selected. In those patients, the etiology of both endocrine disorders, epilepsy and neuropsychiatric disorders was suspected to be common. 1. Various structural CNS abnormalities are the cause of concomitant epilepsy and endocrinopathy, although in some cases a direct impact of a genetic factor on the occurrence of both disorders or a mere coincidence cannot be ruled out. 2. Psychoneurological disorders usually precede the onset of endocrinopathy. 3. For this reason, MR or CT CNS imaging should be performed in any case of central neurological disorders, disorders of behavior, epilepsy, obsessive-compulsive syndrome, but also in patients with delayed psycho-motor development, delayed or accelerated growth and pubertal development. All of the above-mentioned manifestations may be symptoms of structural CNS abnormalities and their early treatment determines the child's future.
Kikukawa, Kaoru; Toyama, Hiroshi; Katayama, Masao
We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lode in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients. (author)
London, Anat; Benhar, Inbal; Schwartz, Michal
Philosophers defined the eye as a window to the soul long before scientists addressed this cliché to determine its scientific basis and clinical relevance. Anatomically and developmentally, the retina is known as an extension of the CNS; it consists of retinal ganglion cells, the axons of which form the optic nerve, whose fibres are, in effect, CNS axons. The eye has unique physical structures and a local array of surface molecules and cytokines, and is host to specialized immune responses similar to those in the brain and spinal cord. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies share characteristics of other CNS pathologies. In this Review, we summarize data that support examination of the eye as a noninvasive approach to the diagnosis of select CNS diseases, and the use of the eye as a valuable model to study the CNS. Translation of eye research to CNS disease, and deciphering the role of immune cells in these two systems, could improve our understanding and, potentially, the treatment of neurodegenerative disorders.
Starzyk, Jerzy; Pituch-Noworolska, Anna; Pietrzyk, Jacek A; Urbanik, Andrzej; Kroczka, Sławomir; Drozdz, Ryszard; Wójcik, Małgorzata
chiasm glioma (2 patients), suprasellar germinal tumor (1 patient), ii) children with Hashimoto encephalopathy (2 patients), iii) children with Prader-Willi syndrome (20 patients), with Klinefelter syndrome (10 patients), with Albright syndrome (9 patients). Of the 49 patients, a group of 6 children representative for individual disorders was selected. In those patients, the etiology of both endocrine disorders, epilepsy and neuropsychiatric disorders was suspected to be common, and the diagnosis was usually delayed. 1. Cranial irradiation and chemotherapy, encephalopathy associated with Hashimoto disease and some of the syndromes with the chromosomal and genetic background are the causes of non-structural CNS abnormalities and coincidence of endocrinopathies, epilepsy and psychoneurologic disorders. 2. MR/CT CNS imaging should be performed in any case of central neurological disorders, disorders of behavior, epilepsy or seizures, but also in patients with delayed psycho-motor development, delayed or accelerated growth and pubertal development. All of the above-mentioned manifestations may be symptoms of structural CNS abnormalities and their early treatment determines the child's future. 3. Excluding structural CNS abnormalities allows for forming suspicions associated with diseases resulting in non-structural disorders of the CNS function, predisposing to coincidence of endocrine and neurological disorders. 4. In the diagnosis of Hashimoto's encephalopathy, a decisive factor is exclusion of structural, infectious, traumatic and metabolic causes, intoxications, epilepsy and presence of neuropsychiatric symptoms in patients with high level of against TPO antibodies. In cases of steroids resistance, a good therapeutic effect may be achieved by plasmapheresis, Rituximab therapy and progestagene inhibition of the menstrual cycle.
Shan, Ling; Dauvilliers, Yves; Siegel, Jerome M
Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system.
Koizumi, J; Ofuku, K; Sakuma, K; Shiraishi, H; Iio, M; Nawano, S
CNS changes in a case of Usher's syndrome associated with schizophrenia-like mental disorder were observed by CT, MRI and PET. The neuro-radiological findings of the case demonstrate the degenerative and metabolic alterations in various regions of cortex, white matter and subcortical areas in the brain. Mental disorder of the case is almost indistinguishable from that of schizophrenia, but the psychotic feature is regarded as an atypical or mixed organic brain syndrome according to the classification in the third edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III). Images PMID:3264568
NOVELTY - For treatment of a CNS disease in a patient, dihydro-isobenzofuran compound (I) in combination with serotonin reuptake inhibitor, is used. USE - For treatment of CNS disease (claimed) including depression, anxiety, bipolar disorder, obsessive compulsory disorder, post traumatic stress d...
Ivachtchenko, Alexandre V; Lavrovsky, Yan; Okun, Ilya
Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2-2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41-3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer's disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis.
Nickols, Hilary Highfield; Conn, P Jeffrey
The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders. Traditional drug discovery efforts targeting GPCRs have focused on developing ligands for orthosteric sites which bind endogenous ligands. Allosteric modulators target a site separate from the orthosteric site to modulate receptor function. These allosteric agents can either potentiate (positive allosteric modulator, PAM) or inhibit (negative allosteric modulator, NAM) the receptor response and often provide much greater subtype selectivity than orthosteric ligands for the same receptors. Experimental evidence has revealed more nuanced pharmacological modes of action of allosteric modulators, with some PAMs showing allosteric agonism in combination with positive allosteric modulation in response to endogenous ligand (ago-potentiators) as well as "bitopic" ligands that interact with both the allosteric and orthosteric sites. Drugs targeting the allosteric site allow for increased drug selectivity and potentially decreased adverse side effects. Promising evidence has demonstrated potential utility of a number of allosteric modulators of GPCRs in multiple CNS disorders, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as psychiatric or neurobehavioral diseases such as anxiety, schizophrenia, and addiction. © 2013.
Antunovic, V.; Samardzic, M.; Levic, Z.; Dragutinovic, G.
An introduction of CT and MRI methods resulted in revolutionary changes in the imaging of central nervous systems diseases. The reliability of the use of MRI in the diagnosis of neurological disorders enabled accurate localization, visualization, and anatomical relation and determination of the nature of different pathological processes in the brain and spinal cord. In the past, it had been very difficult to make such precise diagnosis. A result of this fact is a great improvement of treatment of the patients with C.N.S. disorders. The other advantages are excellent possibilities for an assessment of the results of the therapeutical procedures and accurate follow-up of the cases. This was the reason that the authors wanted to make a review of the MRI and clinical characteristic of different neurological and neurosurgical conditions from their wide clinical practice and to determine and illustrate the importance of MRI in the diseases of the brain and spinal cord. (orig.)
Eissa, T A F; Palomino, O M; Carretero, M E; Gómez-Serranillos, M P
To provide ethnopharmacological information on the use of medicinal plants for central nervous system (CNS) disorders in the Sinai Peninsula region (Egypt). To collect, analyze and evaluate the ethnobotanical knowledge about these medicinal plants in the Sinai Peninsula region with 61,000 km (2) and 379,000 inhabitants. Field work was concluded between March 2006 and May 2011, using semi-structured questionnaire with 700 informants (mean age: 59; 100% men) from 117 settlements of 17 Bedouin tribes. Transects walks in wild herbal plant collection areas and bibliographical review on the collected plants were also conducted. The Interview/ Inhabitant index (I/P), relative importance value of the species and informant consensus factor (FIC) were calculated. More than 300 species were traditionally used in folk medicine in the Sinai Peninsula; 101 of these species belonging to 40 families were reported as useful in different CNS disorders. Only 5 species are endemic of the studied area. All different part plants were used, leaves and aerial parts being the most frequent. Most of the remedies were prepared as infusion or decoction, while oral administration was the most common way to be used. Gastrointestinal (67.3%) and respiratory disorders (42.57%) were also reported as frequently treated by Bedouins with herbal remedies. Only a few species were found where the traditional use is supported by pharmacological studies (Acacia nilotica, Achillea fragrantissima, Ajuga iva or Mentha longifolia). No bibliographical references in the scientific literature were found for 22 species (21.78%); finally, several studies were published with different pharmacological activities than those provided by Bedouins. © 2013 The Authors. Published by Elsevier Ireland Ltd All rights reserved.
Boguszewska-Czubara, Anna; Budzynska, Barbara; Skalicka-Wozniak, Krystyna; Kurzepa, Jacek
Matrix metalloproteinases (MMPs) play a key role in remodelling of the extracellular matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation and survival. Their importance in variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but special attention should be paid on the role of MMPs in the central nervous system (CNS) disorders. Till now, there are not many well documented physiological MMP target proteins in the brain and only some pathological ones. Numerous neurodegenerative diseases is a consequence or result in disturbed remodeling of brain ECM, therefore proper action of MMPs as well as control of their activity may play crucial roles in the development and the progress of these diseases. In present review we discuss the role of metalloproteinase inhibitors, from the well-known natural endogenous tissue inhibitors of metalloproteinases (TIMPs) through exogenous synthetic ones like (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT), tetracyclines, batimastat (BB-94) and FN-439. As the MMP-TIMP system has been well described in physiological development as well as in pathological conditions mainly in neoplasctic diseases, the knowledge about the enzymatic system in mammalian brain tissue remain still poorly understood in this context. Therefore, we focus on MMPs inhibition in the context of physiological function of adult brain as well as pathological conditions including neurodegenerative diseases, brain injuries and others. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Full Text Available Background – There is increasing evidence that the transplanted bone marrow stromal cells (BMSC significantly promote functional recovery after central nervous system (CNS damage in the animal models of various kinds of CNS disorders, including cerebral infarct, brain contusion and spinal cord injury. However, there are several shortages of information when considering clinical application of BMSC transplantation for patients with neurological disorders. In this paper, therefore, we discuss what we should clarify to establish cell transplantation therapy in clinical situation and describe our recent works for this purpose.Methods and Results – The BMSC have the ability to alter their gene expression profile and phenotype in response to the surrounding circumstances and to protect the neurons by producing some neurotrophic factors. They also promote neurite extension and rebuild the neural circuits in the injured CNS. Using optical imaging and MRI techniques, the transplanted BMSC can non-invasively be tracked in the living animals for at least 8 weeks after transplantation. Functional imaging such as PET scan may have the potential to assess the beneficial effects of BMSC transplantation. The BMSC can be expanded using the animal protein-free culture medium, which would maintain their potential of proliferation, migration, and neural differentiation.Conclusion – It is urgent issues to develop clinical imaging technique to track the transplanted cells in the CNS and evaluate the therapeutic significance of BMSC transplantation in order to establish it as a definite therapeutic strategy in clinical situation in the future
Vieta, Eduard; Salagre, Estela; Grande, Iria; Carvalho, André F; Fernandes, Brisa S; Berk, Michael; Birmaher, Boris; Tohen, Mauricio; Suppes, Trisha
Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and
Malykh, Andrei G; Sadaie, M Reza
There is an increasing interest in nootropic drugs for the treatment of CNS disorders. Since the last meta-analysis of the clinical efficacy of piracetam, more information has accumulated. The primary objective of this systematic survey is to evaluate the clinical outcomes as well as the scientific literature relating to the pharmacology, pharmacokinetics/pharmacodynamics, mechanism of action, dosing, toxicology and adverse effects of marketed and investigational drugs. The major focus of the literature search was on articles demonstrating evidence-based clinical investigations during the past 10 years for the following therapeutic categories of CNS disorders: (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety. In this article, piracetam-like compounds are divided into three subgroups based on their chemical structures, known efficacy and intended clinical uses. Subgroup 1 drugs include piracetam, oxiracetam, aniracetam, pramiracetam and phenylpiracetam, which have been used in humans and some of which are available as dietary supplements. Of these, oxiracetam and aniracetam are no longer in clinical use. Pramiracetam reportedly improved cognitive deficits associated with traumatic brain injuries. Although piracetam exhibited no long-term benefits for the treatment of mild cognitive impairments, recent studies demonstrated its neuroprotective effect when used during coronary bypass surgery. It was also effective in the treatment of cognitive disorders of cerebrovascular and traumatic origins; however, its overall effect on lowering depression and anxiety was higher than improving memory. As add-on therapy, it appears to benefit individuals with myoclonus epilepsy and tardive dyskinesia. Phenylpiracetam is more potent than piracetam and is used for a wider range of indications. In combination with a vasodilator drug, piracetam appeared to have an additive beneficial effect on various
Blinder, G.; Corat-Simon, J.; Hershkovitz, E.
We describe a case of two known pathologies of the CNS in an unusual association: the concomitant presentation of the micropituitarism and cortical dysplasia. To our knowledge, this association is unreported to date. (orig.)
Blinder, G. [MAR Bikur Cholim Hospital Jerusalem (MOR-MAR), Jerusalem (Israel); Corat-Simon, J. [Dept. of Radiology, Assaf Harofeh Medical Center, Zrifin, Beer Jakov (Israel); Hershkovitz, E. [Dept. of Pediatrics, Soroka Medical Center, Beer Sheba (Israel)
We describe a case of two known pathologies of the CNS in an unusual association: the concomitant presentation of the micropituitarism and cortical dysplasia. To our knowledge, this association is unreported to date. (orig.)
With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Jennifer H Campbell
Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.
Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C
Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.
Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.
Donnerstag, Frank; Ding, Xiaoqi; Bueltmann, Eva; Zajaczek, Jan; Lanfermann, Heinrich; Pape, Lars; Das, Anibh Martin; Ehrich, Jochen; Hartmann, Hans; Luecke, Thomas; Hoy, Ludwig
Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively. DWI within 24 h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings. DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality. In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome. (orig.)
Donnerstag, Frank; Ding, Xiaoqi; Bueltmann, Eva; Zajaczek, Jan; Lanfermann, Heinrich [Hannover Medical School, Institute of Diagnostic and Therapeutic Neuroradiology, Hannover (Germany); Pape, Lars; Das, Anibh Martin; Ehrich, Jochen; Hartmann, Hans [Hannover Medical School, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover (Germany); Luecke, Thomas [Hannover Medical School, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover (Germany); University of Bochum, Department of Neuropediatrics, Pediatric Hospital, Bochum (Germany); Hoy, Ludwig [Hannover Medical School, Institute of Biometrics, Hannover (Germany)
Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively. DWI within 24 h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings. DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality. In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome. (orig.)
Full Text Available In this special issue of Frontiers in Neuropharmacology, we have asked leading experts to comment and review the evidence that inflammatory cells play a leading role in the pathological processes underlying neurodegenerative disorders. We now seek to draw these various observations together into a conclusion, with the hope that this will inform further work in this area and lead to the identification of new therapeutic targets that will have a disease modifying effect.
Sagrillo-Fagundes, Lucas; Assunção Salustiano, Eugênia Maria; Yen, Philippe Wong; Soliman, Ahmed; Vaillancourt, Cathy
Melatonin is an important neuroprotective factor and its receptors are expressed in the fetal brain. During normal pregnancy, maternal melatonin level increases progressively until term and is highly transferred to the fetus, with an important role in brain formation and differentiation. Maternal melatonin provides the first circadian signal to the fetus. This indolamine is also produced de novo and plays a protective role in the human placenta. In pregnancy disorders, both maternal and placental melatonin levels are decreased. Alteration in maternal melatonin level has been associated with disrupted brain programming with long-term effects. Melatonin has strong antioxidant protective effects directly and indirectly via the activation of its receptors. The fetal brain is highly susceptible to oxygenation variation and oxidative stress that can lead to neuronal development disruption. Based on that, several approaches have been tested as a treatment in case of pregnancy disorders and melatonin, through its neuroprotective effect, has been recently accepted against fetal brain injury. This review provides an overview about the protective effects of melatonin during pregnancy and on fetal brain development.
Full Text Available Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to test the therapeutic potential of glutaminase inhibition. We specifically asked whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAG ERT2 cre/+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction — mimicking pharmacological inhibition — strongly
Kirkman, Matthew A; Pickles, Jessica C; Fairchild, Amy R; Avery, Aimee; Pietsch, Torsten; Jacques, Thomas S; Aquilina, Kristian
Advances in molecular profiling have facilitated the emergence of newly defined entities of central nervous system tumor, including CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Relatively little is known about the clinical behaviour of these newly-characterized tumors. We describe a pediatric male patient with CNS HGNET-BCOR who developed seeding of the tumor into the site of the surgical wound within months of surgery for resection of a residual posterior fossa tumor. This case emphasises three important points. First, CNS HGNET-BCOR can be aggressive tumors that necessitate close clinical and radiological surveillance. Second, surveillance imaging in such cases should incorporate the surgical incision site into the field of view, and this should be closely scrutinised to ensure the timely detection of wound site seeding. Third, wound site seeding may still occur despite the use of meticulous surgical techniques. Copyright © 2018. Published by Elsevier Inc.
Full Text Available Giovanna TrainaDepartment of Economics and Food Sciences, University of Perugia, Perugia, ItalyAbstract: L-carnitine (LC is part of the carnitine shuttle system at the mitochondrial inner membrane (MIM and transports long chain fatty acids over the MIM route. Acetyl-L -carnitine (ALC, the acetyl ester of LC, plays an essential role in intermediary metabolism. To ALC are ascribed neurotrophic actions, antioxidant and antiapoptotic activity, positive effects on mitochondrial metabolism, and stabilization of intracellular membranes. Acylcarnitine and LC supplementation have shown beneficial effects in the treatment of aging, chronic degenerative pathologies and the slowing of the progression of mental deterioration in neurodegenerative diseases, and painful neuropathies. ALC is reported to affect brain energy and phospholipid metabolism and to interact with cell membranes, proteins, and enzymes. It also shows a neuromodulatory effect on synaptic morphology and neurotransmitter synaptic transmission, including that of acetylcholine and dopamine. All these data suggest that ALC can affect several targets in the central nervous system. The roles and effects of LC and ALC have led researchers to investigate carnitine's involvement in a variety of neuropathological states and treatments, including autism, Parkinson's disease, Alzheimer's disease, Down's syndrome, Huntington's disease, cerebellar ataxia, age-associated mental decline, hepatic encephalopathy, and ammonia neurotoxicity. This review summarizes evidence that carnitine analogs play many roles in serious neurological pathologies.Keywords: L-carnitine, acetyl-L-carnitine, brain, neural disorders
Full Text Available Arrival of encephalitogenic T cells at inflammatory foci represents a critical step in development of experimental autoimmune encephalomyelitis (EAE, the animal model for multiple sclerosis. EBI2 and its ligand, 7α,25-OHC, direct immune cell localization in secondary lymphoid organs. CH25H and CYP7B1 hydroxylate cholesterol to 7α,25-OHC. During EAE, we found increased expression of CH25H by microglia and CYP7B1 by CNS-infiltrating immune cells elevating the ligand concentration in the CNS. Two critical pro-inflammatory cytokines, interleukin-23 (IL-23 and interleukin-1 beta (IL-1β, maintained expression of EBI2 in differentiating Th17 cells. In line with this, EBI2 enhanced early migration of encephalitogenic T cells into the CNS in a transfer EAE model. Nonetheless, EBI2 was dispensable in active EAE. Human Th17 cells do also express EBI2, and EBI2 expressing cells are abundant within multiple sclerosis (MS white matter lesions. These findings implicate EBI2 as a mediator of CNS autoimmunity and describe mechanistically its contribution to the migration of autoreactive T cells into inflamed organs.
Full Text Available A major challenge for the treatment of many central nervous system (CNS disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S. I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b may have broader implications for CNS treatment with biopharmaceuticals.
Grupe, Morten; Grunnet, Morten; Bastlund, Jesper F.
The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional character......The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional...... characteristics, expression pattern and pharmacological profile. The focus of the present MiniReview is on the heteromeric α4β2 nAChR, as activity at this subtype contributes to cognitive functioning through interactions with multiple neurotransmitter systems and is implicated in various CNS disorders...... and temporal aspects of neurotransmission as well as higher subtype selectivity, hypothetically resulting in high clinical efficacy with minimal adverse effects. In this MiniReview, we describe the currently identified compounds, which potentiate the effects of agonists at the α4β2 nAChR. The potential...
Hansen, Niels-Chr. G.; Laursen, Christian B.; Jeppesen, Stefan S.
whether the introduction in 2010 of follow-up by CT of thorax and upper abdomen every three months has reduced the incidence of relapse suspected from CNS-symptoms.Results: All 827 NSCLC patients from Funen completing curative treatment from 2005 to 2013 were included. The total number of relapses found...... or III were found.Conclusion: CT-based follow-up has not reduced the incidence of relapse suspected from CNS-symptoms in stage II-IV, and therefore we suggest routine MR of the brain before curative treatment for this group of patients.Number, fractions(%), and [95%CI]Jan. 2005 - June 2010July 2010 - Dec...... after symptoms within 24 months decreased in the 3½ years after the introduction of CT-based follow-up, p < 0,001 (table), but the total fraction presenting with CNS-symptoms did not change, p = 0.296. Relapses after stage I cancer decreased (p = 0.025), while no differences or changes for stages II...
Full text: Clinical suspicion of a developmental anomaly of the central nervous system (CNS) is a frequent indication for performing and magnetic resonance imaging (MRI) examination of the brain. Classification systems for malformation of the CNS are constantly revised according to newer scientific research. Developmental abnormalities can be classified in two main types. The first category consists of disorders of organogenesis in which genetic defects or any ischemic, metabolic, toxic or infectious insult to the developing brain can cause malformation. These malformations result from abnormal neuronal and glial proliferation and from anomalies of neuronal migration and or cortical organization. They are divided into supra- and infratentorial and may involve grey or white matter or both. The second category of congenital brain abnormalities is disorders of histogenesis which result from abnormal cell differentiation with a relatively normal brain appearance. Supratentorial CNS malformations could be divided into anomalies in telencephalic commissure, holoprosencephalies and malformations in cortical development. There are three main telencephalic commissures: the anterior commissure, the hippocampal commissure and the corpus callosum. Their morphology (hypoplasia, hyperplasia, agenesis, dysgenesis, even atrophy) reflects the development of the brain. Their agenesis, complete or partial, is one of the most commonly observed features in the malformations of the brain and is a part of many syndromes. Malformations of cortical development (MCD) are heterogeneous group of disease which result from disruption of 3 main stages of cortical development. The common clinical presentation is refractory epilepsy and or developmental delay. The most common MCD are heterotopias, focal cortical dysplasia, polymicrogyria, schizencephaly, pachygyria and lizencephaly. The exact knowledge of the brain anatomy and embryology is mandatory to provide a better apprehension of the
de Codt, Aloise; Monhonval, Pauline; Bongaerts, Xavier; Belkacemi, Ikram; Tecco, Juan Martin
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
Chanen, Andrew M; Berk, Michael; Thompson, Katherine
Borderline personality disorder (BPD) has been demonstrated to be a reliable and valid construct in young people (adolescents and young adults). Both borderline- and mood-related psychopathology become clinically apparent from puberty through to young adulthood, frequently co-occur, can reinforce one another, and can be difficult to differentiate clinically. This Gordian knot of overlapping clinical features, common risk factors, and precursors to both BPD and mood disorders complicates clinical assessment, prevention, and treatment. Regardless of whether an individual crosses an arbitrary diagnostic threshold, a considerable proportion of young people with borderline- and mood-related psychopathology will develop significant and persistent functional, vocational, and interpersonal impairment and disability during this critical risk and developmental period. There is a clear need for early intervention, but spurious diagnostic certainty risks stigma, misapplication of diagnostic labels, inappropriate treatment, and unfavorable outcomes. This article aims to integrate early intervention for BPD and mood disorders in the clinical context of developmental and phenomenological change and evolution. "Clinical staging," similar to disease staging in general medicine, is presented as a pragmatic, heuristic, and trans-diagnostic framework to guide prevention and intervention. It acknowledges that the early stages of these disorders cannot be disentangled sufficiently to allow for disorder-specific preventive measures and early interventions. Clinical staging defines an individual's location along the continuum of the evolving temporal course of a disorder. Such staging aids differentiation of early or milder clinical phenomena from those that accompany illness progression and chronicity, and suggests the application of appropriate and proportionate intervention strategies.
Saugstad, L F
The maturational theory of brain development comprises manic depressive psychosis and schizophrenia. It holds that the disorders are part of human diversity in growth and maturation, which explains their ubiquity, shared susceptibility genes and multifactorial inheritance. Rate of maturation and age at puberty are the genotype; the disorders are localized at the extremes with normality in between. This is based on the association between onset of puberty and the final regressive event, with pruning of 40% of excitatory synapses leaving the inhibitory ones fairly unchanged. This makes excitability, a fundamental property of nervous tissue, a distinguishing factor: the earlier puberty, the greater excitability--the later puberty, the greater deficit. Biological treatment supports deviation from the norm: neuroleptics are convulsant; antidepressives are anti-epiletogenic. There is an association between onset of puberty and body-build: early maturers are pyknic broad-built, late ones linearly leptosomic. This discrepancy is similar to that in the two disorders, supporting the theory that body-build is the phenotype. Standard of living is the environmental factor, which affects pubertal age and shifts the panorama of mental illness accordingly. Unnatural death has increased with antipsychotics. Other treatment is needed. PUFA deficit has been observed in RBC in both disorders and striking improvements with addition of minor amounts of PUFA. This supports that dietary deficit might cause psychotic development and that prevention is possible. Other neurological disorders also profit from PUFA, underlining a general deficit in the diet.
Full Text Available Takotsubo syndrome (TTS is usually triggered by psychological or physical stress. One of the many physical sources of stress are central nervous system (CNS disorders. CNS disorders most frequently triggering TTS include subarachnoid bleeding, epilepsy, ischemic stroke, migraine, and intracerebral bleeding. More rare CNS-triggers of TTS include posterior reversible encephalopathy syndrome (PRES, amyotrophic lateral sclerosis, encephalitis, or traumatic brain or spinal cord injury. TTS triggered by any of the CNS disorders needs to be recognized since adequate treatment of TTS may improve the general outcome from the CNS disorder as well. Neurologists need to be aware of TTS as a complication of specific CNS disorders but TTS may be triggered also by CNS disorders so far not recognised as causes of TTS.
Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré
BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple,...... barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery....
Caroline Elizabeth Konradt
Full Text Available OBJECTIVE: To verify early experiences of childhood abuse and neglect among young with bipolar disorder (BD, major depression (MDD, and controls. METHOD: Case-control study nested to a population-based cross-sectional study. The diagnosis was performed via the structured clinical interview for DSM-IV Axis I Disorders (SCID. Traumatic events were analyzed using the Portuguese version - Questionário sobre Traumas na Infância (CTQ - based on the Childhood Trauma Questionnaire. RESULTS: The sample comprised 231 adolescents with 95 individuals in the control group, 82 with MDD and 54 with BD (32 of type I and 22 type II. The prevalence of trauma or violence in childhood was 42.2%; among those, 54.7% had BD, 62.2% had MDD and 18.1% were in the control group. Young people with BD or MDD obtained higher means in total CTQ and among their components when compared with those in the control group. DISCUSSION: Reports on early traumatic experiences were more frequent among young people with mood disorders than in the general population, corroborating the literature on the subject. In this sense, the traumatic experiences during childhood seemed to contribute to the onset of the disorder.
Full Text Available Background: Eating Disorders (EDs are characterized by a persistent disturbance of eating or eating-related behavior that significantly impairs physical health or psychosocial functioning. EDs are caused by a complex interaction of genetic, biological, behavioral, psychological, and social factors. Their epidemiology is rising for the past decades, and EDs affect all races, social levels and both genders. Due to the long and expensive treatment, chronic course, and the fact that most of the sufferers do not realize the need for therapy or do not seek treatment, the demand on developing prevention programs, early detection and assessment is essential. Despite the fact, that many new EDs screening tools were developed already, there is a great lack of validated screening instruments, adapted to the Bulgarian conditions. Objects and methods: Our study aimed at eliciting a comprehensive battery for screening of not only specific ED pathology, but also some risk factors, such as negative body image, weight and depressive symptoms. The object of our study consisted of 201 females, aged 18 to 45 (mean 24.65. SCOOF- questionnaire, Eating Disorder Diagnostic Scale (EDDS-5, Body Image Questionnaire-34 and Beck Depression Inventory (BDI were applied. Results: Our preliminary results show that approximately 45% of the tested subjects show some of the: negative body image, eating disorders’ clinical pathology, distorted eating patterns, subclinical eating disorders pathology, overweight/obesity, or depressive symptoms. Conclusion: Our ongoing efforts in area of research also are aimed at developing and refining strategies for preventing and treating ED among adolescents and adults.
Full Text Available Abstract Background Thought and language disorders are main features of adults with schizophrenia and bipolar disorders however studies on such abnormalities are scant in young patients with very early onset psychosis (VEOS. The aim of the present study is to assess the relationship between language and thought disorders in patients with very early onset schizophrenia (SCZ, schizoaffective disorders (SCA and bipolar disorders (BD. Method Forty-one patients (18 SCZ, 16 BD, and 7 SCA with mean age less than 15 years old were assessed through a series of neurocognitive and psycholinguistic tests, including the Thought, Language and Communication Scale (TLC. Results SCZ group performed worse in all tests as well as the TLC, followed by SCA and BD groups respectively. Thought disorders were related to deficits in executive functioning and semantic processing, and the metaphors’ test was the best predictor of TLC functioning. Discussion TD in SCZ, SCA and BD are one of the most important features in patients with VEOS and that the evaluation of metaphor comprehension can be an important instrument in the early detection of this disorder.
Chavushyan, V A; Simonyan, K V; Simonyan, R M; Isoyan, A S; Simonyan, G M; Babakhanyan, M A; Hovhannisyian, L E; Nahapetyan, Kh H; Avetisyan, L G; Simonyan, M A
Excess dietary fructose intake associated with metabolic syndrome and insulin resistance and increased risk of developing type 2 diabetes. Previous animal studies have reported that diabetic animals have significantly impaired behavioural and cognitive functions, pathological synaptic function and impaired expression of glutamate receptors. Correction of the antioxidant status of laboratory rodents largely prevents the development of fructose-induced plurimetabolic changes in the nervous system. We suggest a novel concept of efficiency of Stevia leaves for treatment of central diabetic neuropathy. By in vivo extracellular studies induced spike activity of hippocampal neurons during high frequency stimulation of entorhinal cortex, as well as neurons of basolateral amygdala to high-frequency stimulation of the hippocampus effects of Stevia rebaudiana Bertoni plant evaluated in synaptic activity in the brain of fructose-enriched diet rats. In the conditions of metabolic disorders caused by fructose, antioxidant activity of Stevia rebaudiana was assessed by measuring the NOX activity of the hippocampus, amygdala and spinal cord. In this study, the characteristic features of the metabolic effects of dietary fructose on synaptic plasticity in hippocampal neurons and basolateral amygdala and the state of the NADPH oxidase (NOX) oxidative system of these brain formations are revealed, as well as the prospects for development of multitarget and polyfunctional phytopreparations (with adaptogenic, antioxidant, antidiabetic, nootropic activity) from native raw material of Stevia rebaudiana. Stevia modulates degree of expressiveness of potentiation/depression (approaches but fails to achieve the norm) by shifting the percentage balance in favor of depressor type of responses during high-frequency stimulation, indicating its adaptogenic role in plasticity of neural networks. Under the action of fructose an increase (3-5 times) in specific quantity of total fraction of NOX
Dirani, Leyla Akoury; Salamoun, Mariana
Children with neurodevelopmental disorders who receive early therapeutic interventions present a better developmental pathway than children who do not. Early assessment of neurodevelopmental disorders is the first step in this process. This study aims at describing the variables that are in play in the first assessment of children with autism…
Telgote, Shilpa A; Pendharkar, Shreyas Shrikant; Kelkar, Amol D; Bhojane, Sachin
Very early-onset schizophrenia (defined as an onset of psychosis before 13 years of age) is a rare and severe form of the disorder which is clinically and neurobiologically continuous with the adult-onset disorder. It is rarely reported tic disorder.
Luby, Joan L.; Navsaria, Neha
Background: Childhood bipolar disorder remains a controversial but increasingly diagnosed disorder that is associated with significant impairment, chronic course and treatment resistance. Therefore, the search for prodromes or early markers of risk for later childhood bipolar disorder may be of great importance for prevention and/or early…
Campbell, Jennifer H.; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J.; Tse, Samantha; Miller, Andrew D.; González, R. Gilberto; Salemi, Marco; Burdo, Tricia H.; Williams, Kenneth C.
Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages a...
Cho, Kyung Soo; Yoo, Jeong Hyun; Suh, Jeong Soo; Ryu, Kyung Ha; Hong, Ki Sook; Kim, Hak Jin
Familial erythrophagocytic lymphohistiocytosis is a fatal early childhood disorder characterized by multiorgan lymphohistiocytic infiltration and active hemophagocytosis. Involvement of the central nervous system (CNS) is not uncommon and is characterized by rapidly progressive tissue damage affecting both the gray and white matter. We encountered a case of familial erythrophagocytic lymphohistiocytosis with CNS involvement. Initial T2-weighted MRI of the brain demonstrated high signal intensity in the right thalamus, though after chemotherapy, which led to the relief of neurologic symptoms, this disappeared. After four months. however, the patient's neurologic symptoms recurred, and follow-up T2-weighted MR images showed high signal intensity in the thalami, basal ganglia, and cerebral and cerebellar white matter. Brain MRI is a useful imaging modality for the evaluation of CNS involvement and monitoring the response to treatment
Payne, J L; Baumgartner, R G
THE CNS ROLE has been actualized in a variety of ways. Flexibility-inherent in the role-and the revolution in health care consciousness tend to place the CNS at risk for criticism regarding value to the organization. At Vanderbilt University Medical Center, a CNS task force evaluated the current reality of CNS practice and recommended role changes to include the financial analysis of patient care. After incorporating a financial perspective into our present practice, we have embarked on an interesting journey of post-Master's degree study, that of the tertiary care nurse practitioner. This practice option could elevated the clinical and financial aspects of providing cost-effective health care to a more autonomous role form; however, the transition has been challenging. Since 1990, the American Nurses Association has recommended that nursing school curricula change to meet the needs of the health care environment and provide increased career flexibility through creating one advanced degree incorporating both CNS and NP functions. Swiftly moving past differences and toward similarities will bridge the gap for advanced practice nurses in the future.
Kessing, Lars Vedel; Hansen, Hanne Vibe; Christensen, Ellen Margrethe
BACKGROUND: It is unknown whether young adults with bipolar disorder are able to benefit from early intervention combining optimised pharmacological treatment and group psychoeducation. The aim of the present report was to compare the effects of early intervention among patients with bipolar...... disorder aged 18-25 years to that of patients aged 26 years or older. METHODS: Patients were randomised to early treatment in a specialised outpatient mood disorder clinic versus standard care. The primary outcome was risk of psychiatric re-hospitalisation. RESULTS: A total of 158 patients with mania/bipolar...... different, the observed differences of the point estimates was surprisingly larger for young adults suggesting that young adults with bipolar disorder may benefit even more than older adults from early intervention combining pharmacological treatment and group psychoeducation....
Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N
Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying
Shilpa A Telgote; Shreyas Shrikant Pendharkar; Amol D Kelkar; Sachin Bhojane
Very early-onset schizophrenia (defined as an onset of psychosis before 13 years of age) is a rare and severe form of the disorder which is clinically and neurobiologically continuous with the adult-onset disorder. It is rarely reported
Hooper, Stephen R.; Giuliano, Anthony J.; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Frazier, Jean A.; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.
Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship…
The article analyzes the importance of early care in child development, guiding a neuropsychological perspective of development. The early care model seeks to refer to the set of interventions aimed at children and their work in conjunction with a multidisciplinary team. It presents recommendations for the implementation of programs that allow…
Huizink, A.C.; Van Lier, P.A.C.; Crijnen, A.A.M.
Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized
Huizink, A.C.; Lier, P.A.C. van; Crijnen, A.A.M.
Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized
A.C. Huizink (Anja); P.A.C. van Lier (Pol); A.A.M. Crijnen (Alfons)
textabstractBackground/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based,
Method: We investigated a total of 28 patients aged 18-65 years, were diagnosed as Hypochondriasis or Somatization Disorder according to DSM-IV and 30 healthy controls. All participitans were assessed with The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-1. Data were obtained by using a Sociodemographic Questionnaire and Young Schema Questionnaire-Short Form 3. Results: The main age of patients was 36,71 ± 10.39. Most of the patients were female, married and housewives. All early maladaptive schema scores of patients with somatoform disorders were higher than healthy controls. Conclusion: All early maladaptive schemas have been found to be related to somatoform disorders in this study. The role of not a specific one but a total of maladaptive schemas in etiology may reflect the unspecific general sources of the tendency to somatoform disorders. [JCBPR 2014; 3(2.000: 84-93
Bryant, Richard A
The potentially debilitating effect of posttraumatic stress disorder (PTSD) has created much interest in early intervention strategies that can reduce PTSD. This review critiques the evidence for psychological debriefing approaches and alternate early intervention strategies. The review critiques the randomized controlled trials of psychological debriefing, and early provision of cognitive behavior therapy. The latter approach involves therapy attention on acutely traumatized individuals who are high risk for PTSD development, and particularly in people with acute stress disorder (ASD). Psychological debriefing does not prevent PTSD. Cognitive behaviour therapy strategies have proven efficacy in reducing subsequent PTSD in ASD populations. Despite the promising evidence for early provision of CBT, many people do not benefit from CBT. This review concludes with consideration of major challenges facing early intervention approaches in the context of terrorist attacks and mass disasters.
Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh
BACKGROUND: No study has investigated when preventive treatment with lithium should be initiated in bipolar disorder. AIMS: To compare response rates among patients with bipolar disorder starting treatment with lithium early v. late. METHOD: Nationwide registers were used to identify all patients...... with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed lithium during the period 1995-2012 in Denmark (n = 4714). Lithium responders were defined as patients who, following a stabilisation lithium start-up period of 6 months, continued lithium monotherapy without being admitted...... to hospital. Early v. late intervention was defined in two ways: (a) start of lithium following first contact; and (b) start of lithium following a diagnosis of a single manic/mixed episode. RESULTS: Regardless of the definition used, patients who started lithium early had significantly decreased rates of non...
Benti, Liliane; Manicavasagar, Vijaya; Proudfoot, Judy; Parker, Gordon
The identification of early markers has become a focus for early intervention in bipolar disorder. Using a retrospective, qualitative methodology, the present study compares the early experiences of participants with bipolar disorder to those with unipolar depression up until their first diagnosed episode. The study focuses on differences in early home and school environments as well as putative differences in personality characteristics between the two groups. Finally we a compare and contrast prodromal symptoms in these two populations. Thirty-nine participants, 20 diagnosed with unipolar depression and 19 diagnosed with bipolar disorder, took part in the study. A semi-structured interview was developed to elicit information about participants' experiences prior to their first episode. Participants with bipolar disorder reported disruptive home environments, driven personality features, greater emotion dysregulation and adverse experiences during the school years, whereas participants with depression tended to describe more supportive home environments, and more compliant and introvert personality traits. Retrospective data collection and no corroborative evidence from other family members. No distinction was made between bipolar I and bipolar II disorder nor between melancholic and non-melancholic depression in the sample. Finally the study spanned over a 12-month period which does not allow for the possibility of diagnostic reassignment of some of the bipolar participants to the unipolar condition. These findings indicate that there may be benefits in combining both proximal and distal indicators in identifying a bipolar disorder phenotype which, in turn, may be relevant to the development of early intervention programs for young people with bipolar disorder.
Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit
Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…
Zalaquett, Daniela F; Schönstedt, Marianne G; Angeli, Milagros; Herrrera, Claudia C; Moyano, Andrea C
Autism Spectrum Disorders (ASD) are characterized by impairments in communication and social interaction, as well as restricted and repetitive patterns of behavior. They have a prevalence of 0.6% in the general population, although there are no national statistics. Even though their evolution is variable, it has been observed that early intervention is an important factor determining prognosis. The aim of this study is to update concepts regarding the current available evidence on the importance of early intervention. After analyzing the collected information, the importance of early intervention programs for children with ASD is confirmed, as well as the role of pediatricians and other health professionals in the early detection of these disorders. Copyright © 2015. Publicado por Elsevier España, S.L.U.
Jovev, Martina; Jackson, Henry J
The present study aimed to examine the specificity of schema domains in three personality disorder (PD) groups, namely borderline (BPD), obsessive-compulsive (OCPD), and avoidant PD (AvPD), and to correctly identify the three PD groups on the basis of these schemas. The sample consisted of 48 clinical participants diagnosed with PDs and assigned to 1 of 3 groups on the basis of their Axis II diagnoses (BPD: n = 13; OCPD: n = 13; AvPD: n = 22). High scores on Dependence/Incompetence, Defectiveness/ Shame and Abandonment were found for the BPD group. Such pattern appears to be most consistent with Young's theory of BPD. Consistent with the theory and empirical findings of Beck et al. (1990, 2001), OCPD was associated with elevations on the Unrelenting Standards schema domain, but not on Emotional Inhibition, which was found to be elevated for AvPD. In conclusion, the present study suggests that there are different patterns of schema domains across different PDs and that the Schema Questionnaire (SQ) is potentially useful in differentiating between these PDs.
Larsen, Janne Tidselbak; Munk-Olsen, Trine; Bulik, Cynthia M
Objective: Previous studies evaluating the association between early childhood adversities and eating disorders have yielded conflicting results. The aim of this study is to examine the association between a range of adversities and risk of anorexia nervosa (AN), bulimia nervosa (BN), and eating...
McIntosh, David E.; Trotter, Jeffrey S.
Although published research continues to advocate medication as the first line of treatment for early onset bipolar spectrum disorder (EOBSD; N. Lofthouse & M.A. Fristad, 2004), preliminary research demonstrating the utility of cognitive, cognitive-behavioral, and psychoeducational therapies is promising. It appears as if future treatment of EOBSD…
The goal of this dissertation was to explore two possible early markers of Autism Spectrum Disorder (ASD): visual search superiority, and gaze behavior during face perception. These possible markers were explored as they pertain to both the social deficits in ASD (gaze during face perception) and
Alatyrtsev, V V; Iakunin, Iu A; Burkova, A S; Podkopaev, V N; Afonina, L G
A study was made of the content of creatine kinase-BB (CK-BB) and lactate in cerebrospinal fluid (CSF) of 202 neonates and infants with perinatal CNS injuries. The relationship was found between the rise of the CK-BB content and the gravity of perinatal CNS injuries. The highest content of CK-BB in CSF was marked in neonates with cerebral disorders complicated by infectious and inflammatory diseases (pneumonia, sepsis). Within the first 5 days of life, the children of this group demonstrated the relationship between the content of CK-BB and lactate of CSF. The measurement of the content of CK-BB in CSF should be used for early diagnosis, assessment of the gravity and course of perinatal CNS injuries in neonates and in infants.
The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered
Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo
Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset ( or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.
de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão
Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.
Salzer, Simone; Cropp, Carola; Streeck-Fischer, Annette
Borderline personality disorder (BPD) should be understood as a disorder of development (Streeck-Fischer 2008, 2013) that has its first manifestation in late childhood and adolescence. There are only few treatment studies of adolescents meeting the diagnostic criteria of borderline personality disorder, although early interventions for these patients are urgently needed (see Chanen & McCutcheon 2013). We examined the effectiveness of an inpatient psychodynamic therapy (PDT). Twenty-eight adolescents fulfilling the DSM-IV diagnostic criteria of borderline personality disorder were treated with psychodynamic therapy. The mean duration of treatment was 29.87 weeks (SD = 15.88). Outcomes were remission rates, GAF, GSI, SDQ, IIP and BPI scores. Assessments were made at admission and after treatment. Pre-post comparisons and comparisons with normative data were conducted. At the end of treatment 39.29% of the patients were remitted. We found significant improvements for the GAF, GSI, SDQ, IIP (all p0.001) and the BPI (p = 0.006). These clinically relevant improvements demonstrate the effectiveness of psychodynamic therapy in adolescents with borderline personality disorder and stress the usefulness of an early intervention for these patients.
Meinzer, Michael C; Lewinsohn, Peter M; Pettit, Jeremy W; Seeley, John R; Gau, Jeff M; Chronis-Tuscano, Andrea; Waxmonsky, James G
The aim of this study was to examine the prospective relationship between a history of attention-deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. One thousand five hundred seven participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance-use disorder after mid-adolescence. A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. © 2013 Wiley Periodicals, Inc.
Jäger, Anna Katharina; Saaby, Lasse
Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure....... Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic ß-glucocidase. The absorbed aglycone is then conjugated by methylation......, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABA(A)-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine...
Sands, Mark S; Haskins, Mark E
Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders usually caused by deficient activity of a single lysosomal enzyme. As most lysosomal enzymes are ubiquitously expressed, a deficiency in a single enzyme can affect multiple organ systems, including the central nervous system (CNS). At least 75% of all LSDs have a significant CNS component. Approaches such as bone marrow transplantation (BMT) or enzyme replacement therapy (ERT) can effectively treat the systemic dis...
Ghosal, Malay Kumar; Guha, Prathama; Sinha, Mausumi; Majumdar, Debabrata; Sengupta, Payel
We present three cases of early onset bipolar disorder where dissociative (conversion) symptoms preceded the onset of mania. This case series underscores the significance of dissociative/conversion symptoms as an early atypical presentation in juvenile bipolar disorder.
Block, F.; Reith, W.
Vasculitis is a rare cause for disease of the CNS. The isolated vasculitis of the CNS is restricted to the CNS whereas other forms of vasculitis affect various organs including the CNS. Headache, encephalopathy, focal deficits and epileptic seizures are the major symptoms suggestive for vasculitis. One major criterion of the isolated vasculitis of the CNS is the lack of evidence for other vasculitis forms or for pathology of other organs. Angiography displays multifocal segmental stenosis of intracranial vessels. MRI demonstrates multiple lesions which in part show enhancement after gadolinium. A definite diagnosis can only be made on the grounds of biopsy from leptomeninges and parenchyma. Therapy consists of corticosteroids and cyclophosphamid. (orig.) [de
Anna K. Jäger
Full Text Available Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure. Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic β-glucocidase. The absorbed aglycone is then conjugated by methylation, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABAA-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine oxidase A or B, thereby working as anti-depressants or to improve the conditions of Parkinson’s patients. Flavanols, flavanones and anthocyanidins have protective effects preventing inflammatory processes leading to nerve injury. Flavonoids seem capable of influencing health and mood.
Hajek, Tomas; Franke, Katja; Kolenic, Marian; Capkova, Jana; Matejka, Martin; Propper, Lukas; Uher, Rudolf; Stopkova, Pavla; Novak, Tomas; Paus, Tomas; Kopecek, Miloslav; Spaniel, Filip; Alda, Martin
The greater presence of neurodevelopmental antecedants may differentiate schizophrenia from bipolar disorders (BD). Machine learning/pattern recognition allows us to estimate the biological age of the brain from structural magnetic resonance imaging scans (MRI). The discrepancy between brain and chronological age could contribute to early detection and differentiation of BD and schizophrenia. We estimated brain age in 2 studies focusing on early stages of schizophrenia or BD. In the first study, we recruited 43 participants with first episode of schizophrenia-spectrum disorders (FES) and 43 controls. In the second study, we included 96 offspring of bipolar parents (48 unaffected, 48 affected) and 60 controls. We used relevance vector regression trained on an independent sample of 504 controls to estimate the brain age of study participants from structural MRI. We calculated the brain-age gap estimate (BrainAGE) score by subtracting the chronological age from the brain age. Participants with FES had higher BrainAGE scores than controls (F(1, 83) = 8.79, corrected P = .008, Cohen's d = 0.64). Their brain age was on average 2.64 ± 4.15 years greater than their chronological age (matched t(42) = 4.36, P stages of BD showed comparable BrainAGE scores to controls (F(2,149) = 1.04, corrected P = .70, η2 = 0.01) and comparable brain and chronological age. Early stages of schizophrenia, but not early stages of BD, were associated with advanced BrainAGE scores. Participants with FES showed neurostructural alterations, which made their brains appear 2.64 years older than their chronological age. BrainAGE scores could aid in early differential diagnosis between BD and schizophrenia. © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: email@example.com
Joan Y. Holgate
Full Text Available Stress is a major driving force in alcohol use disorders (AUDs. It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.
Full Text Available According to the literature, inflated responsibility/sensitivity to guilt play a pivotal role in both the genesis and maintenance of Obsessive-Compulsive Disorder (OCD. They may be learned in childhood and adolescence, through particular experiences and parental rearing styles, involving criticism, excessively high standards, and social moralization. Preliminary data on the role of dysfunctional beliefs in the development/maintenance of OCD also show that non-affected family members of OC individuals score higher than controls in domains concerning responsibility, suggesting it might represent a candidate endophenotype for the disorder. Compulsive conducts, that far from being mechanical reactions are instead clearly goal-oriented, may be triggered by the need of preventing responsibility/guilt. Therefore, useful psychological interventions aimed at not only reappraising meanings associated with the specific early experiences connected to hyper-sensitivity to guilt, but also at developing a more general compassionate and forgiving stance towards oneself, may prove particularly effective.
Hartmann, K.M.; Zimmer, A.; Reith, W.
This article gives a review of the most frequent infective agents reasonable for CNS infections in immunocompetent patients as well as their localisation and imaging specifications. MRI scanning is the gold standard to detect inflammatory conditions in the CNS. Imaging can be normal or nonspecifically altered although the infection is culturally or bioptically proven. There are no pathognomonic, pathogen-specific imaging criteria. The localization and dimension of the inflammation depends on the infection pathway. (orig.) [de
Antel, J P; Owens, T
The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...
Park, Emma C; Waller, Glenn; Gannon, Kenneth
The personality disorders are commonly comorbid with the eating disorders. Personality disorder pathology is often suggested to impair the treatment of axis 1 disorders, including the eating disorders. This study examined whether personality disorder cognitions reduce the impact of cognitive behavioural therapy (CBT) for eating disorders, in terms of treatment dropout and change in eating disorder attitudes in the early stages of treatment. Participants were individuals with a diagnosed eating disorder, presenting for individual outpatient CBT. They completed measures of personality disorder cognitions and eating disorder attitudes at sessions one and six of CBT. Drop-out rates prior to session six were recorded. CBT had a relatively rapid onset of action, with a significant reduction in eating disorder attitudes over the first six sessions. Eating disorder attitudes were most strongly associated with cognitions related to anxiety-based personality disorders (avoidant, obsessive-compulsive and dependent). Individuals who dropped out of treatment prematurely had significantly higher levels of dependent personality disorder cognitions than those who remained in treatment. For those who remained in treatment, higher levels of avoidant, histrionic and borderline personality disorder cognitions were associated with a greater change in global eating disorder attitudes. CBT's action and retention of patients might be improved by consideration of such personality disorder cognitions when formulating and treating the eating disorders.
de Lange, Elizabeth CM
Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...
Deirdre S Davis
Full Text Available The CNS (central nervous system is unquestionably the central organ that regulates directly or indirectly all physiological systems in the mammalian body. Yet, when considering the defence of the CNS from pathogens, the CNS has often been considered passive and subservient to the pro-inflammatory responses of the immune system. In this view, neuroinflammatory disorders are examples of when the tail (the immune system wags the dog (the CNS to the detriment of an individual's function and survival.
Pooni, Jyoti; Ninteman, Aafke; Bryant-Waugh, Rachel; Nicholls, Dasha; Mandy, William
To investigate whether young people (8-16 years) with an eating disorder have a higher prevalence of autism spectrum disorder (ASDs) and elevated autistic traits compared to typically developing (TD) peers. Twenty-two participants with early onset eating disorder (EOED) were assessed using standardized ASD measures and compared to IQ matched TD (n = 24) and ASD (n = 20) controls. An ASD diagnosis was no more common in EOED than in TD controls. However, repetitive and stereotyped behavior was more often observed in the EOED group and, compared to TD controls, there was a trend (p = .07) toward greater autistic social impairment in EOED. Whilst participants with EOED did not show increased ASD prevalence, they did have elevated autistic traits of clinical significance, particularly repetitive and stereotyped behavior. Further work is required to determine whether inflexibility and social difficulties in EOED have identical phenomenology and etiology to those seen in ASD. Copyright © 2012 Wiley Periodicals, Inc.
Hooper, Stephen R; Giuliano, Anthony J; Youngstrom, Eric A; Breiger, David; Sikich, Linmarie; Frazier, Jean A; Findling, Robert L; McClellan, Jon; Hamer, Robert M; Vitiello, Benedetto; Lieberman, Jeffrey A
We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship of different variables of illness severity and adaptive behavior to neuropsychological functioning. Participants ranged in age from 8 to 19 years. Diagnostic status was confirmed via structured interview over multiple time points. Domains of neuropsychological functioning included fine-motor, attention, working memory, problem-solving efficiency, inhibitory control, and social cognition. Other variables included intelligence (IQ), academic achievement skills, adaptive behavior, and different measures of illness severity. The two groups did not differ on IQ or on any of the neuropsychological domains. The SZ group performed significantly lower in spelling. A high proportion of individuals in both groups reflected significant intellectual and academic achievement skill deficits. Significant correlations were found between the neurocognitive domains and both illness severity and adaptive behavior variables. There were few differences between the SZ and SA groups on IQ, achievement, or neuropsychological functioning; however, both groups showed significantly high rates of deficits in IQ and basic academic skills. Correlations of the neurocognitive functions with illness severity and adaptive behavior were small to moderate in magnitude. These findings continue to implicate the importance of neurocognitive functioning as a key area of vulnerability in the study of youth with schizophrenia spectrum disorders.
Full Text Available The endocannabinoid system (ECS has been implicated in many physiological functions, including the regulation of appetite, food intake and energy balance, a crucial involvement in brain reward systems and a role in psychophysiological homeostasis (anxiety and stress responses. We first introduce this important regulatory system and chronicle what is known concerning the signal transduction pathways activated upon the binding of endogenous cannabinoid ligands to the Gi/0-coupled CB1 cannabinoid receptor, as well as its interactions with other hormones and neuromodulators which can modify endocannabinoid signaling in the brain. Anorexia nervosa (AN and bulimia nervosa (BN are severe and disabling psychiatric disorders, characterized by profound eating and weight alterations and body image disturbances. Since endocannabinoids modulate eating behavior, it is plausible that endocannabinoid genes may contribute to the biological vulnerability to these diseases. We present and discuss data suggesting an impaired endocannabinoid signaling in these eating disorders, including association of endocannabinoid components gene polymorphisms and altered CB1-receptor expression in AN and BN. Then we discuss recent findings that may provide new avenues for the identification of therapeutic strategies based on the endocannabinod system. In relation with its implications as a reward-related system, the endocannabinoid system is not only a target for cannabis but it also shows interactions with other drugs of abuse. On the other hand, there may be also a possibility to point to the ECS as a potential target for treatment of drug-abuse and addiction. Within this framework we will focus on enzymatic machinery involved in endocannabinoid inactivation (notably fatty acid amide hydrolase or FAAH as a particularly interesting potential target. Since a deregulated endocannabinoid system may be also related to depression, anxiety and pain symptomatology accompanying drug
Carlson-Catalano, J M
Power is necessary for the clinical nurse specialist (CNS) to successfully conduct objectives of practice in bureaucratic hospital settings. To obtain power, the CNS could use strategies of an empowerment theory to fully operationalize roles in hospitals. This article will discuss how the CNS may be empowered utilizing strategies in four empowering categories. In addition, the many benefits of empowering the CNS are reviewed.
Adiel C. Rios
Full Text Available Objective: To characterize the early stages of bipolar disorder (BD, defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. Methods: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a characterized prodromal and first-episode stages of BD or b detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. Results: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed or treatment phase. Conclusions: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.
Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently...... potential IFN-inducing receptor that signals through NF-kB. Receptor activator of NF-kB (RANK) belongs to the TNF-receptor superfamily and has been shown to induce IFN-beta in medullary thymic epithelial cells affecting autoimmune regulatory processes and osteoclast precursor cells in association to bone...
Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh
The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.
... Association. Reactive attachment disorder. In: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing; 2013: ...
Clark, Megan Louise Erin; Vinen, Zoe; Barbaro, Josephine; Dissanayake, Cheryl
Early diagnosis of Autism Spectrum Disorder is considered best practice, increasing access to early intervention. Yet, many children are diagnosed after 3-years. The current study investigated the school age outcomes of children who received an early and later diagnosis of ASD. The cognitive and behavioural outcomes of children diagnosed early (n…
Martinez-Badía, Jose; Martinez-Raga, Jose
Attention-deficit hyperactivity disorder (ADHD) is a complex, heterogeneous and multifactorial neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity and impulsivity. Although the first clinical description of a constellation of symptoms highly resembling to what currently could be diagnosed as ADHD is generally attributed to George F Still in 1902, there are scattered but significant published historical medical, scientific and non-scientific reports, much prior to Still’s lectures, of what is currently conceptualized as ADHD. The present report aimed at exploring the early history of ADHD, prior to the 20th century in the medical literature and in other historical sources, to provide clinicians, researchers and other professionals with a better understanding of the roots and current conceptualization of this disorder. It is possible to find clues and highly suggestive descriptions of individuals presenting symptoms resembling what is currently defined as ADHD in the literature, in paintings or in the Bible. However, the earliest medical reports of individuals with abnormal degrees of inattention, distractibility and overactivity date from the last quarter of the 18th century, included in two of the first textbooks specifically on the subject of mental diseases, published by the German Melchior Adam Weikard and the Scottish Sir Alexander Crichton. During the 19th century some eminent physicians from Germany, France or Great Britain, such as Charles West, Thomas C Albutt, Thomas S Clouston, William W, Ireland, John Haslam, Heinrich Neumann, or Désiré-Magloire Bourneville, among others provided clinical depictions of patients that most likely presently would be diagnosed as having ADHD. Whilst some of the children described by Still and his predecessors may have suffered from a variety of neurological and psychiatric disorders, many of these patients showed clear symptoms of ADHD and may present with comorbid disorders, as
Owens, T; Wekerle, H; Antel, J
The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily on ...
Nowakowski, R. S.
The goals of this review are to: (1) provide a set of concepts to aid in the understanding of complex processes which occur during central nervous system (CNS) development; (2) illustrate how they contribute to our knowlege of adult brain anatomy; and (3) delineate how modifications of normal developmental processes may affect the structure and…
Rotavirus infection may be accompanied by serious complications, e.g. disabilities central nervous system (CNS). Theory rotavirus penetration across the blood-brain barrier and subsequent rota-associated convulsions by the 2-year case-history of the patient. Rotavirosis minor gastrointestinal symptoms may lead to erroneous diagnosis. (author)
Full text: Imaging assessment of brain tumors following surgery is complex and depends upon several factors, including the location of the tumor, the surgical procedure and the disease process for which it was performed. Depending upon these factors, one or a combination of complementary imaging modalities may be required to demonstrate any clinically relevant situation, to assist the surgeon in deciding if repeat surgery is necessary. Conventional magnetic resonance imaging (MRI) can show the shape, size, signal intensity, and enhancement of a brain tumor. It has been widely used to diagnose and differentiate brain tumors and to assess the surgery outcomes. Longitudinal MRI scans have also been applied for the assessment of treatment and response to surgery. The newly developed MRI techniques, including diffusion weighted imaging (DWI), perfusion weighted imaging (PWI) and magnetic resonance spectroscopy (MRS), have the potential to provide the molecular, functional and metabolic information of preoperative and postoperative brain tumors. Postoperative diffusion and perfusion magnetic resonance imaging are especially useful in predicting early functional recovery from new deficits after brain tumor surgery.This lecture will stress the principles, applications, and pitfalls of conventional as well as newly developing functional imaging techniques following operation of brain tumors
Powers, Margaret A; Richter, Sara A; Ackard, Diann M; Cronemeyer, Catherine
Through focus groups, we examined the development and maintenance of an eating disorder in 16 females with type 1 diabetes and an eating disorder. The quotes and qualitative data summaries provide rich insights into understanding why those with type 1 diabetes are at increased risk for eating disorders. Content analyses revealed five themes pertinent to the dual diagnosis (feeling different, difficulty with control/coping, body image, feelings, and quality of life) of which four themes were relevant to eating disorder development. Findings support early identification of those at risk and inform interventions to mitigate development of an eating disorder. © The Author(s) 2015.
Su, Xueyun; Long, Toby; Chen, Lianjun; Fang, Junming
Autism spectrum disorders (ASD) were first reported in China in 1982. Since then, autism and other related disorders have been recognized by both the public and professionals. The importance of early intervention for children with ASD is becoming more accepted throughout China. A survey was designed to investigate the status of early intervention…
Swain, Nathaniel Robert; Eadie, Patricia Ann; Prior, Margot Ruth; Reilly, Sheena
Background: Early identification of Autism Spectrum Disorder (ASD) is currently limited by the absence of reliable biological markers for the disorder, as well as the reliability of screening and assessment tools for children aged between 6 and 18 months. Ongoing research has demonstrated the importance of early social communication skills in…
Montagne, Axel; Gauberti, Maxime; Jullienne, Amandine; Briens, Aurelien; Docagne, Fabian; Vivien, Denis; Maubert, Eric; Macrez, Richard; Defer, Gilles; Raynaud, Jean-Sebastien; Louin, Gaelle; Buisson, Alain; Haelewyn, Benoit
Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuro-inflammation. (authors)
Kerrn-Jespersen, B M; Lindelof, M; Illes, Zsolt
Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is an inflammatory CNS disorder characterized by 1) subacute onset of cerebellar and brainstem symptoms, 2) peripontine contrast-enhancing perivascular lesions with a "salt-and-pepper" appeara...
Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo
After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating
Ýsmet Kýrpýnar; Erdem Deveci; Demet Zihni Çamur; Alperen Kýlýç
Objective: Somatoform disorders are characterized by physical symptoms that suggest a medical condition but that are not fully explained by a medical condition. A number of studies have suggested the efficacy of cognitive behavioral therapy for somatoform disorders. But, while it is clear that somatoform disorders are closely related to a number of cognitive factors, the precise nature of these relationships have not been elucidated yet. The aim of the present study was to determine the relat...
Wymbs, Brian T; McCarty, Carolyn A; Mason, W Alex; King, Kevin M; Baer, John S; Vander Stoep, Ann; McCauley, Elizabeth
Conduct disorder and depression symptoms are well-established risk factors for substance use during adolescence. However, few investigations have examined whether early substance use increases adolescents' risk of developing conduct disorder/depression symptoms. Using the Developmental Pathways Project sample of 521 middle school students (51.6% male), we tested whether substance use (indicated by alcohol and marijuana use, and use-related impairment) in 8th and 9th grade increased risk of conduct disorder and depression symptoms in 9th and 12th grade over and above prior symptoms. We examined whether associations between substance use and conduct disorder/depression symptoms were consistent across self- or parent-reported symptoms and whether associations were moderated by gender. Analyses indicated that, over and above prior symptoms, elevated substance use in 8th grade predicted elevated conduct disorder symptoms in 9th grade, and substance use in 9th grade predicted conduct disorder symptoms in 12th grade. In contrast, substance use failed to predict later depression symptoms independent of prior symptoms. These findings were consistent across self- and parent-reported conduct disorder/depression symptoms. With one exception (association between substance use in 8th grade and self-reported conduct disorder symptoms in 9th grade), relations between early substance use and later conduct disorder symptoms did not differ between boys and girls. Study findings underscore the unique contribution of substance use during early adolescence to the development of conduct disorder symptoms by late adolescence.
Reynolds, Jessica L; Mahato, Ram I
Targeting and delivering macromolecular therapeutics to the central nervous system (CNS) has been a major challenge. The blood-brain barrier (BBB) is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Therefore, much effort has been channelled into improving transport of therapeutics across the BBB and into the CNS including the use of nanoparticles. In this thematic issue, several reviews and original research are presented that address "Nanomedicines for CNS Diseases." The articles in this issue are concentrated on either CNS-HIV disease or CNS tumors. In regards to CNS-HIV disease, there are two reviews that discuss the role of nanoparticles for improving the delivery of HIV therapeutics to the CNS. In addition, there are two original articles focusing on therapies for CNS-HIV, one of them uses nanoparticles for delivery of siRNA specific to a key protein in autophagy to microglia, and another discusses nanoparticle delivery of a soluble mediator to suppress neuroinflammation. Furthermore, a comprehensive review about gene therapy for CNS neurological diseases is also included. Finally, this issue also includes review articles on enhanced drug targeting to CNS tumors. These articles include a review on the use of nanoparticles for CNS tumors, a review on functionalization (ligands) of nanoparticles for drug targeting to the brain tumor by overcoming BBB, and the final review discusses the use of macrophages as a delivery vehicle to CNS tumors. This thematic issue provides a wealth of knowledge on using nanomedicines for CNS diseases.
Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C
Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...
Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas
Aim In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional...... level, the presence of comorbid personality disorders and coping strategies. Methods Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using...... Inventory for Stressful Situations. Results In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders...
Chronis-Tuscano, Andrea; Degnan, Kathryn Amey; Pine, Daniel S.; Perez-Edgar, Koraly; Henderson, Heather A.; Diaz, Yamalis; Raggi, Veronica L.; Fox, Nathan A.
The odds of a lifetime diagnosis of social anxiety disorder increased by 3.79 times for children who had a stable report of behavioral inhibition from their mothers. This finding has important implications for the early identification and prevention of social anxiety disorder.
Pizur-Barnekow, Kris; Doering, Jennifer J.; Willett, Marjorie; Ruminski, Christine; Spring, Molly
The positive impact of healthy relationships on child development is widely accepted. A healthy relationship between mother and child is at risk when a mother experiences symptoms of birth-related posttraumatic stress disorder (PTSD). Mothers of children with special needs are at high risk for this disorder and early intervention (EI)…
Grygas Coogle, Christan; Guerette, Amy R.; Hanline, Mary Frances
The purpose of this study was to obtain an understanding of the unique experiences of families who have a young child at risk for or identified with an autism spectrum disorder and their experiences with early intervention. Thirty-nine parents of children with or at risk for an autism spectrum disorder receiving Part C services in a state in the…
Salomone, E.; Beranova, S.; Bonnet-Brilhault, F.; Lauritsen, M.; Budisteanu, M.; Buitelaar, J.K.; Canal-Bedia, R.; Felhosi, G.; Fletcher-Watson, S.; Freitag, C.; Fuentes, J.; Gallagher, L.; Primo, P. Garcia; Gliga, F.; Gomot, M.; Green, J.; Heimann, M.; Jonsdottir, S.L.; Kaale, A.; Kawa, R.; Kylliainen, A.; Lemcke, S.; Markovska-Simoska, S.; Marschik, P.B.; McConachie, H.; Moilanen, I.; Muratori, F.; Narzisi, A.; Noterdaeme, M.; Oliveira, G.; Oosterling, I.; Pijl, M.; Pop-Jordanova, N.; Poustka, L.; Roeyers, H.; Roge, B.; Sinzig, J.; Vicente, A.; Warreyn, P.; Charman, T.
Little is known about use of early interventions for autism spectrum disorder in Europe. Parents of children with autism spectrum disorder aged 7 years or younger (N = 1680) were recruited through parent organisations in 18 European countries and completed an online survey about the interventions
Salomone, Erica; Beranová, Štepánka; Bonnet-Brilhault, Frédérique; Briciet Lauritsen, Marlene; Budisteanu, Magdalena; Buitelaar, Jan; Canal-Bedia, Ricardo; Felhosi, Gabriella; Fletcher-Watson, Sue; Freitag, Christine; Fuentes, Joaquin; Gallagher, Louise; Garcia Primo, Patricia; Gliga, Fotinica; Gomot, Marie; Green, Jonathan; Heimann, Mikael; Jónsdóttir, Sigridur Loa; Kaale, Anett; Kawa, Rafal; Kylliainen, Anneli; Lemcke, Sanne; Markovska-Simoska, Silvana; Marschik, Peter B; McConachie, Helen; Moilanen, Irma; Muratori, Filippo; Narzisi, Antonio; Noterdaeme, Michele; Oliveira, Guiomar; Oosterling, Iris; Pijl, Mirjam; Pop-Jordanova, Nada; Poustka, Luise; Roeyers, Herbert; Rogé, Bernadette; Sinzig, Judith; Vicente, Astrid; Warreyn, Petra; Charman, Tony
Little is known about use of early interventions for autism spectrum disorder in Europe. Parents of children with autism spectrum disorder aged 7?years or younger (N?=?1680) were recruited through parent organisations in 18 European countries and completed an online survey about the interventions their child received. There was considerable…
Chambers, Nola J.; Wetherby, Amy M.; Stronach, Sheri T.; Njongwe, Nonyameko; Kauchali, Shuaib; Grinker, Richard R.
Culturally appropriate tools are needed for detecting symptoms of autism spectrum disorder in young South African children. The objectives of this study were to (1) adapt and translate into isiZulu existing measures for detecting early signs of autism spectrum disorder, (2) use the measures to characterize and compare behavioural profiles of young…
Jacob, Udeme Samuel; Olisaemeka, Angela Nneka; Edozie, Isioma Sitamalife
The paper attempts to discuss the place of intervention in the developmental and communication disorders of children with intellectual disability for the purpose of providing effective inclusion programme. The definition of early intervention was stated, areas affected by children communication disorder such as language comprehension, fluency,…
DiGuiseppi, Carolyn; Levy, Susan E.; Sabourin, Katherine R.; Soke, Gnakub N.; Rosenberg, Steven; Lee, Li-Ching; Moody, Eric; Schieve, Laura A.
This study examined caregiver-reported medically-attended injuries among 30-68 month old children with autism spectrum disorder (ASD) compared to general population (POP) and non-ASD developmental disorders (DD) controls in the Study to Explore Early Development. Injuries were common in ASD cases (32.3%) as well as POP (30.2%) and DD (27.8%)…
Lewis, Andrew James; Galbally, Megan; Gannon, Tara; Symeonides, Christos
This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders...
Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos
Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.
Lin, Yu-Ju; Yang, Li-Kuang; Gau, Susan Shur-Fen
We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses. Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental disorders, 5th edition would not
Mattace Raso, Giuseppina; Russo, Roberto; Calignano, Antonio; Meli, Rosaria
The existence of acylethanolamides (AEs) in the mammalian brain has been known for decades. Among AEs, palmitoylethanolamide (PEA) is abundant in the central nervous system (CNS) and conspicuously produced by neurons and glial cells. Antihyperalgesic and neuroprotective properties of PEA have been mainly related to the reduction of neuronal firing and to control of inflammation. Growing evidence suggest that PEA may be neuroprotective during CNS neurodegenerative diseases. Advances in the understanding of the physiology and pharmacology of PEA have potentiated its interest as useful biological tool for disease management. Several rapid non-genomic and delayed genomic mechanisms of action have been identified for PEA as peroxisome proliferator-activated receptor (PPAR)-α dependent. First, an early molecular control, through Ca(+2)-activated intermediate- and/or big-conductance K(+) channels opening, drives to rapid neuronal hyperpolarization. This is reinforced by the increase of the inward Cl(-) currents due to the modulation of the gamma aminobutyric acid A receptor and by the desensitization of the transient receptor potential channel type V1. Moreover, the gene transcription-mediated mechanism sustains the long-term anti-inflammatory effects, by reducing pro-inflammatory enzyme expression and increasing neurosteroid synthesis. Overall, the integration of these different modes of action allows PEA to exert an immediate and prolonged efficacious control in neuron signaling either on inflammatory process or neuronal excitability, maintaining cellular homeostasis. In this review, we will discuss the effect of PEA on metabolism, behavior, inflammation and pain perception, related to the control of central functions and the emerging evidence demonstrating its therapeutic efficacy in several neurodegenerative diseases. Copyright © 2014. Published by Elsevier Ltd.
Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo
Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.
Noyes-Grosser, Donna M.; Elbaum, Batya; Wu, Yan; Siegenthaler, Kirsten M.; Cavalari, Rachel S.; Gillis, Jennifer M.; Romanczyk, Raymond G.
Autism spectrum disorder (ASD) can be diagnosed as early as 18 months of age. State Early Intervention (EI) programs under Part C of the Individuals with Disabilities Education Act (IDEA) are serving increasing numbers of children with ASD; however, little is known about outcomes of these services. This study evaluated the impact of EI for…
Rollins, Pamela Rosenthal; Campbell, Michelle; Hoffman, Renee Thibodeau; Self, Kayli
This study examined Pathways Early Autism Intervention, a community-based, parent-mediated, intensive behavioral and developmental intervention program for children with autism spectrum disorders that could be used as a model for state-funded early intervention programs. A single-subject, multiple-baseline, across-participants design was used.…
Little, Lauren M.; Wallisch, Anna; Salley, Brenda; Jamison, Rene
Given that early caregiver concerns may be different for children who go on to receive a diagnosis of autism spectrum disorder versus another developmental disability, early caregiver concerns may differ for girls. Using a community-based sample of children (n = 241), we examined the extent to which gender differences may be related to caregiver…
Mire, Stephen P.; Montgomery, Judy K.
The concept of early intervening services was introduced into public school systems with the implementation of the Individuals With Disabilities Education Improvement Act (IDEA) of 2004. This article describes a program developed for students with speech sound disorders that incorporated concepts of early intervening services, response to…
Oosterling, Iris J.; Wensing, Michel; Swinkels, Sophie H.; van der Gaag, Rutger Jan; Visser, Janne C.; Woudenberg, Tim; Minderaa, Ruud; Steenhuis, Mark-Peter; Buitelaar, Jan K.
Background: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of
Silberg, Judy L; Gillespie, Nathan; Moore, Ashlee A; Eaves, Lindon J; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa
Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children.
Narici, Livio; Nelson, Gregory A.
Exposure to space radiation may have impacts on brain function, either during or following missions. It is most important to determine how low doses of protons and high-LET irradiation elicit changes in brain function. Within this framework, the role of oxidative stress should also be assessed, as well as other possible interaction mechanisms involving, e.g., genetic, environmental, and sex-dependent risk factors. The hippocampus is particularly susceptible to radiation. It plays an essential role in memory formation and consolidation and is one of the most investigated brain components for its responses to radiation. The hippocampus is also one of the first brain structures to be damaged in the pathogenesis of Alzheimer's disease, an important potential late impairment following irradiation. In ‘Section 3: CNS risk’, six papers have been presented focused on these issues. For details the reader is directed to the specific papers. Here a very short summary follows
Nordentoft, Merete; Jeppesen, Pia; Petersen, Lone
, adherence to treatment, comorbid drug abuse, relapse and readmission. Some benefits persist after cessation of the intervention. Conclusions: Early intervention in schizophrenia is justified to reduce the negative personal and social impact of prolonged periods of untreated symptoms. Furthermore, phase......Abstract Aim: To examine the rationale and evidence supporting an early intervention approach in schizophrenia. Methods: A selective literature review was conducted. Results: During the onset of schizophrenia, there is often a significant delay between the emergence of psychotic symptoms...
Krupa Hitesh Shah
Full Text Available Introduction: A female encounters various menstrual disorders from puberty to menopause. We evaluated menstrual disturbances in post-menarche age and young adult age. Aim: To know the prevalence and impact of menstrual abnormalities at early adolescent and young adult age and to evaluate course of disorders identified at early adolescent age. Materials and Methods: A cross-sectional survey was carried out through self-administered questionnaire on 367 consented students at Melaka Manipal Medical College at Manipal, during December 2015- April 2016. Data were analysed by Statistical Package for the Social Sciences (SPSS 16.0 software. Results: Prevalence and pattern of menstrual disorders at early adolescent and at young adult age were noted. The mean age of menarche was 12.1 ±1.1 years. Menorrhagia was the most frequent (14.7% and 11.7% and polymenorrhea (7.6 % and 6% was least frequent menstrual disorder at adolescent age and young adult age respectively. Resolution of pubertal menstrual disorders was observed in all disorders, but noticed highest in oligomenorrhea (91%, (p-value <0.05. Prevalence of menstrual related disorder like dysmenorrhea was 88.7% at adolescent age and 67.6% at the young adult age. It was statistically significant reduction. Hindrance in academic performance and social behavior was noted more at young adult age, which was in 23.9% and 46.7% respectively (p-value <0.05. Conclusion: The most prevalent menstrual abnormality was menorrhagia at the early adolescent and the young adult age. Associated the most prevalent menstrual related symptoms were dysmenorrhea at early adolescent age, and premenstrual symptom at the young adult age. The study demonstrates the natural course (decreasing prevalence of all menstrual disorders from early adolescent to young adult age.
Funke, S.; Gardeitchik, T.; Kouwenberg, D.; Mohamed, M.; Wortmann, S.B.; Korsch, E.; Adamowicz, M.; Al-Gazali, L.; Wevers, R.A.; Horvath, A.; Lefeber, D.J.; Morava, E.
Congenital disorders of glycosylation (CDG) are a rapidly growing family of inborn errors. Screening for CDG in suspected cases is usually performed in the first year of life by serum transferrin isoelectric focusing or mass spectrometry. Based on the transferrin analysis patients can be
Carlson, Gabrielle A.
This article examined some of the reasons for confusion and controversy surrounding the frequency of diagnosis of bipolar disorder, especially in prepubertal children. Four case vignettes are used to articulate questions surrounding manifestations of euphoria and grandiosity, informant variance, diagnostic implications of medication-induced…
Petersen, Jennifer L.; Hyde, Janet S.
Peer sexual harassment is a pervasive problem in schools and is associated with a variety of negative mental health outcomes. Objectification theory suggests that sexual attention in the form of peer harassment directs unwanted attention to the victim's body and may lead to a desire to alter the body via disordered eating. In the current study, we…
Andersen, Stine Linding; Andersen, Stig; Vestergaard, Peter
of abnormal maternal thyroid function was 12.5% in the sub-cohort and significantly higher among cases of ASD (17.9%; aHR = 1.5 [CI 1.1-2.1]), but not among other types of neurodevelopmental disorders (febrile seizures: 12.7%; epilepsy: 13.1%; SDD: 12.6%; and ADHD: 14.0%). However, evaluation of subtypes......: The design was a case-cohort study within the Danish National Birth Cohort (1997-2003). From the eligible cohort of 71,706 women, a random 12% sub-cohort (n = 7624) was selected, and all women (n = 2276) whose child was diagnosed with seizures, specific developmental disorder (SDD), autism spectrum disorder......BACKGROUND: Maternal thyroid dysfunction may adversely affect fetal brain development, but more evidence is needed to refine this hypothesis. The aim of this study was to evaluate potential fetal programming by abnormal maternal thyroid function on child neurodevelopmental disorders. METHODS...
Chung, Tae Woong
Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by proliferation of benign histiocytes, and this commonly involves the liver, spleen, lymph nodes, bone marrow and central nervous system (CNS). We report here on the CT and MR imaging findings in a case of CNS HLH that showed multiple ring enhancing masses mimicking abscess or another mass on the CT and MR imaging. emophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by nonmalignant diffuse infiltration of multiple organs, including the central nervous system (CNS), by lymphocytes and histiocytes (1). Many radiologic reports describing diffuse white matter infiltrations, parenchymal atrophy and calcification have been published, but the characteristics of these findings remain non-specific, especially in immunocompromised patients. We present here a case of HLH in a 3-year-old boy who presented with multiple ring enhancing lesions involving the brain. In conclusion, although the CT and MRI findings of HLH with ring enhancing parenchymal lesions are nonspecific and mimic abscess, and especially in the immunosuppressed patients, increased diffusion at the center on DWI may be a finding of HLH to differentiate it from abscess, which has restricted diffusion at the center. However, the pathologic correlation with DWI according to the lesion stage certainly needs further study with a larger number of patients
Gleiter, C H; Deckert, J
In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.
Yates, William R; Meller, William H; Lund, Brian C; Thurber, Steve; Grambsch, Patricia L
The self-reported number of children was compared for men and women from the National Epidemiologic Survey of Alcoholism and Related Conditions Survey (NESARC). Subjects with a diagnosis of major depressive disorder or bipolar disorder were compared to those without an axis I disorder. The effect of age, gender, marriage and diagnostic status on number of children was completed using multivariate analyses. Men with a history of major depressive disorder but not bipolar disorder reported higher rates of childlessness and lower mean number of children. This reduced number of children was related to an early age of onset of MDD. Thirty percent of men with an age of onset of MDD before 22 were childless compared to only 18.9% of men without an axis I disorder (Odds ratio=1.82, 95% CI=1.45-2.27). No effect of mood disorder on number of children was found in women with major depression or bipolar disorder. This study suggests that an early age of onset of major depressive disorder contributes to childlessness in men.
Allen-Meares, Paula; MacDonald, Megan; McGee, Kristin
Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social communication skills as well as repetitive, restricted or stereotyped behaviors (1). Early interventionists are often found at the forefront of assessment, evaluation, and early intervention services for children with ASD. The role of an early intervention specialist may include assessing developmental history, providing group and individual counseling, working in partnership with families on home, school, and community environments, mobilizing school and community resources, and assisting in the development of positive early intervention strategies (2, 3). The commonality among these roles resides in the importance of providing up-to-date, relevant information to families and children. The purpose of this review is to provide pertinent up-to-date knowledge for early interventionists to help inform practice in working with individuals with ASD, including common behavioral models of intervention. PMID:27840812
Allen-Meares, Paula; MacDonald, Megan; McGee, Kristin
Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social communication skills as well as repetitive, restricted or stereotyped behaviors (1). Early interventionists are often found at the forefront of assessment, evaluation, and early intervention services for children with ASD. The role of an early intervention specialist may include assessing developmental history, providing group and individual counseling, working in partnership with families on home, school, and community environments, mobilizing school and community resources, and assisting in the development of positive early intervention strategies (2, 3). The commonality among these roles resides in the importance of providing up-to-date, relevant information to families and children. The purpose of this review is to provide pertinent up-to-date knowledge for early interventionists to help inform practice in working with individuals with ASD, including common behavioral models of intervention.
Full Text Available Autism spectrum disorder (ASD is a pervasive developmental disorder characterized by deficits in social communication skills as well as repetitive, restricted or stereotyped behaviors (1. Early interventionists are often found at the forefront of assessment, evaluation and early intervention services for children with ASD. The role of an early intervention specialist may include, assessing developmental history, providing group and individual counseling, working in partnership with families on home, school, and community environments, mobilizing school and community resources and assisting in the development of positive early intervention strategies (2, 3. The commonality amongst these roles resides in the importance of providing up-to-date, relevant information to families and children. The purpose of this review is to provide pertinent up-to-date knowledge for early interventionists to help inform practice in working with individuals with ASD, including common behavioral models of intervention.
Kapornai, Krisztina; Gentzler, Amy L; Tepper, Ping; Kiss, Eniko; Mayer, László; Tamás, Zsuzsanna; Kovacs, Maria; Vetró, Agnes
We investigate the relations of early atypical characteristics (perinatal problems, developmental delay, and difficult temperament) and onset-age (as well as severity of) first major depressive disorder (MDD) and first internalizing disorder in a clinical sample of depressed children in Hungary. Participants were 371 children (ages 7-14) with MDD, and their biological mothers, recruited through multiple clinical sites. Diagnoses (via DSM-IV criteria) and onset dates of disorders were finalized "best estimate" psychiatrists, and based on multiple information sources. Mothers provided developmental data in a structured interview. Difficult temperament predicted earlier onset of MDD and first internalizing disorder, but its effect was ameliorated if the family was intact during early childhood. Further, the importance of difficult temperament decreased as a function of time. Perinatal problems and developmental delay did not impact onset ages of disorders, and none of the early childhood characteristics associated with MDD episode severity. Children with MDD may have added disadvantage of earlier onset if they had a difficult temperament in infancy. Because early temperament mirrors physiological reactivity and regulatory capacity, it can affect various areas of functioning related to psychopathology. Early caregiver stability may attenuate some adverse effects of difficult infant temperament.
The present invention relates to the use of sleep spindles as a novel biomarker for early diagnosis of synucleinopathies, in particular Parkinson's disease (PD). The method is based on automatic detection of sleep spindles. The method may be combined with measurements of one or more further...
Schroeder, Stephen R.; Courtemanche, Andrea
There is a very substantial literature over the past 50 years on the advantages of early detection and intervention on the cognitive, communicative, and social-emotional development of infants and toddlers at risk for developmental delay due to premature birth or social disadvantage. Most of these studies excluded children with severe delays or…
Full Text Available Raffaella Devescovi,1 Lorenzo Monasta,2 Alice Mancini,3 Maura Bin,1 Valerio Vellante,1 Marco Carrozzi,1 Costanza Colombi4 1Division of Child Neurology and Psychiatry, 2Clinical Epidemiology and Public Health Research Unit, Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 4Department of Psychiatry, University of Michigan Health System, Ann Arbor, MI, USA Background: Early diagnosis combined with an early intervention program, such as the Early Start Denver Model (ESDM, can positively influence the early natural history of autism spectrum disorders. This study evaluated the effectiveness of an early ESDM-inspired intervention, in a small group of toddlers, delivered at low intensity by the Italian Public Health System.Methods: Twenty-one toddlers at risk for autism spectrum disorders, aged 20–36 months, received 3 hours/wk of one-to-one ESDM-inspired intervention by trained therapists, combined with parents’ and teachers’ active engagement in ecological implementation of treatment. The mean duration of treatment was 15 months. Cognitive and communication skills, as well as severity of autism symptoms, were assessed by using standardized measures at pre-intervention (Time 0 [T0]; mean age =27 months and post-intervention (Time 1 [T1]; mean age =42 months.Results: Children made statistically significant improvements in the language and cognitive domains, as demonstrated by a series of nonparametric Wilcoxon tests for paired data. Regarding severity of autism symptoms, younger age at diagnosis was positively associated with greater improvement at post-assessment.Conclusion: Our results are consistent with the literature that underlines the importance of early diagnosis and early intervention, since prompt diagnosis can reduce the severity of autism symptoms and improve cognitive and language skills in younger children
Shen, Mark D; Nordahl, Christine W; Young, Gregory S; Wootton-Gorges, Sandra L; Lee, Aaron; Liston, Sarah E; Harrington, Kayla R; Ozonoff, Sally; Amaral, David G
Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic
Sihvola, Elina; Keski-Rahkonen, Anna; Dick, Danielle M.; Hoek, Hans W.; Raevuori, Anu; Rose, Richard J.; Pulkkinen, Lea; Marttunen, Mauri; Kaprio, Jaakko
Objective: The purpose of this study is to analyze the developmental relationships of adolescent-onset Axis I mental disorders and eating disorders (EDs). Method: One thousand three hundred eighteen adolescent twins born from 1983 to 1987 completed a professionally administered semistructured
Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326
M. N. Mamedov
Full Text Available Early glucose metabolism disorders (GMD are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM. Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.
Green, Jonathan; Leadbitter, Kathy; Kay, Catherine; Sharma, Kishan
Syndromic autism has been described in children adopted after orphanage rearing. We investigated whether the same existed in children adopted after family breakdown. Families of 54/60 adopted children aged 6?11?years (mean 102?months; SD 20; 45?% male) returned screening questionnaires for autism spectrum disorder (ASD); 21/54 (39?%) screened positive. Detailed in-person phenotyping of screen positive cases showed ASD in 6/54 (11?%), Broad ASD (sub threshold traits) in 10/54 (18.5?%); 5/54 (9...
Hur, Eun-Mi; Lee, Byoung Dae
Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.
Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.
Nordentoft, Merete; Jeppesen, Pia; Petersen, Lone
and this relationship holds even after controlling for the potential confounding variable of premorbid functioning. In Norway, the early Treatment and Intervention in PSychosis study demonstrated that duration of untreated psychosis is amenable to intervention with the combination of educational campaigns...... and the initiation of treatment. The average duration of untreated psychosis is around 1–2 years. During this period, brain function may continue to deteriorate and social networks can be irreversibly damaged. Studies have consistently linked longer duration of untreated psychosis with poorer outcomes......, adherence to treatment, comorbid drug abuse, relapse and readmission. Some benefits persist after cessation of the intervention. Conclusions: Early intervention in schizophrenia is justified to reduce the negative personal and social impact of prolonged periods of untreated symptoms. Furthermore, phase...
Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas; Christensen, Ellen Margrethe; Kessing, Lars Vedel
In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional level, the presence of comorbid personality disorders and coping strategies. Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using the Functional Assessment Short Test. Cognitive complaints were assessed using the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, the presence of comorbid personality disorders using the Standardized Assessment of Personality - Abbreviated Scale and coping style using the Coping Inventory for Stressful Situations. In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders. Finally, they exhibited a trend towards using less adaptive coping styles. It cannot be omitted that some patients may have progressed from BD II to BD I. Most measures were based on patient self report. Overall, BD II was associated with a higher disease burden. Clinically, it is important to differentiate BD II from BD I and research wise, there is a need for tailoring and testing specific interventions towards BD II. Copyright © 2016 Elsevier B.V. All rights reserved.
Devescovi, Raffaella; Monasta, Lorenzo; Mancini, Alice; Bin, Maura; Vellante, Valerio; Carrozzi, Marco; Colombi, Costanza
Early diagnosis combined with an early intervention program, such as the Early Start Denver Model (ESDM), can positively influence the early natural history of autism spectrum disorders. This study evaluated the effectiveness of an early ESDM-inspired intervention, in a small group of toddlers, delivered at low intensity by the Italian Public Health System. Twenty-one toddlers at risk for autism spectrum disorders, aged 20-36 months, received 3 hours/wk of one-to-one ESDM-inspired intervention by trained therapists, combined with parents' and teachers' active engagement in ecological implementation of treatment. The mean duration of treatment was 15 months. Cognitive and communication skills, as well as severity of autism symptoms, were assessed by using standardized measures at pre-intervention (Time 0 [T0]; mean age =27 months) and post-intervention (Time 1 [T1]; mean age =42 months). Children made statistically significant improvements in the language and cognitive domains, as demonstrated by a series of nonparametric Wilcoxon tests for paired data. Regarding severity of autism symptoms, younger age at diagnosis was positively associated with greater improvement at post-assessment. Our results are consistent with the literature that underlines the importance of early diagnosis and early intervention, since prompt diagnosis can reduce the severity of autism symptoms and improve cognitive and language skills in younger children. Particularly in toddlers, it seems that an intervention model based on the ESDM principles, involving the active engagement of parents and nursery school teachers, may be effective even when the individual treatment is delivered at low intensity. Furthermore, our study supports the adaptation and the positive impact of the ESDM entirely sustained by the Italian Public Health System.
Purpose: to describe specificities of early diagnosis method for junior school age children’s posture disorders. Material: in pedagogic experiment 156 junior school age children (boys and girls of 7-10 years’ age) participated. All children had no experience of training in sport circles. For determination of uniformity of the tested we fulfilled experts’ examination for presence or absence of external signs of posture disorders in frontal plane. The children’s examination was conducted by qua...
Zeanah, Charles H; Carter, Alice S; Cohen, Julie; Egger, Helen; Gleason, Mary Margaret; Keren, Miri; Lieberman, Alicia; Mulrooney, Kathleen; Oser, Cindy
The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized. © 2016 Michigan Association for Infant Mental Health.
Maldonado, Lizmarie; Huang, Yangxin; Chen, Ren; Kasen, Stephanie; Cohen, Patricia; Chen, Henian
Purpose To examine the association between early adolescent anxiety disorders and self-esteem development from early adolescence to young adulthood. Methods Self-esteem was measured at mean ages 13, 16 and 22 for 821 participants from the Children in the Community Study, a population-based longitudinal cohort. Anxiety disorders were measured at mean age 13 years. Multilevel growth models were employed to analyze the change in self-esteem from early adolescence to young adulthood and to evaluate whether adolescent anxiety disorders predict both average and slope of self-esteem development. Results Self-esteem increased during adolescence and continued to increase in young adulthood. Girls had lower average self-esteem than boys, but this difference disappeared when examining the effect of anxiety. Adolescents with anxiety disorder had lower self-esteem, on average, compared with healthy adolescents (effect size (ES) =−0.35, pself-esteem (ES=−0.30, pself-esteem from adolescence to young-adulthood ( =−0.1, pself-esteem development. Conclusions All but one of the assessed adolescent anxiety disorders were related to lower self-esteem, with social phobia having the greatest impact. OCD predicted a decline in self-esteem trajectory with age. The importance of raising self-esteem in adolescents with anxiety and other mental disorders is discussed. PMID:23648133
Blankley, Gaynor; Galbally, Megan; Snellen, Martien; Power, Josephine; Lewis, Andrew J
This study examines pregnancy and early infant outcomes of pregnant women with a clinical diagnosis of Borderline Personality Disorder presenting for obstetric services to a major metropolitan maternity hospital in Victoria, Australia. A retrospective case review of pregnancy and early infant outcomes on 42 women who had been diagnosed with Borderline Personality Disorder via psychiatric assessment using DSM-IV-R criteria was undertaken. Outcomes were compared with a control group of 14,313 consisting of women and infants of non-affected women from the same hospital over the same period of time. Women presenting for obstetric services with a clinical diagnosis of Borderline Personality Disorder experienced considerable psychosocial impairment. They anticipated birth as traumatic and frequently requested early delivery. High comorbidity with substance abuse was found and high rates of referral to child protective services. Mothers with Borderline Personality Disorder were significantly more likely to have negative birth outcomes such as lowered Apgar scores, prematurity and special care nursery referral when compared with controls. These findings offer preliminary evidence to be considered by clinicians in developing treatments and services for the perinatal care of women with Borderline Personality Disorder and their infants. Further research is required in order to develop evidence informed clinical guidelines for the management of women with Borderline Personality Disorder and their infants. © The Royal Australian and New Zealand College of Psychiatrists 2015.
Maldonado, Lizmarie; Huang, Yangxin; Chen, Ren; Kasen, Stephanie; Cohen, Patricia; Chen, Henian
To examine the association between early adolescent anxiety disorders and self-esteem development from early adolescence through young adulthood. Self-esteem was measured at mean ages 13, 16, and 22 for 821 participants from the Children in the Community Study, a population-based longitudinal cohort. Anxiety disorders were measured at mean age 13 years. Multilevel growth models were employed to analyze the change in self-esteem from early adolescence to young adulthood and to evaluate whether adolescent anxiety disorders predict both average and slope of self-esteem development. Self-esteem increased during adolescence and continued to increase in young adulthood. Girls had lower average self-esteem than boys, but this difference disappeared when examining the effect of anxiety. Adolescents with anxiety disorder had lower self-esteem, on average, compared with healthy adolescents (effect size [ES] = -.35, p self-esteem (ES = -.30, p self-esteem from adolescence to young adulthood (β = -.1, p self-esteem development. All but one of the assessed adolescent anxiety disorders were related to lower self-esteem, with social phobia having the greatest impact. OCD predicted a decline in self-esteem trajectory with age. The importance of raising self-esteem in adolescents with anxiety and other mental disorders is discussed. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia
the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental......-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included...
Hellström, Lone; Bech, Per; Nordentoft, Merete
that Individual Placement and Support (IPS) has a positive effect on employment when provided to people with severe mental illness. This modified IPS intervention is aimed at supporting people with recently diagnosed anxiety or affective disorders in regaining their ability to work and facilitate their return......Anxiety and affective disorders can be disabling and have a major impact on the ability to work. In Denmark, people with a mental disorder, and mainly non-psychotic disorders, represent a substantial and increasing part of those receiving disability pensions. Previous studies have indicated...... to work or education.Aim: To investigate whether an early modified IPS intervention has an effect on employment and education when provided to people with recently diagnosed anxiety or affective disorders in a Danish context.Methods/design: The trial is a randomised, assessor-blinded, clinical superiority...
La Maison, Carolina; Munhoz, Tiago N; Santos, Iná S; Anselmi, Luciana; Barros, Fernando C; Matijasevich, Alicia
The present study aimed to evaluate the prevalence of psychiatric disorders in early adolescence, to examine the distribution of psychiatric disorders by maternal and child characteristics and to evaluate the occurrence of psychiatric comorbidities. This was a prospective cohort study of all live births in the city of Pelotas, Brazil, in 2004 (n = 4231). A total of 3562 subjects were evaluated at 11 years of age. Psychiatric disorders were assessed using the Development and Well-Being Assessment. Crude and adjusted logistic regression was used to investigate risk factors for any psychiatric disorder. According to DSM-5 criteria, the overall prevalence of psychiatric disorders was 13.2% (n = 471), 15.6% among the boys and 10.7% among the girls. The most common disorders were anxiety disorders (4.3%), any attention deficit/hyperactivity disorder (4.0%) and any conduct/oppositional disorder (2.8%). Low maternal education, smoking during pregnancy, the presence of moods symptoms during pregnancy or maternal chronic and severe depressive symptoms in the first years of the adolescent´s life, male gender, 5-min Apgar score mental health care services in this age group.
Rajewska-Rager, Aleksandra; Sibilski, Piotr; Lepczyńska, Natalia
In recent years much attention has been given to determine risk factors for suicide among adults with bipolar disorder. Such studies concerning children and youths, which would also take into account the specificity of the developmental age, are still too few. The ability to identify risk factors for children and youths with mood disorders, as well as the possibility to monitor them, is an essential element in preventing suicidal behaviours. Previous studies have clearly indicated that in the group of patients with an early onset of the bipolar disorder the occurrence of suicidal thoughts and intentions were significantly increased. Identifying the risk of suicide is hindered further by the complexity of the phenomenon, which is a compound interaction of various factors: biological, environmental, sociological, psychological and clinical. This is especially true with young adults suffering from mental illness and presenting a number of other psychopathological symptoms. The following paper introduces and reviews the results of current studies, which analysed the risk factors for suicide among children and youths with bipolar spectrum or already diagnosed with bipolar disorder. For this purpose we conducted the overview of recent years literature available in PubMed/MEDLINE database, including the following search criteria: early onset bipolar disorder, bipolar disorder in children and young people, the spectrum of bipolar disorder, and suicidal ideation, suicidal intent, suicide.
Full Text Available Previous studies have shown that numerous sprouts originating from a neuroma, after nerve injury in neonatal animals, can invade spinal nerve roots. In this study the border between the central and peripheral nervous system (CNS-PNS border of ventral roots in kittens was examined with both light and electron microscopy after early postnatal sciatic nerve resection. A transient ingrowth of substance P positive axons was observed into the CNS, but no spouts remained 6 weeks after the injury. Using serial sections and electron microscopy it was possible to identify small bundles of unmyelinated axons that penetrated from the root fascicles for a short distance into the CNS. These axons ended blindly, sometimes with a growth cone-like terminal swelling filled with vesicles. The axon bundles were accompanied by p75 positive cells in both the root fascicles and the pia mater, but not in the CNS. It may thus be suggested that neurotrophin presenting p75 positive cells could facilitate axonal growth into the pia mater and that the lack of such cells in the CNS compartment might contribute to the failure of growth into the CNS. A maldevelopment of myelin sheaths at the CNS-PNS border of motor axons was observed and it seems possible that this could have consequences for the propagation of action potential across this region after neonatal nerve injury.
De Panfilis, Chiara; Marchesi, Carlo; Cabrino, Chiara; Monici, Alberto; Politi, Virginia; Rossi, Matteo; Maggini, Carlo
Despite obvious clinical need, factors underlying early treatment discontinuation among 'real world' borderline personality disorder (BPD) patients are still unknown. This study investigates individual characteristics that can predict early (Disorders, fourth edition (DSM-IV) Personality. Sociodemographic, clinical and personality variables potentially relevant for dropout were assessed for all participants at baseline. Early dropouts (n=54) were compared to continuers (n=108) on all measures. Logistic regression was then used to identify independent predictors of early dropout. A history of suicide attempts predicted early discontinuation, whereas the presence of an eating disorder and of avoidant personality features protected from early dropout. If confirmed, these findings may help clinicians operating in general psychiatric settings with estimating the risk of premature treatment discontinuation, and stress the need to specifically address suicidal behaviours in order to improve treatment retention among borderline outpatients. In this regard, implementing general psychiatric care with specialised, evidence-based psychotherapeutic interventions may be deemed necessary. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Kaushik, Deepak Kumar; Hahn, Jennifer Nancy; Yong, V Wee
Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer's disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN's role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN's involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction. Copyright © 2015 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.
Full Text Available MicroRNAs (miRNAs, small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer’s disease, multiple sclerosis, traumatic brain injuries, Parkinson’s disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders.
Stoicea, Nicoleta; Du, Amy; Lakis, D. Christie; Tipton, Courtney; Arias-Morales, Carlos E.; Bergese, Sergio D.
MicroRNAs (miRNAs), small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer's disease, multiple sclerosis, traumatic brain injuries, Parkinson's disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders. PMID:26904099
Full Text Available During the past few decades, scientific evidence has been accumulated concerning the possible adverse effects of the exposure to environmental chemicals on the well-being of wildlife and human populations. One large and growing group of such compounds of anthropogenic or natural origin is referred to as endocrine-disrupting chemicals (EDCs, due to their deleterious action on the endocrine system. This concern was first focused on the control of reproductive function particularly in males, but has later been expanded to include all possible endocrine functions. The present review describes the underlying physiology behind the cascade of developmental events that occur during sexual differentiation of males and the specific role of androgen in the masculinization process and proper organogenesis of the external male genitalia. The impact of the genetic background, environmental exposures and lifestyle factors in the etiology of hypospadias, cryptorchidism and testicular cancer are reviewed and the possible role of EDCs in the development of these reproductive disorders is discussed critically. Finally, the possible direct and programming effects of exposures in utero to widely use therapeutic compounds, environmental estrogens and other chemicals on the incidence of reproductive abnormalities and poor semen quality in humans are also highlighted.
Maniaci, G; La Cascia, C; Picone, F; Lipari, A; Cannizzaro, C; La Barbera, D
Several treatment options for gambling disorder (GD) have been tested in recent years; however dropout levels still remain high. This study aims to evaluate whether the presence of psychiatric comorbidities predicts treatment outcome according to Millon's evolutionary theory, following a six-month therapy for GD. The role of severity, duration of the disorder, typology of gambling (mainly online or offline) and pharmacological treatment were also analysed. The recruitment included 194 pathological gamblers (PGs) to be compared with 78 healthy controls (HCs). Psychological assessment included the South Oaks Gambling Screen and the Millon Clinical Multiaxial Inventory-III. The "treatment failure" group (n = 70) comprised PGs who prematurely dropped out of the treatment whereas the "abstinent group" (n = 124) included PGs who completed the treatment regardless of whether the outcome was successful or not. As expected, the presence of psychiatric comorbidities was highlighted as a significant predictor in dropping out of the therapy. Specifically negativistic personality disorder, antisocial personality disorder, drug dependence and PTSD were associated with early dropout. These variables were predictive of treatment outcome independently from the typology of gambling, severity, duration of the disorder and pharmacological treatment. Implications for psychological and psychiatric care are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.
Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S
Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.
Full Text Available In 18 months, 850 patients were referred to Muhammad Ali Parkinson Center (MAPC. Among them, 810 patients had typical Parkinson disease (PD and 212 had PD for ≤5 years. Among the 212 patients with early PD, 27 (12.7% had freezing of gait (FOG. Forty of the 850 had atypical parkinsonism. Among these 40 patients, all of whom had symptoms for ≤5 years, 12 (30.0% had FOG. FOG improved with levodopa in 21/27 patients with typical PD but did not improve in the 12 patients with atypical parkinsonism. FOG was associated with falls in both groups of patients. We believe that FOG unresponsive to levodopa in typical PD resembles FOG in atypical parkinsonism. We thus compared the 6 typical PD patients with FOG unresponsive to levodopa plus the 12 patients with atypical parkinsonism with the 21 patients with typical PD responsive to levodopa. We compared them by tests of locomotion and postural stability. Among the patients with FOG unresponsive to levodopa, postural stability was more impaired than locomotion. This finding leads us to believe that, in these patients, postural stability, not locomotion, is the principal problem underlying FOG.
Skillgate, Eva; Côté, Pierre; Cassidy, J. David
Objective To determine whether the results from previous research suggesting that early intensive health care delays recovery from whiplash-associated disorders (WADs) were confounded by expectations of recovery and whether the association between early health care intensity and time to recovery......; 95% CI,.68-.90) had significantly slower recovery. Conclusions Our study adds to the existing evidence that early intensive care is associated with slower recovery from WAD, independent of expectation of recovery. The results have policy implications and suggest that the optimal management of WADs...
Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A
Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Brodzeller, Katharine L.; Ottley, Jennifer R.; Jung, Jeesun; Coogle, Christan G.
The inclusive education of children with disabilities is considered best practice, yet many early childhood educators feel unprepared to deliver appropriate instruction for children with disabilities and often require supports to successfully meet the children's unique needs. Young children experiencing autism spectrum disorder are being diagnosed…
Samadi, Sayyed Ali; Mahmoodizadeh, Ameneh
Omid early intervention resource kit containing information booklets on autism spectrum disorders (ASD) and related issues, five packs of tangible selected playthings and communication facilitating aids was developed and evaluated with 65 Iranian parents. Beside a pretest before the resource kit deliverance, parents in the control group took part…
van der Meere, Jacob; Börger, Norbert; Pirila, Silja
The aim of the present study is to investigate visual orientation in hospitalized boys with severe early onset conduct disorder and borderline intellectual functioning. It is tested whether boys with the dual diagnosis have a stronger action-oriented response style to visual-cued go signals than the
Pottegård, Anton; Bjerregaard, B. K.; Kortegaard, L. S.
Knowledge of patterns of treatment discontinuation in attention-deficit/hyperactivity disorder (ADHD) drug treatment is of importance, for both the clinical practice and the study of long-term treatment outcomes. The purpose of this study was to describe early discontinuation of ADHD drug treatme...
Bundgaard, Anne Katrine F.; Asmussen, Jette; Pedersen, Nadia S.
This study investigated whether early signs of attention deficit hyperactivity disorder (ADHD) in toddlers aged 2-3 years are associated with disturbed sleep and activity levels. Participants were recruited from the Odense Child Cohort, and children scoring above the 93rd percentile on the ADHD...
Smith, Isabel M.; Koegel, Robert L.; Koegel, Lynn K.; Openden, Daniel A.; Fossum, Kristin L.; Bryson, Susan E.
The Nova Scotia early intensive behavior intervention model--NS EIBI (Bryson et al., 2007) for children with autistic spectrum disorders was designed to be feasible and sustainable in community settings. It combines parent training and naturalistic one-to-one behavior intervention employing Pivotal Response Treatment--PRT (R. Koegel & Koegel,…
Guthrie, Whitney; Swineford, Lauren B.; Nottke, Charly; Wetherby, Amy M.
Background: Although a diagnosis of autism spectrum disorder (ASD) appears to be stable in children as young as age three, few studies have explored stability of a diagnosis in younger children. Predictive value of diagnostic tools for toddlers and patterns of symptom change are important considerations for clinicians making early diagnoses. Most…
This article briefly reports on three early contributions to the understanding of visual agnosia as a syndrome sui generis. The authors of the respective papers worked in different fields such as physiology, ophthalmology, and neurology, and, although they were not in direct contact with each other, their results converged upon a consistent view of a nervous disorder that they called psychic blindness.
Wiggins, Lisa D.; Levy, Susan E.; Daniels, Julie; Schieve, Laura; Croen, Lisa A.; DiGuiseppi, Carolyn; Blaskey, Lisa; Giarelli, Ellen; Lee, Li-Ching; Pinto-Martin, Jennifer; Reynolds, Ann; Rice, Catherine; Rosenberg, Cordelia Robinson; Thompson, Patrick; Yeargin-Allsopp, Marshalyn; Young, Lisa; Schendel, Diana
This study examined the phenotypic profiles of children aged 30-68 months in the Study to Explore Early Development (SEED). Children classified as autism spectrum disorder (ASD), developmental delay (DD) with ASD symptoms, DD without ASD symptoms, and population comparison (POP) differed significantly from each other on cognitive, adaptive,…
Yaari, Maya; Yitzhak, Neta; Harel, Ayelet; Friedlander, Edwa; Bar-Oz, Benjamin; Eventov-Friedman, Smadar; Mankuta, David; Gamliel, Ifat; Yirmiya, Nurit
Stability and change in early autism spectrum disorder risk were examined in a cohort of 99 preterm infants (?34 weeks of gestation) using the Autism Observation Scale for Infants at 8 and 12 months and the Autism Diagnostic Observation Schedule--Toddler Module at 18 months. A total of 21 infants were identified at risk by the Autism Observation…
Sonuga-Barke, Edmund J. S.; Halperin, Jeffrey M.
Early intervention approaches have rarely been implemented for the prevention of attention deficit/hyperactivity disorder (ADHD). In this paper we explore whether such an approach may represent an important new direction for therapeutic innovation. We propose that such an approach is most likely to be of value when grounded in and informed by…
Detection of children with a developmental disorder, such as cerebral palsy, at an early age is notoriously difficult. Recently, a new form of neuromotor assessment of young infants was developed, based on the assessment of the quality of general movements (GMs). GMs are movements of the fetus and
Campbell, Brian M.; Charych, Erik; Lee, Anna W.; Möller, Thomas
The kynurenine pathway (KP) metabolizes the essential amino acid tryptophan and generates a number of neuroactive metabolites collectively called the kynurenines. Segregated into at least two distinct branches, often termed the “neurotoxic” and “neuroprotective” arms of the KP, they are regulated by the two enzymes kynurenine 3-monooxygenase and kynurenine aminotransferase, respectively. Interestingly, several enzymes in the pathway are under tight control of inflammatory mediators. Recent years have seen a tremendous increase in our understanding of neuroinflammation in CNS disease. This review will focus on the regulation of the KP by inflammatory mediators as it pertains to neurodegenerative and psychiatric disorders. PMID:24567701
Tsuchiya, Kenji; Agerbo, Esben; Mortensen, Preben Bo
of a conditional logistic regression analysis. RESULTS: Among 947 subjects with bipolar disorder and 47,350 controls, those having experienced the parental suicide were significantly associated with an increased risk for BPD (incidence rate ratios: 1.83 [95% confidence interval: 1.07 to 3.12] for paternal suicide......BACKGROUND: Previous studies have suggested that early parental death may be associated with the emergence of bipolar disorder in later life. However, it remains unknown whether this association applies specifically to parental death due to suicide or only to early parental death. The present study...... were born in 1960 or later and were first admitted to or had first contact with Danish psychiatric facilities between 1981 and 1998 with a diagnosis of bipolar disorder, and fifty age-matched controls per case were extracted. The effects of the deaths of relatives were estimated by means...
Full Text Available Childhood substance abuse and delinquency often progress to harder substances and antisocial personality disorder and carries deleterious consequences for self, family and community at large. Early management of such cases poses several clinical and management challenges, as highlighted in the present case. The treatment seeking for this sub-population is very low in spite of community surveys showing a worrisome pattern of substance use among younger population. Further, very few specialty clinics and trained manpower exist in the country to manage early onset substance use. Whether conduct disorder be cause or consequence for drug use is debatable, in view of shared risk factors. The present case helps to understand need for comprehensive assessment for identifying risk factors and comorbid conditions. Only pharmacological management does not help, psychosocial management must be delivered. Several prevention strategies may also help if these risk factors are identified before progression to illicit substance use disorder.
Rafaela Torres Portugal Leite
Full Text Available Introduction. Bipolar disorder (BD implies risk of suicide. The age at onset (AAO of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.
Straube, W; Römer, T; Zeenni, L; Loh, M
The early pregnancy factor (EPF) seems to be very helpful in clinical applications such as early detection of pregnancy, differential diagnosis of failure of fertilization or implementation and prognosis of a fertilized ovum. Our purpose was to investigate the diagnostic value of single and serial measurement of EPF, especially in the differential diagnosis of abortion and extrauterine pregnancy. Women with a history of 6-16 weeks amenorrhoea with/without vaginal bleeding were included in the prospective study. The EPF-test system was carried out by means of the rosette inhibition method. EPF proved to be always positive in normal pregnant women and always negative in nonpregnant controls. In case of threatened abortion the prognosis was good, when the EPF values were positive, and poor when they became negative. Patients suffering from spontaneous and missed abortion mostly showed negative EPF-values. This was also true in ectopic pregnancies. The sensitivity and specificity of EPF-test system were 83%. The positive predictive value was observed to be 54% and the negative predictive value 95%. The EPF as an early embryonic signal may be a suitable parameter for the clinical use detecting pregnancy disturbances very early.
Kawakami, Norito; Abdulghani, Emad Abdulrazaq; Alonso, Jordi; Bromet, Evelyn; Bruffaerts, Ronny; de Almeida, Jose Miguel Caldas; Chiu, Wai Tat; de Girolamo, Giovanni; de Graaf, Ron; Fayyad, John; Ferry, Finola; Florescu, Silvia; Gureje, Oye; Hu, Chiyi; Lakoma, Matthew D.; LeBlanc, William; Lee, Sing; Levinson, Daphna; Malhotra, Savita; Matschinger, Herbert; Medina-Mora, Maria Elena; Nakamura, Yosikazu; Browne, Mark A. Oakley; Okoliyski, Michail; Posada-Villa, Jose; Sampson, Nancy A.; Viana, Maria Carmen; Kessler, Ronald C.
Background Better information on the human capital costs of early-onset mental disorders could increase sensitivity of policy-makers to the value of expanding initiatives for early detection-treatment. Data are presented on one important aspect of these costs: the associations of early-onset mental disorders with adult household income. Methods Data come from the WHO World Mental Health (WMH) Surveys in eleven high income, five upper-middle income, and six low/lower-middle income countries. Information about 15 lifetime DSM-IV mental disorders as of age of completing education, retrospectively assessed with the WHO Composite International Diagnostic Interview, was used to predict current household income among respondents ages 18-64 (n = 37,741) controlling for level of education. Gross associations were decomposed to evaluate mediating effects through major components of household income. Results Early-onset mental disorders are associated with significantly reduced household income in high and upper-middle income countries but not low/lower-middle income countries, with associations consistently stronger among women than men. Total associations are largely due to low personal earnings (increased unemployment, decreased earnings among the employed) and spouse earnings (decreased probabilities of marriage and, if married, spouse employment and low earnings of employed spouses). Individual-level effect sizes are equivalent to 16-33% of median within-country household income, while population-level effect sizes are in the range 1.0-1.4% of Gross Household Income. Conclusions Early mental disorders are associated with substantial decrements in income net of education at both individual and societal levels. Policy-makers should take these associations into consideration in making healthcare research and treatment resource allocation decisions. PMID:22521149
Advances in the fields of cognitive and affective developmental neuroscience, developmental psychopathology, neurobiology, genetics, and applied behavior analysis have contributed to a more optimistic outcome for individuals with autism spectrum disorder (ASD). These advances have led to new methods for early detection and more effective treatments. For the first time, prevention of ASD is plausible. Prevention will entail detecting infants at risk before the full syndrome is present and implementing treatments designed to alter the course of early behavioral and brain development. This article describes a developmental model of risk, risk processes, symptom emergence, and adaptation in ASD that offers a framework for understanding early brain plasticity in ASD and its role in prevention of the disorder.
Bronsard, Guillaume; Auquier, Pascal; Boyer, Laurent
Early child maltreatment has been widely associated with the development of mental disorders in both childhood and adulthood. However, such association cannot be systematically established, as only few factors are observed regularly, such as high prevalence of comorbidities and externalized disorders. Similarly, the association between early abuse and cortisol secretion anomalies has been well-documented. Whereas early hypercortisolism followed by hypocortisolism was often described, the results proved inconsistent and at times contradictory. The physiopathological mechanisms are quite complex and varied, including mixed neurotoxicity and stress response anomalies, linked to circadian rhythm disturbances. One of the difficulties inherent to research on this topic is to better define maltreatment in childhood. Studying children's groups at risk of maltreatment, such as children followed by juvenile justice or in child welfare systems, could be a very good tool, provided that social, judiciary, and mental health professionals are able to work together and implement common research objectives. Copyright © 2017 Elsevier Ltd. All rights reserved.
Allen, Karina L; Crosby, Ross D; Oddy, Wendy H; Byrne, Susan M
Adolescence is a period of developmental risk for eating disorders and eating disorder symptoms. This study aimed to describe the prevalence and trajectory of five core eating disorder behaviours (binge eating, purging, fasting, following strict dietary rules, and hard exercise for weight control) and a continuous index of dietary restraint and eating, weight and shape concerns, in a cohort of male and female adolescents followed from 14 to 20 years. It also aimed to determine the effect of early adolescent depressive symptoms on the prevalence and trajectory of these different eating disorder symptoms. Participants (N = 1,383; 49% male) were drawn from the Western Australian Pregnancy Cohort (Raine) Study, a prospective cohort study that has followed participants from pre-birth to age 20 years. An adapted version of the Eating Disorder Examination-Questionnaire was used to assess eating disorder symptoms at ages 14, 17 and 20 years. The Beck Depression Inventory for Youth was used to assess depressive symptoms at age 14. Longitudinal changes in the prevalence of eating disorder symptoms were tested using generalised estimating equations and linear mixed models. Symptom trajectories varied according to the eating disorder symptom studied, participant sex, and the presence of depressive symptoms in early adolescence. For males, eating disorder symptoms tended to be stable (for purging, fasting and hard exercise) or decreasing (for binge eating and global symptom scores) from 14 to 17 years, and then stable to 20 years. For females, fasting and global symptom scores increased from age 14 to peak in prevalence at age 17. Rates of binge eating in females were stable from age 14 to age 17 and increased significantly thereafter, whilst rates of purging and hard exercise increased from age 14 to age 17, and then remained elevated through to age 20. Depressive symptoms at age 14 impacted on eating disorder symptom trajectories in females, but not in males. Prevention
Storebø, Ole Jakob; Simonsen, Erik
BACKGROUND: Several studies report associations between adults with borderline personality disorder (BPD) and a history of attention-deficit hyperactivity (ADHD) symptoms in childhood. AIMS: To explore the association between BPD and a history of ADHD in childhood. METHOD: A comprehensive search......: Most of the 15 articles showed a statistical association between ADHD and BPD. The data, most strongly provided a basis for the hypotheses that ADHD is either an early developmental stage of BPD, or that the two disorders share an environmental and genetic aetiology. Furthermore, one of the disorders...... seems to give a synergic effect, reinforce the other or complicate the disorders. In one prospective study, the risk factor for children with ADHD to develop BPD was as high as odds ratio 13.16. No studies have looked at treatment of ADHD as a mediator of the risk for BPD. CONCLUSIONS: Many studies...
Katzman, Martin A; Habert, Jeffrey; McIntosh, Diane; MacQueen, Glenda M; Milev, Roumen V; McIntyre, Roger S; Blier, Pierre
Abstract Major depressive disorder is an often chronic and recurring illness. Left untreated, major depressive disorder may result in progressive alterations in brain morphometry and circuit function. Recent findings, however, suggest that pharmacotherapy may halt and possibly reverse those effects. These findings, together with evidence that a delay in treatment is associated with poorer clinical outcomes, underscore the urgency of rapidly treating depression to full recovery. Early optimized treatment, using measurement-based care and customizing treatment to the individual patient, may afford the best possible outcomes for each patient. The aim of this article is to present recommendations for using a patient-centered approach to rapidly provide optimal pharmacological treatment to patients with major depressive disorder. Offering major depressive disorder treatment determined by individual patient characteristics (e.g., predominant symptoms, medical history, comorbidities), patient preferences and expectations, and, critically, their own definition of wellness provides the best opportunity for full functional recovery. PMID:29024974
It Is used to "label’ (e.g., glucose labelled with an isotope of carbon), autoradlography can used to study metabolism (e.g., uptake of dopamIne In...defined dysfunctions, Such as autism and dementia, and to obtain detailed Information regarding brain function even In subjects who cannot actively...man. Ann NY Acad Sc 508: 1-537. Courchesne E (In press) Cerebellar changes In autism . In J Swann and A Messer (Eds) Disorders of the developing
Thériault, Marie-Claude G; Bécue, Jean-Cyprien; Lespérance, Paul; Chouinard, Sylvain; Rouleau, Guy A; Richer, Francois
Chronic tic disorders (TD) are associated with a number of psychological problems such as attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive behavior (OCB), oppositional-defiant disorder (ODD) as well as anxious and depressive symptoms. ODD is often considered a risk factor for many psychological symptoms and recent work suggests that different ODD dimensions show independent predictions of later psychological problems. This study examined the longitudinal predictions between ODD dimensions of Irritability and Defiance and the most frequent comorbidities in TD from childhood to early adulthood. From an initial sample of 135, parent reports were obtained on 58 participants with TD using standard clinical questionnaires and semi-structured interviews. Defiance symptoms decreased from baseline to follow-up whereas Irritability symptoms were more stable over time. In multiple regressions, Irritability in childhood predicted anxiety and OCB in early adulthood while Defiance in childhood predicted ADHD and conduct disorder symptoms in early adulthood. No developmental link was found for depressive symptoms. Results indicate that ODD dimensions are developmentally linked to both internalizing and externalizing adult mental health symptoms in TD. Copyright © 2018. Published by Elsevier B.V.
Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.
Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305
Dereu, Mieke; Warreyn, Petra; Raymaekers, Ruth; Meirsschaut, Mieke; Pattyn, Griet; Schietecatte, Inge; Roeyers, Herbert
A new screening instrument for ASD was developed that can be filled out by child care workers: the Checklist for Early Signs of Developmental Disorders (CESDD). The predictive validity of the CESDD was evaluated in a population of 6,808 children between 3 and 39 months attending day-care centres in Flanders. The CESDD had a sensitivity of .80 and a specificity of .94. Based on the screening procedure used in this study, 41 children were diagnosed with ASD or got a working diagnosis of ASD. Thus, including child care workers' report on signs of ASD in screening procedures can help to identify cases of ASD at a young age.
Grund, Julius; Schulz, Wolfgang
The Influence of Media Consumption During Early Childhood on Media Use and Psychological Disorders in Adolescence There are many studies that suggest that there is a link between high media consumption and psychological, physiological and social disorders. Nevertheless, there are also inconsistent results, methodical limitations and a lack of longitudinal studies. The present study analyses habits of media consumption in children and adolescents, the influence of different early childhood risk factors on the use of the media in adolescence and the links between early childhood media consumption and disorders in adolescence. The source of the data is the longitudinal project Future Family III. 249 families participated in the last data collection in the adolescence. Adolescents use the media more than five hours per day on average, nearly fifty percent of these adolescents can be considered as internet addicted and a majority consumes violent contents. A low socioeconomic status, low socio-emotional competences and low intelligence of the child as well as unfavorable educational style and psychological stress of the mother are risk factors for the media use in adolescence. Adolescents with a migration background have an increased risk of internet and computer game dependency. On the other hand, the overall utilization of media in the early childhood has only a low predictive power. The results indicate that these connections seem to be more complex than assumed. There is a need for more longitudinal studies in order to get a better understanding of the consequences of media consumption.
Brinkman, William B; Epstein, Jeffery N; Auinger, Peggy; Tamm, Leanne; Froehlich, Tanya E
The association of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) with tobacco and alcohol use has not been assessed in a young adolescent sample representative of the U.S. population. Data are from the 2000-2004 National Health and Nutrition Examination Survey, a cross-sectional sample representative of the U.S. population. Participants were age 12-15 years (N=2517). Exposure variables included diagnosis of ADHD and CD, and counts of ADHD and CD symptoms based on caregiver responses to the Diagnostic Interview Schedule for Children. Primary outcomes were adolescent-report of any use of tobacco or alcohol and age of initiating use. Multivariate logistic regression and Cox proportional hazard models were conducted. Adolescents with ADHD+CD diagnoses had a 3- to 5-fold increased likelihood of using tobacco and alcohol and initiated use at a younger age compared to those with neither disorder. Having ADHD alone was associated with an increased likelihood of tobacco use but not alcohol use. Hyperactive-impulsive symptom counts were not independently associated with any outcome, while every one symptom increase in inattention increased the likelihood of tobacco and alcohol use by 8-10%. Although participants with a diagnosis of CD alone (compared to those without ADHD or CD) did not have a higher likelihood of tobacco or alcohol use, for every one symptom increase in CD symptoms the odds of tobacco use increased by 31%. ADHD and CD diagnoses and symptomatology are linked to higher risk for a range of tobacco and alcohol use outcomes among young adolescents in the U.S. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily
The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.
Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha
To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially
Phillips, Anthony George; Hongaard-Andersen, Peter; Moscicki, Richard A; Sahakian, Barbara; Quirion, Rémi; Krishnan, K Ranga Rama; Race, Tim
Central nervous system (CNS) diseases and, in particular, mental health disorders, are becoming recognized as the health challenge of the 21(st) century. Currently, at least 10% of the global population is affected by a mental health disorder, a figure that is set to increase year on year. Meanwhile, the rate of development of new CNS drugs has not increased for many years, despite unprecedented levels of investment. In response to this state of affairs, the Collegium Internationale Neuro-Psychopharmacologicum (CINP) convened a summit to discuss ways to reverse this disturbing trend through new partnerships to accelerate CNS drug discovery. The objectives of the Summit were to explore the issues affecting the value chain (i.e. the chain of activities or stakeholders that a company engages in/with to deliver a product to market) in brain research, thereby gaining insights from key stakeholders and developing actions to address unmet needs; to identify achievable objectives to address the issues; to develop action plans to bring about measurable improvements across the value chain and accelerate CNS drug discovery; and finally, to communicate recommendations to governments, the research and development community, and other relevant stakeholders. Summit outputs include the following action plans, aligned to the pressure points within the brain research-drug development value chain: Code of conduct dealing with conflict of interest issues, Prevention, early diagnosis, and treatment, Linking science and regulation, Patient involvement in trial design, definition of endpoints, etc., Novel trial design, Reproduction and confirmation of data, Update of intellectual property (IP) laws to facilitate repurposing and combination therapy (low priority), Large-scale, global patient registries, Editorials on nomenclature, biomarkers, and diagnostic tools, and Public awareness, with brain disease advocates to attend G8 meetings and World Economic Forum (WEF) Annual meetings in
Kumsta, Robert; Sonuga-Barke, Edmund; Rutter, Michael
There is a debate over whether disruptive behaviour should be regarded as a central component of, or rather as an epiphenomenon with little diagnostic value for, psychopathy. To test whether callous-unemotional traits and conduct disorder can be dissociated in the English and Romanian Adoptee Study, a prospective longitudinal study of adopted individuals with a history of severe early institutional deprivation. The Child and Adolescent Psychiatric Assessment was used to establish DSM-IV diagnoses for conduct disorder (and also oppositional defiant disorder) at the 15-year follow-up stage. The Inventory of Callous-Unemotional Traits questionnaire was administered to assess psychopathy traits. There was no significant association between callous-unemotional traits and conduct disorder, both according to parent and youth self-report assessed categorically and dimensionally after controlling for confounds. The majority of individuals with high callous-unemotional traits did not show conduct disorder in this special sample of children. This supports the view that, while common, an overlap between these aspects of psychopathology is not inevitable and so provides evidence for the dissociation of these two concepts. In terms of classification, we argue for a diagnostic scheme where psychopathy can be diagnosed independently of conduct disorder.
Larsen, Kenneth; Aasland, Astrid; Diseth, Trond H.
Early identification of Autism Spectrum Disorders (ASD) has the potential to elicit effective early intervention, improving children's level of functioning and developmental trajectories as well as reducing parental stress. Multiple sources of information, including several informants may facilitate early identification. This study examined the…
Full Text Available Abstract Background Differentiating between bipolar spectrum disorder (BD and attention deficit hyperactivity disorder (ADHD in childhood and adolescence is difficult because the clinical presentation is influenced by ongoing neural development, causing considerable symptom overlap. Motor problems and neurological soft signs have been associated with ADHD for decades. Little is known about motor skills in BD. Here we assess the diagnostic accuracy of neuromotor deviations in differentiating ADHD from BD in clinical practice. We also investigate if these deviations exist in concurrent ADHD and BD, thus indicating true comorbidity Methods 64 patients 6-18 years (31 girls, 33 boys fulfilling the diagnostic criteria of BD, ADHD combined subtype (ADHD-C or comorbid BD and ADHD-C, were compared using an age-standardized neuromotor test; NUBU. Categorical variables were analyzed using cross table with two-tailed chi square test or Fisher's exact test when appropriate. Continuous variables were analyzed by Kruskal-Wallis test and, if significant, Mann-Whitney U test and ROC plots. Results The ADHD-C group and the comorbid ADHD-C and BD group both showed significantly more neurological soft signs (p less than 0.01 and lower mean static coordination percentile (p less than 0.01 than the BD group. The positive predictive value of NUBU in the diagnosis of ADHD-C with or without concurrent BD was 89% (80-95 for total soft signs and 87% (79-95 for static coordination below the 7.5 percentile. Conclusion An age-standardized neuromotor test battery may promote diagnostic accuracy in differentiating ADHD from BD in clinical practice, and help evaluating whether symptoms of ADHD in children who have BD reflect symptom overlap or real comorbidity. This may have important implications for everyday diagnostic work.
Jennifer L Hudson
Full Text Available BACKGROUND: To inform early intervention practice, the present research examines how child anxiety, behavioural inhibition, maternal overinvolvement, maternal negativity, mother-child attachment and maternal anxiety, as assessed at age four, predict anxiety at age nine. METHOD: 202 children (102 behaviourally inhibited and 100 behaviourally uninhibited aged 3-4 years were initially recruited and the predictors outlined above were assessed. Diagnostic assessments, using the Anxiety Disorders Interview Schedule, were then conducted five years later. RESULTS: Behavioural inhibition, maternal anxiety, and maternal overinvolvement were significant predictors of clinical anxiety, even after controlling for baseline anxiety (p.1. CONCLUSIONS: Preschool children who show anxiety, are inhibited, have overinvolved mothers and mothers with anxiety disorders are at increased risk for anxiety in middle childhood. These factors can be used to identify suitable participants for early intervention and can be targeted within intervention programs.
Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B
Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.
This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders. This literature suggests that the preconception and perinatal periods offer important opportunities for the prevention of deleterious fetal exposures. As such, the perinatal period is a critical period where future mental health prevention efforts should be focused and prevention models developed. Interventions grounded in evidence-based recommendations for the perinatal period could take the form of public health, universal and more targeted interventions. If successful, such interventions are likely to have lifelong effects on (mental) health. PMID:24559477
Full Text Available Purpose: to describe specificities of early diagnosis method for junior school age children’s posture disorders. Material: in pedagogic experiment 156 junior school age children (boys and girls of 7-10 years’ age participated. All children had no experience of training in sport circles. For determination of uniformity of the tested we fulfilled experts’ examination for presence or absence of external signs of posture disorders in frontal plane. The children’s examination was conducted by qualified specialists at the beginning and at the end of experiment. For determination of early signs of muscular asymmetry in torso right and left sides of the tested children we used methodic, based on registration of tonic vibration reflex. Results: the pupils’ examination permitted to form a group of 108 persons, who did not have external signs of posture disorders. It was proved that it would be purposeful to take prophylaxis measures at very early stages of imbalance in muscular system’s work. Traditional approach in the form of prophylaxis examination can not give confident information about initial stage of imbalance in muscular system’s work in child’s organism. Conclusions: it was found that imbalance of motor nervous centers reflex excitability on both sides of backbone (if no purposeful prophylaxis measures are taken can result in muscular tonus asymmetry on right and left sides of torso in lumbar spine area.
Crawford, Jennifer M; Warne, Garry; Grover, Sonia; Southwell, Bridget R; Hutson, John M
Controversy persists surrounding early management of disorders of sex development. We assessed genital appearance, gender identity, and quality of life in prepubertal children who have had early surgical intervention. Children treated for disorders of sex development who were 5 to 10 years of age were eligible (n = 54). Children were scored (modified Creighton scale) for anatomical and cosmetic outcome, and both patients and parents completed PedsQL quality-of-life and gender identity questionnaires, with ethics approval. Of 54 patients, 41 presented for review. Treatment began at 13.2 (1.8-250.1) months (median; range) and were reviewed at 7.5 +/- 2.1 (mean +/- SD) years of age. Nineteen were raised as girls and 22 as boys. Girls had good (85%) or satisfactory (15%) anatomical/cosmetic outcome, whereas 52% boys had good, 38% satisfactory, and 10% poor cosmetic outcomes. On gender identity questionnaire, boys scored 3.9 +/- 0.4 (mean +/- SD) and girls 3.6 +/- 0.5; 1 of 19 boys and 3 of 19 girls had lower scores, suggesting risk of gender identity disorder. Quality-of-life scores were 80+ for physical and 65 to 80 for psychosocial scores. Early intervention is generally associated with positive outcomes for patients and parents. Girls had better anatomical outcomes than boys, and gender dysphoria risks were low in both sexes.
Bosl, William J; Tager-Flusberg, Helen; Nelson, Charles A
Autism spectrum disorder (ASD) is a complex and heterogeneous disorder, diagnosed on the basis of behavioral symptoms during the second year of life or later. Finding scalable biomarkers for early detection is challenging because of the variability in presentation of the disorder and the need for simple measurements that could be implemented routinely during well-baby checkups. EEG is a relatively easy-to-use, low cost brain measurement tool that is being increasingly explored as a potential clinical tool for monitoring atypical brain development. EEG measurements were collected from 99 infants with an older sibling diagnosed with ASD, and 89 low risk controls, beginning at 3 months of age and continuing until 36 months of age. Nonlinear features were computed from EEG signals and used as input to statistical learning methods. Prediction of the clinical diagnostic outcome of ASD or not ASD was highly accurate when using EEG measurements from as early as 3 months of age. Specificity, sensitivity and PPV were high, exceeding 95% at some ages. Prediction of ADOS calibrated severity scores for all infants in the study using only EEG data taken as early as 3 months of age was strongly correlated with the actual measured scores. This suggests that useful digital biomarkers might be extracted from EEG measurements.
Storebø, Ole Jakob; Simonsen, Erik
Several studies report associations between adults with borderline personality disorder (BPD) and a history of attention-deficit hyperactivity (ADHD) symptoms in childhood. To explore the association between BPD and a history of ADHD in childhood. A comprehensive search of EMBASE, PsychInfo and Medline and hand-searching yielded 238 "hits". Fifteen articles were found to have sufficient quality and relevance to be included in the final review. The data were considered in six possible explanatory psychopathological models of the association between ADHD and BPD. Most of the 15 articles showed a statistical association between ADHD and BPD. The data, most strongly provided a basis for the hypotheses that ADHD is either an early developmental stage of BPD, or that the two disorders share an environmental and genetic aetiology. Furthermore, one of the disorders seems to give a synergic effect, reinforce the other or complicate the disorders. In one prospective study, the risk factor for children with ADHD to develop BPD was as high as odds ratio 13.16. No studies have looked at treatment of ADHD as a mediator of the risk for BPD. Many studies pointed at shared aetiology or the risk for development of one disorder, when the other disorder is present. The data do not evaluate how treatment factors or other factors mediate the risk or how overlap of diagnostic criteria adds to the statistical association. More research is much needed, in particular studies looking at early intervention and which treatment of ADHD that might prevent later development of BPD.
Rodgers, Rachel F; Paxton, Susan J
Depressive and eating disorder symptoms are highly comorbid. To date, however, little is known regarding the efficacy of existing programs in decreasing concurrent eating disorder and depressive symptoms. We conducted a systematic review of selective and indicated controlled prevention and early intervention programs that assessed both eating disorder and depressive symptoms. We identified a total of 26 studies. The large majority of identified interventions (92%) were successful in decreasing eating disorder symptoms. However fewer than half (42%) were successful in decreasing both eating disorder and depressive symptoms. Intervention and participant characteristics did not predict success in decreasing depressive symptoms. Indicated prevention and early intervention programs targeting eating disorder symptoms are limited in their success in decreasing concurrent depressive symptoms. Further efforts to develop more efficient interventions that are successful in decreasing both eating disorder and depressive symptoms are warranted.
Castagnini, Augusto; Foldager, Leslie; Caffo, Ernesto
Background Mental disorders show varying degrees of continuity from childhood to adulthood. This study addresses the relationship of child and adolescent mental disorders to early adult psychiatric morbidity. Methods From a population at risk of 830,819 children and adolescents aged 6–16 years, we...... and substance use disorders. Conclusions These findings suggest that individuals with psychiatric antecedents in childhood and adolescence had a high risk of being referred for treatment in early adulthood, and many mental disorders for which they required treatment revealed both homotypic and heterotypic...
Gladysz, J [Akademia Medyczna, Poznan (Poland)
Irradiation of the CNS of mice with 4000 to 7600 R produces transitional disorder of the permeability of vascular walls, followed by a permanent (irreversible) degenerative lesion of blood capillaries and the surrounding astrogial cells. Intensity of this alterations may however not be the same in different terminal blood vessels. It is very likely that the above described lesion appearing in the acute phase can be the main cause of further alterations in the CNS which are observed in late phase of postradiation disease.
Metallothioneins (MTs) are low-molecular-weight (6-7 kDa) nonenzymatic proteins (60-68 amino acid residues, 25-30% being cysteine) expressed ubiquitous in the animal kingdom. In the central nervous system (CNS), three MT isoforms are known, namely MT-I to MT-III. MT-I and MT-II (MT...
Vinen, Zoe; Clark, Megan; Paynter, Jessica; Dissanayake, Cheryl
This study followed children with Autism Spectrum Disorder (ASD) from early intervention into their early schooling years, when they were aged between 6 and 9 years, on autism symptom severity and cognitive functioning. The children, matched at pre-intervention, were compared on type of community provided service: 31 were in receipt of community-based group Early Start Denver Model and 28 had received other community provisions for ASD. Irrespective of groups, cognitive functioning was found to have significantly improved by school age compared to pre-intervention. Autism symptom severity increased during the same developmental period, seemingly driven by an increase in restricted and repetitive behaviours over time. In contrast, both groups displayed improved social affect by school age.
Bukhovets, B. O.; Romanchuk, A. P.
The article represents therapy of Bobath such as one of the most effective author method which use in correction psychomotor development of children with disorders of musculoskeletal system. Bobath method is not new in the correction of movement disorders since last century and still supplementing and improving. In this work highlight topic of the effective use Bobath therapy in correction of psychomotor development in children age 3 – 6 years with organic involvement CNS. the experiment w...
Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John
The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.
VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R
People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.
Swain, Nathaniel Robert; Eadie, Patricia Ann; Prior, Margot Ruth; Reilly, Sheena
Early identification of Autism Spectrum Disorder (ASD) is currently limited by the absence of reliable biological markers for the disorder, as well as the reliability of screening and assessment tools for children aged between 6 and 18 months. Ongoing research has demonstrated the importance of early social communication skills in differentiating children later diagnosed with ASD from their typically developing (TD) peers, but researchers have not yet investigated whether these differences can be detected using community-ascertained systematic observation data as early as 12 months. To investigate whether differences in early social communication skills can be detected at 12 months of age, comparing children later diagnosed with ASD, and TD peers; and to determine whether differences remain when groupings are based on age of subsequent ASD diagnosis. From a prospective community-ascertained sample, we collected data on children in early life, then conducted retrospective analyses for those children who were later diagnosed with ASD by the age of 7 years, compared with matched TD peers. We analysed standardized observational data of early communication skills, collected using the Communication and Symbolic Behavior Scales-Developmental Profile (CSBS-DP) Behavior Sample, when participants were 12 months of age. Children in the ASD group exhibited significantly lower social communication skills than the TD group, including on the Total score and Social and Symbolic Composite scores of the CSBS-DP Behavior Sample. Differences on the Total score and Social Composite were also detected for both early and late ASD diagnosis groups when compared with the TD group. These findings give further support for the importance of social communication in assessing children at risk of ASD as early as 12 months of age. Future research could evaluate the sensitivity and specificity of direct observation of these early communication skills as diagnostic indicators for ASD at 12 months
Zeanah, Charles H; Lieberman, Alicia
Infant mental health is explicitly relational in its focus, and therefore a diagnostic classification system for early childhood disorders should include attention not only to within-the-child psychopathology but also between child and caregiver psychopathology. In this article, we begin by providing a review of previous efforts to introduce this approach that date back more than 30 years. Next, we introduce changes proposed in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-5 (ZERO TO THREE, in press). In a major change from previous attempts, the DC:0-5 includes an Axis I "Relationship Specific Disorder of Early Childhood." This disorder intends to capture disordered behavior that is limited to one caregiver relationship rather than cross contextually. An axial characterization is continued from the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-3R (ZERO TO THREE, 2005), but two major changes are introduced. First, the DC:0-5 proposes to simplify ratings of relationship adaptation/maladaptation, and to expand what is rated so that in addition to characterizing the child's relationship with his or her primary caregiver, there also is a characterization of the network of family relationships in which the child develops. This includes coparenting relationships and the entire network of close relationships that impinge on the young child's development and adaptation. © 2016 Michigan Association for Infant Mental Health.
Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M
SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep
Cosci, Fiammetta; Fava, Giovanni A; Sonino, Nicoletta
Affective disturbances involving alterations of mood, anxiety and irritability may be early symptoms of medical illnesses. The aim of this paper was to provide a systematic review of the literature with qualitative data synthesis. MEDLINE, PsycINFO, EMBASE, Cochrane, and ISI Web of Science were systematically searched from inception to February 2014. Search terms were 'prodrome/early symptom', combined using the Boolean 'AND' operator with 'anxiety/depression/mania/hypomania/irritability/irritable mood/hostility', combined with the Boolean 'AND' operator with 'medical illness/medical disorder'. PRISMA guidelines were followed. A total of 21 studies met the inclusion criteria and were analyzed. Depression was found to be the most common affective prodrome of medical disorders and was consistently reported in Cushing's syndrome, hypothyroidism, hyperparathyroidism, pancreatic and lung cancer, myocardial infarction, Wilson's disease, and AIDS. Mania, anxiety and irritability were less frequent. Physicians may not pursue medical workup of cases that appear to be psychiatric in nature. They should be alerted that disturbances in mood, anxiety and irritability may antedate the appearance of a medical disorder.
Liu, T Y; Chen, Y S; Su, T P; Hsieh, J C; Chen, L F
This study investigates the cortical abnormalities of early emotion perception in patients with major depressive disorder (MDD) and bipolar disorder (BD) using gamma oscillations. Twenty-three MDD patients, twenty-five BD patients, and twenty-four normal controls were enrolled and their event-related magnetoencephalographic responses were recorded during implicit emotional tasks. Our results demonstrated abnormal gamma activity within 100 ms in the emotion-related regions (amygdala, orbitofrontal (OFC) cortex, anterior insula (AI), and superior temporal pole) in the MDD patients, suggesting that these patients may have dysfunctions or negativity biases in perceptual binding of emotional features at very early stage. Decreased left superior medial frontal cortex (smFC) responses to happy faces in the MDD patients were correlated with their serious level of depression symptoms, indicating that decreased smFC activity perhaps underlies irregular positive emotion processing in depressed patients. In the BD patients, we showed abnormal activation in visual regions (inferior/middle occipital and middle temporal cortices) which responded to emotional faces within 100 ms, supporting that the BD patients may hyperactively respond to emotional features in perceptual binding. The discriminant function of gamma activation in the left smFC, right medial OFC, right AI/inferior OFC, and the right precentral cortex accurately classified 89.6% of patients as unipolar/bipolar disorders.
Papousek, Mechthild; de Chuquisengo, Ruth Wollwerth
The author introduces both the concept and practice of Integrative Parent-Infant Psychotherapy (IPI-P), a treatment specifically designed for the most frequent developmental problems and psychological needs of infants and their parents. Based on growing knowledge from interdisciplinary infancy research, both basic and clinical, IPI-P has been developed and practised in the "Munich Interdisciplinary Research and Intervention Program" for early regulatory and relationship disorders since the early nineties. Preverbal parent-infant communication represents both the port of entry into the system and the main focus of diagnostics, developmental counselling, interaction guidance, or psychodynamic psychotherapy of distorted communication and distressed/disordered relationships. The method of videomicroanalysis during video-feedback with the parent has proven particularly efficient--while observing, reliving and working through brief episodes of recorded parent-infant interaction. The author illustrates the diagnostic and therapeutic procedures with excerpts from psychotherapy of a toddler with an age-specific regulatory disorder in the context of severely distressed primary relationships.
Dawson-Squibb, John-Joe; Davids, Eugene Lee; de Vries, Petrus J
EarlyBird and EarlyBird Plus are parent education and training programmes designed by the UK National Autistic Society in 1997 and 2003, having been delivered to more than 27,000 families in 14 countries. These group-based programmes aim to (1) support parents immediately after diagnosis of autism spectrum disorder, (2) empower parents, encouraging a positive perception of their child's autism spectrum disorder and (3) help parents establish good practice. In the absence of any previous comprehensive review, we performed a scoping review of all peer-reviewed publications on EarlyBird/EarlyBird Plus. A search was conducted between February and June 2016 using EbscoHost, Sabinet, SAGE Journals, Directory of Open Access Journals, BioMed Central, Scopus, ScienceDirect and grey literature. Two reviewers independently screened titles and abstracts for inclusion. In total, 18 articles were identified: 16 from the United Kingdom and 2 from New Zealand. We reviewed the context, study populations, design, outcome measures, whether focus was on parental perception, parental change or child changes and programme feasibility. Strong parental support for the acceptability but lower level evidence of efficacy of EarlyBird/EarlyBird Plus was found. Future research should consider randomised controlled trials. There is no research on EarlyBird/EarlyBird Plus in low-resource settings; therefore, we recommend broader feasibility evaluation of EarlyBird/EarlyBird Plus including accessibility, cultural appropriateness and scalability.
Discusses social learning family therapy hypotheses on the development and sustenance of conduct disorder in early childhood, together with treatment approaches that use parents as the primary agents of change. Reviews research showing that parent training procedures hold much promise for the treatment of conduct disorder in childhood. (JPB)
Barbaro, Josephine; Dissanayake, Cheryl
The Social Attention and Communication Study involved the successful implementation of developmental surveillance of the early markers of autism spectrum disorders in a community-based setting. The objective in the current study was to determine the most discriminating and predictive markers of autism spectrum disorders used in the Social…
van den Hof, Malon; Blokhuis, Charlotte; Cohen, Sophie; Scherpbier, Henriette J.; Wit, Ferdinand W. N. M.; Pistorius, M. C. M.; Kootstra, Neeltje A.; Teunissen, Charlotte E.; Mathot, Ron A. A.; Pajkrt, Dasja
Background: Paediatric data on CNS penetration of antiretroviral drugs are scarce. Objectives: To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function. Patients and methods: Antiretroviral drug levels were measured in paired
Gold, Mark S.; Blum, Kenneth; Oscar-Berman, Marlene; Braverman, Eric R.
Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor self-esteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with > 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches. PMID:24393762
Barghadouch, Amina; Carlsson, Jessica; Norredam, Marie
Studies show a high level of mental health problems among refugee children and adults. This study aimed to examine psychiatric disorders among refugee children in early adulthood. A total of 15,264 young adult refugees, who obtained residence permission January 1, 1993 to December 31, 2010, were...... matched 1:6 on age and sex with 99,313 Danish-born children. Rate ratios (RR) of having a first-time in- or outpatient hospital diagnosis with an affective (F30-39), psychotic (F29-30), neurotic (F40-48), or any psychiatric disorder (F00-99) according to ICD-10 were computed. Refugees had higher RRs...... of psychotic (RR: 1.81, 95%CI: 1.41-2.32) and nervous (RR: 1.28, 95% CI: 1.14-1.43) disorders compared with Danish-born children. The RRs of having an affective disorder among refugees was 0.74 (95% CI: 0.60-0.90) compared with Danish-born children. Sex, geographical origin, migrant status, household income...
Rotholz, David A; Kinsman, Anne M; Lacy, Kathi K; Charles, Jane
To provide an example of a successful, novel statewide effort to increase early identification of young children at risk for autism spectrum disorder (ASD) using a 2-tiered screening process with enhanced quality assessment, interagency policy collaboration and coordination. The South Carolina Act Early Team (SCAET) provided focused collaboration among leaders representing state agencies, universities, health care systems, private organizations, and families to improve quality of life for children with ASD. Specific focus was on implementing policy changes and training to result in earlier identification and home-based behavioral intervention for young children at risk for ASD. Policy changes, training, and modified state agency practices were accomplished. Presumptive eligibility, on the basis of a 2-tiered screening process was implemented by BabyNet (South Carolina's Early Intervention Program) in collaboration with the lead agency for developmental disability services. There was a fivefold increase in children eligible for early intensive behavioral intervention without waiting for a diagnosis of ASD, avoiding long waits for diagnostic evaluations. Only 16 children (2.5%) were later found not to have ASD from a comprehensive evaluation. Improvements in early identification and intervention are feasible through collaborative policy change. The South Carolina Act Early Team and its key stakeholders committed to improving outcomes for this population used existing tools and methods in new ways to improve early identification of children with ASD and to make available evidence-based intervention services. This example should be replicable in other states with key stakeholders working collaboratively for the benefit of young children with ASD. Copyright © 2017 by the American Academy of Pediatrics.
Additive effect of congenital heart disease and early developmental disorders on attention-deficit/hyperactivity disorder and autism spectrum disorder: a nationwide population-based longitudinal study.
Tsao, Pei-Chen; Lee, Yu-Sheng; Jeng, Mei-Jy; Hsu, Ju-Wei; Huang, Kai-Lin; Tsai, Shih-Jen; Chen, Mu-Hong; Soong, Wen-Jue; Kou, Yu Ru
In this retrospective nationwide population-based case-control study, we investigated the impact of congenital heart disease (CHD) on the development of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), which remains unclear. Children aged disorders (EDD) that were diagnosed before ADHD and ASD diagnosis were also analyzed. The incidence rates of perinatal comorbidities, EDD, ADHD, and ASD were higher in the CHD group than in the control group. Multivariate Cox regression analysis revealed that the CHD group had an increased risk of developing ADHD (adjusted hazard ratio [aHR] 2.52, 95% confidence interval CI 1.96-3.25) and ASD (aHR 1.97, 95% CI 1.11-3.52) after adjusting for confounding comorbidities. EDD, but not perinatal comorbidities were also independent risk factors for ADHD and ASD after adjustment. Subgroup analysis indicated that the risk for ADHD (HR 16.59, 95% CI 12.17-22.60) and ASD (HR 80.68, 95% CI 39.96-176.12) was greatly increased in CHD subjects with EDD than in non-CHD subjects without EDD. These findings suggested that CHD at birth and EDD during early childhood were two independent risk factors for ADHD and ASD and that concurrent CHD and EDD might additively increase these risks.
Kwiatkowski, Sebastian; Dołegowska, Barbara; Kwiatkowska, Ewa; Rzepka, Rafał; Marczuk, Natalia; Loj, Beata; Torbè, Andrzej
Preeclampsia (PE) and intrauterine growth restriction (IUGR) are separate disease entities that have frequently been reported as sharing the same pathogenesis. In both of them, angiogenesis disorders and generalized endothelial damage with an accompanying inflammation are the dominant symptoms. In this study, we attempted to prove that both these processes demonstrate the same profile in early PE, late PE and IUGR patients, while the only difference is in the degree of exacerbation of the lesions. In 167 patients divided into four groups, three of those with early PE, late PE and IUGR and one control group, fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), high sensitive c-reactive protein (hsCRP) and fibronectin were determined. The behavior of these parameters in each of the groups was studied, and correlations between them were sought for. Higher concentrations of sFlt-1, hsCRP and fibronectin and a lower concentration of PlGF were found in the study groups compared to the control group. Significant correlations were observed between the factors concerned. The higher values of disordered angiogenesis markers, endothelial damage markers and inflammatory markers both in the PE and the intrauterine growth restriction (IUGR) groups suggest the existence of shared disorders in the development of these pathologies. The correlations between disordered angiogenesis markers and endothelial damage markers argue in favor of a mutual relationship between these two processes in the development of pathologies evolving as secondary to placental ischemia. The results obtained confirm that the lesion profiles are the same in both PE and IUGR patients, which can be utilized in developing common diagnostic criteria.
Reichborn-Kjennerud, T; Czajkowski, N; Ystrøm, E; Ørstavik, R; Aggen, S H; Tambs, K; Torgersen, S; Neale, M C; Røysamb, E; Krueger, R F; Knudsen, G P; Kendler, K S
Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.
Nakano, Yuko; Hatanaka, Yuki; Ikebuchi, Emi; Shimizu, Teruo; Nanko, Shinichiro; Utsumii, Takeshi
In this report, we describe a case of Neuro-Behçet's disease with early onset of bipolar mood disorder. A 53-year-old man with neuropathy including dysphasia and dyslalia developed bipolar mood disorder with anxiety, agitation, depressive mood, talkativeness, hyperkinesias, and appetite rise, and soon exhibited severe personality deterioration. Oral aphthae, cell proliferation and elevated IL-6 levels in spinal fluid, and the patient's clinical downhill course with remission and relapse in spite of good reaction to steroid preparation indicated the possibility of Neuro-Behçet's disease. Brain MRI showed clear swelling of the brain stem area, especially in the pons, in the active phase with low signal in T1-weighted images contrasting with clear high signal in T2-weighted images and FLAIR. At the time of remission, atrophy of the brain stem was shown. These findings were consistent with the view reported in recent years concerning the brain image of Neuro-Behçet's disease, which seemed to be useful for the differential diagnosis. This case manifested two outstanding clinical features. First, it showed bipolar mood swing or mixed state distinguishable from disinhibition or euphoria in deteriorated personality, which is common in this condition. A clear bipolar mood disorder has not been described until now in Neuro-Behçet's disease. Second, subclinical dysthymia or hypomanic phase occurred before clear onset of the disease. In Neuro-Behçet's disease, it is currently considered that psychiatric symptoms may appear in the early stage, but there is controversy as to whether they can precede the other symptoms. Our case indicated very early onset of psychiatric symptoms in this condition.
Full Text Available HIV-positive children and adolescents are at increased risk of both central nervous system (CNS sequelae and mental disorders owing to a number of factors, including the impact of HIV infection on the brain, social determinants of health (e.g. poverty and orphanhood and psychosocial stressors related to living with HIV. Every effort should be made to identify perinatally HIV-infected children and initiate them on antiretroviral therapy early in life. HIV clinicians should ideally screen for mental health and neurocognitive problems, as part of the routine monitoring of children attending antiretroviral clinics. This guideline is intended as a reference tool for HIV clinicians to support the early identification, screening and management of mental health disorders and/or CNS impairment in children and adolescents. This guideline covers mental disorders (section 1 and HIV-associated neurocognitive disorders (section 2 among children and adolescents.
Phillips-Howard, P. A.; ter Kuile, F. O.
CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are associated with the quinoline and artemisinin derivatives. Chloroquine, once considered too
Juliana Belo Diniz
Full Text Available INTRODUCTION: In obsessive-compulsive disorder, early treatment discontinuation can hamper the effectiveness of first-line treatments. OBJECTIVE: This study aimed to investigate the clinical correlates of early treatment discontinuation among obsessive-compulsive disorder patients. METHODS: A group of patients who stopped taking selective serotonin reuptake inhibitors (SSRIs or stopped participating in cognitive behavioral therapy before completion of the first twelve weeks (total n = 41; n = 16 for cognitive behavioral therapy and n = 25 for SSRIs were compared with a paired sample of compliant patients (n = 41. Demographic and clinical characteristics were obtained at baseline using structured clinical interviews. Chisquare and Mann-Whitney tests were used when indicated. Variables presenting a p value <0.15 for the difference between groups were selected for inclusion in a logistic regression analysis that used an interaction model with treatment dropout as the response variable. RESULTS: Agoraphobia was only present in one (2.4% patient who completed the twelve-week therapy, whereas it was present in six (15.0% patients who dropped out (p = 0.044. Social phobia was present in eight (19.5% patients who completed the twelve-week therapy and eighteen (45% patients who dropped out (p = 0.014. Generalized anxiety disorder was present in eight (19.5% patients who completed the twelve-week therapy and twenty (50% dropouts (p = 0.004, and somatization disorder was not present in any of the patients who completed the twelveweek therapy; however, it was present in six (15% dropouts (p = 0.010. According to the logistic regression model, treatment modality (p = 0.05, agoraphobia, the Brown Assessment of Beliefs Scale scores (p = 0.03 and the Beck Anxiety Inventory (p = 0.02 scores were significantly associated with the probability of treatment discontinuation irrespective of interactions with other variables. DISCUSSION AND CONCLUSION: Early treatment
Rane, N.; Quaghebeur, G.
Corporeal and central nervous system (CNS) axis chemotherapy and radiotherapy have long been used for the effective treatment and prophylaxis of CNS, body malignancies, and leukaemias. However, they are not without their problems. Following the proliferation of magnetic resonance neuroimaging in recent years it has become clear that the spectrum of toxicity that these therapies produce ranges from subclinical white matter changes to overt brain necrosis. The effects are both direct and indirect and via different pathological mechanisms. Chronic and progressive changes can be detected many years after the initial intervention. In addition to leucoencephalopathic changes, grey matter changes are now well described. Changes may be difficult to distinguish from tumour recurrence, though may be reversible and remediable, and are thus very important to differentiate. In this review toxic effects are classified and their imaging appearances discussed, with reference to specific syndromes.
Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry
Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.
Muhammad O Chohan
Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.
Kushner, M.J.; Tobin, M.; Fazekas, F.; Chawluk, J.; Jamieson, D.; Freundlich, B.; Grenell, S.; Freemen, L.; Reivich, M.
We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery
Xu, Yun; Yang, Jian; Yao, Jing; Chen, Jun; Zhuang, Xiangxiang; Wang, Wenxiang; Zhang, Xiaoli; Lee, Gabrielle T.
The purpose of this study was to pilot test the effects of a culturally adapted early intervention influenced by the Early Start Denver Model (ESDM) on reduction of autism symptoms and severity categorization for young children with autism spectrum disorders in China. Participants were randomly assigned to either the control or intervention…
Laghari, Altaf Ali; Ahmed, Syed Ijlal; Jabbar, Adnan; Shamim, Muhammad Shahzad
Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumour that is uniformly fatal. The rarity of the disease and the poor response to treatment makes it difficult to reach a consensus with regards to treatment options. In this review, the authors have discussed different treatment modalities used in the management of PCNSL including chemotherapy, surgery and radiation, as well as the results of recent clinical trials on treatment options for PCNSL.
Turygin, Nicole; Matson, Johnny L; Konst, Matthew; Williams, Lindsey
Parental concerns related to communication are an oft-cited reason that children present to early intervention clinics. We examine the relationship between early communication first concerns (FCs) and symptoms of ASD. The present study included 3173 toddlers at risk for developmental delay. The Battelle Developmental Inventory, 2nd edition and the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT) were used to examine developmental quotient scores and autism symptoms. Significant results were observed with respect to FC group and gender. A significant effect of FC-Communication group was observed with respect to developmental quotient overall and subscale scores, as well as autism symptom scores. Those with communication disorders are a heterogeneous population and do not account for all children who will meet criteria for a diagnosis of an ASD.
Wirth, R.H.; Rothenberger, W.; Gillmann, H.; Wetzel, H.P.; Kaufmann, H.; Staedtisches Krankenanstalten Ludwigshafen am Rhein
Thallium myocardial scintiscanning has gained great clinical importance in the early detection of myocardial ischaemias which are still invisible in the ECG, in the assessment of the location and size of myocardial infarctions, and in the identification of infarctions masked by disturbed ventricular stimulus conduction or pacemaker ECG. The significantly higher sensitivity and specificity compared with ECG after work proves that myocardial scintiscanning after work plays an important role in the diagnosis of early stages of coronary heart diseases. A positive scintiscan points out a significant stenosis of the coronary artery, even if the ECG after work is negative, and is an indication for coronary angiography. In contrast, negative ECG and scintiscanning findings in a patient with anginose or atypical coronary disorders indicate that it is not a case of coronary disease. The detection of a reduced coronary reserve in cases of so-called critical coronary stenosis enables the earliest possible taking of therapeutical measures to preserve functional myocardial tissue. (orig.) [de
Mayfield, Jody; Blednov, Yuri A; Harris, R Adron
G protein-coupled inwardly rectifying potassium (GIRK) channels are widely expressed throughout the brain and mediate the inhibitory effects of many neurotransmitters. As a result, these channels are important for normal CNS function and have also been implicated in Down syndrome, Parkinson's disease, psychiatric disorders, epilepsy, and drug addiction. Knockout mouse models have provided extensive insight into the significance of GIRK channels under these conditions. This review examines the behavioral and genetic evidence from animal models and genetic association studies in humans linking GIRK channels with CNS disorders. We further explore the possibility that subunit-selective modulators and other advanced research tools will be instrumental in establishing the role of individual GIRK subunits in drug addiction and other relevant CNS diseases and in potentially advancing treatment options for these disorders. © 2015 Elsevier Inc. All rights reserved.
Choi, C.O.; Park, K.N.; Park, S.H.
The Korea Atomic Energy research Institute (KAERI) strives to provide utilizing facilities on and around the Hanaro reactor in order to activate advanced researches by neutron application. As one of the facilities to be installed, the conceptual design work of CNS was started in 1996 with a project schedule of 5 years so that its installation work can be finished by the year 2000. And the major engineering targets of this CNS facility are established for a minimum physical interference with the present facilities of the Hanaro, a reach-out of very-high-gain factors in the cold neutron flux, a simplicity of the maintenance of the facility, and a safety in the operation of the facility as well as the reactor. For the conceptual design of Hanaro CNS, the experience of utilization and production of cold neutron at WWR-M reactor Gatchina, Russia has been used with that of elaborations for PIK reactor in design for neutron guide systems and instruments. (author)
Full Text Available Abstract Background Prevalence of depressive disorders among adolescents has varied across studies. The present study aims to assess current and lifetime prevalence and characteristics of adolescent Major Depressive Disorder (MDD, Dysthymia and Depression NOS among adolescents in Central Norway in addition to socio-demographics and use of mental health care. Method In the Youth and Mental Health Study a representative sample of 2432 junior high school students (mean age 14.9 years, SD = 0.6 from two counties in Central Norway were screened with the Mood and Feelings Questionnaire (MFQ. A subset of 345 of these adolescents (72.5% girls, 220 high scorers (MFQ = > 26, 74 middle scorers (MFQ 7-25, and 50 low scorers (MFQ Results Almost one in four subjects (23% had life-time depression. Prevalences of current Major Depressive Disorder (MDD, Dysthymia and "Double depression" were 2.6%, 1.0% and 0.6%, respectively, and for Depression NOS 6.3%. All depressive disorders were characterized by long duration of episodes with large variations, and for any depressive disorder onset before 12 years of age. In multivariate analyses MDD and Dysthymia were most strongly associated with gender and not living with both biological parents. There was no gender difference for Depression NOS. Although a considerable number of depressed subjects had received mental health care, the reason for contact with services was seldom due to affective symptoms. Less than 20% had been in contact with specialist mental health services. Conclusion High rates of Depression NOS, early onset of depressive episodes, long duration, and low use of specialized services point to the need for improved diagnostic assessment and treatment for young individuals.
Gandubert, Catherine; Carrière, Isabelle; Escot, Chantal; Soulier, Maryvonne; Hermès, Aziz; Boulet, Patrick; Ritchie, Karen; Chaudieu, Isabelle
Our objective is to evaluate the mental status of primary early breast cancer survivors according to DSM-IV criteria, distinguishing new psychiatric diagnosis, which started after the cancer diagnosis from relapse. A comparative study of 144 breast cancer survivors and 125 women without previous history of cancer was carried out. Neuropsychiatric symptomatology was assessed retrospectively using standardized psychiatric examinations (Mini International Neuropsychiatric Interview, Watson's Post-Traumatic Stress Disorder Inventory) over three successive periods, 'before cancer' (from childhood to 3 years before the interview), 'around the cancer event' (the last 3 years including the time of diagnosis and treatment), and 'currently' (the last 2 weeks). Increased rates of anxiety and mood disorders were observed following a diagnosis of breast cancer compared with controls (generalized anxiety disorder (GAD) and major depressive disorder (MDD); 10.4 vs 1.6% and 19.4 vs 8.8%, respectively). The cancer disease promoted the development of dysthymia (n=4 new cases/6 two-year prevalent cases) and PTSD (7/7) and the re-emergence of MDD (n=21 relapses/28 three-year prevalent cases) and GAD (10/15). No improvement in serious mood disorders such as MDD (16.0 vs 7.2%) and dysthymia (4.2 vs 0%) was reported at the time of interview, more than 1.75 years (median time) after the cancer surgery, the prevalence being 2-4 times greater in breast cancer survivors than in controls. Despite significant advances in treatment, a diagnosis of breast cancer is highly associated with various forms of psychopathology, regardless of psychiatric history, with symptoms persisting after treatment. These results may assist clinicians in planning mental healthcare for women with breast cancer.
Webb, Sara Jane; Jones, Emily J H; Kelly, Jean; Dawson, Geraldine
The first Autism Research Matrix (IACC, 2003) listed the identification of behavioural and biological markers of risk for autism as a top priority. This emphasis was based on the hypothesis that intervention with infants at-risk, at an early age when the brain is developing and before core autism symptoms have emerged, could significantly alter the developmental trajectory of children at risk for the disorder and impact long-range outcome. Research has provided support for specific models of early autism intervention (e.g., Early Start Denver Model) for improving outcomes in young children with autism, based on both behavioural and brain activity measures. Although great strides have been made in ability to identify risk markers for autism in younger infant/toddler samples, how and when to intervene during the prodromal state remains a critical question. Emerging evidence suggests that abnormal brain circuitry in autism precedes altered social behaviours; thus, an intervention designed to promote early social engagement and reciprocity potentially could steer brain development back toward the normal trajectory and remit or reduce the expression of symptoms.
Slavich, George M; Monroe, Scott M; Gotlib, Ian H
Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss. Copyright © 2011 Elsevier Ltd. All rights reserved.
Full Text Available Introduction: Autism spectrum disorders (ASD comprise typical or infantile autism (Kanner syndrome, Asperger’s disorder and atypical autism or pervasive developmental disorder - not otherwise specified. The syndrome is characterized by deficits in (1 verbal and nonverbal communication, (2 reciprocal social interaction and (3 repetitive patterns of behaviour, interests and activities. Early behavioural interventions are based on learning theory and behaviour therapy. They take into account specific deficits in perception, emotional reactions, social interaction and communication. In Germany, these comprehensive models are not widely evaluated and implemented. Research questions: * What are the clinical effectiveness and safety of early behavioural or skills-based early interventions in autism compared to other interventions or to treatment as usual? * What are specific factors responsible for the effectiveness? * What are the cost-effectiveness and cost consequences of different early interventions in autism? * Which legal, social and ethical aspects are relevant with regard to the implementation of the respective interventions in persons with autism? Methods: Following a systematic review of the literature, controlled studies on early behavioural or skills-based interventions published since 2000 in English or German with children until the age of twelve are included and critically appraised. Studies must have at least ten participants per intervention group. Results: In total, 15 publications based on 14 studies, eight systematic reviews and one health economic study are included. Most studies evaluate early interventions based upon the Lovaas model (Early intensive behavioural treatment (EIBT, Applied behavioural analysis (ABA. Other evaluate pragmatic interventions or interventions based on other theoretical models like specific parent interventions, responsive education and prelinguistic milieu teaching, joint attention, symbolic play, and
Weinmann, Stefan; Schwarzbach, Christoph; Begemann, Matthias; Roll, Stephanie; Vauth, Christoph; Willich, Stefan N; Greiner, Wolfgang
Autism spectrum disorders (ASD) comprise typical or infantile autism (Kanner syndrome), Asperger's disorder and atypical autism or pervasive developmental disorder - not otherwise specified. The syndrome is characterized by deficits in (1) verbal and nonverbal communication, (2) reciprocal social interaction and (3) repetitive patterns of behaviour, interests and activities. Early behavioural interventions are based on learning theory and behaviour therapy. They take into account specific deficits in perception, emotional reactions, social interaction and communication. In Germany, these comprehensive models are not widely evaluated and implemented. What are the clinical effectiveness and safety of early behavioural or skills-based early interventions in autism compared to other interventions or to treatment as usual?What are specific factors responsible for the effectiveness?What are the cost-effectiveness and cost consequences of different early interventions in autism?Which legal, social and ethical aspects are relevant with regard to the implementation of the respective interventions in persons with autism? Following a systematic review of the literature, controlled studies on early behavioural or skills-based interventions published since 2000 in English or German with children until the age of twelve are included and critically appraised. Studies must have at least ten participants per intervention group. In total, 15 publications based on 14 studies, eight systematic reviews and one health economic study are included. Most studies evaluate early interventions based upon the Lovaas model (Early intensive behavioural treatment (EIBT), Applied behavioural analysis (ABA)). Other evaluate pragmatic interventions or interventions based on other theoretical models like specific parent interventions, responsive education and prelinguistic milieu teaching, joint attention, symbolic play, and picture exchange communication system. Behaviour analytic interventions
Weinmann, Stefan; Schwarzbach, Christoph; Begemann, Matthias; Roll, Stephanie; Vauth, Christoph; Willich, Stefan N.; Greiner, Wolfgang
Introduction Autism spectrum disorders (ASD) comprise typical or infantile autism (Kanner syndrome), Asperger’s disorder and atypical autism or pervasive developmental disorder - not otherwise specified. The syndrome is characterized by deficits in (1) verbal and nonverbal communication, (2) reciprocal social interaction and (3) repetitive patterns of behaviour, interests and activities. Early behavioural interventions are based on learning theory and behaviour therapy. They take into account specific deficits in perception, emotional reactions, social interaction and communication. In Germany, these comprehensive models are not widely evaluated and implemented. Research questions What are the clinical effectiveness and safety of early behavioural or skills-based early interventions in autism compared to other interventions or to treatment as usual? What are specific factors responsible for the effectiveness? What are the cost-effectiveness and cost consequences of different early interventions in autism? Which legal, social and ethical aspects are relevant with regard to the implementation of the respective interventions in persons with autism? Methods Following a systematic review of the literature, controlled studies on early behavioural or skills-based interventions published since 2000 in English or German with children until the age of twelve are included and critically appraised. Studies must have at least ten participants per intervention group. Results In total, 15 publications based on 14 studies, eight systematic reviews and one health economic study are included. Most studies evaluate early interventions based upon the Lovaas model (Early intensive behavioural treatment (EIBT), Applied behavioural analysis (ABA)). Other evaluate pragmatic interventions or interventions based on other theoretical models like specific parent interventions, responsive education and prelinguistic milieu teaching, joint attention, symbolic play, and picture exchange
Huber, Christian G; Hochstrasser, Lisa; Meister, Klara; Schimmelmann, Benno G; Lambert, Martin
Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied. This study assessed the association between age at onset, an agitated-aggressive syndrome, and its potential correlates in a prospective sample of 52 FEP patients with early-onset and adult-onset followed up for 12months. Twenty-six patients conformed to the criteria of early-onset psychosis. Early age at onset was associated with antisocial personality disorder (p=0.004; φc=0.39), a history of legal involvement (p=0.005; φc=0.39), and higher rates of lifetime substance use disorder (SUD; p=0.002; φc=0.42). Early-onset patients had significantly higher PANSS-EC scores over the course of observation (F(1,44.4)=5.39; p=0.025; d=0.656), but no significant group differences emerged for the remaining PANSS subscores. PANSS-EC scores were correlated positively with antisocial personality disorder and forensic history at 6weeks, 3months, 6months, and 12months, and with lifetime substance use disorder at 3months and 6months. Patients with early onset psychosis may have increased levels of agitation/aggressiveness, and, more likely, antisocial personality disorder, forensic history, and lifetime substance use disorder. These variables were linked to suicidality, aggressiveness, and involuntary treatment. Copyright © 2016 Elsevier B.V. All rights reserved.
Yokoyama, Takashi; Hiyoshi, Yasuhiko; Fujimoto, Takeo
This study was designed to evaluate the efficacy of CNS-prophylaxis with high-dose methotrexate (MTX). Seventy children with previously untreated acute lymphoblastic leukemia (ALL) entered to this study between July 1978 and December 1980. According to initial white blood count (WBC), they were stratified to induce remission with; vincristine and prednine in low initial WBC ( lt 25,000/mm 3 ) group and these two agents plus adriamycin in high initial WBC ( gt 25,000/mm 3 ) group. After inducing remission, 62 children who achieved CR, received different CNS-prophlaxis; using a regimen of three doses of weekly high-dose MTX (1,000 mg/m 2 ) 6-hour infusion, which was repeated every 12 weeks-Group A (n = 14); high-dose MTX followed by 2400 rad cranial irradiation plus three doses of i.t. MT X-Group B (n = 15), 2400 rad cranial irradiation plus three doses of i.t. MTX-Group C (n = 16), and in 17 patients with high initial WBC, same as in Group A-Group D (n = 17). During an intravenous 6-h infusion of MTX at a dose of 1,000 mg/m 2 , the CSF concentration of MTX rose to 2.3 +- 2.4 x 10 -6 M after initiation of infusion and remained in 10 -7 M level for 48 hours. CNS-leukemia terminated complete remission in one of 14 children in Group A, two of 15 in Group B, two of 16 in Group C and two of 17 in Group D. The cumulative incidence of CNS-leukemia at 20 months calculated by the technique of Kaplan and Meier was 0% i n Group A, 18.1% in Group B, 7.1% in Group C and 50.8% in Group D. There was no statistical difference among Groups A, B and C. These data suggested that CNS-prophylaxis with high-dose intravenous MTX was effective as well as 2400 rad cranial irradiation plus three doses of i.t. MTX in childhood ALL with low initial WBC. (author)
Wartberg, L; Kriston, L; Kramer, M; Schwedler, A; Lincoln, T M; Kammerl, R
Internet gaming disorder (IGD) has been included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Currently, associations between IGD in early adolescence and mental health are largely unexplained. In the present study, the relation of IGD with adolescent and parental mental health was investigated for the first time. We surveyed 1095 family dyads (an adolescent aged 12-14 years and a related parent) with a standardized questionnaire for IGD as well as for adolescent and parental mental health. We conducted linear (dimensional approach) and logistic (categorical approach) regression analyses. Both with dimensional and categorical approaches, we observed statistically significant associations between IGD and male gender, a higher degree of adolescent antisocial behavior, anger control problems, emotional distress, self-esteem problems, hyperactivity/inattention and parental anxiety (linear regression model: corrected R 2 =0.41, logistic regression model: Nagelkerke's R 2 =0.41). IGD appears to be associated with internalizing and externalizing problems in adolescents. Moreover, the findings of the present study provide first evidence that not only adolescent but also parental mental health is relevant to IGD in early adolescence. Adolescent and parental mental health should be considered in prevention and intervention programs for IGD in adolescence. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Georg G. von Polier
Full Text Available Background. A growing body of evidence suggests an association between altered hypothalamic-pituitary-adrenal axis reactivity and the development of persistent antisocial behavior in children. However the effects of altered cortisol levels remain poorly understood in the complex context of conduct disorder, callous-unemotional (CU personality traits, and frequent comorbidities, such as attention deficit hyperactivity disorder (ADHD. The aim of the current study was to investigate associations among CU traits, antisocial behavior, and comorbid ADHD symptomatology with cortisol levels in male children and adolescents. Methods. The study included 37 boys with early-onset conduct disorder (EO-CD, mean age 11.9 years and 38 healthy boys (mean age 12.5 years. Participants were subjected to multiple daytime salivary cortisol measurements and a psychometric characterization. Results. Subjects in the EO-CD group with elevated CU traits showed a diminished cortisol awakening response compared to healthy participants. In the EO-CD group, high CU traits and impulsivity were associated with decreased diurnal cortisol levels, while associations with antisocial behavior were not detected. The cortisol awakening response was significantly inversely associated with hyperactivity (P=0.02 and marginally significant with CU traits (P=0.07. Conclusions. These results indicate a specific association between CU traits and a diminished stress response, which is not explained by antisocial behavior in general.
Full Text Available Celestial Navigation System (CNS has characteristics of accurate orientation and strong autonomy and has been widely used in Hypersonic Vehicle. Since the CNS location and orientation mainly depend upon the inertial reference that contains errors caused by gyro drifts and other error factors, traditional Strap-down Inertial Navigation System (SINS/CNS positioning algorithm setting the position error between SINS and CNS as measurement is not effective. The model of altitude azimuth, platform error angles, and horizontal position is designed, and the SINS/CNS tightly integrated algorithm is designed, in which CNS altitude azimuth is set as measurement information. GPF (Gaussian particle filter is introduced to solve the problem of nonlinear filtering. The results of simulation show that the precision of SINS/CNS algorithm which reaches 130 m using three stars is improved effectively.
Cluver, Catherine; Novikova, Natalia; Koopmans, Corine M; West, Helen M
Hypertensive disorders in pregnancy are significant contributors to maternal and perinatal morbidity and mortality. These disorders include well-controlled chronic hypertension, gestational hypertension (pregnancy-induced hypertension) and mild pre-eclampsia. The definitive treatment for these disorders is planned early delivery and the alternative is to manage the pregnancy expectantly if severe uncontrolled hypertension is not present, with close maternal and fetal monitoring. There are benefits and risks associated with both, so it is important to establish the safest option. To assess the benefits and risks of a policy of planned early delivery versus a policy of expectant management in pregnant women with hypertensive disorders, at or near term (from 34 weeks onwards). We searched Cochrane Pregnancy and Childbirth Trials Register (12 January 2016) and reference lists of retrieved studies. Randomised trials of a policy of planned early delivery (by induction of labour or by caesarean section) compared with a policy of delayed delivery ("expectant management") for women with hypertensive disorders from 34 weeks' gestation. Cluster-randomised trials would have been eligible for inclusion in this review, but we found none.Studies using a quasi-randomised design are not eligible for inclusion in this review. Similarly, studies using a cross-over design are not eligible for inclusion, because they are not a suitable study design for investigating hypertensive disorders in pregnancy. Two review authors independently assessed eligibility and risks of bias. Two review authors independently extracted data. Data were checked for accuracy. We included five studies (involving 1819 women) in this review.There was a lower risk of composite maternal mortality and severe morbidity for women randomised to receive planned early delivery (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83, two studies, 1459 women (evidence graded high)). There were no clear
Warren, Zachary; McPheeters, Melissa L; Sathe, Nila; Foss-Feig, Jennifer H; Glasser, Allison; Veenstra-Vanderweele, Jeremy
Early intensive behavioral and developmental interventions for young children with autism spectrum disorders (ASDs) may enhance developmental outcomes. To systematically review evidence regarding such interventions for children aged 12 and younger with ASDs. We searched Medline, PsycINFO, and ERIC (Education Resources Information Center) from 2000 to May 2010. Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria. Two reviewers independently extracted data regarding participant and intervention characteristics, assessment techniques, and outcomes and assigned overall quality and strength-of-evidence ratings using predetermined criteria. Thirty-four unique studies met inclusion criteria. Seventeen studies were case series; 2 were randomized controlled trials. We rated 1 study as good quality, 10 as fair quality, and 23 as poor quality. The strength of the evidence overall ranged from insufficient to low. Studies of University of California Los Angeles/Lovaas-based interventions and variants reported clinically significant gains in language and cognitive skills in some children, as did 1 randomized controlled trial of an early intensive developmental intervention approach (the Early Start Denver Model). Specific parent-training approaches yielded gains in short-term language function and some challenging behaviors. Data suggest that subgroups of children displayed more prominent gains across studies, but participant characteristics associated with greater gains are not well understood. Studies of Lovaas-based approaches and early intensive behavioral intervention variants and the Early Start Denver Model resulted in some improvements in cognitive performance, language skills, and adaptive behavior skills in some young children with ASDs, although the literature is limited by methodologic concerns.
Guthrie, Whitney; Swineford, Lauren B; Nottke, Charly; Wetherby, Amy M
Although a diagnosis of autism spectrum disorder (ASD) appears to be stable in children as young as age three, few studies have explored stability of a diagnosis in younger children. Predictive value of diagnostic tools for toddlers and patterns of symptom change are important considerations for clinicians making early diagnoses. Most findings come from high-risk samples, but reports on children screened in community settings are also needed. Stability of diagnosis and Autism Diagnostic Observation Schedule – Toddler Module (ADOS-T) classifications and scores was examined across two time points in a sample of 82 children identified through the FIRST WORDS Project.Children received two comprehensive diagnostic evaluations at average ages of 19.39 (SD = 2.12) and 36.89 (SD = 3.85) months. Stability was 100% when confirming and ruling out a diagnosis of ASD based on a comprehensive diagnostic evaluation that included clinic and home observations,although diagnosis was initially deferred for 17% of the sample. Receiver Operating Characteristic curves revealed excellent sensitivity and acceptable specificity for the ADOS-T compared to concurrent diagnosis. Logistic regressions indicated good predictive value of initial ADOS-T scores for follow-up diagnosis. Finally, both ASD and Non-ASD children demonstrated a decrease in Social Affect scores (i.e.,improvement), whereas children with ASD demonstrated an increase in Restricted and Repetitive Behavior scores (i.e., worsening), changes that were accounted for by nonverbal developmental level in mixed model analyses. Short-term stability was documented for children diagnosed at 19 months on average, although a minority of children initially showed unclear diagnostic presentations.Findings highlight utility of the ADOS-T in making early diagnoses and predicting follow-up diagnoses. Children with ASD demonstrated improvement in social communication behaviors and unfolding of repetitive behaviors, suggesting that certain
Goodwin Renee D
Full Text Available Abstract Background The objective of this study was to examine the association between infection early in life and mental disorders among youth in the community. Methods Data were drawn from the MECA (Methods in Epidemiology of Child and Adolescent psychopathology, a community-based study of 1,285 youth in the United States conducted in 1992. Multiple logistic regression analyses were used to investigate the association between parent/caregiver-reported infection early in life and DSM/DISC diagnoses of mental disorders at ages 9-17. Results Infection early in life was associated with a significantly increased odds of major depression (OR = 3.9, social phobia (OR = 5.8, overanxious disorder (OR = 6.1, panic disorder (OR = 12.1, and oppositional defiant disorder (OR = 3.7. Conclusions These findings are consistent with and extend previous results by providing new evidence suggesting a link between infection early in life and increased risk of depression and anxiety disorders among youth. These results should be considered preliminary. Replication of these findings with longitudinal epidemiologic data is needed. Possible mechanisms are discussed.
Crissman Halley P
Full Text Available Abstract Background Clinical research on psychological aspects of disorders of sex development (DSD has focused on psychosexual differentiation with relatively little attention directed toward parents' experiences of early clinical management and their influence on patient and family psychosocial adaptation. Objectives To characterize parental experiences in the early clinical care of children born with DSD. Study Design Content analysis of interviews with parents (n = 41 of 28 children, newborn to 6 years, with DSD. Results Four major domains emerged as salient to parents: (1 the gender assignment process, (2 decisions regarding genital surgery, (3 disclosing information about their child's DSD, and (4 interacting with healthcare providers. Findings suggested discordance between scientific and parental understandings of the determinants of "sex" and "gender." Parents' expectations regarding the benefits of genital surgery appear largely met; however, parents still had concerns about their child's future physical, social and sexual development. Two areas experienced by many parents as particularly stressful were: (1 uncertainties regarding diagnosis and optimal management, and (2 conflicts between maintaining privacy versus disclosing the condition to access social support. Conclusions Parents' experiences and gaps in understanding can be used to inform the clinical care of patients with DSD and their families. Improving communication between parents and providers (and between parents and their support providers throughout the early clinical management process may be important in decreasing stress and improving outcomes for families of children with DSD.
DeVincent, Carla; Gadow, Kenneth D; Strong, Greg; Schwartz, Joseph; Cuva, Simone
The early identification of children with autism spectrum disorders (ASDs) is critical for the remediation of developmental deficits. This study examined the clinical utility of ASD scoring algorithms for the Early Childhood Inventory-4 (ECI-4), a DSM-IV-referenced rating scale, as a practical solution for screening 3- to 5-year-old children for ASD in medical and public school settings. Parents/teachers completed the ECI-4 for 3- to 5-year-old clinic referrals with an ASD (n = 196) or non-ASD psychiatric (n = 135) diagnosis. Children attending early childhood (i.e., day care, preschool, Head Start) programs were also rated by their parents (n = 507) and teachers (n = 407). Stepwise logistic regression was used to generate ASD scoring algorithms for the ECI-4. Receiver operating characteristic analyses generally indicated high levels of sensitivity/specificity for recommended ASD cutoff scores for parent (clinic: 0.96/0.80; preschool: 0.92/0.96) and teacher (clinic: 0.81/0.79; preschool: 0.97/0.92) ratings. Findings indicate that the ECI-4 shows promise as a clinically useful screening measure for ASD in clinic-referred and preschool children.
Gotthard G. Tribl
Full Text Available Objective To describe characteristics of REM sleep behavior disorder in Wilson’s disease. Method Questionnaire-based interviews (patients and relatives, neurological examinations, two-week prospective dream-diary, video-polysomnography, transcranial sonography, MRI. Results Four Wilson’s disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. Conclusion This first description of REM sleep behavior disorder in Wilson’s disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson’s disease and adds further evidence to the parallelism of Parkinson’s disease and Wilson’s disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in α-synucleinopathies. In Wilson’s disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson’s disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in “pre-clinical” Parkinson’s disease.
Charles, Nora E; Mathias, Charles W; Acheson, Ashley; Bray, Bethany C; Ryan, Stacy R; Lake, Sarah L; Liang, Yuanyuan; Dougherty, Donald M
Individuals with a family history of substance use disorders (Family History Positive) are more likely to have early-onset substance use (i.e., prior to age 15), which may contribute to their higher rates of substance use disorders. One factor that may differentiate Family History Positive youth who engage in early-onset substance use from other Family History Positive youth is exposure to stressors. The aim of this study was to quantify how exposure to stressors from age 11-15 varies as a function of family history of substance use disorders and early-onset substance use. Self-reported stressors were prospectively compared in a sample of predominately (78.9%) Hispanic youth that included 68 Family History Positive youth (50% female) who initiated substance use by age 15 and demographically matched non-users with (n = 136; 52.9% female) and without (n = 75; 54.7% female) family histories of substance use disorders. Stressors were assessed at 6-month intervals for up to 4 years. Both the severity of stressors and the degree to which stressors were caused by an individual's own behavior were evaluated. All three groups differed from one another in overall exposure to stressors and rates of increase in stressors over time, with Family History Positive youth who engaged in early-onset substance use reporting the greatest exposure to stressors. Group differences were more pronounced for stressors caused by the participants' behavior. Family History Positive users had higher cumulative severity of stressors of this type, both overall and across time. These results indicate greater exposure to stressors among Family History Positive youth with early-onset substance use, and suggest that higher rates of behavior-dependent stressors may be particularly related to early-onset use.
Doba, Karyn; Berna, Guillaume; Constant, Emilie; Nandrino, Jean-Louis
This study examines the impact of self-differentiation, alexithymia and psychological distress on eating disorder symptoms in young and middle adolescence. Four hundred fifty-one adolescents completed self-report measures. Early and middle adolescents were categorized into two groups (12-14 years and 15-17 years) to represent distinct developmental stages. Significant differences were found between younger and older adolescents. The association between low self-differentiation and both eating disorders symptoms and psychological dimensions related to eating attitudes was stronger in early adolescence than in middle adolescence. The association between low self-differentiation and eating disorder symptoms was mediated by alexithymia and psychological distress in middle adolescence. Taken together, these findings suggest that self-differentiation could be useful in understanding psychological distress and alexithymia in eating disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.
Carl J. Dunst
Full Text Available Incorporating the interests and preferences of young children with autism spectrum disorders into interventions to promote prosocial behavior and decrease behavior excesses has emerged as a promising practice for addressing the core features of autism. The efficacy of interest-based early intervention practices was examined in a meta-analysis of 24 studies including 78 children 2 to 6 years of age diagnosed with autism spectrum disorders. Effect size analyses of intervention versus nonintervention conditions and high-interest versus low-interest contrasts indicated that interest-based intervention practices were effective in terms of increasing prosocial and decreasing aberrant child behavior. Additionally, interest-based interventions that focused on two of the three core features of autism spectrum disorders (poor communication, poor interpersonal relationships were found most effective in influencing child outcomes. Implications for very early intervention are discussed in terms addressing the behavior markers of autism spectrum disorders before they become firmly established.
Vlamings, Petra Hendrika Johanna Maria; Jonkman, Lisa Marthe; van Daalen, Emma; van der Gaag, Rutger Jan; Kemner, Chantal
A detailed visual processing style has been noted in autism spectrum disorder (ASD); this contributes to problems in face processing and has been directly related to abnormal processing of spatial frequencies (SFs). Little is known about the early development of face processing in ASD and the relation with abnormal SF processing. We investigated whether young ASD children show abnormalities in low spatial frequency (LSF, global) and high spatial frequency (HSF, detailed) processing and explored whether these are crucially involved in the early development of face processing. Three- to 4-year-old children with ASD (n = 22) were compared with developmentally delayed children without ASD (n = 17). Spatial frequency processing was studied by recording visual evoked potentials from visual brain areas while children passively viewed gratings (HSF/LSF). In addition, children watched face stimuli with different expressions, filtered to include only HSF or LSF. Enhanced activity in visual brain areas was found in response to HSF versus LSF information in children with ASD, in contrast to control subjects. Furthermore, facial-expression processing was also primarily driven by detail in ASD. Enhanced visual processing of detailed (HSF) information is present early in ASD and occurs for neutral (gratings), as well as for socially relevant stimuli (facial expressions). These data indicate that there is a general abnormality in visual SF processing in early ASD and are in agreement with suggestions that a fast LSF subcortical face processing route might be affected in ASD. This could suggest that abnormal visual processing is causative in the development of social problems in ASD. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Hazlett, Heather Cody; Gu, Hongbin; Munsell, Brent C; Kim, Sun Hyung; Styner, Martin; Wolff, Jason J; Elison, Jed T; Swanson, Meghan R; Zhu, Hongtu; Botteron, Kelly N; Collins, D Louis; Constantino, John N; Dager, Stephen R; Estes, Annette M; Evans, Alan C; Fonov, Vladimir S; Gerig, Guido; Kostopoulos, Penelope; McKinstry, Robert C; Pandey, Juhi; Paterson, Sarah; Pruett, John R; Schultz, Robert T; Shaw, Dennis W; Zwaigenbaum, Lonnie; Piven, Joseph
Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.
Sara A. Freedman
Full Text Available Background: Posttraumatic stress disorder (PTSD develops in approximately 20% of people exposed to a traumatic event, and studies have shown that cognitive-behavioral therapy (CBT is effective as a treatment for chronic PTSD. It has also been shown to prevent PTSD when delivered early after a traumatic event. However, studies have shown that uptake of early treatment is generally low, and therefore, the need to provide interventions through other mediums has been identified. The use of technology may overcome barriers to treatment. Objective: This paper describes a randomized controlled trial that will examine an early CBT intervention for PTSD. The treatment incorporates virtual reality (VR as a method for delivering exposure-based elements of the treatment. The intervention is Internet based, such that the therapist and patient will “meet” in a secure online site. This site will also include multi-media components of the treatment (such as videos, audios, VR that can be accessed by the patient between sessions. Method: Two hundred patients arriving to a Level 1 emergency department following a motor vehicle accident will be randomly assigned to either treatment or control groups. Inclusion criteria are age 18–65, PTSD symptoms 2 weeks posttrauma related to current trauma, no suicidality, no psychosis. Patients will be assessed by telephone by a team blind to the study group, on four occasions: before and after treatment, and 6 and 12 months posttreatment. The primary outcome is PTSD symptoms at follow up. Secondary outcomes include depression and cost effectiveness. Analyses will be on an intention-to-treat basis. Discussion: The results will provide more insight into the effects of preventive interventions, in general, and Internet-based early interventions, in particular, on PTSD, in an injured population, during the acute phase after trauma. We will discuss possible strengths and limitations.
Wang, Danyang; Wu, Lin-Ping
-related disease, such as neurodegeneration and disorders, suitable, safe and effective drug delivery nanocarriers have to been developed to overcome the blood brain barrier (BBB), which is the most inflexible barrier in human body. Here, we highlight the structure and function of barriers in the central nervous...... system (CNS) and summary several types of nanomaterials which can be potentially used in the brain delivery nucleic acid....
Yasui, Masayuki; Ota, Kiichiro; Sasajima, Kazuhisa; Iwata, Shiro.
The long term intake of unbalanced mineral diets has been reported to be one of the pathogenetic factors of central nervous system (CNS) degeneration, and the unbalanced mineral distribution in the bones clinically is expressed as a metabolic bone disorder or deposition of neurotoxic minerals/metals. The unbalanced mineral or metal diets in animals provoke the unbalanced mineral distribution in bones and soft tissues. In this study, the calcium (Ca), magnesium (Mg), zinc (Zn), aluminum (Al) and manganese (Mn) contents in the CNS and the bones of rats maintained on unbalanced mineral diets were analyzed to investigate the roles of bone on CNS degeneration. Male Wistar rats were maintained for 90 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca-Mg diet, (D) low Ca-Mg diet with high Al. Al and Mn contents were determined in the frontal cortex, spinal cord, lumbar spine and femur using inductively coupled plasma emission spectrometry (ICP) for Ca, Mg and Zn, and neutron activation analysis (NAA) for Al and Mn. Intake of low Ca and Mg with added Al in rats led to the abnormal distribution of metals or minerals in the bones and in the CNS. These results illustrate that unbalanced mineral diets and metal-metal interactions may lead to the irregular deposition of Al and Mn in the bones and ultimately in the CNS, thus inducing CNS degeneration. (author)
Dunst, Carl J.; Trivette, Carol M.; Hamby, Deborah W.
Incorporating the interests and preferences of young children with autism spectrum disorders into interventions to promote prosocial behavior and decrease behavior excesses has emerged as a promising practice for addressing the core features of autism. The efficacy of interest-based early intervention practices was examined in a meta-analysis of 24 studies including 78 children 2 to 6 years of age diagnosed with autism spectrum disorders. Effect size analyses of intervention versus noninterve...
Mazer, Angela Kaline; Cleare, Anthony J; Young, Allan H; Juruena, Mario F
Borderline Personality Disorder (BPD) and Bipolar Affective Disorder (BD) have clinical characteristics in common which often make their differential diagnosis difficult. The history of early life stress (ELS) may be a differentiating factor between BPD and BD, as well as its association with clinical manifestations and specific neuroendocrine responses in each of these diagnoses. Assessing and comparing patients with BD and BPD for factors related to symptomatology, etiopathogenesis and neuroendocrine markers. The study sample consisted of 51 women, divided into 3 groups: patients with a clinical diagnosis of BPD (n = 20) and BD (n = 16) and healthy controls (HC, n = 15). Standardized instruments were used for the clinical evaluation, while the history of ELS was quantified with the Childhood Trauma Questionnaire (CTQ), and classified according to the subtypes: emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect. The functioning of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring a single plasma cortisol sample. Patients with BPD presented with more severe psychiatric symptoms of: anxiety, impulsivity, depression, hopelessness and suicidal ideation than those with BD. The history of ELS was identified as significantly more prevalent and more severe in patients (BPD and BP) than in HC. Emotional abuse, emotional neglect and physical neglect also showed differences and were higher in BPD than BD patients. BPD patients had greater severity of ELS overall and in the subtypes of emotional abuse, emotional neglect and physical neglect than BD patients. The presence of ELS in patients with BPD and BP showed significant difference with lower cortisol levels when compared to HC. The endocrine evaluation showed no significant differences between the diagnoses of BPD and BD. Cortisol measured in patients with BPD was significantly lower compared to HC in the presence of emotional neglect and physical
Cross, Shane P M; Scott, Jan; Hickie, Ian B
Transition from at-risk state to full syndromal mental disorders is underexplored for unipolar and bipolar disorders compared with psychosis. Prospective, trans-diagnostic study of rates and predictors of early transition from sub-threshold to full syndromal mental disorder. One-year outcome of 243 consenting youth aged 15-25 years with a sub-syndromal presentation of a potentially severe mental disorder. Survival analysis and odds ratio (OR) for predictors of transition identified from baseline clinical and demographic ratings. About 17% ( n =36) experienced transition to a major mental disorder. Independent of syndromal diagnosis, transition was significantly more likely in individuals who were NEET (not in education, employment or training), in females and in those with more negative psychological symptoms (e.g. social withdrawal). NEET status and negative symptoms are modifiable predictors of illness trajectory across diagnostic categories and are not specific to transition to psychosis. I.B.H. has been a Commissioner in Australia's National Mental Health Commission since 2012. He was a board member of headspace: National Youth Mental Health Foundation until January 2012. He has led a range of community-based and pharmaceutical industry-supported depression awareness and education and training programmes. He has led projects for health professionals and the community supported by governmental, community agency and pharmaceutical industry partners (Wyeth, Eli Lilly, Servier, Pfizer, AstraZeneca) for the identification and management of depression and anxiety. He has received honoraria for presentations of his own work at educational seminars supported by a number of non-government organisations and the pharmaceutical industry (including Servier, Pfizer, AstraZeneca and Eli Lilly). He is a member of the Medical Advisory Panel for Medibank Private and also a board member of Psychosis Australia Trust. He leads an investigator-initiated study of the effects of
Philipsen, Alexandra; Lam, Alexandra P; Breit, Sigrid; Lücke, Caroline; Müller, Helge H; Matthies, Swantje
The main purpose of this study was to examine whether adult patients with attention deficit hyperactivity disorder (ADHD) demonstrate sets of dysfunctional cognitive beliefs and behavioural tendencies according to Jeffrey Young's schema-focused therapy model. Sets of dysfunctional beliefs (maladaptive schemas) were assessed with the Young Schema Questionnaire (YSQ-S2) in 78 adult ADHD patients and 80 control subjects. Patients with ADHD scored significantly higher than the control group on almost all maladaptive schemas. The 'Failure', 'Defectiveness/Shame', 'Subjugation' and 'Emotional Deprivation' schemas were most pronounced in adult ADHD patients, while only 'Vulnerability to Harm or Illness' did not differ between the two groups. The schemas which were most pronounced in adult patients with ADHD correspond well with their learning histories and core symptoms. By demonstrating the existence of early maladaptive schemas in adults suffering from ADHD, this study suggests that schema theory may usefully be applied to adult ADHD therapy.
Gozzetti, Alessandro; Cerase, Alfonso
Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease.
Fujiyoshi, Kenji; Fukuyama, Hidenao; Akiguchi, Ichiro; Kameyama, Masakuni; Nishimura, Toshio.
A 71-year-old male was admitted to Kohka Public Hospital on January 4, 1980, because of frequent vomiting and recent memory loss. Two weeks before admission upper G-I series showed no abnormalities. Physical and neurological examinations revealed no abnormalities except for slightly apathetic appearance and recent memory loss. Mild pleocytosis and marked increase of protein in CSF were observed. CT scan on January 17 showed high density areas in both medial sides of temporal lobes with remarkable contrast enhancement. His memory and, consciousness disturbances gradually aggravated, accompanied by abnormal density spreading around the ventricle walls like ventriculitis. He was transfered to Kyoto University Hospital on March 17, and malignant lymphoma was diagnosed on the basis of CSF cytology. Radiation and chemotherapy alleviated the CNS involvement and he regained normal mental function. On June 16, he developed pneumonia followed by status epilepticus. Autopsy findings revealed no lymphoid cell infiltration, but fibrous tissues in both hippocampal gyri and lymphomatous cells in the liver, which could not be suspected on clinical examinations. Apparent malignant lymphoma cells were not found in lymph nodes. This case indicated peculiar evolution of malignant lymphoma from liver to CNS or vice versa. We could not decide which organ was primary. CT findings of this case was very interesting; they resembled ventriculitis, which simulate tumors such as medulloblastoma or ependymoma spreading under ependymal lining. (author)
Full Text Available Bipolar disorder (BD is a severe psychiatric illness with a consistent genetic influence, involving complex interactions between numerous genes and environmental factors. Immediate early genes (IEGs are activated in the brain in response to environmental stimuli, such as stress. The potential to translate environmental stimuli into long-term changes in brain has led to increased interest in a potential role for these genes influencing risk for psychiatric disorders. Our recent finding using network-based approach has shown that the regulatory unit of early growth response gene 3 (EGR3 of IEGs family was robustly repressed in postmortem prefrontal cortex of BD patients. As a central transcription factor, EGR3 regulates an array of target genes that mediate critical neurobiological processes such as synaptic plasticity, memory and cognition. Considering that EGR3 expression is induced by brain-derived neurotrophic factor (BDNF that has been consistently related to BD pathophysiology, we suggest a link between BDNF and EGR3 and their potential role in BD. A growing body of data from our group and others has shown that peripheral BDNF levels are reduced during mood episodes and also with illness progression. In this same vein, BDNF has been proposed as an important growth factor in the impaired cellular resilience related to BD. Taken together with the fact that EGR3 regulates the expression of the neurotrophin receptor p75NTR and may also indirectly induce BDNF expression, here we propose a feed-forward gene regulatory network involving EGR3 and BDNF and its potential role in BD.
Hennig, Timo; Jaya, Edo S; Lincoln, Tania M
Although a childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) is known to be linked to psychotic experiences and psychotic disorders in later life, the developmental trajectories that could explain this association are unknown. Using a sample from the prospective population-based Avon Longitudinal Study of Parents and Children (ALSPAC) (N = 8247), we hypothesized that the previously reported association of ADHD combined subtype in childhood and psychotic experiences in early adolescence is mediated by traumatic events and by involvement in bullying. Moreover, we expected this mediation to be specific to ADHD and tested this by comparison with specific phobia. Children with ADHD combined subtype at age 7 were more often involved in bullying at age 10 (OR 3.635, 95% CI 1.973-6.697) and had more psychotic experiences at age 12 (OR 3.362, 95% CI 1.781-6.348). Moreover, children who were involved in bullying had more psychotic experiences (2.005, 95% CI 1.684-2.388). Bullying was a significant mediator between ADHD and psychotic experiences accounting for 41%-50% of the effect. Traumatic events from birth to age 11 were also significantly associated with ADHD combined subtype and psychotic experiences; however, there was no evidence of mediation. Specific phobia was significantly associated with psychotic experiences, but not with bullying. To conclude, bullying is a relevant translating mechanism from ADHD in childhood to psychotic experiences in early adolescence. Interventions that eliminate bullying in children with ADHD could potentially reduce the risk of having psychotic experiences in later life by up to 50%. Clinicians should thus screen for bullying in routine assessments of children with ADHD. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: firstname.lastname@example.org.
Full Text Available In chronic PTSD, a preattentive neural alarm system responds rapidly to emotional information, leading to increased prefrontal cortex (PFC activation at early processing stages (<100 ms. Enhanced PFC responses are followed by a reduction in occipito-temporal activity during later processing stages. However, it remains unknown if this neuronal pattern is a result of a long lasting mental disorder or if it represents changes in brain function as direct consequences of severe trauma.The present study investigates early fear network activity in acutely traumatized patients with PTSD. It focuses on the question whether dysfunctions previously observed in chronic PTSD patients are already present shortly after trauma exposure. We recorded neuromagnetic activity towards emotional pictures in seven acutely traumatized PTSD patients between one and seven weeks after trauma exposure and compared brain responses to a balanced healthy control sample. Inverse modelling served for mapping sources of differential activation in the brain.Compared to the control group, acutely traumatized PTSD patients showed an enhanced PFC response to high-arousing pictures between 60 to 80 ms. This rapid prefrontal hypervigilance towards arousing pictorial stimuli was sustained during 120-300 ms, where it was accompanied by a reduced affective modulation of occipito-temporal neural processing.Our findings indicate that the hypervigilance-avoidance pattern seen in chronic PTSD is not necessarily a product of an endured mental disorder, but arises as an almost immediate result of severe traumatisation. Thus, traumatic experiences can influence emotion processing strongly, leading to long-lasting changes in trauma network activation and expediting a chronic manifestation of maladaptive cognitive and behavioral symptoms.
Full Text Available Several studies report increased reward sensitivity towards food in overweight individuals. By contrast, data is inconclusive with respect to response inhibition in overweight individuals without binge eating disorder (BED. Hence, the latter was addressed in the present study in a group of overweight/obese females with and without BED and a normal-weight control group without eating disorders.A group of women with BED (n = 29, a group of overweight women without BED (n = 33 and normal-weight females (n = 30 participated in a pictorial priming paradigm, with food items (relevant primes and office utensils (neutral primes and color blobs (neutral primes as stimuli. Increased response priming effects (i.e. priming with switches between stimulus categories were taken as indicators of deficient behavioral inhibition.Priming effects for neutral primes were moderate and comparable across all groups. However, primes associated with the food task set lead to increased priming effects in both overweight groups. But, effects were comparable for overweight/obese participants with and without BED.Results suggest that early response inhibition in the context of food is impaired in overweight individuals compared to normal-weight individuals.
Lofthouse, Nicholas; Fristad, Mary; Splaingard, Mark; Kelleher, Kelly; Hayes, John; Resko, Susan
As research on sleep difficulties associated with Early-Onset Bipolar Spectrum Disorders (EBSD) is limited, a web-based survey was developed to further explore these problems. 494 parents of 4-to-12 year-olds, identified by parents as being diagnosed with EBSD, completed a web survey about past and current EBSD-related sleep problems. The survey included Children's Sleep Habits Questionnaire (CSHQ) items and sleep problems from the International Classification of Sleep Disorders 2nd edition. Nearly all parents reported some type of past or current EBSD-sleep problem. Most occurred during a worst mood period, particularly with mixed manic-depressive symptoms. Symptoms caused impairments at home, school, or with peers in 96.9% of the sample and across all three contexts in 64.0% of children. Sleep problems were also noted after three-day weekends and Spring and Fall Daylight Savings time changes. Findings, study limitations, and implications for treatment and etiology are discussed.
Batool, Naila; Shehzadi, Humaira; Riaz, Muhammad Naveed; Riaz, Muhammad Akram
To examine the mediating role of maladaptive schemas between permissive/authoritarian parenting by fathers and personality disorders, including histrionic, antisocial, narcissistic and depressive attitudes among adults. This cross-sectional study was conducted at the University of Sargodha, Sargodha, Pakistan, and comprised university students. Data was collected by administering the parental authority questionnaire, the young schema questionnaire and the personality diagnostic questionnaire. SPSS 23 was used for data analysis. The study was completed in one year. It was started from June 2014 and ended in June 2015. Of the 200 participants who were handed the questionnaires, 100(50%) returned it fully filled up. Of them, 87(87%) were women and 13(13%) were men. All scales had greater than 0.70 alpha reliability coefficients. The values of skewness for all scales ranged from 0.10 to 0.86.Permissive parenting style had positive correlation with histrionic (pAuthoritarian parenting had positive correlation with early maladaptive schemas (pauthoritarian parenting styles led to personality disorders among offspring in the adult phase of their lives.
Jackman, Angela R.; Biggs, Sarah N.; Walter, Lisa M.; Embuldeniya, Upeka S.; Davey, Margot J.; Nixon, Gillian M.; Anderson, Vicki; Trinder, John; Horne, Rosemary S. C.
Objectives: To characterize health-related quality of life (QOL) in preschool children with sleep disordered breathing (SDB) and their families compared with nonsnoring control patients in the community. It was hypothesized that children with SDB and their families would have poorer QOL than control children, that a relationship would be found between SDB severity and QOL, and that even children with mild SDB and their families would have reduced QOL. Participants and Methods: A clinical sample of preschool children (3-5 y) with SDB diagnosed by gold standard polysomnography (primary snoring, PS = 56, mild obstructive sleep apnea, OSA = 35, moderate/severe OSA = 24) and control children recruited from the community (n = 38) were studied. Parents completed health-related QOL and parenting stress questionnaires. Results: Children and families in the PS and mild OSA groups had consistently poorer QOL than control children (both P Biggs SN; Walter LM; Embuldeniya US; Davey MJ; Nixon GM; Anderson V; Trinder J; Horne RSC. Sleep disordered breathing in early childhood: quality of life for children and families. SLEEP 2013;36(11):1639-1646. PMID:24179296
Kim, Jane; Tol, Wietse A; Shrestha, Abina; Kafle, Hari Maya; Rayamajhi, Rajin; Luitel, Nagendra P; Thapa, Lily; Surkan, Pamela J
Persistent complex bereavement disorder (PCBD) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), has not been well studied in socioculturally diverse populations. Thus, this qualitative study examined (a) how widows in Nepal understand grief, (b) whether a local construct of PCBD exists, and (c) its comparability with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), terminology. Using an adapted Explanatory Model Interview Catalogue (EMIC) framework, semistructured interviews with 25 widows and 12 key informants, as well as three focus-group discussions (n = 20), were conducted between October 2014 and April 2015. Through an inductive grounded theory-based approach, we used the constant comparative method, iteratively coding transcripts to identify themes and patterns in the data. Also, we created two lists of grief responses, one of early reactions and another all reactions to grief, based on the frequency of mention. No single term for grief was reported. Widows reported a local construct of PCBD, which was broadly compatible with DSM-5 terminology but with important variation reflecting societal influence. Surviving torture during conflict, economic and family stressors, and discrimination were mentioned as important determinants that prolong and complicate grief. Suicidal ideation was common, with about 31% and 62% of widows reporting past-year and lifetime suicidality, respectively. Findings may not be generalizable to all Nepali widows; participants were recruited from a non-governmental organization, from Kathmandu and its neighboring districts, and were primarily of reproductive age. While PCBD symptoms proposed in DSM-5 were mentioned as relevant by study participants, some components may need adaptation for use in non-Western settings, such as Nepal.
Christopher M Treleaven
Full Text Available Niemann-Pick A (NPA disease is a lysosomal storage disorder (LSD caused by a deficiency in acid sphingomyelinase (ASM activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO mice could be partially alleviated by intracerebroventricular (ICV infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat.
Christoffersen, Gert R J; Schachtman, Todd R
The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.
Barbaro, Josephine; Dissanayake, Cheryl
The Social Attention and Communication Study involved the successful implementation of developmental surveillance of the early markers of autism spectrum disorders in a community-based setting. The objective in the current study was to determine the most discriminating and predictive markers of autism spectrum disorders used in the Social Attention and Communication Study at 12, 18 and 24 months of age, so that these could be used to identify children with autism spectrum disorders with greater accuracy. The percentage of 'yes/no' responses for each behavioural marker was compared between children with autistic disorder (n = 39), autism spectrum disorder (n = 50) and developmental and/or language delay (n = 20) from 12 to 24 months, with a logistic regression also conducted at 24 months. Across all ages, the recurring key markers of both autistic disorder and autism spectrum disorder were deficits in eye contact and pointing, and from 18 months, deficits in showing became an important marker. In combination, these behaviours, along with pretend play, were found to be the best group of predictors for a best estimate diagnostic classification of autistic disorder/autism spectrum disorder at 24 months. It is argued that the identified markers should be monitored repeatedly during the second year of life by community health-care professionals.
Lyubimova, N.; Coultas, P.; Martin, R.
Full text: Radioprotection using the minor groove binding DNA ligand Hoechst 33342 has been demonstrated in vitro, and more recently in vivo, in mouse lung. Intravenous administration was used for the lung studies, and both endothelial and alveolar epithelial cells-showed good up-take. Radiation damage to the endothelial cell population has also been postulated as important in late developing radionecrosis of spinal cord and brain. Endothelial cell density in brain can be readily determined by a fluorescent-histochemical technique. Treatment with a monoamine oxidase inhibitor and subsequent injection with L-DOPA results in an accumulation of dopamine (DA) in CNS endothelial cells. DA is converted to a fluorophore by exposure to paraformaldehyde, and cell numbers assayed by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed the loss, within 24 hours, of a sensitive subpopulation comprising about 15% of the endothelial cells. Ten minutes after intravenous injection of Hoechst 33342 (80mg/kg) the ligand is confined by its limited penetration to the endothelial cells in mouse brain. When we irradiated at this time, there was protection against early endothelial cell loss. Ablation of the sensitive subpopulation in unprotected mice takes place over a dose range of 1 to 3 Gy γ-rays, but doses between 12 to 20 Gy are required in the presence of ligand. This protection equates to a very high dose modification factor of about 7 and possibly reflects a suppression of apoptosis in the sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole and how the observed protection affects late CNS necrosis development has yet to be determined. However present results clearly show potential for the use of DNA-binding radioprotectors with limited penetration for investigations into the relative significance of
Warreyn, Petra; Van der Paelt, Sara; Demurie, Ellen; Roeyers, Herbert
Although sibling interactions play an important role in children’s early development, they are rarely studied in very young children with an older brother or sister with autism spectrum disorder (ASD). This study used a naturalistic, observational method to compare interactions between 18-month-old infants and their older sibling with ASD (n = 22) with a control group of 18-month-old infants and their typically developing (TD) older sibling (n = 29). In addition, role (a)symmetry and the influence of gender were evaluated. Sibling interactions in ASD-dyads were characterized by higher levels of negativity. Although somewhat less pronounced in ASD-dyads, role asymmetry was present in both groups, with the older child taking the dominant position. Finally, siblings pairs with an older sister were characterized by more positive behaviours. Since differences in sibling interactions may alter the developmental trajectories of both siblings, these early relationships should be taken into account in future ASD research and interventions. PMID:29543814
Fortea-Sevilla, M Sol; Escandell-Bermúdez, M Olga; Castro-Sánchez, José Juan; Martos-Pérez, Juan
The latest research findings show the importance of early intervention in children with autism spectrum disorder (ASD) in all areas of development, including language. The use of augmentative and alternative communication systems (AACS) favors linguistic and communicative development. To show the effectiveness of AACS to develop oral language in non-verbal toddlers diagnosed with ASD. Thirty children (25 males and 5 females) diagnosed with ASD when they were between 18 and 30 months of age, through the instruments ADOS and ADIR. None of them displayed oral language development at the time of assessment. An intervention program in the area of language was designed based on the use of total communication by the therapist and training the child in the Picture Exchange Communication System (PECS). One year later, the formal aspects of language were assessed with the PLON-R because oral language had been developed. All the children had developed oral language to some extent over a one-year period. Early intervention and the use of AACS with visual props favor the development of oral language in children with ASD in the first years of life.
Poletti, Sara; Aggio, Veronica; Brioschi, Silvia; Bollettini, Irene; Falini, Andrea; Colombo, Cristina; Benedetti, Francesco
Major Depressive Disorder (MDD) is a worldwide-spread pathology, characterized by lifetime-recurrent episodes. Adverse childhood experiences (ACE) increase the lifetime risk of developing depression and affect the structure of the brain. Recent stressful events (RSE) can trigger the onset of depressive episodes, and affect grey matter volume. The aim of our study is to analyse the effect of both early and recent stress events on white matter microstructure in MDD patients and healthy volunteers. Sixty-five MDD inpatients and fifty-nine healthy controls underwent MRI acquisition of diffusion tensor images with a 3.0T scanner. Severity of ACE and RSE was rated, respectively, on the Risky Families Questionnaire and on the Social Readjustment Rating Scale. A significant effect of diagnosis was observed, with MDD subjects showing reduced fractional anisotropy (FA) and axial diffusivity (AD) compared to healthy controls in all the major association, projection and commissural tracts. In patients with MDD, but not in healthy controls, both ACE and RSE correlated with measures of WM microstructure: ACE correlated negatively with AD and MD, whereas RSE correlated negatively with FA. The two diagnostic groups differed for age and education, previous and current medications, and treatment periods. Exposure to both early and recent stress exerts a widespread effect on WM microstructure of MDD patients, with a different impact possibly depending from the developmental period in which the stress has occurred. Copyright © 2017 Elsevier B.V. All rights reserved.
G. M. Lutokhin
Full Text Available The rehabilitation potential in ischemic stroke depends both on the localization and size of cerebral infarction and on many other factors ensuring the restoration of neuron function in the ischemic penumbra. Sleep-disordered breathing (SDB appears as intermittent episodes of apnea and hypopnea, which are accompanied by hypoxemia and tissue hypoxia, and may slow early functional recovery in patients.Objective: to evaluate the impact of SDB on early neurological recovery in patients with ischemic stroke and to identify predictors of unfavorable functional outcome.Patients and methods. A total of 56 patients (24 men, 32 women; mean age 62±15 years with ischemic stroke were examined. All the patients underwent brain magnetic resonance imaging. Neurological deficit was assessed using the National Institutes of Health Stroke Scale (NIHSS, modified Rankin Scale (mRS on admission and at 3 weeks. To identify SDB, cardiorespiratory monitoring was performed on 2–5 days after the onset of the disease. The total number of episodes of SDB, apnea, hypopnea, apnea-hypopnea index (AHI, hypoxemia index, and the total time with arterial oxygen saturation < 90% (desaturation time < 90% were recorded. Results and discussion. At baseline, the median NIHSS score was 6 (range 4–10 and the median mRS score was 3 (range 2–5. After 3 weeks, the median NIHSS score was 3 (range 1.5–5 and the median mRS score was 1 (range 0–3. According to the degree of achieved functional independence, the patients were divided into 2 groups: 1 40 functionally independent patients (a mRS score of ≤2; 2 16 patients in need of assistance/care (a mRS score of ≥3. The groups were matched for age, sex, localization of cerebral infarction, degree of cerebral atherosclerosis, and incidence of cardiac pathology. At the same time, at baseline Group 2 had a more severity of neurological deficit (p=0.001 and respiratory disorders (p<0.04 and more frequently large and
Levy, Boaz; Celen-Demirtas, Selda; Surguladze, Tinatin; Eranio, Sara; Ellison, James
Cost-prohibitive factors currently prevent a warranted integration of neuropsychological screenings into routine psychiatric evaluations, as a standard of care. To overcome this challenge, the current study examined the psychometric properties of a new computerized measure-the CNS Screen. One hundred and twenty six psychiatric inpatients completed the CNS Screen, the Montreal Cognitive Assessment (MoCA), and the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR₁₆) on the day of hospital discharge. Statistical analysis established convergent validity with a moderate correlation between the self-administered CNS Screen and the clinician-administered MoCA (r=0.64). Discriminant validity was implicated by a non-significant correlation with the QIDS-SR₁₆. Concurrent validity was supported by a moderate, negative correlation with patients' age (r=-0.62). In addition, consistent with previous findings, patients with psychotic disorders exhibited significantly poorer performance on the CNS Screen than patients with a mood disorder. Similarly, patients with a formal disability status scored significantly lower than other patients. The CNS Screen was well tolerated by all patients. With further development, this type of measure may provide a cost-effective approach to expanding neuropsychological screenings on inpatient psychiatric units. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
SYMPTOM PRESENTATIONS AND CLASSIFICATION OF AUTISM SPECTRUM DISORDER IN EARLY CHILDHOOD: APPLICATION TO THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD (DC:0-5).
Soto, Timothy; Giserman Kiss, Ivy; Carter, Alice S
Over the past 5 years, a great deal of information about the early course of autism spectrum disorder (ASD) has emerged from longitudinal prospective studies of infants at high risk for developing ASD based on a previously diagnosed older sibling. The current article describes early ASD symptom presentations and outlines the rationale for defining a new disorder, Early Atypical Autism Spectrum Disorder (EA-ASD) to accompany ASD in the new revision of the ZERO TO THREE Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-5) (in press) alternative diagnostic classification manual. EA-ASD is designed to identify children who are 9 to 36 months of age presenting with a minimum of (a) two social-communication symptoms and (b) one repetitive and restricted behavior symptom as well as (c) evidence of impairment, with the intention of providing these children with appropriately tailored services and improving the likelihood of optimizing their development. © 2016 Michigan Association for Infant Mental Health.
Full Text Available Objective:Evidence suggests that early-onset obsessive-compulsive disorder (OCD is an etiologically distinct subtype of OCD. The objective of the present work was to search for neurocognitive endophenotypes of early-onset OCD based on assessments of attention, memory, and executive function in patients with the disorder and their unaffected siblings.Methods:We compared the performance of 40 adult patients with early-onset OCD, 40 of their unaffected siblings, and 40 unrelated healthy controls on a neuropsychological battery designed for this study. We searched for associations among test performance, demographic variables (age, sex and years of education and clinical symptoms of early-onset OCD.Results:Patients performed significantly worse than healthy controls on the Tower of Hanoi, and the Stroop and Wisconsin tests, indicating impairments in planning, mental flexibility and inhibitory control. The performance of the unaffected first-degree siblings of patients with early-onset OCD on the Stroop and Wisconsin tests also differed from that of healthy controls. Symptom severity in early-onset OCD was strongly correlated with performance on the Tower of Hanoi.Conclusions:Our findings support the existence of specific executive function deficits in patients with early-onset OCD. Relatives presented an intermediate phenotype between patients and controls, suggesting that executive functions such as mental flexibility and response inhibition may be considered candidate endophenotypes of early-onset OCD.
Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S
This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.
Bayer, Jordana K; Rapee, Ronald M; Hiscock, Harriet; Ukoumunne, Obioha C; Mihalopoulos, Cathrine; Clifford, Susan; Wake, Melissa
The World Health Organization predicts that by 2030 internalising problems (e.g. depression and anxiety) will be second only to HIV/AIDS in international burden of disease. Internalising problems affect 1 in 7 school aged children, impacting on peer relations, school engagement, and later mental health, relationships and employment. The development of early childhood prevention for internalising problems is in its infancy. The current study follows two successful 'efficacy' trials of a parenting group intervention to reduce internalising disorders in temperamentally inhibited preschool children. Cool Little Kids is a population-level randomised trial to determine the impacts of systematically screening preschoolers for inhibition then offering a parenting group intervention, on child internalising problems and economic costs at school entry. This randomised trial will be conducted within the preschool service system, attended by more than 95% of Australian children in the year before starting school. In early 2011, preschool services in four local government areas in Melbourne, Australia, will distribute the screening tool. The ≈16% (n≈500) with temperamental inhibition will enter the trial. Intervention parents will be offered Cool Little Kids, a 6-session group program in the local community, focusing on ways to develop their child's bravery skills by reducing overprotective parenting interactions. Outcomes one and two years post-baseline will comprise child internalising diagnoses and symptoms, parenting interactions, and parent wellbeing. An economic evaluation (cost-consequences framework) will compare incremental differences in costs of the intervention versus control children to incremental differences in outcomes, from a societal perspective. Analyses will use the intention-to-treat principle, using logistic and linear regression models (binary and continuous outcomes respectively) to compare outcomes between the trial arms. This trial addresses gaps
Full Text Available Abstract Background The World Health Organization predicts that by 2030 internalising problems (e.g. depression and anxiety will be second only to HIV/AIDS in international burden of disease. Internalising problems affect 1 in 7 school aged children, impacting on peer relations, school engagement, and later mental health, relationships and employment. The development of early childhood prevention for internalising problems is in its infancy. The current study follows two successful 'efficacy' trials of a parenting group intervention to reduce internalising disorders in temperamentally inhibited preschool children. Cool Little Kids is a population-level randomised trial to determine the impacts of systematically screening preschoolers for inhibition then offering a parenting group intervention, on child internalising problems and economic costs at school entry. Methods/Design This randomised trial will be conducted within the preschool service system, attended by more than 95% of Australian children in the year before starting school. In early 2011, preschool services in four local government areas in Melbourne, Australia, will distribute the screening tool. The ≈16% (n≈500 with temperamental inhibition will enter the trial. Intervention parents will be offered Cool Little Kids, a 6-session group program in the local community, focusing on ways to develop their child's bravery skills by reducing overprotective parenting interactions. Outcomes one and two years post-baseline will comprise child internalising diagnoses and symptoms, parenting interactions, and parent wellbeing. An economic evaluation (cost-consequences framework will compare incremental differences in costs of the intervention versus control children to incremental differences in outcomes, from a societal perspective. Analyses will use the intention-to-treat principle, using logistic and linear regression models (binary and continuous outcomes respectively to compare outcomes
Herbrecht, Evelyn; Kievit, Esther; Spiegel, René; Dima, Diana; Goth, Kirstin; Schmeck, Klaus
In autism spectrum disorders (ASDs), impairments in fundamental social abilities and a lack of interest in social stimuli become apparent early in life. These impairments are thought to negatively affect further brain and behavioural development. Early intensive interventions can help to attenuate social-development and other risk factors and, thus, to ameliorate the deficits associated with ASDs. We present FIAS, an intensive early intervention approach for young children with ASD, which aims at developing children's social motivation. During 18 days, therapists work continuously for 6 h a day with the affected child, involving the whole family in a day care setting. Follow-up care at home over 1 year as well as fresh-up interventions and inclusion in kindergarten or a play group should stabilise the effects and help to respond to further challenges. Here, we present observations from the first 12 patients (25-48 months of age) treated according to the FIAS approach. We evaluated changes in core autistic symptoms and level of functioning after the 18 days of intensive intervention. Beyond standardised assessment, two innovative video-based instruments (Autism Behaviour Coding System and Evaluationsfragebogen) have been developed to assess autistic symptoms and interaction parameters during intervention. Improvements were noted in most core autistic symptom domains, with the highest effect sizes in domains like eye contact, communication, repetitive behaviour, imitation, motivation and reciprocity. In addition, the level of functioning significantly improved. The first evaluation of the FIAS approach shows promising results, as the FIAS intervention appears to improve core autistic symptom domains as well as the level of everyday functioning. Limitations of this study are the small sample size and the lack of a control group. A more comprehensive and longitudinal evaluation is in progress; this will focus on the stability of the observed effects and will attempt to
Full Text Available OBJECTIVE: To determine how early musculoskeletal disorders (MSDs develop in dental professionals and to explore the potential differences among distinct dental specialties. MATERIAL AND METHODS: 271 dental postgraduates majoring in five dental specialties were recruited, i.e., orthodontics, prosthodontics, endodontics, periodontics and alveolar surgery. 254 age-matched non-dental postgraduates served as the control. The standardized Nordic questionnaire on MSDs and a self-report questionnaire regarding correlative factors (only for dental postgraduates were answered through emails. Reliability of responses was assessed applying test-retest method. RESULTS: The intraclass correlation coefficient of participants' answers ranged from 0.89 to 0.96. Dental postgraduates had significantly higher prevalence of MSDs than the control group, especially at neck, upper back and lower back. In all dental specialties included, high prevalence of MSDs was reported at neck (47.5%-69.8%, shoulders (50.8%-65.1%, lower back (27.1%-51.2% and upper back (25.6%-46.5%, with lower prevalence at elbows (5.1%-18.6%, hips (3.4%-16.3% and ankles (5.1%-11.6%. Periodontics students reported the worst MSDs in most body regions except wrists and knees, which were more prevalent for prosthodontic and alveolar surgery students, respectively. Furthermore, year of clinical work, clinical hours per week and desk hours per week were found as risk factors for MSDs, whereas physical exercise and rest between patients as protective factors. CONCLUSIONS: High and specialty-related MSDs afflict dental professionals even since very early stage of careers. Prevention aimed at the specialty-related characteristics and the risk/protective factors revealed in this study should be introduced to dental personnel as early as possible.
Benarous, Xavier; Consoli, Angèle; Milhiet, Vanessa; Cohen, David
In recent decades, ongoing research programmes on primary prevention and early identification of bipolar disorder (BD) have been developed. The aim of this article is to review the principal forms of evidence that support preventive interventions for BD in children and adolescents and the main challenges associated with these programmes. We performed a literature review of the main computerised databases (MEDLINE, PUBMED) and a manual search of the literature relevant to prospective and retrospective studies of prodromal symptoms, premorbid stages, risk factors, and early intervention programmes for BD. Genetic and environmental risk factors of BD were identified. Most of the algorithms used to measure the risk of developing BD and the early interventions programmes focused on the familial risk. The prodromal signs varied greatly and were age dependent. During adolescence, depressive episodes associated with genetic or environmental risk factors predicted the onset of hypomanic/manic episodes over subsequent years. In prepubertal children, the lack of specificity of clinical markers and difficulties in mood assessment were seen as impeding preventive interventions at these ages. Despite encouraging results, biomarkers have not thus far been sufficiently validated in youth samples to serve as screening tools for prevention. Additional longitudinal studies in youths at high risk of developing BD should include repeated measures of putative biomarkers. Staging models have been developed as an integrative approach to specify the individual level of risk based on clinical (e.g. prodromal symptoms and familial history of BD) and non-clinical (e.g. biomarkers and neuroimaging) data. However, there is still a lack of empirically validated studies that measure the benefits of using these models to design preventive intervention programmes.
Wilson, S; DiRago, A C; Iacono, W G
A well-established body of literature demonstrates concurrent associations between personality traits and major depressive disorder (MDD), but there have been relatively few investigations of their dynamic interplay over time. Prospective inter-relationships between late-adolescent personality and MDD in early adulthood were examined in a community sample of male and female twins from the Minnesota Twin Family Study (MTFS; n = 1252). Participants were classified into naturally occurring MDD groups based on the timing (adolescent versus adult onset) and course (chronic/recurrent versus remitting) of MDD. MDD diagnoses were assessed at ages 17, 20, 24 and 29 years, and personality traits [negative emotionality (NEM), positive emotionality (PEM) and constraint (CON)] were assessed at ages 17, 24 and 29 years. Multilevel modeling (MLM) analyses indicated that higher age-17 NEM was associated with the subsequent development of MDD, and any MDD, regardless of onset or course, was associated with higher NEM up to age 29. Moreover, the chronic/recurrent MDD groups failed to show the normative decrease in NEM from late adolescence to early adulthood. Lower age-17 PEM was also associated with the subsequent development of MDD but only among the chronic/recurrent MDD groups. Finally, the adolescent-onset MDD groups reported lower age-17 CON relative to the never-depressed and adult-onset MDD groups. Taken together, the results speak to the role of personality traits for conferring risk for the onset of MDD in late adolescence and early adulthood, in addition to the pernicious implications of chronic/recurrent MDD, particularly when it onsets during adolescence, for adaptive personality development.
Full Text Available Background: Tumors of the central nervous system in the pediatric age group occur relatively frequently during the early years of life. Brain tumors are the most common solid malignancies of childhood and only second to acute childhood leukemia. Squash cytology is an indispensable diagnostic aid to central nervous system (CNS lesions. The definitive diagnosis of brain lesions is confirmed by histological examination. Aim: To study the cytology of CNS lesions in pediatric population and correlate it with histopathology. Materials and Methods: One hundred and fifty cases of CNS lesions in pediatric patients were studied over a period of 2 years. Intraoperative squash smears were prepared, stained with hematoxylin and eosin, and examined. Remaining sample was subjected to histopathological examination. Results: Medulloblastoma (24.0% was the most frequently encountered tumor followed by pilocyctic astrocytoma (21.33% and ependymoma (13.33%. Diagnostic accuracy of squash smear technique was 94.67% when compared with histological diagnosis. Conclusion: Smear cytology is a fairly accurate tool for intraoperative CNS consultations.
Brown, Melissa A; Weinberg, Rebecca B
Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4 + and CD8 + T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis. By modulating the character and magnitude of the myelin-reactive T cell response and regulating BBB integrity, innate cells affect both disease initiation and progression. Two classes of innate cells, mast cells and innate lymphoid cells (ILCs), have been best studied in models of allergic and gastrointestinal inflammatory diseases. Yet, there is emerging evidence that these cell types also exert a profound influence in CNS inflammatory disease. Both cell types are residents within the meninges and can be activated early in disease to express a wide variety of disease-modifying cytokines and chemokines. In this review, we discuss how mast cells and ILCs can have either disease-promoting or -protecting effects on MS and other CNS inflammatory diseases and how sex hormones may influence this outcome. These observations suggest that targeting these cells and their unique mediators can be exploited therapeutically.
Choi, Karmel W; Shaffer, Kelly M; Zale, Emily L; Funes, Christopher J; Koenen, Karestan C; Tehan, Tara; Rosand, Jonathan; Vranceanu, Ana-Maria
posttraumatic stress disorder symptoms during admission is the single most important way to identify the majority of those likely to suffer from chronic posttraumatic stress disorder following discharge. Addressing early posttraumatic stress disorder symptoms and their psychosocial correlates during admission may help prevent chronic posttraumatic stress disorder in these at-risk caregivers.
Franklin, R.J.M.; Blakemore, W.F.; Cambridge Univ.
This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)
Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice
CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959
Miller, Meghan; Young, Gregory S.; Hutman, Ted; Johnson, Scott; Schwichtenberg, A. J.; Ozonoff, Sally
Background: We evaluated early pragmatic language skills in preschool-age siblings of children with autism spectrum disorder (ASD), and examined correspondence between pragmatic language impairments and general language difficulties, autism symptomatology, and clinical outcomes. Methods: Participants were younger siblings of children with ASD…
Nieto, Rebeca Garcia; Castellanos, F. Xavier
Despite the nosological distinction between bipolar disorder and schizophrenia, there is increasing evidence that these conditions share phenomenological characteristics. To examine the similarities in their patterns of cognitive impairment, we conducted a meta-analysis from 12 studies of Early Onset Schizophrenia (EOS) and 12 studies of Pediatric…
Ben-Sasson, A.; Soto, T. W.; Martinez-Pedraza, F.; Carter, A. S.
Background: Sensory over-responsivity (SOR) affects many individuals with autism spectrum disorders (ASD), often leading to stressful encounters during daily routines. Methods: This study describes the associations between early SOR symptoms and the longitudinal course of restrictions in family life activities and parenting stress across three…
Chronis, Andrea M.; Lahey, Benjamin B.; Pelham, William E., Jr.; Williams, Stephanie Hall; Baumann, Barbara L.; Kipp, Heidi; Jones, Heather A.; Rathouz, Paul J.
Children with attention-deficit/hyperactivity disorder (ADHD) are at risk for adverse outcomes such as substance abuse and criminality, particularly if they develop conduct problems. Little is known about early predictors of the developmental course of conduct problems among children with ADHD, however. Parental psychopathology and parenting …
Feil, Edward G.; Small, Jason W.; Seeley, John R.; Walker, Hill M.; Golly, Annemieke; Forness, Steven R.
This study evaluated the efficacy of the Preschool First Step (PFS) to Success early intervention for children at risk for attention deficit hyperactivity disorder (ADHD). PFS is a targeted intervention for children 3-5 years old with externalizing behavior problems and addresses secondary prevention goals and objectives. As part of a larger…
Clement, Sarah C; Schouten-van Meeteren, Antoinette Y N; Boot, Annemieke M; Claahsen-van der Grinten, Hedy L; Granzen, Bernd; Sen Han, K; Janssens, Geert O; Michiels, Erna M; van Trotsenburg, A S Paul; Vandertop, W Peter; van Vuurden, Dannis G; Kremer, Leontien C M; Caron, Hubert N; van Santen, Hanneke M
Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients
Clement, Sarah C.; Schouten-van Meeteren, Antoinette Y. N.; Boot, Annemieke M.; Claahsen-van der Grinten, Hedy L.; Granzen, Bernd; Sen Han, K.; Janssens, Geert O.; Michiels, Erna M.; van Trotsenburg, A. S. Paul; Vandertop, W. Peter; van Vuurden, Dannis G.; Kremer, Leontien C. M.; Caron, Hubert N.; van Santen, Hanneke M.
Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients
Clement, S.C.; Schouten-van Meeteren, A.Y.; Boot, A.M.; Claahsen-van der Grinten, H.L.; Granzen, B.; Han, K.; Janssens, G.O.; Michiels, E.M.; Trotsenburg, A.S. van; Vandertop, W.P.; Vuurden, D.G. van; Kremer, L.C.; Caron, H.N.; Santen, H.M. van
Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >/= 2 years after diagnosis. Patients
Lewis, Timothy J.; Mitchell, Barbara S.
Students with emotional and behavioral disorders are at great risk for long-term negative outcomes. Researchers and practitioners alike acknowledge the need for evidence-based, preventive, and early intervention strategies. Accordingly, in this chapter an expanded view of prevention is presented as a series of data driven decisions to guide…
Klages, Tricia; Geller, Barbara; Tillman, Rebecca; Bolhofner, Kristine; Zimerman, Betsy
Objective: To examine the prevalence of encopresis/enuresis, relationship between maternal hostility and encopresis, parent-child concordance of reporting encopresis/enuresis, and familial aggregation of enuresis in subjects with a prepubertal and early adolescent bipolar-I disorder phenotype (PEA-BP), attention-deficit/hyperactivity disorder…
Alotaibi, Faihan; Almalki, Nabil
The present study sought to examine parents' perceptions of early interventions and related services for children with autism spectrum disorder (ASD) in Saudi Arabia. In this study a survey was distributed to a sample of 80 parents with children who have ASD. Parents also were asked open-ended questions to enable them to provide suggestions. The…
Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.
Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…
Pfennig, Andrea; Leopold, Karolina; Ritter, Philipp; Böhme, Anne; Severus, Emanuel; Bauer, Michael
Prospective study designs ideally allow patients to be followed from the first manifestations of the illness or even from an at-risk stage. It can thus provide data on the predictive value of changes in clinical symptomatology, cognition or further biological markers to broaden our understanding of the etiopathology and symptomatic trajectory of bipolar disorders. The scope of this narrative review is to summarize evidence from prospectively collected data on psychopathological and other clinical and biological changes in the early developmental course of bipolar disorders. The narrative review was based on a literature search conducted in February 2016 within the PubMed library for prospective study data of persons in antecedent and early manifest stages of manifest bipolar disorder published within the last 15 years. A total of 19 prospective studies were included. Regarding psychopathological features; personality, temperament and character traits as well as changes in sleep and circadian rhythm, the evidence suggests that risk factors for the development of bipolar disorder can already be described and should be studied further to understand their interaction, mediation with other factors and timing in the developmental process of bipolar disorder. Apart from the positive family history, childhood anxiety, sleep problems, subthreshold (hypo)manic symptoms and certain character traits/emotionality should be identified and monitored already in clinical practice as their presence likely increases risk of bipolar disorder. Up to date no substantiated evidence was found from prospective studies addressing cognitive features, life events, immunological parameters and morphological central nervous system changes as potential risk factors for bipolar disorder. For an improved understanding of episodic disorders, longitudinal data collection is essential. Since the etiology of bipolar disorders is complex, a number of potential risk factors have been proposed
Full Text Available Abstract Background The importance of staying active instead of bed rest has been acknowledged in the management of musculoskeletal disorders (MSDs. This emphasizes the potential benefits of adjusting work to fit the employee's remaining work ability. Despite part-time sick leave being an official option in many countries, its effectiveness has not been studied yet. We have designed a randomized controlled study to assess the health effects of early part-time sick leave compared to conventional full-day sick leave. Our hypothesis is that if work time is temporarily reduced and work load adjusted at the early stages of disability, employees with MSDs will have less disability days and faster return to regular work duties than employees on a conventional sick leave. Methods/Design The study population will consist of 600 employees, who seek medical advice from an occupational physician due to musculoskeletal pain. The inclusion requires that they have not been on a sick leave for longer than 14 days prior to the visit. Based on the physician's judgement, the severity of the symptoms must indicate a need for conventional sick leave, but the employee is considered to be able to work part-time without any additional risk. Half of the employees are randomly allocated to part-time sick leave group and their work time is reduced by 40–60%, whereas in the control group work load is totally eliminated with conventional sick leave. The main outcomes are the number of days from the initial visit to return to regular work activities, and the total number of sick leave days during 12 and 24 months of follow-up. The costs and benefits as well as the feasibility of early part-time sick leave will also be evaluated. Conclusion This is the first randomised trial to our knowledge on the effectiveness of early part-time sick leave compared to conventional full-time sick leave in the management of MSDs. The data collection continues until 2011, but preliminary
Martimo, Kari-Pekka; Kaila-Kangas, Leena; Kausto, Johanna; Takala, Esa-Pekka; Ketola, Ritva; Riihimäki, Hilkka; Luukkonen, Ritva; Karppinen, Jaro; Miranda, Helena; Viikari-Juntura, Eira
The importance of staying active instead of bed rest has been acknowledged in the management of musculoskeletal disorders (MSDs). This emphasizes the potential benefits of adjusting work to fit the employee's remaining work ability. Despite part-time sick leave being an official option in many countries, its effectiveness has not been studied yet. We have designed a randomized controlled study to assess the health effects of early part-time sick leave compared to conventional full-day sick leave. Our hypothesis is that if work time is temporarily reduced and work load adjusted at the early stages of disability, employees with MSDs will have less disability days and faster return to regular work duties than employees on a conventional sick leave. The study population will consist of 600 employees, who seek medical advice from an occupational physician due to musculoskeletal pain. The inclusion requires that they have not been on a sick leave for longer than 14 days prior to the visit. Based on the physician's judgement, the severity of the symptoms must indicate a need for conventional sick leave, but the employee is considered to be able to work part-time without any additional risk. Half of the employees are randomly allocated to part-time sick leave group and their work time is reduced by 40-60%, whereas in the control group work load is totally eliminated with conventional sick leave. The main outcomes are the number of days from the initial visit to return to regular work activities, and the total number of sick leave days during 12 and 24 months of follow-up. The costs and benefits as well as the feasibility of early part-time sick leave will also be evaluated. This is the first randomised trial to our knowledge on the effectiveness of early part-time sick leave compared to conventional full-time sick leave in the management of MSDs. The data collection continues until 2011, but preliminary results on the feasibility of part-time sick leave will be available
Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine
Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.
Johnson, Mark H.; Gliga, Teodora; Jones, Emily; Charman, Tony
Background: Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are two of the most common neurodevelopmental disorders, with a high degree of co-occurrence. Methods: Prospective longitudinal studies of infants who later meet criteria for ASD or ADHD offer the opportunity to determine whether the two disorders share…
Lambert, Martin; Schöttle, Daniel; Sengutta, Mary; Ruppelt, Friederike; Rohenkohl, Anja; Luedecke, Daniel; Nawara, Luise Antonia; Galling, Britta; Falk, Anne-Lena; Wittmann, Linus; Niehaus, Vivien; Sarikaya, Gizem; Handwerk, Ute; Rothländer, Wiebke; Rietschel, Liz; Gagern, Charlotte; Lange, Benjamin; Meigel-Schleiff, Christina; Naber, Dieter; Schulte-Markwort, Michael; Krüger, Helmut; Unger, Hans-Peter; Sippel, Sven; Ott, Sabine; Romer, Georg; Daubmann, Anne; Wegscheider, Karl; Correll, Christoph U; Schimmelmann, Benno G; Bock, Thomas; Gallinat, Jürgen; Karow, Anne
The Integrated Care in Early Psychosis (ACCESS III) Study examined the efficacy and cost-effectiveness of a combined intervention consisting of strategies to improve early detection and quality of care (integrated care including therapeutic assertive community treatment) in adolescents and young adults in the early phase of a severe psychotic disorder from 2011 to 2014. This is a prospective, single-centre, 1-year cohort study comparing an intervention condition (early detection plus integrated care, n = 120) to the historical control condition (standard care, SC, n = 105) for adolescents and young adults aged 12-29 years suffering from a severe, early-phase psychotic disorder (i.e. within 2 years of treatment). Primary outcome is the rate of combined symptomatic (i.e. Positive and Negative Syndrome Scale (PANSS) criteria) and functional (i.e. Global Assessment of Functioning scale (GAF) ≥ 60 points criterion) remission over at least 6 months at study endpoint. Secondary outcome comprises the comparison of the reduction in the duration of untreated psychosis within the 4-year study duration between integrated care and SC, course of psychopathology, functioning, quality of life, satisfaction with care, cost and quality-adjusted life years (QALYs) in comparison to a historical control group. To the authors' knowledge, this is the first study assessing the efficacy and cost-effectiveness of a combined intervention consisting of early detection strategies and strategies to improve quality of care in both adolescents and young adults with early-phase psychosis. The results will be published in 2016. © 2016 John Wiley & Sons Australia, Ltd.
Dittrich, Katja; Boedeker, Katja; Kluczniok, Dorothea; Jaite, Charlotte; Hindi Attar, Catherine; Fuehrer, Daniel; Herpertz, Sabine C; Brunner, Romuald; Winter, Sibylle Maria; Heinz, Andreas; Roepke, Stefan; Heim, Christine; Bermpohl, Felix
Early life maltreatment (ELM), borderline personality disorder (BPD) and major depressive disorder (MDD) have been shown to increase the potential of abuse. Emotion regulation is an identified mediator for the association of ELM and BPD with abuse potential. Until now, there has been no study to account for the co-occurrence of these risk factors in one analysis, although BPD and MDD are known as common sequelae of ELM. This is paired with a lack of studies investigating the effects of abuse potential on child well-being.AimsOur study aims at (a) disentangling the effects of maternal ELM, MDD and BPD on abuse potential; (b) exploring the role of emotion regulation as a mediator; and (c) testing for intergenerational effects of abuse potential on child psychopathology. The research design included 114 mothers with/without ELM, BPD and MDD in remission and their children, all of which were between 5 and 12 years of age. A path analysis was conducted to investigate the multiple associations between our variables. ELM, MDD and BPD were all associated with abuse potential, with emotion regulation acting as a mediator for BPD and MDD. Furthermore, an elevated abuse potential was related to higher psychopathology in the child. History of ELM as well as the common sequelae, BPD and MDD, pose risks for child abuse. Our findings suggest improvement of emotion regulation as a potential target for intervention programs. These programs should also aim at non-substantiated cases because even an elevated abuse potential affected child mental health.Declaration of interestNone.
Zeng, Yin-Ting; Hwu, Wuh-Liang; Torng, Pao-Chuan; Lee, Ni-Chung; Shieh, Jeng-Yi; Lu, Lu; Chien, Yin-Hsiu
Patients with infantile-onset Pompe disease (IOPD) can be treated by recombinant human acid alpha glucosidase (rhGAA) replacement beginning at birth with excellent survival rates, but they still commonly present with speech disorders. This study investigated the progress of speech disorders in these early-treated patients and ascertained the relationship with treatments. Speech disorders, including hypernasal resonance, articulation disorders, and speech intelligibility, were scored by speech-language pathologists using auditory perception in seven early-treated patients over a period of 6 years. Statistical analysis of the first and last evaluations of the patients was performed with the Wilcoxon signed-rank test. A total of 29 speech samples were analyzed. All the patients suffered from hypernasality, articulation disorder, and impairment in speech intelligibility at the age of 3 years. The conditions were stable, and 2 patients developed normal or near normal speech during follow-up. Speech therapy and a high dose of rhGAA appeared to improve articulation in 6 of the 7 patients (86%, p = 0.028) by decreasing the omission of consonants, which consequently increased speech intelligibility (p = 0.041). Severity of hypernasality greatly reduced only in 2 patients (29%, p = 0.131). Speech disorders were common even in early and successfully treated patients with IOPD; however, aggressive speech therapy and high-dose rhGAA could improve their speech disorders. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Wang, Qingzhong; Shelton, Richard C; Dwivedi, Yogesh
Gene-environment interaction contributes to the risks of psychiatric disorders. Interactions between FKBP5 gene variants and early-life stress may enhance the risk not only for mood disorder, but also for a number of other behavioral phenotypes. The aim of the present study was to review and conduct a meta-analysis on the results from published studies examining interaction between FKBP5 gene variants and early-life stress and their associations with stress-related disorders such as major depression and PTSD. A literature search was conducted using PsychINFO and PubMed databases until May 2017. A total of 14 studies with a pooled total of 15109 participants met the inclusion criteria, the results of which were combined and a meta-analysis was performed using the differences in correlations as the effect measure. Based on literature, rs1360780, rs3800373, and rs9470080 SNPs were selected within the FKBP5 gene and systematic review was conducted. Based on the Comprehensive Meta-Analysis software, no publication bias was detected. Sensitivity analysis and credibility of meta-analysis results also indicated that the analyses were stable. The meta-analysis showed that individuals who carry T allele of rs1360780, C-allele of rs3800373 or T-allele of rs9470080 exposed to early-life trauma had higher risks for depression or PTSD. The effects of ethnicity, age, sex, and different stress measures were not examined due to limited sample size. These results provide strong evidence of interactions between FKBP5 genotypes and early-life stress, which could pose a significant risk factor for stress-associated disorders such as major depression and PTSD. Copyright © 2017 Elsevier B.V. All rights reserved.
Appu, Abhilash P; Arun, Peethambaran; Krishnan, Jishnu K S; Moffett, John R; Namboodiri, Aryan M A
The blood brain barrier (BBB) is critical for maintaining central nervous system (CNS) homeostasis by restricting entry of potentially toxic substances. However, the BBB is a major obstacle in the treatment of neurotoxicity and neurological disorders due to the restrictive nature of the barrier to many medications. Intranasal delivery of active enzymes to the brain has therapeutic potential for the treatment of numerous CNS enzyme deficiency disorders and CNS toxicity caused by chemical threat agents. The aim of this work is to provide a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain with therapeutic bioavailability. We tested intranasal delivery of chloramphenicol acetyltransferase (CAT), a relatively large (75kD) enzyme, in its active form into different regions of the brain. CAT was delivered intranasally to anaesthetized rats and enzyme activity was measured in different regions using a highly specific High Performance Thin Layer Chromatography (HP-TLC)-radiometry coupled assay. Active enzyme reached all examined areas of the brain within 15min (the earliest time point tested). In addition, the yield of enzyme activity in the brain was almost doubled in the brains of rats pre-treated with matrix metalloproteinase-9 (MMP-9). Intranasal administration of active enzymes in conjunction with MMP-9 to the CNS is both rapid and effective. The present results suggest that intranasal enzyme therapy is a promising method for counteracting CNS chemical threat poisoning, as well as for treating CNS enzyme deficiency disorders. Published by Elsevier B.V.
Fellner, María Dolores; Durand, Karina A; Solernou, Veronica; Bosaleh, Andrea; Balbarrey, Ziomara; García de Dávila, María T; Rodríguez, Marcelo; Irazu, Lucía; Alonio, Lidia V; Picconi, María A
High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n=58) and without (n=47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n=6) and without (n=6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47log EBVgEq/10(5) PBMC or 2.30; 2.60; 4.47loggEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.
Stone, Wendy L; McMahon, Caitlin R; Yoder, Paul J; Walden, Tedra A
To compare the early social-communicative development of younger siblings of children with autism spectrum disorders (ASDs) with that of younger siblings of children with typical development, using parental report and child-based measures. Group comparison. Vanderbilt University, between July 1, 2003, and July 31, 2006. Younger siblings of children with ASD (n = 64) and younger siblings of children with typical development (n = 42) between the ages of 12 and 23 months (mean, 16 months). Main Exposure Having a sibling with an ASD. Child-based measures included a cognitive assessment; an interactive screening tool assessing play, imitation, and communication; and a rating of autism symptoms. Parental report measures were an interview of social-communicative interactions and a questionnaire assessing language and communication skills. Younger siblings of children with ASD demonstrated weaker performance in nonverbal problem solving (mean difference [MD], 5.91; 95% confidence interval [CI], 2.48-9.34), directing attention (MD, 0.52; 95% CI, 0.07-0.97), understanding words (MD, 33.30; 95% CI, 3.11-63.48), understanding phrases (MD, 4.56; 95% CI, 1.85-7.27), gesture use (MD, 1.49; 95% CI, 0.51-2.47), and social-communicative interactions with parents (MD, 1.32; 95% CI, 0.27-2.37), and had increased autism symptoms (MD, 2.54; 95% CI, 1.05-4.03), relative to control siblings. A substantial minority of the ASD sibling group exhibited lower performance relative to controls. Significant correlations between child-based measures and parental reports assessing similar constructs were found (r = -0.74 to 0.53; P range, .000-.002). The weaker performance found for children in the ASD sibling group may represent early-emerging features of the broader autism phenotype, thus highlighting the importance of developmental surveillance for younger siblings.
Villain, Hélène; Benkahoul, Aïcha; Birmes, Philippe; Ferry, Barbara; Roullet, Pascal
Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the "city-like" test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans.
Sturm, Dominik; Orr, Brent A; Toprak, Umut H
with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration...
Hyland, Philip; Shevlin, Mark; Elklit, Ask
history of any anxiety and mood disorder, parental history of self-harming behaviour, advanced paternal age, gender, urban dwelling, economic deprivation, family dissolution, and childhood adversity were used to predict diagnosis of both anxiety and mood disorders from ages 10 to 21 years. Results: Binary...... logistic regression analysis showed that being female and a parental history of a mood or anxiety disorder are the strongest predictors of both disorders. Economic deprivation, and family dissolution also increase likelihood of both disorders. Urban dwelling and childhood adversity are predictors...... of anxiety disorders but not mood disorders. Conclusion: Between the ages of 10 and 21 years, anxiety and mood disorders share many common risk factors. However, urban dwelling and childhood adversity appear to be unique predictors of anxiety disorders. Results suggest there is no dominant factor...
Soo Jin Park
Full Text Available Central nervous system (CNS inflammatory demyelinating diseases (IDDs are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS, neuromyelitis optica spectrum disorder (NMOSD, and idiopathic transverse myelitis (ITM. Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls. Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs.
Kramer, Ueli; Keller, Sabine; Caspar, Franz; de Roten, Yves; Despland, Jean-Nicolas; Kolly, Stéphane
Difficulty in emotion regulation is a hallmark feature of patients with borderline personality disorder (BPD). Therefore, change in the frequency of certain patients' coping strategies-aiming at emotion regulation-are among the most promising mechanisms of change in treatments for BPD. In parallel, it was highlighted that therapist responsiveness significantly contributed to outcome across treatment approaches (Stiles, 2009). Based on a randomized controlled trial (Kramer et al., 2014), the present process-outcome mediation analysis aims at examining the patient's early change in frequency of coping strategies-in particular the decrease in behavioral forms of coping-as potential mechanism of change in responsive treatments for BPD. A total of 57 patients with BPD were included in the present analysis, out of whom 27 were randomly assigned to a 10-session psychiatric treatment and 30 to a 10-session psychiatric treatment augmented with the responsive intervention of the motive-oriented therapeutic relationship (Caspar, 2007). The 1st, 5th, and 9th session of each therapy were transcribed and analyzed using the Coping Action Pattern Rating Scale (Perry et al., 2005; 171 sessions analyzed in total), a validated observer-rated method for assessing coping strategies in the therapy process. Psychological distress was assessed using the OQ-45 at intake, after Session 5, and after Session 10. The results confirmed a responsiveness effect associated with the motive-oriented therapeutic relationship and showed a significant decrease in frequency of behavioral forms of coping, F(1, 54) = 3.09, p = .05, d = .56, which was not different between the 2 conditions. In addition, we demonstrated that the early decrease in behavioral forms of coping between Sessions 1 and 5 partially mediated the link between the group assignment and the change in psychological distress between Sessions 5 and 10. These results shed light on the centrality of therapist responsiveness in treatments for
A comprehensive literature stresses a high percentage of severe childhood maltreatment in the history of many psychotically ill patients treated in mental health services. Early childhood abuse seems to be associated among other things with a more severe clinical state, a more chronic course of illness and a more unfavourable psychosocial adaptation. In order not to jump to unwarranted causal conclusions, several conceptual und methodological problems have to be clarified before. From a conceptual perspective psychotic disorders diagnosed according to conventional criteria define only a minor subgroup within a much broader psychosis continuum in general population. Early childhood abuse has to be differentiated according to type, severity, timing, and context. The rates of early childhood abuse are high in general population. The methods of measurement of psychotic symptoms on the one side, of early trauma on the other side have to be critically evaluated. There is an empirically well founded association of childhood maltreatment and psychological and psychosomatic morbidity during adult years in general. In order to establish a potential conditional link also to psychotic disorders, clinical populations have to be compared to adequate control groups at least. A systematic literature search shows a very small number of studies including control groups at all. These studies underline that early childhood abuse may be significantly associated to the risk of psychosis indeed. The conditional role of early childhood abuse, however, has to be investigated only within a multifactorial biopsychosocial model of psychotic illness.
Lutaif, N.A. [Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Palazzo, R. Jr [Departamento de Telemática, Faculdade de Engenharia Elétrica e Computação, Universidade Estadual de Campinas, Campinas, SP (Brazil); Gontijo, J.A.R. [Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil)
Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.
Lutaif, N.A.; Palazzo, R. Jr; Gontijo, J.A.R.
Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile
Full Text Available Both brain structural abnormalities and neurocognitive impairments are core features of schizophrenia. We have previously reported enlargements in subcortical brain structure volumes and impairment of neurocognitive functioning as measured by the MATRICS Cognitive Consensus Battery (MCCB in early onset schizophrenia spectrum disorders (EOS. To our knowledge, no previous study has investigated whether neurocognitive performance and volumetric abnormalities in subcortical brain structures are related in EOS.Twenty-four patients with EOS and 33 healthy controls (HC were included in the study. Relationships between the caudate nucleus, the lateral and fourth ventricles volumes and neurocognitive performance were investigated with multivariate linear regression analyses. Intracranial volume, age, antipsychotic medication and IQ were included as independent predictor-variables.The caudate volume was negatively correlated with verbal learning performance uniquely in the EOS group (r=-.454, p=.034. There were comparable positive correlations between the lateral ventricular volume and the processing speed, attention and reasoning and problem solving domains for both the EOS patients and the healthy controls. Antipsychotic medication was related to ventricular enlargements, but did not affect the brain structure-function relationship.Enlargement of the caudate volume was related to poorer verbal learning performance in patients with EOS. Despite a 32% enlargement of the lateral ventricles in the EOS group, associations to processing speed, attention and reasoning and problem solving were similar for both the EOS and the HC groups.
Boecker-Schlier, Regina; Buchmann, Arlette F.; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M.; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred
Abstract Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. PMID:27694318
Hudac, Caitlin M; DesChamps, Trent D; Arnett, Anne B; Cairney, Brianna E; Ma, Ruqian; Webb, Sara Jane; Bernier, Raphael A
Children with autism spectrum disorder (ASD) exhibit difficulties processing and encoding sensory information in daily life. Cognitive response to environmental change in control individuals is naturally dynamic, meaning it habituates or reduces over time as one becomes accustomed to the deviance. The origin of atypical response to deviance in ASD may relate to differences in this dynamic habituation. The current study of 133 children and young adults with and without ASD examined classic electrophysiological responses (MMN and P3a), as well as temporal patterns of habituation (i.e., N1 and P3a change over time) in response to a passive auditory oddball task. Individuals with ASD showed an overall heightened sensitivity to change as exhibited by greater P3a amplitude to novel sounds. Moreover, youth with ASD showed dynamic ERP differences, including slower attenuation of the N1 response to infrequent tones and the P3a response to novel sounds. Dynamic ERP responses were related to parent ratings of auditory sensory-seeking behaviors, but not general cognition. As the first large-scale study to characterize temporal dynamics of auditory ERPs in ASD, our results provide compelling evidence that heightened response to auditory deviance in ASD is largely driven by early sensitivity and prolonged processing of auditory deviance. Copyright © 2018 Elsevier Inc. All rights reserved.
Haraldsen, I R; Haug, E; Falch, J; Egeland, T; Opjordsmoen, S
Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment at months 3 and 12. The study included 33 EO-GID patients who were approved for sex reassignment and a control group of 122 healthy Norwegians (males, n=77; females, n=45). Male patients (n=12) received an oral dose of 50 mug ethinylestradiol daily for the first 3 months and 100 mug daily thereafter. Female patients (n=21) received 250 mg testosterone enantate intramuscularly every third week. BMD, TBF and TLBM were estimated using dual energy X-ray absorptiometry (DXA). In male patients, the DXA measurements except TBF were significantly lower compared to their same-sex control group at baseline and did not change during treatment. In female patients, the DXA measurements were slightly higher than in same-sex controls at baseline and also remained unchanged during treatment. In conclusion, this study reports that body composition and bone density of EO-GID patients show less pronounced sex differences compared to controls and that bone density was unaffected by cross-sex hormone treatment.
Holz, Nathalie E; Boecker-Schlier, Regina; Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred
Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2-19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years).CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. © The Author (2016). Published by Oxford University Press. For Permissions, please email: email@example.com.
Rachel C. Leung
Full Text Available Social cognition is impaired in autism spectrum disorder (ASD. The ability to perceive and interpret affect is integral to successful social functioning and has an extended developmental course. However, the neural mechanisms underlying emotional face processing in ASD are unclear. Using magnetoencephalography (MEG, the present study explored neural activation during implicit emotional face processing in young adults with and without ASD. Twenty-six young adults with ASD and 26 healthy controls were recruited. Participants indicated the location of a scrambled pattern (target that was presented alongside a happy or angry face. Emotion-related activation sources for each emotion were estimated using the Empirical Bayes Beamformer (pcorr ≤ 0.001 in Statistical Parametric Mapping 12 (SPM12. Emotional faces elicited elevated fusiform, amygdala and anterior insula and reduced anterior cingulate cortex (ACC activity in adults with ASD relative to controls. Within group comparisons revealed that angry vs. happy faces elicited distinct neural activity in typically developing adults; there was no distinction in young adults with ASD. Our data suggest difficulties in affect processing in ASD reflect atypical recruitment of traditional emotional processing areas. These early differences may contribute to difficulties in deriving social reward from faces, ascribing salience to faces, and an immature threat processing system, which collectively could result in deficits in emotional face processing.
Edwards, A; Brebner, C; McCormack, P; MacDougall, C
There is strong evidence that early intervention (EI) can improve outcomes for children with autism spectrum disorder (ASD), and consequently, the importance of EI has been widely promoted to families of children with ASD. However, the perspectives of parents of children with ASD regarding the EI message have not been widely examined. This study used qualitative methods to explore parental perspectives on the EI message. Semi-structured interviews were undertaken with 14 participants from 12 family units to explore the perspectives of parents of children with ASD on the EI message. Thematic analysis was undertaken on the data. Three central themes were constructed following data analysis: (i) parents' initial perceptions of EI following their child's diagnosis with ASD; (ii) the consequences (both positive and negative) of the EI message; and (iii) parents' perspectives on life after EI. The results of this study indicated that parents were acutely aware of the importance of EI, and although this provided parents with hope immediately post-diagnosis, it also placed pressure on parental decision-making regarding which intervention approaches to access for their children with ASD. The results of this study highlight the importance of carefully considering how health messages, specifically the importance of EI, are communicated to families of children with ASD. Furthermore, the findings of this study also highlight the need for allied health professionals to communicate openly with parents about the anticipated outcomes of EI programmes. © 2016 John Wiley & Sons Ltd.
Van de Bittner, Genevieve C; Ricq, Emily L; Hooker, Jacob M
Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test-retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available
The Fifth CNS International Steam Generator Conference was held on November 26-29, 2006 in Toronto, Ontario, Canada. In contrast with other conferences which focus on specific aspects, this conference provided a wide ranging forum on nuclear steam generator technology from life-cycle management to inspection and maintenance, functional and structural performance characteristics to design architecture. The 5th conference has adopted the theme: 'Management of Real-Life Equipment Conditions and Solutions for the Future'. This theme is appropriate at a time of transition in the industry when plants are looking to optimize the performance of existing assets, prevent costly degradation and unavailability, while looking ahead for new steam generator investments in life-extension, replacements and new-build. More than 50 technical papers were presented in sessions that gave an insight to the scope: life management strategies; fouling, cleaning and chemistry; replacement strategies and new build design; materials degradation; condition assessment/fitness for service; inspection advancements and experience; and thermal hydraulic performance
Olino, Thomas M.; Seeley, John R.; Lewinsohn, Peter M.
Conduct disorder (CD) is associated with a number of adverse psychosocial outcomes in adulthood. There is consistent evidence that CD is predictive of antisocial behavior, but mixed evidence that CD is predictive of other externalizing and internalizing disorders. Further, externalizing and internalizing disorders are often associated with similar…
Developmentally Sensitive Diagnostic Criteria for Mental Health Disorders in Early Childhood: The Diagnostic and Statistical Manual of Mental Disorders-IV, the Research Diagnostic Criteria-Preschool Age, and the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood-Revised
Egger, Helen L.; Emde, Robert N.
As the infant mental health field has turned its focus to the presentation, course, and treatment of clinically significant mental health disorders, the need for reliable and valid criteria for identifying and assessing mental health symptoms and disorders in early childhood has become urgent. In this article we offer a critical perspective on…
Lee, In Ho; Kim, Sung Tae; Kim, Hyung-Jin; Kim, Keon Ha; Jeon, Pyoung; Byun, Hong Sik
Purpose: It is difficult to differentiate CNS lymphoma from other tumors such as malignant gliomas, metastases, or meningiomas with conventional MR imaging, because the imaging findings are overlapped between these tumors. The purpose of this study is to investigate the perfusion weighted MR imaging findings of CNS lymphomas and to compare the relative cerebral blood volume ratios between CNS lymphomas and other tumors such as high grade gliomas, metastases, or meningiomas. Materials and methods: We retrospectively reviewed MRI findings and clinical records in 13 patients with pathologically proven CNS lymphoma between January 2006 and November 2008. We evaluated the relative cerebral blood volume ratios of tumor, which were obtained by dividing the values obtained from the normal white matter on MRI. Results: Total 13 patients (M:F = 8:5; age range 46-67 years, mean age 52.3 years) were included. The CNS lymphomas showed relatively low values of maximum relative CBV ratio in most patients regardless of primary or secondary CNS lymphoma. Conclusion: Perfusion weighted image may be helpful in the diagnosis of CNS lymphoma in spite of primary or secondary or B cell or T cell.
Liddelow Shane A
Full Text Available Abstract Tracing the exact origins of modern science can be a difficult but rewarding pursuit. It is possible for the astute reader to follow the background of any subject through the many important surviving texts from the classical and ancient world. While empirical investigations have been described by many since the time of Aristotle and scientific methods have been employed since the Middle Ages, the beginnings of modern science are generally accepted to have originated during the 'scientific revolution' of the 16th and 17th centuries in Europe. The scientific method is so fundamental to modern science that some philosophers consider earlier investigations as 'pre-science'. Notwithstanding this, the insight that can be gained from the study of the beginnings of a subject can prove important in the understanding of work more recently completed. As this journal undergoes an expansion in focus and nomenclature from cerebrospinal fluid (CSF into all barriers of the central nervous system (CNS, this review traces the history of both the blood-CSF and blood-brain barriers from as early as it was possible to find references, to the time when modern concepts were established at the beginning of the 20th century.
Manwaring, Stacy S; Mead, Danielle L; Swineford, Lauren; Thurm, Audrey
Nonverbal communication abilities, including gesture use, are impaired in autism spectrum disorder (ASD). However, little is known about how common gestures may influence or be influenced by other areas of development. To examine the relationships between gesture, fine motor and language in young children with ASD compared with a comparison group using multiple measures and methods in a structural equation modelling framework. Participants included 110 children with ASD and a non-ASD comparison group of 87 children (that included children with developmental delays (DD) or typical development (TD)), from 12 to 48 months of age. A construct of gesture use as measured by the Communication and Symbolic Behavior Scales-Developmental Profile Caregiver Questionnaire (CQ) and the Autism Diagnostic Observation Schedule (ADOS), as well as fine motor from the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales-II (VABS-II) was examined using second-order confirmatory factor analysis (CFA). A series of structural equation models then examined concurrent relationships between the aforementioned latent gesture construct and expressive and receptive language. A series of hierarchical regression analyses was run in a subsample of 36 children with ASD with longitudinal data to determine how gesture factor scores predicted later language outcomes. Across study groups, the gesture CFA model with indicators of gesture use from both the CQ (parent-reported) and ADOS (direct observation), and measures of fine motor provided good fit with all indicators significantly and strongly loading onto one gesture factor. This model of gesture use, controlling for age, was found to correlate strongly with concurrent expressive and receptive language. The correlations between gestures and concurrent language were similar in magnitude in both the ASD and non-ASD groups. In the longitudinal subsample of children with ASD, gestures at time 1 predicted later receptive (but not
Mouthaan, Joanne; Sijbrandij, Marit; de Vries, Giel-Jan; Reitsma, Johannes B; van de Schoot, Rens; Goslings, J Carel; Luitse, Jan S K; Bakker, Fred C; Gersons, Berthold P R; Olff, Miranda
Posttraumatic stress disorder (PTSD) develops in 10-20% of injury patients. We developed a novel, self-guided Internet-based intervention (called Trauma TIPS) based on techniques from cognitive behavioral therapy (CBT) to prevent the onset of PTSD symptoms. To determine whether Trauma TIPS is effective in preventing the onset of PTSD symptoms in injury patients. Adult, level 1 trauma center patients were randomly assigned to receive the fully automated Trauma TIPS Internet intervention (n=151) or to receive no early intervention (n=149). Trauma TIPS consisted of psychoeducation, in vivo exposure, and stress management techniques. Both groups were free to use care as usual (nonprotocolized talks with hospital staff). PTSD symptom severity was assessed at 1, 3, 6, and 12 months post injury with a clinical interview (Clinician-Administered PTSD Scale) by blinded trained interviewers and self-report instrument (Impact of Event Scale-Revised). Secondary outcomes were acute anxiety and arousal (assessed online), self-reported depressive and anxiety symptoms (Hospital Anxiety and Depression Scale), and mental health care utilization. Intervention usage was documented. The mean number of intervention logins was 1.7, SD 2.5, median 1, interquartile range (IQR) 1-2. Thirty-four patients in the intervention group did not log in (22.5%), 63 (41.7%) logged in once, and 54 (35.8%) logged in multiple times (mean 3.6, SD 3.5, median 3, IQR 2-4). On clinician-assessed and self-reported PTSD symptoms, both the intervention and control group showed a significant decrease over time (PInternet-based early intervention in the prevention of PTSD symptoms for an unselected population of injury patients. Moreover, uptake was relatively low since one-fifth of individuals did not log in to the intervention. Future research should therefore focus on innovative strategies to increase intervention usage, for example, adding gameplay, embedding it in a blended care context, and targeting high
The Electronic Navigation Research Institute (ENRI) held its third International Workshop on ATM / CNS in 2013 with the theme of "Drafting the future sky". There is worldwide activity taking place in the research and development of modern air traffic management (ATM) and its enabling technologies in Communication, Navigation and Surveillance (CNS). Pioneering work is necessary to contribute to the global harmonization of air traffic management and control. At this workshop, leading experts in research, industry and academia from around the world met to share their ideas and approaches on ATM/CNS related topics.
Lisyany, N.I.; Liubich, L.D.
Autoimmune hypothesis as to the development of radiation-induced brain injuries stands high among the concepts of the CNS post-radiation damage pathogenesis. To study the changes occurring in a living organism affected by a small-dose radiation due to incorporated radionuclides as well as to create adequate models are of critical importance in the post-Chernobyl period. The effects of chronic small-dose inner radiation on the development of autoimmune responses were evaluated by determining the level of the CNS proteins and protein-induced antibodies to the CNS components. (author)
of estradiol treatment we were able to revert some of these alterations using PI3K/Akt/GSK3. Overall these results demonstrate that synaptic dysfunction following PA might be produced by early changes in the actin organization and long-term misfolding and aggregation of proteins in the PSDs. Therefore, we hypothesize that the synaptic and neuronal cytoskeleton changes induced by PA in the rat CNS could lead to the cellular dysfunction and death in adult animals. Estradiol appears as a new therapeutic tool to slacken the damage induces by perinatal asphyxia on the CNS.
Reinert, Line; Harder, Louis Andreas; Holm, Christian
Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections in neurons, which act as reservoirs of virus for subsequent reactivation......, it is not known what cell type mediates the role of TLR3 in the immunological control of HSV, and it is not known whether TLR3 sensing occurs prior to or after CNS entry. Here, we show that in mice TLR3 provides early control of HSV-2 infection immediately after entry into the CNS by mediating type I IFN...... responses in astrocytes. Tlr3-/- mice were hypersusceptible to HSV-2 infection in the CNS after vaginal inoculation. HSV-2 exhibited broader neurotropism in Tlr3-/- mice than it did in WT mice, with astrocytes being most abundantly infected. Tlr3-/- mice did not exhibit a global defect in innate immune...
Bedford, Rachael; Pickles, Andrew; Lord, Catherine
Motor milestones such as the onset of walking are important developmental markers, not only for later motor skills but also for more widespread social-cognitive development. The aim of the current study was to test whether gross motor abilities, specifically the onset of walking, predicted the subsequent rate of language development in a large cohort of children with autism spectrum disorder (ASD). We ran growth curve models for expressive and receptive language measured at 2, 3, 5 and 9 years in 209 autistic children. Measures of gross motor, visual reception and autism symptoms were collected at the 2 year visit. In Model 1, walking onset was included as a predictor of the slope of language development. Model 2 included a measure of non-verbal IQ and autism symptom severity as covariates. The final model, Model 3, additionally covaried for gross motor ability. In the first model, parent-reported age of walking onset significantly predicted the subsequent rate of language development although the relationship became non-significant when gross motor skill, non-verbal ability and autism severity scores were included (Models 2 & 3). Gross motor score, however, did remain a significant predictor of both expressive and receptive language development. Taken together, the model results provide some evidence that early motor abilities in young children with ASD can have longitudinal cross-domain influences, potentially contributing, in part, to the linguistic difficulties that characterise ASD. Autism Res 2016, 9: 993-1001. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
Bourseul, Jean-Sébastien; Molina, Anais; Lintanf, Mael; Houx, Laetitia; Chaléat-Valayer, Emmanuelle; Pons, Christelle; Brochard, Sylvain
To report current evidence regarding the safety of intramuscular botulinum toxin injection (BTI) in children with orthopedic- and neurologic-related musculoskeletal disorders >2 years of age. PubMed, Cochrane Library, and ScienceDirect, Google Scholar, and Web of Science. Two reviewers independently selected studies based on predetermined inclusion criteria. Data relating to the aim were extracted. Methodologic quality was graded independently by 2 reviewers using the Physiotherapy Evidence Database scale for randomized controlled trials (RCTs) and the Downs and Black evaluation tool for non-RCTs. Level of evidence was determined using the modified Sackett scale. Data of 473 infants were analyzed. Fifty-five infants had cerebral palsy, 112 had obstetric brachial plexus palsy, 257 had clubfoot, and 44 had congenital torticollis. No studies reported any severe adverse event that could be attributed to the BTI. The rate of mild to moderate adverse events reported varied from 5% to 25%. Results regarding efficacy were preliminary, dependent on the pathology, and limited by the small number of studies and their low levels of evidence. BTI is already widely used as an early treatment for this age group. The safety profile of BTI in infants appears similar to that of older children and risks appear more related to the severity of the pathology and the location of the injections than to the toxin itself. Regarding effectiveness, other studies with higher levels of evidence should be carried out for each specific pathology. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Reinwald, Jonathan Rochus; Becker, Robert; Mallien, Anne Stephanie; Falfan-Melgoza, Claudia; Sack, Markus; Clemm von Hohenberg, Christian; Braun, Urs; Cosa Linan, Alejandro; Gass, Natalia; Vasilescu, Andrei-Nicolae; Tollens, Fabian; Lebhardt, Philipp; Pfeiffer, Natascha; Inta, Dragos; Meyer-Lindenberg, Andreas; Gass, Peter; Sartorius, Alexander; Weber-Fahr, Wolfgang
To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for neurodevelopmental psychiatric disorders such as schizophrenia. Although changes in resting-state brain connectivity are a transdiagnostic key finding in neurodevelopmental diseases, a characterization of imaging correlates elicited by early-life social stress is lacking. We performed resting-state functional magnetic resonance imaging of postweaning social isolation rats (N = 23) 9 weeks after isolation. Addressing well-established transdiagnostic connectivity changes of psychiatric disorders, we focused on altered frontal and posterior connectivity using a seed-based approach. Then, we examined changes in regional network architecture and global topology using graph theoretical analysis. Seed-based analyses demonstrated reduced functional connectivity in frontal brain regions and increased functional connectivity in posterior brain regions of postweaning social isolation rats. Graph analyses revealed a shift of the regional architecture, characterized by loss of dominance of frontal regions and emergence of nonfrontal regions, correlating to our behavioral results, and a reduced modularity in isolation-reared rats. Our result of functional connectivity alterations in the frontal brain supports previous investigations postulating social neural circuits, including prefrontal brain regions, as key pathways for risk for mental disorders arising through social stressors. We extend this knowledge by demonstrating more widespread changes of brain network organization elicited by early-life social stress, namely a shift of hubness and dysmodularity. Our results highly resemble core alterations in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and attention-deficit/hyperactivity disorder in humans. Copyright © 2017
Thayer, Zaneta; Barbosa-Leiker, Celestina; McDonell, Michael; Nelson, Lonnie; Buchwald, Dedra; Manson, Spero
Among American Indians, prior research has found associations between early life trauma and the development of post-traumatic stress disorder (PTSD) in adulthood. Given the physiological changes associated with PTSD, early life trauma could indirectly contribute to chronic disease risk. However, the impact of early life trauma on adult physical health in this population has not been previously investigated. We evaluated associations among early life trauma, PTSD, and 13 physiological biomarkers that index cardiovascular, metabolic, neuroendocrine, anthropometric, and immune function in adulthood by conducting correlation and structural equation modeling path analyses (N = 197). Physiological systems were analyzed individually as well as in a composite measure of allostatic load. We found early life trauma was related to PTSD, which in turn was related to elevated allostatic load in adulthood. Among the various components of allostatic load, the neuroendocrine system was the only one significantly related to early life stress and subsequent PTSD development. Changes in allostatic load might reflect adaptive adjustments that maximize short-term survival by enhancing stress reactivity, but at a cost to later health. Interventions should focus on improving access to resources for children who experience early life trauma in order to avoid PTSD and other harmful sequelae. © 2016 Wiley Periodicals, Inc.
Treffert, Darold A
Three conditions -- Hyperlexia (children who read early), Einstein syndrome (children who speak late), and "Blindisms" (in children with impaired vision) -- can present with "autistic-like" symptoms, traits, and behaviors that need to be differentiated from autistic disorder. Careful attention to that critical difference has important epidemiologic, etiologic, treatment, and outcome implications. This paper describes these conditions, makes suggestions for proper identification that can prevent unnecessary worry and distress for parents and other caregivers, and suggests appropriate management.
Fulton, Elizabeth; Eapen, Valsamma; Črnčec, Rudi; Walter, Amelia; Rogers, Sally
The presence of maladaptive behaviors in young people with autism spectrum disorder (ASD) can significantly limit engagement in treatment programs, as well as compromise future educational and vocational opportunities. This study aimed to explore whether the Early Start Denver Model (ESDM) treatment approach reduced maladaptive behaviors in preschool-aged children with ASD in a community-based long day care setting. The level of maladaptive behavior of 38 children with ASD was rated using an ...
Elizabeth eFulton; Elizabeth eFulton; Valsamma eEapen; Valsamma eEapen; Rudi eČrnčec; Amelia eWalter; Amelia eWalter; Sally eRogers
The presence of maladaptive behaviors in young people with Autism Spectrum Disorder (ASD) can significantly limit engagement in treatment programs, as well as compromise future educational and vocational opportunities. This study aimed to explore whether the Early Start Denver Model (ESDM) treatment approach reduced maladaptive behaviors in preschool-aged children with ASD in a community-based long day care setting. The level of maladaptive behavior of 38 children with ASD was rated using an ...
Rodríguez de Lores Arnaiz Georgina
Full Text Available Abstract Background Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP, a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC, known to antagonize the GABA-A postsynaptic receptor subtype. Results We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg and convulsant (7.5 mg/kg doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity. Conclusion Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process
Larsen, Janne Tidselbak; Munk-Olsen, Trine; Bulik, Cynthia M; Thornton, Laura M; Koch, Susanne Vinkel; Mortensen, Preben Bo; Petersen, Liselotte
Previous studies evaluating the association between early childhood adversities and eating disorders have yielded conflicting results. The aim of this study is to examine the association between a range of adversities and risk of anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS) in 495,244 women. In this nationwide, register-based cohort study, nine types of early childhood adversity (family disruption, residential instability, placement in out-of-home care, familial death, parental somatic illness, parental psychiatric illness, parental disability, severe parental criminality, and parental substance use disorder) were defined and exposure during the first 6 years of life was determined. Hazard ratios for eating disorders were calculated using Cox regression. Few adversities were significantly associated with AN, and for each, the presence of the adversity was associated with lower risk for AN. BN, and EDNOS were positively associated with several types of adversities. AN rates were unchanged or reduced by up to 54% by adversities, whereas rates of BN and EDNOS were unchanged or increased by adversities by up to 49 and 89%, respectively. Our findings indicate that childhood adversities appear to be associated with an increased risk of BN and in particular EDNOS, whereas they seem to be either unassociated or associated with a decreased risk of AN. © 2017 Wiley Periodicals, Inc.
Suorsa, Kristina I; Mullins, Alexandria J; Tackett, Alayna P; Reyes, Kristy J Scott; Austin, Paul; Baskin, Laurence; Bernabé, Kerlly; Cheng, Earl; Fried, Allyson; Frimberger, Dominic; Galan, Denise; Gonzalez, Lynette; Greenfield, Saul; Kropp, Bradley; Meyer, Sabrina; Meyer, Theresa; Nokoff, Natalie; Palmer, Blake; Poppas, Dix; Paradis, Alethea; Yerkes, Elizabeth; Wisniewski, Amy B; Mullins, Larry L
We examined the psychosocial characteristics of parents of children with disorders of sex development at early presentation to a disorders of sex development clinic. Parental anxiety, depression, quality of life, illness uncertainty and posttraumatic stress symptoms were assessed. Additionally we evaluated the relationship of assigned child gender to parental outcomes. A total of 51 parents of children with ambiguous or atypical genitalia were recruited from 7 centers specializing in treatment of disorders of sex development. At initial assessment no child had undergone genitoplasty. Parents completed the Cosmetic Appearance Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, SF-36, Parent Perception of Uncertainty Scale and Impact of Event Scale-Revised. A large percentage of parents (54.5%) were dissatisfied with the genital appearance of their child, and a small but significant percentage reported symptoms of anxiety, depression, diminished quality of life, uncertainty and posttraumatic stress. Few gender differences emerged. Although many parents function well, a subset experience significant psychological distress around the time of diagnosis of a disorder of sex development in their child. Early screening to assess the need for psychosocial interventions is warranted. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Torras-Mañá, Montserrat; Guillamón-Valenzuela, Montserrat; Ramírez-Mallafré, Ariadna; Brun-Gasca, Carme; Fornieles-Deu, Albert
Language disorder (LD) is a neurodevelopmental disorder, and early diagnosis has an impact on speech therapy practice. The aim of this work is to test the usefulness of the Cognitive and Language scales of the Bayley-III in the early diagnosis of LD. In a longitudinal study, a clinical sample of 187 children with diagnostic hypothesis of communication disorders at 4.5 years was assessed with the Bayley-III before age 3.5 years and subsequently with other scales of different psychological and psycholinguistic functions. The results indicate that children with LD scored significantly lower than their control groups in all subtests and compounds of the Bayley-III. Additionally, low scores on the Language composite in the Bayley-III predicted lower scores in the Auditory-vocal Channel of the ITPA. A significant correlation was obtained between the Cognitive Scale of the Bayley-III and the General Cognitive Scale of the MSCA and the Mental Processing Composite of the K-ABC. We can draw the conclusion that the Cognitive and Language scales of the Bayley-III are a useful instrument for early diagnosis of LD, and can also discriminate more severe forms of LD.
Lokugamage, A U; Hotopf, M; Hardy, R; Mishra, G; Butterworth, S; Wadsworth, M E J; Kuh, D
Jacobs and Bovasso reported (Psychological Medicine 2000, 30, 669-678) that maternal death in childhood and chronic severe depression in adulthood were associated with subsequent breast cancer. We have examined the effects of parental loss in childhood and psychiatric disorder in adult life on breast cancer risk using a national birth cohort study. Eighty-three cases of breast cancer were diagnosed in a study of 2253 women followed from birth to age 59 years. Cox proportional hazards models were used to test whether breast cancer rates were higher in women who experienced parental death and divorce before age 16, psychiatric disorders between 15 and 32 years, symptoms of anxiety and depression at 36 years, or use of antidepressant medication at 31 or 36 years than in women who did not have these experiences. There was no overall association between parental death, parental divorce or psychiatric disorder and the incidence of breast cancer. There was some evidence that women with more severe psychiatric disorders between the ages of 15 and 32 years were more likely to develop breast cancer early. The interaction between parental divorce and severe psychiatric disorder was non-significant (p=0.1); however, the group who experienced both these events had an increased breast cancer risk compared with those who experienced neither [hazard ratio (HR) 2.64, 95% confidence interval (CI) 1.13-6.19]. Our study does not provide strong support for the hypothesis that early loss or adult psychiatric disorders are associated with breast cancer. A meta-analysis is needed that uses data from all available cohort studies and investigates possible interactive effects on breast cancer risk.
Vad Winkler, Laura; Andersen, Marianne; Hørder, Kirsten
BACKGROUND:: Craniopharyngiomas are slow-growing tumors, which can either be asymptomatic or present themselves with visual, neuropsychiatric or endocrine disturbances. Eating disorders (EDs) are syndromes with unknown etiology, associated with multiple endocrine abnormalities. In pediatric cases...... the possibility of an as yet unidentified structural hypothalamic disorder to be implicated in the etiopathogeny of ED. (c) 2008 by Wiley Periodicals, Inc. Int J Eat Disord, 2009....
Block, Michelle L; Calderón-Garcidueñas, Lilian
Air pollution has been implicated as a chronic source of neuroinflammation and reactive oxygen species (ROS) that produce neuropathology and central nervous system (CNS) disease. Stroke incidence and Alzheimer's and Parkinson's disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain; systemic effects that impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that microglial activation and changes in the blood-brain barrier are key components. Here we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS, culminating in CNS disease.
Jul 8, 2014 ... information that they represent. The extensive ... physiology and behaviour in the wild type and in these mutants .... taste information is processed in the CNS. 2. ..... gene affecting the specificity of the chemosensory neurons of.
Jacinta Nwamaka Nwogu
Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.
Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.
Kristin R Wildsmith
Full Text Available Apolipoprotein E (ApoE is the strongest genetic risk factor for Alzheimer's disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4 each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer's disease (AD. Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS, we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis.
George, Melissa W; Fairchild, Amanda J; Mark Cummings, E; Davies, Patrick T
Disordered eating behaviors, including frequent dieting, unhealthy weight control behaviors (e.g., vomiting and skipping meals for weight loss) and binge eating are prevalent among adolescents. While negative, conflict-ridden family environments have long been implicated as problematic and a contributing factor to the development of disordered eating, few studies have examined the influence of marital conflict exposure in childhood to understand the development of these behaviors in adolescence. The current study investigates the impact of marital conflict, children's emotional insecurity about the marital relationship, and disordered eating behaviors in early adolescence in a prospective, longitudinal study of a community sample of 236 families in Midwest and Northeast regions of the U.S. Full structural mediation analyses utilizing robust latent constructs of marital conflict and emotional insecurity about the marital relationship, support children's emotional insecurity as an explanatory mechanism for the influence of marital conflict on adolescent disordered eating behaviors. Findings are discussed with important implications for the long-term impact of marital conflict and the development of disordered eating in adolescence. Copyright © 2014 Elsevier Ltd. All rights reserved.
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
Zeanah, Charles H.; Gleason, Mary Margaret
Background: Though noted in the clinical literature for more than 50 years, attachment disorders have been studied systematically only recently. In part because of the ubiquity of attachments in humans, determining when aberrant behavior is best explained as an attachment disorder as opposed to insecure attachment has led to some confusion. In…
Skodol, Andrew E.; Bender, Donna S.; Pagano, Maria E.; Shea, M. Tracie; Yen, Shirley; Sanislow, Charles A.; Grilo, Carlos M.; Daversa, Maria T.; Stout, Robert L.; Zanarini, Mary C.; McGlashan, Thomas H.; Gunderson, John G.
Objective--Recent follow-along studies of personality disorders have shown significant improvement in psychopathology over time. The purpose of this study was to prospectively investigate the association between positive childhood experiences related to resiliency and remission from personality disorder. Method--Five hundred twenty patients with…
Gardeitchik, T.; Humphrey, M.; Nation, J.; Boneh, A.
OBJECTIVES: To characterize dietary habits and eating patterns in patients with a urea cycle disorder (UCD), and to identify dietary habits that may serve as clues to lead to earlier diagnosis of these disorders. STUDY DESIGN: This was a retrospective study of clinical and dietary data from hospital
Christiansz, Jessica A.; Gray, Kylie M.; Taffe, John; Tonge, Bruce J.
Changes to the DSM-5 Autism Spectrum Disorder (ASD) criteria raised concerns among parents and practitioners that the criteria may exclude some children with Pervasive Developmental Disorder (PDD). Few studies have examined DSM-5 sensitivity and specificity in children less than 5 years of age. This study evaluated 185 children aged 20-55 months…
Reichow, Brian; Barton, Erin E; Boyd, Brian A; Hume, Kara
The rising prevalence of autism spectrum disorders (ASD) increases the need for evidence-based behavioral treatments to lessen the impact of symptoms on children's functioning. At present, there are no curative or psychopharmacological therapies to effectively treat all symptoms of the disorder. Early intensive behavioral intervention (EIBI), a treatment based on the principles of applied behavior analysis delivered for multiple years at an intensity of 20 to 40 hours per week, is one of the more well-established treatments for ASD. To systematically review the evidence for the effectiveness of EIBI in increasing the functional behaviors and skills of young children with ASD. We searched the following databases on 22 November 2011: CENTRAL (2011 Issue 4), MEDLINE (1948 to November Week 2, 2011), EMBASE (1980 to Week 46, 2011), PsycINFO (1806 to November Week 3, 2011), CINAHL (1937 to current), ERIC (1966 to current), Sociological Abstracts (1952 to current), Social Science Citation Index (1970 to current), WorldCat, metaRegister of Controlled Trials, and Networked Digital Library of Theses and Dissertations. We also searched the reference lists of published papers. Randomized control trials (RCTs), quasi-randomized control trials, or clinical control trials (CCTs) in which EIBI was compared to a no-treatment or treatment-as-usual control condition. Participants must have been less than six years of age at treatment onset and assigned to their study condition prior to commencing treatment. Two authors independently selected and appraised studies for inclusion and assessed the risk of bias in each included study. All outcome data were continuous, from which standardized mean difference effect sizes with small sample correction were calculated. We conducted random-effects meta-analysis where possible, which means we assumed individual studies would provide different estimates of treatment effects. One RCT and four CCTs with a total of 203 participants were included
subjects with a periSylvian HA in this range, all have indications of subtle neurological dysfunction: JLM mild learning disorder; mild dyslexia JS...made available, it is possible that "early intervention " techniques might be developed that could relieve these individuals of their terrible...mild dyslexia , 2) stuttering, 3) central auditory dysfunction, and 4) hyperactivity/ substance addiction. Plante and colleagues (see references) have
James A. McCubbin
Full Text Available Hypertension has been linked to impaired cognitive/CNS function, and some of these changes may precede development of frank essential hypertension. The stress and fatigue of sleep deprivation may exacerbate these cognitive changes in young adults at risk. We hypothesize that individuals at risk for hypertension will show significant declines in cognitive function during a night of sleep deprivation. Fifty-one young adults were recruited for 28-hour total sleep deprivation studies. Hypertension risk was assessed by mildly elevated resting blood pressure and by family history of hypertension. A series of cognitive memory tasks was given at four test sessions across the sleep deprivation period. Although initially comparable in cognitive performance, persons at risk showed larger declines across the night for several indices of working memory, including code substitution, category, and order recall. These results suggest that cognitive/CNS changes may parallel or precede blood pressure dysregulation in the early stages of hypertension development. The role of CNS changes in the etiology of essential hypertension is discussed.
Nicolini, Humberto; López, Yaumara; Genis-Mendoza, Alma D; Manrique, Viana; Lopez-Canovas, Lilia; Niubo, Esperanza; Hernández, Lázaro; Bobes, María A; Riverón, Ana M; López-Casamichana, Mavil; Flores, Julio; Lanzagorta, Nuria; De la Fuente-Sandoval, Camilo; Santana, Daniel
Infection with group A Streptococcus (StrepA) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> meancontrol + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2=5.27, P=0.022, df=1, n=49). The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.
Mouthaan, Joanne; Sijbrandij, Marit; Reitsma, Johannes B; Luitse, Jan S K; Goslings, J Carel; Gersons, Berthold P R; Olff, Miranda
OBJECTIVE: Pharmacological intervention during traumatic memory consolidation has been suggested to prevent posttraumatic stress disorder (PTSD). The aim of this study was to examine the association between prescription of early pharmacotherapy and the risk of developing PTSD symptoms following
Mouthaan, Joanne; Sijbrandij, Marit; Reitsma, Johannes B.; Luitse, Jan S. K.; Goslings, J. Carel; Gersons, Berthold P. R.; Olff, Miranda
Pharmacological intervention during traumatic memory consolidation has been suggested to prevent posttraumatic stress disorder (PTSD). The aim of this study was to examine the association between prescription of early pharmacotherapy and the risk of developing PTSD symptoms following traumatic
Winther, Jo; Carlsson, Anthony; Vance, Alasdair
Oppositional defiant disorder (ODD) or conduct disorder (CD) occurs when children's disruptive and antisocial behaviours start to interfere with their academic, emotional and/or social development. Recently, there has been a considerable investment to implement national school-based early intervention programs to help prevent the onset of ODD/CD. This paper describes the delivery of the Royal Children's Hospital, Child and Adolescent Mental Health Service and Schools Early Action Program: a whole school, multi-level, multidisciplinary approach to address emerging ODD/CD and pre- versus post-delivery assessment in 40 schools over a 4-year period (2007-2010). All children from preparatory to grade 3 (ages 4-10 years) were screened for conduct problems (n = 8546) using the Strengths and Difficulties Questionnaire. Universal, targeted and indicated interventions were delivered in school settings. In total, 304 children participated in the targeted group program where the Child Behaviour Checklist was used as a pre- and post-intervention measure. Cohen's d effect sizes and a reliability change index were calculated to determine clinical significance. Significant reductions in both parent- and teacher-reported internalizing and externalizing symptoms were noted. Parent, teacher and child feedback were very positive. A future randomized controlled trial of the program would address potential placebo and selection bias effects. © 2013 Wiley Publishing Asia Pty Ltd.
Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A.; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C.; Mackay, Clare E.
Abstract See Postuma (doi:10.1093/aww131) for a scientific commentary on this article. Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson’s disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson’s disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson’s disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson’s disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson’s disease and 10 control subjects received 123I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye
Khalifa, Najat; Duggan, Conor; Howard, Rick; Lumsden, John
Early-onset alcohol abuse (EOAA) was previously found to both mediate and moderate the effect of childhood conduct disorder (CD) on adult antisocial behavior (ASB) in an American community sample of young adults (Howard, R., Finn, P. R., Gallagher, J., & Jose, P. (2011). Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behavior. Journal of Forensic Psychiatry and Psychology. Advance online publication. doi:10.1080/14789949.2011.641996). This study tested whether this result would generalize to a British forensic sample comprising 100 male forensic patients with confirmed personality disorder. Results confirmed that those in whom EOAA co-occurred with CD showed the highest level of personality pathology, particularly Cluster B traits and antisocial/borderline comorbidity. Those with co-occurring CD with EOAA, compared with those showing only CD, showed more violence in their criminal history and greater recreational drug use. Regression analysis showed that both EOAA and CD predicted adult ASB when covariates were controlled. Further analysis showed that EOAA significantly mediated but did not moderate the effect of CD on ASB. The failure to demonstrate an exacerbating effect of EOAA on the relationship between CD and ASB likely reflects the high prevalence of CD in this forensic sample. Some implications of these findings are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
Fairweather-Schmidt, A K; Wade, T D
We investigated the genetic and environmental contributions to disordered eating (DE) between early and late adolescence in order to determine whether different sources of heritability and environmental risk contributed to these peak times of emergence of eating disorders. Adolescent female twins from the Australian Twin Registry were interviewed over the telephone with the Eating Disorder Examination (EDE). Data were collected at 12-15 and 16-19 years (wave 1: N = 699, 351 pairs; wave 3: N = 499, 247 pairs). Assessments also involved self-report measures related to negative life events and weight-related peer teasing. Unstandardized estimates from the bivariate Cholesky decomposition model showed both genetic influences and non-shared environmental influences increased over adolescence, but shared environmental influences decreased. While non-shared environmental sources active at ages 12-15 years continued to contribute at 16-19 years, new sources of both additive genetic and non-shared environmental risk were introduced at ages 16-19 years. Weight-related peer teasing in early-mid adolescence predicted increases of DE in later adolescence, while negative life events did not. Two-thirds of the heritable influence contributing to DE in late adolescence was unique to this age group. During late adolescence independent sources of genetic risk, as well as environmental influences are likely to be related in part to peer teasing, appear key antecedents in growth of DE.
Wong, Gloria H Y; Hui, Christy L M; Tang, Jennifer Y M; Chang, Wing-Chung; Chan, Sherry K W; Xu, Jia-Qi; Lin, Jessie J X; Lai, Dik-Chee; Tam, Wendy; Kok, Joy; Chung, Dicky; Hung, S F; Chen, Eric Y H
Hong Kong is among the first few cities in Asia to have implemented early intervention for psychosis in 2001. Substantial changes in psychosis service have since taken place. We reviewed available outcome data in Hong Kong, with reference to the philosophy of early intervention in psychosis, discussing experience and lessons learned from the implementation process, and future opportunities and challenges. Data accumulated in the past decade provided evidence for the benefits and significance of early intervention programmes: patients under the care of early intervention service showed improved functioning, milder symptoms, and fewer hospitalizations and suicides. Early intervention is more cost-effective compared with standard care. Stigma and misconception remains an issue, and public awareness campaigns are underway. In recent years, a critical mass is being formed, and Hong Kong has witnessed the unfolding of public service extension, new projects and organizations, and increasing interest from the community. Several major platforms are in place for coherent efforts, including the public Early Assessment Service for Young people with psychosis (EASY) programme, the Psychosis Studies and Intervention (PSI) research unit, the independent Hong Kong Early Psychosis Intervention Society (EPISO), the Jockey Club Early Psychosis (JCEP) project, and the postgraduate Psychological Medicine (Psychosis Studies) programme. The first decade of early intervention work has been promising; consolidation and further development is needed on many fronts of research, service and education. Copyright Â© 2012 Elsevier B.V. All rights reserved.
Mazlum, Betül; Anlar, Banu; Kalkanoğlu-Sivri, H Serap; Karlı-Oğuz, Kader; Özusta, Şeniz; Ünal, Fatih
Phenylketonuria is one of the most prevalent autosomal recessive hereditary disorders in Turkey. If untreated, it results in severe brain damage and can also be associated with autism in certain patients. We present a three-year old boy who exhibited the symptoms of autism and was subsequently diagnosed with phenylketonuria. This case illustrates that because the majority of autism cases are idiopathic, an occasional patient with a metabolic disorder might be overlooked especially in the era of newborn screening. We also discuss the possible pathogenetic processes leading to autistic symptoms in phenylketonuria, and wish to draw attention to the possibility of cases missed in the screening program because of less than 100% coverage or insufficient food intake before blood sampling. Clinicians should keep in mind the possibility of treatable disorders in children with autism even when such disorders appear unlikely.
Full Text Available As a first step towards discovery of genes expressed from only one allele in the CNS, we used a tiling array assay for DNA sequences that are both methylated and unmethylated (the MAUD assay. We analyzed regulatory regions of the entire mouse brain transcriptome, and found that approximately 10% of the genes assayed showed dual DNA methylation patterns. They include a large subset of genes that display marks of both active and silent, i.e., poised, chromatin during development, consistent with a link between differential DNA methylation and lineage-specific differentiation within the CNS. Sixty-five of the MAUD hits and 57 other genes whose function is of relevance to CNS development and/or disorders were tested for allele-specific expression in F(1 hybrid clonal neural stem cell (NSC lines. Eight MAUD hits and one additional gene showed such expression. They include Lgi1, which causes a subtype of inherited epilepsy that displays autosomal dominance with incomplete penetrance; Gfra2, a receptor for glial cell line-derived neurotrophic factor GDNF that has been linked to kindling epilepsy; Unc5a, a netrin-1 receptor important in neurodevelopment; and Cspg4, a membrane chondroitin sulfate proteoglycan associated with malignant melanoma and astrocytoma in human. Three of the genes, Camk2a, Kcnc4, and Unc5a, show preferential expression of the same allele in all clonal NSC lines tested. The other six genes show a stochastic pattern of monoallelic expression in some NSC lines and bi-allelic expression in others. These results support the estimate that 1-2% of genes expressed in the CNS may be subject to allelic exclusion, and demonstrate that the group includes genes implicated in major disorders of the CNS as well as neurodevelopment.
Barnes, Rachel D; Ivezaj, Valentina; Pittman, Brian P; Grilo, Carlos M
Individuals seeking weight loss treatment have diverse pretreatment weight trajectories, and once enrolled, individuals' response to weight loss treatments also varies greatly and may be influenced by the presence of binge-eating disorder (BED). Reported average weight losses may obscure these considerable differences. This study examined whether BED status and different weight-related change variables are associated with successful weight loss treatment outcomes in a controlled treatment study. Participants (N = 89) with overweight/obesity, with and without BED, participated in a 3-month weight loss trial in primary care with 3- and 12-month follow-ups. We tested the prognostic significance of four weight-related change variables (the last supper, early weight loss, pretreatment weight trajectory, weight suppression) on outcomes (weight loss-overall, weight loss-"subsequent," weight loss during second half of treatment). Early weight loss was positively associated with weight loss-overall at post-treatment, and at 3-month and 12-month follow-up. Early weight loss was positively associated with weight loss-subsequent at post-treatment only. No other weight-related variables were significantly associated with weight loss. Models including BED status and treatment condition were not significant. Participants with early weight loss were more likely to continue losing weight, regardless of BED status or treatment condition. The results highlight the importance of early dedication to weight loss treatment to increase the likelihood of positive outcomes. © 2018 Wiley Periodicals, Inc.
Pedersen, Liselotte; Rasmussen, Kirsten; Elsass, Peter
People with a major mental disorder are at increased risk of committing crimes, especially violent crimes, compared with the general population. Sub-groups have been identified based on age of onset of anti-social or violent behaviour. Mentally disordered offenders with early onset anti-social...
Pedersen, Liselotte; Rasmussen, Kirsten; Elsass, Peter
People with a major mental disorder are at increased risk of committing crimes, especially violent crimes, compared with the general population. Sub-groups have been identified based on age of onset of anti-social or violent behaviour. Mentally disordered offenders with early onset anti-social be...
Ketcheson, Leah; Hauck, Janet; Ulrich, Dale
Despite evidence suggesting one of the earliest indicators of an eventual autism spectrum disorder diagnoses is an early motor delay, there remain very few interventions targeting motor behavior as the primary outcome for young children with autism spectrum disorder. The aim of this pilot study was to measure the efficacy of an intensive motor…
Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John
The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of...
Goldstein, Benjamin I; Carnethon, Mercedes R; Matthews, Karen A; McIntyre, Roger S; Miller, Gregory E; Raghuveer, Geetha; Stoney, Catherine M; Wasiak, Hank; McCrindle, Brian W
In the 2011 "Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents," several medical conditions among youth were identified that predispose to accelerated atherosclerosis and early cardiovascular disease (CVD), and risk stratification and management strategies for youth with these conditions were elaborated. Major depressive disorder (MDD) and bipolar disorder (BD) among youth satisfy the criteria set for, and therefore merit inclusion among, Expert Panel tier II moderate-risk conditions. The combined prevalence of MDD and BD among adolescents in the United States is ≈10%, at least 10 times greater than the prevalence of the existing moderate-risk conditions combined. The high prevalence of MDD and BD underscores the importance of positioning these diseases alongside other pediatric diseases previously identified as moderate risk for CVD. The overall objective of this statement is to increase awareness and recognition of MDD and BD among youth as moderate-risk conditions for early CVD. To achieve this objective, the primary specific aims of this statement are to (1) summarize evidence that MDD and BD are tier II moderate-risk conditions associated with accelerated atherosclerosis and early CVD and (2) position MDD and BD as tier II moderate-risk conditions that require the application of risk stratification and management strategies in accordance with Expert Panel recommendations. In this scientific statement, there is an integration of the various factors that putatively underlie the association of MDD and BD with CVD, including pathophysiological mechanisms, traditional CVD risk factors, behavioral and environmental factors, and psychiatric medications. © 2015 American Heart Association, Inc.
Howard, Richard; Finn, Peter; Jose, Paul; Gallagher, Jennifer
This study tested the hypothesis that adolescent-onset alcohol abuse (AOAA) would both mediate and moderate the effect of childhood conduct disorder on antisocial behaviour in late adolescence and early adulthood. A sample comprising 504 young men and women strategically recruited from the community were grouped using the criteria of the Diagnostic and Statistical Manual (DSM-IV, American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: APA), as follows: neither childhood conduct disorder (CCD) nor alcohol abuse/dependence; CCD but no alcohol abuse or dependence; alcohol abuse/dependence but no CCD; both CCD and alcohol abuse/dependence. The outcome measure was the sum of positive responses to 55 interview items capturing a variety of antisocial behaviours engaged in since age 15. Severity of lifetime alcohol-related and CCD problems served as predictor variables in regression analysis. Antisocial behaviour problems were greatest in individuals with a history of co-occurring conduct disorder (CD) and alcohol abuse/dependence. While CCD was strongly predictive of adult antisocial behaviour, this effect was both mediated and moderated (exacerbated) by AOAA.
Stice, Eric; Presnell, Katherine; Bearman, Sarah Kate
Used interview data from a community study to test whether early menarche partially accounts for increased depression, eating pathology, substance abuse, and comorbid psychopathology among adolescent girls. Found that menarche prior to 11.6 years related to elevated depression and substance abuse. Findings support assertion that early menarche is…
Janvier, Yvette M.; Harris, Jill F.; Coffield, Caroline N.; Louis, Barbara; Xie, Ming; Cidav, Zuleyha; Mandell, David S.
Early diagnosis of autism typically is associated with earlier access to intervention and improved outcomes. Daycares and preschools largely have been ignored as possible venues for early identification. This may be especially important for minority children in the United States who are typically diagnosed with autism later than White children,…
Full Text Available The brain is constantly exposed to external and internal input and to function in an ever-changing environment we are dependent on processes that enable the brain to adapt to new stimuli. Exposure to postnatal environmental stimuli can interfere with vital adaption processes and cause long-term changes in physiological function and behaviour. Early-life alterations in brain function may result in impaired ability to adapt to new situations, in altered sensitivity to challenges later in life and thereby mediate risk or protection for psychopathology such as alcohol use disorders (AUD. In clinical research the studies of mechanisms, mediators and causal relation between early environmental factors and vulnerability to AUD are restricted and attempts are made to find valid animal models for studies of the early-life influence on the brain. This review focuses on rodent models and the effects of adverse and naturalistic conditions on peptide networks within the brain and pituitary gland. Importantly, the consequences of alcohol addiction are not discussed but rather neurobiological alterations that can cause risk consumption and vulnerability to addiction. The article reviews earlier results and includes new data with emphasis on endogenous opioid peptides but also oxytocin and vasopressin. These peptides are vital for developmental processes and it is hypothesized that early-life changes in peptide networks may interfere with neuronal processes and thereby contribute the individual vulnerability for AUD. The summarized results indicate a link between early-life rearing conditions, opioids and ethanol consumption and that the ethanol-induced effects and the treatment with opioid antagonists later in life are dependent on early-life experiences. Endogenous opioids are therefore of interest to further study in the early-life impact on individual differences in vulnerability to AUD and treatment outcome.
Trigg, M.E.; Makuch, R.; Glaubiger, D.
Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS
Ryberg, Kayce H
The Early Start Denver Model (ESDM) is a manualized comprehensive therapy for toddlers with autism spectrum disorder. It emphasizes interpersonal engagement through synchrony, rhythms, and reciprocity to decrease symptom severity and accelerate cognitive, social-emotional, and language development. To systematically review evidence regarding the use of the ESDM as an intervention for young children with autism spectrum disorder. PubMed, Scopus, Web of Science, Embase, and CINAHL were searched from 2010-2015 using predetermined inclusion criteria. Study methodology, participant characteristics, and outcomes were evaluated and quality of evidence was assigned. Eight articles met inclusion criteria and consisted of two randomized controlled trials, four controlled trials, and two observational cohort studies. Evidence quality ranged from low to high. The ESDM is an effective intervention that improves cognition, language, and adaptive behavior. ESDM strategies delivered in community group settings and in the home by parents have potential to be efficacious and feasible. © The Author(s) 2015.
Rohrer, Lisa M.; Cicchetti, Dante; Rogosch, Fred A.; Toth, Sheree L.; Maughan, Angeline
Research has shown that children of depressed mothers are at risk for problems in a variety of developmental domains; however, little is known about the effects of maternal depression on children’s emerging understanding of false beliefs. In this study, three false belief tasks were administered to five-year-old children whose mothers had either met criteria for major depressive disorder within the first 20 months of the child’s life (n = 91) or had never been depressed (n = 50). Significant difficulties in performance were found among the children of depressed mothers, especially those whose mothers had experienced early and recent recurrent depressive disorder. Regardless of diagnostic status, children whose mothers exhibited negativity during problem-solving tasks administered at an earlier developmental period also were less likely to demonstrate false belief understanding. These effects remained even after child verbal ability was controlled. PMID:21244156
Rohrer, Lisa M; Cicchetti, Dante; Rogosch, Fred A; Toth, Sheree L; Maughan, Angeline
Research has shown that children of depressed mothers are at risk for problems in a variety of developmental domains; however, little is known about the effects of maternal depression on children's emerging understanding of false beliefs. In this study, 3 false belief tasks were administered to 5-year-old children whose mothers had either met criteria for major depressive disorder within the first 20 months of the child's life (n = 91) or had never been depressed (n = 50). Significant difficulties in performance were found among the children of depressed mothers, especially those whose mothers had experienced early and recent recurrent depressive disorder. Regardless of diagnostic status, children whose mothers exhibited negativity during problem-solving tasks administered at an earlier developmental period also were less likely to demonstrate false belief understanding. These effects remained even after child verbal ability was controlled.
Hlavnička, Jan; Čmejla, Roman; Tykalová, Tereza; Šonka, Karel; Růžička, Evžen; Rusz, Jan
For generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson's disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration. We compared speech recordings of 50 subjects with rapid eye movement sleep behaviour disorder (RBD), 30 newly diagnosed, untreated PD patients and 50 healthy controls, and showed that subliminal parkinsonian speech deficits can be reliably captured even in RBD patients, which are at high risk of developing PD or other synucleinopathies. Thus, automated vocal analysis should soon be able to contribute to screening and diagnostic procedures for prodromal parkinsonian neurodegeneration in natural environments.
Pira, Shamira; Durr, Georges; Pawliuk, Nicole; Joober, Ridha; Malla, Ashok
Specialized early intervention services for first-episode psychosis should treat a proportion of patients without using inpatient beds. This study compared such service users by their initial mode of treatment before entry-inpatient (N=157) or outpatient (N=102). On entry to a Montreal early intervention service, the groups were compared on baseline clinical and functional variables and on hospitalizations during two years of treatment. Initial presentation at an emergency service, shorter duration of untreated psychosis, lower functioning level, and aggressive and bizarre behavior were associated with the inpatient entry mode to early intervention services. During follow-up, individuals entering as inpatients spent more days hospitalized than those entering as outpatients, and their time to rehospitalization was shorter. Results suggest that entry into early intervention services via the hospital emergency department and presentation with behavioral and functional disturbances were more predictive than core psychotic symptoms of hospital inpatient status on referral to an early intervention service.
Viikari-Juntura, Eira; Kausto, Johanna; Shiri, Rahman; Kaila-Kangas, Leena; Takala, Esa-Pekka; Karppinen, Jaro; Miranda, Helena; Luukkonen, Ritva; Martimo, Kari-Pekka
The purpose of this study was to assess the effects of early part-time sick leave on return to work (RTW) and sickness absence among patients with musculoskeletal disorders. A randomized controlled trial was conducted in six occupational health units of medium- and large-size enterprises. Patients aged 18-60 years with musculoskeletal disorders (N=63) unable to perform their regular work were randomly allocated to part- or full-time sick leave. In the former group, workload was reduced by restricting work time by about a half. Remaining work tasks were modified when necessary, as specified in a "fit note" from the physician. The main outcomes were time to return to regular work activities and sickness absence during 12-month follow-up. Time to RTW sustained for ≥4 weeks was shorter in the intervention group (median 12 versus 20 days, P=0.10). Hazard ratio of RTW adjusted for age was 1.60 [95% confidence interval (95% CI) 0.98-2.63] and 1.76 (95% CI 1.21-2.56) after further adjustment for pain interference with sleep and previous sickness absence at baseline. Total sickness absence during the 12-month follow-up was about 20% lower in the intervention than the control group. Compliance with the intervention was high with no discontinuations of part-time sick leave due to musculoskeletal reasons. Early part-time sick leave may provide a faster and more sustainable return to regular duties than full-time sick leave among patients with musculoskeletal disorders. This is the first study to show that work participation can be safely increased with early part-time sick leave.
Background Coagulase-negative staphylococci (CNS) cause usually subclinical or mild clinical bovine mastitis, which often remains persistent. Symptoms are usually mild, mostly only comprising slight changes in the appearance of milk and possibly slight swelling. However, clinical mastitis with severe signs has also been reported. The reasons for the differences in clinical expression are largely unknown. Macrophages play an important role in the innate immunity of the udder. This study examined phagocytosis and killing by mouse macrophage cells of three CNS species: Staphylococcus chromogenes (15 isolates), Staphylococcus agnetis (6 isolates) and Staphylococcus simulans (15 isolates). Staphylococcus aureus (7 isolates) was also included as a control. Results All the studied CNS species were phagocytosed by macrophages, but S. simulans resisted phagocytosis more effectively than the other CNS species. Only S. chromogenes was substantially killed by macrophages. Significant variations between isolates were seen in both phagocytosis and killing by macrophages and were more common in the killing assays. Significant differences between single CNS species and S. aureus were observed in both assays. Conclusion This study demonstrated that differences in the phagocytosis and killing of mastitis-causing staphylococci by macrophages exist at both the species and isolate level. PMID:24207012
Bolton, Patrick F; Golding, Jean; Emond, Alan; Steer, Colin D
To chart the emergence of precursors and early signs of autism spectrum disorder (ASD) and autistic traits in the Avon Longitudinal Study of Parents and Children, a prospective longitudinal cohort study of the surviving offspring of 14,541 pregnant women from southwestern England with an expected delivery date between April 1991 and December 1992. Parents' contemporaneous reports of their infant's development (241 questionnaire responses collected up to 30 months of age) were examined in relation to the diagnosis of autism spectrum disorder by age 11 years (n = 86) and a measure of autistic traits, derived by factor analysis. Among the children later diagnosed with ASD, concerns about vision and hearing were more often reported in the first year, and differences in social, communication, and fine motor skills were evident from 6 months of age. Repetitive behaviors and differences in play, imitation, and feeding habits were reported in the second year. Differences in temperament emerged at 24 months of age and bowel habit by 30 months. All of these early signs were strongly associated with the presence of autistic traits in the rest of the population and these differences were often evident in the first year of development. Over the first 30 months of development, the best predictors of both later ASD and autistic traits included the Social Achievement and Communication scores from the Denver Developmental Screening Test, measures of communicative skills (Vocabulary and Combines Words) from the MacArthur Infant Communicative Development Inventories, and a repetitive behavior score. Precursors, early signs, and other developmental differences were reported in the first year of development among children from the general population who later developed autism spectrum disorder and subtler autistic traits. Other differences emerged and unfolded as development progressed. The findings confirm the long-held suspicion that early differences underscore the multifaceted
Sgandurra, Giuseppina; Bartalena, Laura; Cioni, Giovanni
BACKGROUND: Preterm infants are at risk for neurodevelopmental disorders, including motor, cognitive or behavioural problems, which may potentially be modified by early intervention. The EU CareToy Project Consortium (http://www.caretoy.eu) has developed a new modular system for intensive...... parents will sign a written informed consent for participation, will be randomized in CareToy training and control groups at baseline (T0). CareToy group will perform four weeks of personalized activities with the CareToy system, customized by the rehabilitation staff. The control group will continue...
Humphreys, Betsy P.
Universal developmental screening during pediatric well child care detects early delays in development and is a critical gateway to early intervention for young children at risk for Autism Spectrum Disorders (ASD). Developmental screening practices are highly variable, and few studies have examined screening utilization for children at risk for…
Developmentally sensitive diagnostic criteria for mental health disorders in early childhood: the diagnostic and statistical manual of mental disorders-IV, the research diagnostic criteria-preschool age, and the diagnostic classification of mental health and developmental disorders of infancy and early childhood-revised.
Egger, Helen L; Emde, Robert N
As the infant mental health field has turned its focus to the presentation, course, and treatment of clinically significant mental health disorders, the need for reliable and valid criteria for identifying and assessing mental health symptoms and disorders in early childhood has become urgent. In this article we offer a critical perspective on diagnostic classification of mental health disorders in young children. We place the issue of early childhood diagnosis within the context of classification of psychopathology at other ages and describe, in some detail, diagnostic classifications that have been developed specifically for young children, including the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-3R; ZERO TO THREE, 2005), a diagnostic classification for mental health symptoms and disorders in infants, toddlers, and preschoolers. We briefly outline the role of diagnostic classification in clinical assessment and treatment planning. Last, we review the limitations of current approaches to the diagnostic classification of mental health disorders in young children. PsycINFO Database Record (c) 2010 APA, all rights reserved.
Miller, Meghan; Young, Gregory S; Hutman, Ted; Johnson, Scott; Schwichtenberg, A J; Ozonoff, Sally
We evaluated early pragmatic language skills in preschool-age siblings of children with autism spectrum disorder (ASD), and examined correspondence between pragmatic language impairments and general language difficulties, autism symptomatology, and clinical outcomes. Participants were younger siblings of children with ASD (high-risk, n = 188) or typical development (low-risk, n = 119) who were part of a prospective study of infants at risk for ASD; siblings without ASD outcomes were included in analyses. Pragmatic language skills were measured via the Language Use Inventory (LUI). At 36 months, the high-risk group had significantly lower parent-rated pragmatic language scores than the low-risk group. When defining pragmatic language impairment (PLI) as scores below the 10(th) percentile on the LUI, 35% of the high-risk group was identified with PLI versus 10% of the low-risk group. Children with PLI had higher rates of general language impairment (16%), defined as scores below the 10(th) percentile on the Receptive or Expressive Language subscales of the Mullen Scales of Early Learning, relative to those without PLI (3%), but most did not evidence general language impairments. Children with PLI had significantly higher ADOS scores than those without PLI and had higher rates of clinician-rated atypical clinical best estimate outcomes (49%) relative to those without PLI (15%). Pragmatic language problems are present in some siblings of children with ASD as early as 36 months of age. As the new DSM-5 diagnosis of Social (Pragmatic) Communication Disorder (SCD) is thought to occur more frequently in family members of individuals with ASD, it is possible that some of these siblings will meet criteria for SCD as they get older. Close monitoring of early pragmatic language development in young children at familial risk for ASD is warranted. © 2014 Association for Child and Adolescent Mental Health.
Moor, Stephanie; Crowe, Marie; Luty, Sue; Carter, Janet; Joyce, Peter R
The age of the first episode of illness in Bipolar Disorder has been shown to be an important predictor of outcome with early onset, particularly onset before puberty, associated with greater comorbidity, a poorer quality of life and greatest impairment in functioning. Baseline data from a psychotherapy study was used to examine the prevalence of other comorbid psychiatric conditions and the impact of onset at an early age on both self harming behaviour and suicide attempts in young people with Bipolar Disorder. This study of 100 adolescents and young adults (aged 15-36 years) with Bipolar Disorder showed that comorbid conditions were very common, even at the start of their bipolar illness. Comorbidity increased as the age of onset decreased with very early onset (self harmed and attempted suicide with high lethal intent. Self harming behaviour was predicted by having a lifetime diagnoses of Borderline Personality Disorder and Panic Disorder along with an early age of onset of Bipolar Disorder. In contrast, previous suicide attempts were predicted by greater comorbidity and not by very early (<13 years) age of onset. Copyright © 2011 Elsevier B.V. All rights reserved.
Tsuchiya, Kenji; Agerbo, Esben; Mortensen, Preben Bo
of a conditional logistic regression analysis. RESULTS: Among 947 subjects with bipolar disorder and 47,350 controls, those having experienced the parental suicide were significantly associated with an increased risk for BPD (incidence rate ratios: 1.83 [95% confidence interval: 1.07 to 3.12] for paternal suicide......, 3.44 [1.97 to 6.00] for maternal suicide), whereas the non-suicidal death of parents showed no such association. Those having experienced maternal suicide at some point before reaching 10 years of age were seven times as likely to develop bipolar disorder. LIMITATIONS: The cohort members were...
van Boxtel, Geert J.M.; Cluitmans, Pierre J.M.; Raymann, Roy J.E.M.; Ouwerkerk, Martin; Denissen, Ad J.M.; Dekker, Marian K.J.; Sitskoorn, Margriet M.; Vermetten, E.; Germain, A.; Neylan, T.C.
Measures of heart rate variability (HRV) are sensitive indices of autonomic nervous system functioning, capable of distinguishing activity of its two constituent branches, the sympathetic and parasympathetic nervous systems. As such, these measures are possibly useful as early markers of
Farr, O M; Ko, B-J; Joung, K E; Zaichenko, L; Usher, N; Tsoukas, M; Thakkar, B; Davis, C R; Crowell, J A; Mantzoros, C S
There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular disease. However, whether and how these interact is not clear. We analyzed data from a cross-sectional and longitudinal study to determine how PTSD severity influences obesity, insulin sensitivity, and key measures and biomarkers of cardiovascular risk. We then looked at how PTSD and early life adversity may interact to impact these same outcomes. PTSD severity is associated with increasing risk of obesity, diabetes, and cardiovascular disease, with higher symptoms correlating with higher values of BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin sensitivity. PTSD and early life adversity have an additive effect on these metabolic outcomes. The longitudinal study confirmed findings from the cross sectional study and showed that fat mass, leptin, CRP, sICAM-1, and sTNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk. Copyright © 2015 Elsevier B.V. All rights reserved.
Alerie Guzman De La Fuente
Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.
Hilton, Brett J; Bradke, Frank
In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. Here, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS. © 2017. Published by The Company of Biologists Ltd.
Makinodan, Manabu; Iwata, Keiko; Ikawa, Daisuke; Yamashita, Yasunori; Yamamuro, Kazuhiko; Toritsuka, Michihiro; Kimoto, Sohei; Okumura, Kazuki; Yamauchi, Takahira; Yoshino, Hiroki; Tsujii, Masatsugu; Sugiyama, Toshiro; Tsuchiya, Kenji; Mori, Norio; Matsuzaki, Hideo; Kishimoto, Toshifumi
Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired social interaction, poor communication skills, and repetitive/restrictive behaviors. Elevated blood levels of pro-inflammatory cytokines have been reported in subjects with autism spectrum disorder. On the other hand, early childhood adverse experience also increases blood levels of these cytokines. Since social experience of children with autism spectrum disorder is generally unlike to typically developing children, we hypothesized that social interaction during childhood contribute to pro-inflammatory cytokine expression in subjects with autism spectrum disorder. We compared revised Autism Diagnostic Interview scores and expression levels of pro-inflammatory cytokines in peripheral blood mononuclear cells of subjects with autism spectrum disorder (n = 30). The score of domain A on the revised Autism Diagnostic Interview, indicating social interaction impairment in early childhood, was negatively correlated with tumor necrosis factor-α mRNA expression level in peripheral blood mononuclear cells but not interleukin-1β or -6. Consistently, tumor necrosis factor-α mRNA expression was markedly low in subjects with autism spectrum disorder compared to typically developing children who presumably experienced the regular levels of social interaction. These findings suggest that the low blood levels of tumor necrosis factor-α mRNA in subjects with autism spectrum disorder might be due to impaired social interaction in early childhood. Copyright © 2016 Elsevier Ltd. All rights reserved.
Westwood, Thomas D., E-mail: firstname.lastname@example.org [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Hogan, Celia, E-mail: email@example.com [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom); Julyan, Peter J., E-mail: Peter.Julyan@christie.nhs.uk [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Coutts, Glyn, E-mail: Glyn.Coutts@christie.nhs.uk [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Bonington, Suzie, E-mail: firstname.lastname@example.org [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Carrington, Bernadette, E-mail: Bernadette.Carrington@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Taylor, Ben, E-mail: Ben.email@example.com [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Khoo, Saye, E-mail: S.H.Khoo@liverpool.ac.uk [Department of Infectious Diseases and Tropical Medicine, Royal Liverpool Hospital, Liverpool (United Kingdom); Bonington, Alec, E-mail: Alec.Bonington@pat.nhs.uk [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom)
Background and purpose: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. Methods: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. Results: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. Conclusion: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.
Westwood, Thomas D.; Hogan, Celia; Julyan, Peter J.; Coutts, Glyn; Bonington, Suzie; Carrington, Bernadette; Taylor, Ben; Khoo, Saye; Bonington, Alec
Background and purpose: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. Methods: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. Results: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. Conclusion: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort
Gonenc, Atilla; Frazier, Jean A.; Crowley, David J.; Moore, Constance M.
Objective: Transverse relaxation time (T2) imaging provides the opportunity to examine membrane fluidity, which can affect a number of cellular functions. The objective of the present work was to examine T2 abnormalities in children with unmodified DSM-IV-TR bipolar disorder (BD) in bilateral cingulate-paracingulate (CPC) white matter. Method: A…
Vissenberg, R.; van den Boogaard, E.; van Wely, M.; van der Post, J. A.; Fliers, E.; Bisschop, P. H.; Goddijn, M.
Thyroid disorders are associated with pregnancy complications. Universal screening is currently not recommended because of a lack of evidence on the effectiveness of treatment. Women with hyperthyroidism and hypothyroidism evidently require treatment but this is less clear for women with subclinical
Jung, Jaehee; Forbes, Gordon B.
Multiple measures of body dissatisfaction and behaviors associated with disordered eating were studied in 258 White girls, 223 White boys, 106 Black girls, and 82 Black boys. All participants were unpaid volunteers between the ages of 12 and 15 attending six middle schools in Delaware and Maryland. On two self-ideal figure drawing discrepancy…
Post, Robert M.; Leverich, Gabriele S.; Kupka, Ralph W.; Keck, Paul E.; McElroy, Susan L.; Altshuler, Lori L.; Frye, Mark A.; Luckenbaugh, David A.; Rowe, Michael; Grunze, Heinz; Suppes, Trisha; Nolen, Willem A.
Objective: We examined the influence of age at onset of illness and the delay in time to first treatment on morbidity in adulthood. Method: 529 adult outpatients with a mean age of 42 years, who entered our research network from 1996 through 2001 and who were diagnosed with bipolar disorder
Kushner, Nicole Blake
With the increasing prevalence of autism diagnoses, large percentage of diagnosed individuals with comorbid language difficulties, and negative effects of these difficulties on language development and overall functioning, research on language acquisition in children diagnosed with autism spectrum disorder is essential. The current study used data…
Kay, Catherine; Green, Jonathan
Reactive Attachment Disorder (RAD) remains one of the least evidence-based areas of DSM and ICD nosology. Recent evidence from severely deprived institutional samples has informed review of RAD criteria for DSM-V; however, this data is not necessarily generalizable to expectable child environments in the developed world. We provide the first…
Holz, N.E.; Boecker-Schlier, R.; Buchmann, A.F.; Blomeyer, D.; Jennen-Steinmetz, C.; Baumeister, S.; Plichta, M.M.; Cattrell, A.; Schumann, G.; Esser, G.; Schmidt, M.; Buitelaar, J.K.; Meyer-Lindenberg, A.; Banaschewski, T.; Brandeis, D.; Laucht, M.
Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At
Scruggs, Thomas E.; And Others
Sixteen studies were analyzed that employed single-subject designs focusing on conduct disorders in preschoolers. Results indicated that reinforcement produced most positive outcomes, followed by punishment, timeout, and differential attention. Subject characteristics such as sex, handicapping condition, and target behavior typically bore little…
Wehman, Paul H.; Schall, Carol M.; McDonough, Jennifer; Kregel, John; Brooke, Valerie; Molinelli, Alissa; Ham, Whitney; Graham, Carolyn W.; Riehle, J. Erin; Collins, Holly T.; Thiss, Weston
For most youth with autism spectrum disorders (ASD), employment upon graduation from high school or college is elusive. Employment rates are reported in many studies to be very low despite many years of intensive special education services. This paper presented the preliminary results of a randomized clinical trial of Project SEARCH plus ASD…
Mouthaan, Joanne; Sijbrandij, Marit; de Vries, Giel-Jan; Reitsma, Johannes B.; van de Schoot, Rens; Goslings, J. Carel; Luitse, Jan S. K.; Bakker, Fred C.; Gersons, Berthold P. R.; Olff, Miranda
Background: Posttraumatic stress disorder (PTSD) develops in 10-20% of injury patients. We developed a novel, self-guided Internet-based intervention (called Trauma TIPS) based on techniques from cognitive behavioral therapy (CBT) to prevent the onset of PTSD symptoms. Objective: To determine
Mouthaan, J.; Sijbrandij, M.; de Vries, G.J.; Reitsma, J.B.; van de Schoot, R.; Goslings, J.C.; Luitse, J.S.K.; Bakker, F.C.; Gersons, B.P.R.; Olff, M.
Background: Posttraumatic stress disorder (PTSD) develops in 10-20% of injury patients. We developed a novel, self-guided Internet-based intervention (called Trauma TIPS) based on techniques from cognitive behavioral therapy (CBT) to prevent the onset of PTSD symptoms. Objective: To determine
Sijbrandij, Marit; Olff, Miranda; Opmeer, Brent C.; Carlier, Ingrid V. E.; Gersons, Berthold P. R.
Background: This study examined the accuracy of the 17-item. Dutch version of the Davidson Trauma Scale (DTS) and the four-item SPAN (Startle, Physiological Arousal, Anger and Numbness) to detect survivors at risk for posttraumatic stress disorder (PTSD) within the first 2 weeks after the trauma.
Zander, Eric; Bölte, Sven
The possible effect of the DSM-5 impairment criterion on diagnosing autism spectrum disorder (ASD) in young children was examined in 127 children aged 20-47 months with a DSM-IV-TR clinical consensus diagnosis of ASD. The composite score of the Vineland Adaptive Behavior Scales (VABS) served as a proxy for the DSM-5 impairment criterion. When…
Bishop, Somer L.; Farmer, Cristan; Thurm, Audrey
Nonverbal IQ (NVIQ) was examined in 84 individuals with autism spectrum disorder (ASD) followed from age 2 to 19. Most adults who scored in the range of intellectual disability also received scores below 70 as children, and the majority of adults with scores in the average range had scored in this range by age 3. However, within the lower ranges…
Falter, Christine M.; Braeutigam, Sven; Nathan, Roger; Carrington, Sarah; Bailey, Anthony J.
We compared judgements of the simultaneity or asynchrony of visual stimuli in individuals with autism spectrum disorders (ASD) and typically-developing controls using Magnetoencephalography (MEG). Two vertical bars were presented simultaneously or non-simultaneously with two different stimulus onset
Turner, Hannah; Marshall, Emily; Wood, Francesca; Stopa, Lusia; Waller, Glenn
Whilst studies have consistently identified early symptom reduction as an important predictor of treatment outcome, the impact of early change on common comorbid features has not been investigated. This study of CBT for eating disorders explored patterns of early change in eating pathology and longer-term change in personality pathology, anxiety and depression. It also explored the impact of early change in eating pathology on overall change in personality pathology, anxiety and depression. Participants were 179 adults diagnosed with eating disorders who were offered a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment and following the 6th session. They also completed measures of personality disorder cognitions, anxiety and depression at the start and end of treatment. There were significant changes in eating pathology over the first six sessions of treatment. Significant improvements were also seen in personality disorder pathology, anxiety and depression by the end of therapy. Effect sizes were medium to large for both completer and intention to treat analyses. Early changes in eating pathology were associated with later changes in common comorbid features, with early reduction in restraint being a key predictor. These findings demonstrate that early symptom change can be achieved in CBT for eating disorders when delivered in routine clinical practice. Such change has long-term benefits that go beyond the domain of eating pathology, enhancing change in personality pathology, anxiety and depression. Copyright © 2015 Elsevier Ltd. All rights reserved.
Krug, I; Villarejo, C; Jiménez-Murcia, S; Perpiñá, C; Vilarrasa, N; Granero, R; Cebolla, A; Botella, C; Montserrat-Gil de Bernabe, M; Penelo, E; Casella, S; Islam, M A; Orekhova, E; Casanueva, F F; Karwautz, A; Menchón, J M; Treasure, J; Fernández-Aranda, F
This study aimed to examine whether there is an association between individual, social and family influences and dysfunctional eating patterns early in life and the likelihood of developing a subsequent underweight eating disorder (ED) or obesity. The total sample comprised 152 individuals (underweight ED, n = 45; obese patients, n = 65; healthy controls; n = 42) from Barcelona, Spain. The Cross-Cultural Questionnaire (CCQ) was used to assess early eating influences as well as individual and family eating patterns and attitudes towards food. Even though a few shared eating influences emerged for both groups, unique factors were also observed. Whereas relationship with friends, teasing about eating habits by family members and the mass media were of specific relevance to the underweight ED group, the patient's own physical appearance, body dissatisfaction, teasing about eating habits by friends, teasing about body shape by family members and dysfunctional eating patterns were unique to obesity. Overlapping environmental risk factors provide evidence for integral prevention and intervention approaches that simultaneously tackle a range of weight-related problems. The unique factors might be important for targeting high-risk individuals. Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.
Knappe, Susanne; Beesdo-Baum, Katja; Wittchen, Hans-Ulrich
Within the last decade, social anxiety disorder (SAD) has been identified as a highly prevalent and burdensome disorder. Both the characterization of its symptomatology and effective treatment options are widely documented. Studies particularly indicate that SAD aggregates in families and has its onset in early adolescence. Given the family as an important context for children's cognitive, emotional and behavioural development, familial risk factors could be expected to significantly contribute to the reliable detection of populations at risk for SAD. Reviewing studies on familial risk factors for SAD argues for the importance of parental psychopathology and unfavourable family environment, but also denotes to several shortcomings such as cross-sectional designs, short follow-up periods, diverging methodologies and the focus on isolated factors. Using a prospective longitudinal study that covers the high-risk period for SAD, including a broader spectrum of putative risk factors may help to overcome many of the methodological limitations. This review sets out to develop a more family-oriented approach for predicting the onset and maintenance of SAD that may be fruitful to derive targeted prevention and early intervention in SAD.
B. K. Bansal
Full Text Available Aim: The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. Materials and Methods: The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana and those of subclinical mastitis collected during routine screening of state dairy farms, were subjected to microbial culture. Identification of CNS organisms was done by standard biochemical tests. Antibiotic sensitivity testing, based on 30 antibiotics belonging to 12 groups, was done on 58 randomly selected CNS isolates (clinical isolates: 41, subclinical isolates: 17. Results: Isolates were highly susceptible to chloramphenicol (98.3%, gentamicin (93.1%, streptomycin (91.4%, linezolid (91.4%, ceftixozime (87.9%, cloxacillin (86.2%, clotrimazole (86.2%, bacitracin (86.2%, enrofloxacin (84.5% and ceftrioxone + tazobactum (70.7%, while resistance was observed against amoxicillin (77.6%, penicillin (75.9%, ampicillin (74.1% and cefoperazone (51.7%. Overall, isolates from clinical cases of mastitis had a higher resistance than subclinical isolates. Conclusion: CNS isolates were susceptible to chloramphenicol, gentamicin and streptomycin, while higher resistance was recorded against routinely used penicillin group.
Bansal, B K; Gupta, D K; Shafi, T A; Sharma, S
The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS) strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana and those of subclinical mastitis collected during routine screening of state dairy farms, were subjected to microbial culture. Identification of CNS organisms was done by standard biochemical tests. Antibiotic sensitivity testing, based on 30 antibiotics belonging to 12 groups, was done on 58 randomly selected CNS isolates (clinical isolates: 41, subclinical isolates: 17). Isolates were highly susceptible to chloramphenicol (98.3%), gentamicin (93.1%), streptomycin (91.4%), linezolid (91.4%), ceftixozime (87.9%), cloxacillin (86.2%), clotrimazole (86.2%), bacitracin (86.2%), enrofloxacin (84.5%) and ceftrioxone + tazobactum (70.7%), while resistance was observed against amoxicillin (77.6%), penicillin (75.9%), ampicillin (74.1%) and cefoperazone (51.7%). Overall, isolates from clinical cases of mastitis had a higher resistance than subclinical isolates. CNS isolates were susceptible to chloramphenicol, gentamicin and streptomycin, while higher resistance was recorded against routinely used penicillin group.
B. K. Bansal; D. K. Gupta; T. A. Shafi; S. Sharma
Aim: The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS) strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. Materials and Methods: The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences Univer...
Crespin, Graciela; Laznik, Marie-Christine; Cherif Idrissi El Ganouni, Oussama; Sarradet, Jean-Louis; Bauby, Colette; Dandres, Anne-Marie; Ruiz, Emeline; Bursztejn, Claude; Xavier, Jean; Falissard, Bruno; Bodeau, Nicolas; Cohen, David; Saint-Georges, Catherine
Background The need for early treatment of autism spectrum disorders (ASD) necessitates early screening. Very few tools have been prospectively tested with infants of less than 12 months of age. The PREAUT grid is based on dyadic assessment through interaction and shared emotion and showed good metrics for predicting ASD in very-high-risk infants with West syndrome. Methods We assessed the ability of the PREAUT grid to predict ASD in low-risk individuals by prospectively following and screening 12,179 infants with the PREAUT grid at four (PREAUT-4) and nine (PREAUT-9) months of age. A sample of 4,835 toddlers completed the Checklist for Autism in Toddlers (CHAT) at 24 months (CHAT-24) of age. Children who were positive at one screening (N = 100) were proposed a clinical assessment (including the Children Autism Rating Scale, a Developmental Quotient, and an ICD-10-based clinical diagnosis if appropriate) in the third year of life. A randomly selected sample of 1,100 individuals who were negative at all screenings was followed by the PMI team from three to five years of age to identify prospective false negative cases. The clinical outcome was available for 45% (N = 45) of positive children and 52.6% (N = 579) of negative children. Results Of the 100 children who screened positive, 45 received a diagnosis at follow-up. Among those receiving a diagnosis, 22 were healthy, 10 were diagnosed with ASD, seven with intellectual disability (ID), and six had another developmental disorder. Thus, 50% of infants positive at one screening subsequently received a neurodevelopmental diagnosis. The PREAUT grid scores were significantly associated with medium and high ASD risk status on the CHAT at 24 months (odds ratio of 12.1 (95%CI: 3.0–36.8), p screening instruments increased the Se but not PPV estimates [PREAUT and CHAT combined: Se = 67.9 to 77.7%, PPV = 19.0 to 28.0%]. Conclusions The PREAUT grid can contribute to very early detection of ASD and its combination with the
Slade, Tim; Swift, Wendy; Mewton, Louise; Kypri, Kypros; Lynskey, Michael T; Butterworth, Peter; Tibbetts, Joel; McCraw, Stacey; Upton, Emily
Harmful alcohol consumption, particularly alcohol use disorder (AUD), is a worldwide health priority, contributing substantially to global morbidity and mortality. The peak age of onset of AUD is 18-24, thus a deeper understanding of the young adult experience is vital if we are to identify modifiable risk factors and intervene early in the developmental course of this disabling disorder. Critical unanswered questions include: How soon after drinking initiation do AUD symptoms begin to emerge? Which symptoms come first? Do the symptoms unfold in a predictable pattern? In what ways do the emerging symptoms interact with individual, peer, family and environmental risk factors to impact on the transition to disorder? The proposed RADAR study will examine the prospective development of AUD symptoms over the young adulthood (18-24) years. We will capitalise on an existing cohort of 1911 community-based adolescents who were recruited at age 13 and have completed a baseline and five annual follow-up assessments as part of an observational cohort study. We will interview these adolescents every 6 months between the ages of 19 and 23 to derive monthly histories of both alcohol use and AUD symptomatology, along with a comprehensive battery of risk and protective factor scales hypothesised to predict the emergence and course of AUD. The results of this study will inform the natural history of AUD and will be used to identify specific targets for prevention and early intervention of AUD. Ethical approval has already been granted for the study (UNSW HREC 10144). We will disseminate the results of the study through published manuscripts, conferences and seminar presentations. Data used in published manuscripts will be made available through a suitable online repository (eg, Dryad-datadryad.org). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly
Brown, Amy; McClelland, Jessica; Boysen, Elena; Mountford, Victoria; Glennon, Danielle; Schmidt, Ulrike
Eating disorders (EDs) are disabling disorders, predominantly affecting adolescents and young adults. Untreated symptoms have lasting effects on brain, body and behaviour. Care pathway-related barriers often prevent early detection and treatment of ED. The aim of this study was to assess the feasibility and acceptability of FREED (First Episode and Rapid Early Intervention for Eating Disorder), a novel service for young people (aged 18-25 years) with recent ED onset (≤3 years), embedded in a specialist adult National Health Service ED service. Specifically, we assessed the impact of FREED on duration of time until specialist service contact (DUSC), duration of untreated ED (DUED) and wait-times for assessment and treatment compared with patients seen earlier in our service. Acceptability of FREED was also assessed. Sixty individuals were recruited from September 2014 to August 2015. Fifty-one of these were compared with 89 patients seen earlier. FREED patients, from areas with minimal National Health Service gatekeeping (14/51), had markedly shorter DUSC and DUED than controls (DUSC: 12.4 months vs. 16.2 months; DUED 13.0 months vs. 19.1 months), whereas those with complex gatekeeping (37/51) had shorter DUED (17.7 months), but longer DUSC (16.9 months) than controls. FREED patients waited significantly less time for both assessment and treatment than controls, had significantly better treatment uptake and were highly satisfied with the process of starting treatment. FREED is a feasible and acceptable service which successfully reduced waiting times. Reductions in DUSC and DUED depend on gatekeeping arrangements. More research is required to establish clinical outcomes of FREED. © 2016 John Wiley & Sons Australia, Ltd.
van Meijel, Els P M; Gigengack, Maj R; Verlinden, Eva; Opmeer, Brent C; Heij, Hugo A; Goslings, J Carel; Bloemers, Frank W; Luitse, Jan S K; Boer, Frits; Grootenhuis, Martha A; Lindauer, Ramón J L
Children and their parents are at risk of posttraumatic stress disorder (PTSD) following injury due to pediatric accidental trauma. Screening could help predict those at greatest risk and provide an opportunity for monitoring so that early intervention may be provided. The purpose of this study was to evaluate the Screening Tool for Early Predictors of Posttraumatic Stress Disorder (STEPP) in a mixed-trauma sample in a non-English speaking country (the Netherlands). Children aged 8-18 and one of their parents were recruited in two academic level I trauma centers. The STEPP was assessed in 161 children (mean age 13.9 years) and 156 parents within one week of the accident. Three months later, clinical diagnoses and symptoms of PTSD were assessed in 147 children and 135 parents. We used the Anxiety Disorders Interview Schedule for DSM-IV - Child and Parent version, the Children's Revised Impact of Event Scale and the Impact of Event Scale-Revised. Receiver Operating Characteristic analyses were performed to estimate the Areas Under the Curve as a measure of performance and to determine the optimal cut-off score in our sample. Sensitivity, specificity, positive and negative predictive values were calculated. The aim was to maximize both sensitivity and negative predictive values. PTSD was diagnosed in 12% of the children; 10% of their parents scored above the cut-off point for PTSD. At the originally recommended cut-off scores (4 for children, 3 for parents), the sensitivity in our sample was 41% for children and 54% for parents. Negative predictive values were 92% for both groups. Adjusting the cut-off scores to 2 improved sensitivity to 82% for children and 92% for parents, with negative predictive values of 92% and 96%, respectively. With adjusted cut-off scores, the STEPP performed well: 82% of the children and 92% of the parents with a subsequent positive diagnosis were identified correctly. Special attention in the screening procedure is required because of a
Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel
Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.
Cao, Jianqin; Liu, Quanying; Li, Yang; Yang, Jun; Gu, Ruolei; Liang, Jin; Qi, Yanyan; Wu, Haiyan; Liu, Xun
Previous studies of patients with social anxiety have demonstrated abnormal early processing of facial stimuli in social contexts. In other words, patients with social anxiety disorder (SAD) tend to exhibit enhanced early facial processing when compared to healthy controls. Few studies have examined the temporal electrophysiological event-related potential (ERP)-indexed profiles when an individual with SAD compares faces to objects in SAD. Systematic comparisons of ERPs to facial/object stimuli before and after therapy are also lacking. We used a passive visual detection paradigm with upright and inverted faces/objects, which are known to elicit early P1 and N170 components, to study abnormal early face processing and subsequent improvements in this measure in patients with SAD. Seventeen patients with SAD and 17 matched control participants performed a passive visual detection paradigm task while undergoing EEG. The healthy controls were compared to patients with SAD pre-therapy to test the hypothesis that patients with SAD have early hypervigilance to facial cues. We compared patients with SAD before and after therapy to test the hypothesis that the early hypervigilance to facial cues in patients with SAD can be alleviated. Compared to healthy control (HC) participants, patients with SAD had more robust P1-N170 slope but no amplitude effects in response to both upright and inverted faces and objects. Interestingly, we found that patients with SAD had reduced P1 responses to all objects and faces after therapy, but had selectively reduced N170 responses to faces, and especially inverted faces. Interestingly, the slope from P1 to N170 in patients with SAD was flatter post-therapy than pre-therapy. Furthermore, the amplitude of N170 evoked by the facial stimuli was correlated with scores on the interaction anxiousness scale (IAS) after therapy. Our results did not provide electrophysiological support for the early hypervigilance hypothesis in SAD to faces, but
Full Text Available The article, based on the analysis of contemporary scientific literature, presented data on the etiology, pathogenesis, clinical features of cognitive epileptiform disintegration — a special version of autism spectrum disorders. The authors proposed a diagnostic algorithm of this condition in children on the basis of comprehensive clinical examination using brain MRI, EEG monitoring during activity and sleep. MRI identified specific changes in brain structure (macrocephaly, cerebellar hyperplasia, hypoplasia of the corpus callosum, hypoplasia of the thalamus, and others. and specific epileptiform activity on EEG during activity and sleep (changes the focal character in the fronto-central and left temporal areas in the absence or infrequent epileptic seizures, reduction of inhibitory neurotransmitter GABA in the blood 2–3 times. The developed methods enable timely diagnosis to diagnose cognitive epileptiform disintegration with autistic spectrum disorders and appoint pathogenetic treatment with drugs neurometabolic and neuroprotective action, and anticonvulsants.
Raknim, Paweeya; Lan, Kun-Chan
Diagnosing brain disorders, such as Parkinson's disease (PD) or Alzheimer's disease, is often difficult, especially in the early stages. Moreover, it has been estimated that nearly 40% of people with PD may not be diagnosed. Traditionally, the diagnosis of neurological disorders, such as PD, often required a doctor to observe the patient over time to recognize signs of rigidity in movement. The pedestrian dead reckoning (PDR) system is a self-contained technique that has been widely used for indoor localization. In this work we propose a PDR-based method to continuously monitor and record the patient's gait characteristics using a smartphone. Seventeen patients were studied over a period of 1 year. During the year it became apparent that 1 of the patients was actually developing PD. To the best of our knowledge, our work is the first attempt to use sensors in a smartphone to help identify patients in their early stages of neurological disease. On average, the accuracy of our step length estimation was about 98%. Using a binary classification method-namely, support vector machine-we carried out a case study and showed that it was feasible to identify changes in the walking patterns of a PD patient with an accuracy of 94%. Using 1 year of gait trace data obtained from the users' phones, our work provides a first step to experimentally show the possibility of applying smartphone sensor data to provide early warnings to potential PD patients to encourage them to seek medical assistance and thus help doctors diagnose this disease earlier.
Lahiri, Debomoy K.; Sokol, Deborah K.; Erickson, Craig; Ray, Balmiki; Ho, Chang Y.; Maloney, Bryan
Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer’s disease (AD) associated amyloid-β precursor protein (APP), especially its neuroprotective processing product, secrete...
Essig, M.; Giesel, F.; Le-Huu, M.; Stieltjes, B.; Tengg, H. von; Weber, M.-A.
Today there are several indications for cerebral perfusion MRI. The major indications routinely used in increasing numbers of imaging centers include cerebrovascular disease, tumor imaging and recently psychiatric disorders. Perfusion MRI is based on the injection of a gadolinium chelate and the rapid acquisition of images as the bolus of contrast agent passes through the blood vessels in the brain. The contrast agent causes a signal change; this signal change over time can be analysed to measure cerebral hemodynamics. The quality of brain perfusion studies is very dependent on the contrast agent used: a robust and strong signal decrease with a compact bolus is needed. MultiHance (gadobenate dimeglumine, Gd-BOPTA) is the first of a new class of paramagnetic MR contrast agents with a weak affinity for serum proteins. Due to the interaction of Gd-BOPTA with serum albumin, MultiHance presents with significantly higher T1- and T2-relaxivities enabling a sharper bolus profile. This article reviews the indications of perfusion MRI and the performance of MultiHance in MR perfusion of different diseases. Previous studies using perfusion MRI for a variety of purposes required the use of double dose of contrast agent to achieve a sufficiently large signal drop to enable the acquisition of a clear input function and the calculation of perfusion rCBV and rCBF maps of adequate quality. Recent studies with Multi-Hance suggest that only a single dose of this agent is needed to cause a signal drop of about 30% which is sufficient to allow the calculation of high quality rCBV and rCBF maps. (orig.)
Watson, Hunna J.; Von Holle, Ann; Hamer, Robert M.; Berg, Cecilie Knoph; Torgersen, Leila; Magnus, Per; Stoltenberg, Camilla; Sullivan, Patrick; Reichborn-Kjennerud, Ted; Bulik, Cynthia M.
Background The objective of this study was to validate previously published rates of remission, continuation, and incidence of broadly defined eating disorders during pregnancy. The previous rate modeling was done by our group (Bulik et al. 2007) and yielded participants halfway into recruitment of the planned 100,000 pregnancies in the Norwegian Mother and Child (MoBa) Cohort at the Norwegian Institute of Public Health. This study aimed to internally validate the findings with the completed cohort. Methods 77267 pregnant women enrolled at 17 weeks gestation between 2001 and 2009 were included. Participants were split into a “training” sample (n=41243) based on participants in the MoBa version 2 dataset of the original study and a “validation” sample (n=36024) comprising individuals in the MoBa version 5 dataset that were not in the original study (Bulik et al. 2007). Internal validation of all original rate models involved fitting a calibration model to compare model parameters between the “training” and “validation” samples as well as bootstrap estimates of bias in the entire version 5 dataset. Results Remission, continuation, and incidence estimates from the “training” sample remained stable when evaluated via a split sample validation procedure. Pre-pregnancy prevalence estimates in the “validation” sample were 0.1% for anorexia nervosa, 1.0% for bulimia nervosa (BN), 3.3% for binge eating disorder (BED), and 0.1% for purging disorder (EDNOS-P). In early pregnancy, estimates were 0.2% for BN, 4.8% for BED, and eating disorders during pregnancy. Eating disorders during pregnancy were relatively common, occurring in nearly 1 in every 20 women, although almost all were cases of BED. Pregnancy was a window of remission from BN but a window of vulnerability for onset and continuation of BED. Training to detect the signs and symptoms of eating disorders by obstetricians/gynecologists and interventions to enhance pregnancy and neonatal outcomes
Flor, Herta; Nikolajsen, Lone; Jensen, Troels Staehelin
might be a phenomenon of the CNS that is related to plastic changes at several levels of the neuraxis and especially the cortex. Here, we discuss the evidence for putative pathophysiological mechanisms with an emphasis on central, and in particular cortical, changes. We cite both animal and human...
S. Grisariu (Sigal); B. Avni (Batia); T.T. Batchelor (Tracy); M.J. van den Bent (Martin); F. Bokstein (Felix); D. Schiff (David); O. Kuittinen (Outi); M.C. Chamberlain (Marc C.); P. Roth (Patrick); A. Nemets (Anatoly); E. Shalom (Edna); D. Ben-Yehuda (Dina); T. Siegal (Tali)
textabstractNeurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%.
, their receptors and neurotrophins (TGFb, TGFb-Receptor, bFGF, bFGF-Receptor, VEGF, NT-3, NT-4/5, NGF); angiogenesis; and growth cone formation. Hence, MT-I+II enhance CNS tissue repair as seen clearly after the cryogenic injury, after which MT-I+II promote substitution of the necrotic lesion cavity with a glial...
One of the most important events during central nervous system (CNS) development is the communication between cells. Cell-to-cell signaling implicates the interaction between a signaling molecules (or ligands) and their receptors. Ligand-receptor interaction is a tightly regulated process and is
Bek, V.; Pribylova, O.; Abrahamova, J.; Hynieova, H.; Hrodek, O.
The prophylactic treatment of the CNS was conducted by cobalt teletherapy of the cranium and by intrathecal application of MTX after the induction of primary remission in 70 children with acute leukemia throughout 5 years up to the end of 1978. The method of the combined radio- and chemoprophylaxis of the CNS was being changed during the years, especially as far as the radiation dose for the cranium was concerned. A detailed analysis made in a group of 59 children with the minimum interval of 18 months from the beginning of the treatment showed the best results after the application of a dose of 24 Gy/3 weeks. Following this procedure the relapse of leukemia in the CNS occurred in 9% only, whereas on the application of doses of 20 Gy and lower it occurred in 35 to 40%. On the whole 24 out of 59 children, i.e. 41%, are surviving, 35 children, i.e. 59%, died. Mostly complete, but only temporary, epilation was an invariable consequence of the irradiation of the cranium. The somnolence syndrome was only sporadically observed. It cannot be excluded, however, that some of its forms in patients discharged from hospital escaped attention. No case was recorded of serious impairment of the CNS of the leukoencephalopathic type. Up to now the psychomotor, intellectual and emotional development of the surviving children has been normal. (author)
Skutle, Arvid; Bu, Eli Torild Hellandsjø; Jellestad, Finn Konow; van Emmerik-van Oortmerssen, Katelijne; Dom, Geert; Verspreet, Sofie; Carpentier, Pieter Jan; Ramos-Quiroga, Josep Antoni; Franck, Johan; Konstenius, Maija; Kaye, Sharlene; Demetrovics, Zsolt; Barta, Csaba; Fatséas, Melina; Auriacombe, Marc; Johnson, Brian; Faraone, Stephen V; Levin, Frances R; Allsop, Steve; Carruthers, Susan; Schoevers, Robert A; Koeter, Maarten W J; van den Brink, Wim; Moggi, Franz; Møller, Merete; van de Glind, Geurt
The prevalence of ADHD among patients with substance use disorder (SUD) is substantial. This study addressed the following research questions: Are early developmental, temperamental and educational problems overrepresented among SUD patients with ADHD compared to SUD patients without ADHD? Do this comorbid group receive early help for their ADHD, and are there signs of self-medicating with illicit central stimulants? An international, multi-centre cross-sectional study was carried out involving seven European countries, with 1205 patients in treatment for SUD. The mean age was 40 years and 27% of the sample was female. All participants were interviewed with the Mini International Neuropsychiatric Interview Plus and the Conners' Adult ADHD Diagnostic Interview for DSM-IV. SUD patients with ADHD ( n = 196; 16.3% of the total sample) had a significantly slower infant development than SUD patients without ADHD ( n = 1,009; 83.4%), had greater problems controlling their temperament, and had lower educational attainment. Only 24 (12%) of the current ADHD positive patients had been diagnosed and treated during childhood and/or adolescence. Finally, SUD patients with ADHD were more likely to have central stimulants or cannabis as their primary substance of abuse, whereas alcohol use was more likely to be the primary substance of abuse in SUD patients without ADHD. The results emphasize the importance of early identification of ADHD and targeted interventions in the health and school system, as well as in the addiction field.
Zendarski, Nardia; Sciberras, Emma; Mensah, Fiona; Hiscock, Harriet
Examine academic achievement of students with attention-deficit hyperactivity disorder (ADHD) during the early high school period and identify potentially modifiable risk factors for low achievement. Data were collected through surveys (adolescent, parent, and teacher) and direct assessment of Australian adolescents (12-15 yr; n = 130) with ADHD in early high school (i.e., US middle and high school grades). Academic achievement outcomes were measured by linking to individual performance on the National Assessment Program-Literacy and Numeracy (NAPLAN) tests, direct assessment of reading and math, and teacher report of academic competence. Linear regression models examined associations between adolescent, parent/family, and school factors and NAPLAN domain scores. Students with ADHD had lower NAPLAN scores on all domains and fewer met minimum academic standards in comparison with state benchmarks. The poorest results were for persuasive writing. Poor achievement was associated with lower intelligence quotient across all academic domains. Adolescent inattention, bullying, poor family management, male sex, and attending a low socioeconomic status school were associated with lower achievement on specific domains. Students with ADHD are at increased academic risk during the middle school and early high school period. In addition to academic support, interventions targeting modifiable factors including inattention, bullying, and poor family management may improve academic achievement across this critical period.
Lin, Qiong-Xi; Wu, Gui-Hua; Zhang, Ling; Wang, Zeng-Jian; Pan, Ning; Xu, Cai-Juan; Jing, Jin; Jin, Yu
To explore the recognition ability and abnormal processing characteristics to basic emotional faces in the early phase in children with autism spectrum disorders (ASD). Photos of Chinese static faces with four basic emotions (fearful, happy, angry and sad) were used as stimulus. Twenty-five ASD children and twenty-two age- and gender-matched typical developed children (normal controls) were asked to match the emotional faces with words. Event-related potential (ERP) data were recorded concurrently. N170 latencies for total emotion and fearful face in the left temporal region were faster than in the right one in normal controls (P<0.05), but the results were not noted in ASD children. Further, N170 latencies in the left temporal region of ASD children were slower than normal controls for total emotion, fearful and happy faces (P<0.05), and their N170 latencies in the right temporal region were prone to slower than normal controls for angry and fearful faces. The holistic perception speed of emotional faces in the early cognitive processing phase in ASD children is slower than normal controls. The lateralized response in the early phase of recognizing emotional faces may be aberrant in children with ASD.
Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Hastrup, Lene Halling; Hjorthøj, Carsten; Nordentoft, Merete
The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants were dichotomized based on DUP, treatment delay, and time from first symptom until start of SEI treatment. The groups were analyzed with regard to treatment response on psychopathology, level of functioning, and cognitive functioning. The participants with a short DUP had a tendency to respond better to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment for participants with a short total treatment delay could mean that prolonged SEI treatment is more beneficial than treatment as usual (TAU) so long as it is provided in the early years of illness and not just in the early years after diagnosis. THE EARLIER THE BETTER: The duration of untreated psychosis influences the long-term outcomes of treatment. Nikolai Albert, at the Copenhagen Mental Health Centre, and a team of Danish researchers have investigated the effects of a specialized early intervention program (OPUS) in 400 patients diagnosed with schizophrenia spectrum disorders and compared the effects of OPUS after two and five years. Their findings suggest that five years of specialized early intervention was most beneficial when the total duration from symptom start to
Bavle, Abhishek A; Lin, Frank Y; Parsons, D Williams
Recent advances in genome-scale sequencing methods have resulted in a significant increase in our understanding of the biology of human cancers. When applied to pediatric central nervous system (CNS) tumors, these remarkable technological breakthroughs have facilitated the molecular characterization of multiple tumor types, provided new insights into the genetic basis of these cancers, and prompted innovative strategies that are changing the management paradigm in pediatric neuro-oncology. Genomic tests have begun to affect medical decision making in a number of ways, from delineating histopathologically similar tumor types into distinct molecular subgroups that correlate with clinical characteristics, to guiding the addition of novel therapeutic agents for patients with high-risk or poor-prognosis tumors, or alternatively, reducing treatment intensity for those with a favorable prognosis. Genomic sequencing has also had a significant impact on translational research strategies in pediatric CNS tumors, resulting in wide-ranging applications that have the potential to direct the rational preclinical screening of novel therapeutic agents, shed light on tumor heterogeneity and evolution, and highlight differences (or similarities) between pediatric and adult CNS tumors. Finally, in addition to allowing the identification of somatic (tumor-specific) mutations, the analysis of patient-matched constitutional (germline) DNA has facilitated the detection of pathogenic germline alterations in cancer genes in patients with CNS tumors, with critical implications for genetic counseling and tumor surveillance strategies for children with familial predisposition syndromes. As our understanding of the molecular landscape of pediatric CNS tumors continues to advance, innovative applications of genomic sequencing hold significant promise for further improving the care of children with these cancers.
Full Text Available Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.
Foulds, James A; Boden, Joseph M; Newton-Howes, Giles M; Mulder, Roger T; Horwood, L John
There has been a great deal of evidence showing that high novelty seeking (NS) is a risk factor for the development of substance use disorders (SUDs). However, the possible causal role of NS in SUDs is unconfirmed. The aim of this study was to examine the associations between NS at age 16 and SUDs from ages 18 to 35 years, net of a series of covariate factors. Longitudinal study of a birth cohort. Christchurch, New Zealand. General community sample with sample sizes ranging from n = 1011 (age 21) to n = 962 (age 35). The Composite International Diagnostic Interview was used to derive DSM-IV diagnoses of alcohol, nicotine, cannabis and other illicit SUDs at four time intervals from ages 18 to 35. NS was measured at age 16 using the Tridimensional Personality Questionnaire. An increase in NS was associated with increases in the prevalence of all four SUDs at age 18-35. Following adjustment for a broad range of covariate factors, estimated effect sizes (odds ratios) were reducing in magnitude, but remained moderate to large. Adjusted odds ratios of SUDs for the highest NS quartile compared to with the lowest were 2.0 [95% confidence interval (CI) = 1.5, 2.7] for alcohol; 1.8 (95% CI = 1.3, 2.7) for nicotine; 3.6 (95% CI = 2.4, 5.6) for cannabis and 5.1 (95% CI = 2.9, 9.2) for other illicit substances. The association between high novelty seeking and substance use disorders is not explained by common underlying individual factors and environmental exposures. This is consistent with the view that novelty seeking may play a causal role in the development of substance use disorders. © 2017 Society for the Study of Addiction.
Peluso, Michael J; Spudich, Serena
The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.
Benjet, Corina; Borges, Guilherme; Méndez, Enrique; Albor, Yesica; Casanova, Leticia; Orozco, Ricardo; Curiel, Teresa; Fleiz, Clara; Medina-Mora, María Elena
Half of mental disorders have their first onset before adulthood when the presence of a disorder may be particularly disruptive to developmental milestones. Retrospective prevalence estimates have been shown to underestimate the burden of mental illness and scarce data are available on the incidence of disorders throughout the adolescent period, especially in developing countries. Thus, the objective was to determine the incidence of mental disorders in an 8-year period from adolescence to young adulthood, onset of service use and their predictors in a Mexican cohort. 1071 respondents from a representative two-wave panel sample participated in the Mexican Adolescent Mental Health Survey in 2005 and in the follow-up survey in 2013. Disorders were evaluated with the World Mental Health Composite International Diagnostic Interview. 37.9% experienced the onset of a psychiatric disorder and 28.4% sought services for the first time. Substance use disorders had the greatest incidence, followed by mood and behavior disorders, anxiety disorders and lastly eating disorders. Sex, age, school dropout, childhood adversities and prior mental disorders predicted the onset of new disorders. Being female, having more educated parents and most classes of disorder predicted first time service use. These findings contribute to a paradigm shift in conceptions of mental disorder similar to how we think of common physical afflictions as near universal experiences across the life course, but less frequent at any given moment. Adolescents are particularly vulnerable. Therefore, public health policy should focus on early universal promotion of positive mental health and structural determinants of mental health.
Hudson, J. L.; Dodd, Helen F.
Background: To inform early intervention practice, the present research examines how child anxiety, behavioural inhibition, maternal overinvolvement, maternal negativity, mother-child attachment and maternal anxiety, as assessed at age four, predict anxiety at age nine.\\ud \\ud Method: 202 children (102 behaviourally inhibited and 100 behaviourally uninhibited) aged 3–4 years were initially recruited and the predictors outlined above were assessed. Diagnostic assessments, using the Anxiety Dis...
Silva,Daniela Polo Camargo da; Lopez,Priscila Suman; Ribeiro,Georgea Espíndola; Luna,Marcos Otávio de Mesquita; Lyra,João César; Montovani,Jair Cortez
INTRODUCTION: Early diagnosis of hearing loss minimizes its impact on child development. We studied factors that influence the effectiveness of screening programs.OBJECTIVE: To investigate the relationship between gender, weight at birth, gestational age, risk factors for hearing loss, venue for newborn hearing screening and "pass" and "fail" results in the retest.METHODS: Prospective cohort study was carried out in a tertiary referral hospital. The screening was performed in 565 newborns thr...
Wang, Kesheng; Liu, Ying; Ouedraogo, Youssoufou; Wang, Nianyang; Xie, Xin; Xu, Chun; Luo, Xingguang
Early alcohol, tobacco and drug use prior to 18 years old are comorbid and correlated. This study included 6239 adults with major depressive disorder (MDD) in the past year and 72,010 controls from the combined data of 2013 and 2014 National Survey on Drug Use and Health (NSDUH). To deal with multicollinearity existing among 17 variables related to early alcohol, tobacco and drug use prior to 18 years old, we used principal component analysis (PCA) to infer PC scores and then use weighted multiple logistic regression analyses to estimate the associations of potential factors and PC scores with MDD. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The overall prevalence of MDD was 6.7%. The first four PCs could explain 57% of the total variance. Weighted multiple logistic regression showed that PC 1 (a measure of psychotherapeutic drugs and illicit drugs other than marijuana use), PC 2 (a measure of cocaine and hallucinogens), PC 3 (a measure of early alcohol, cigarettes, and marijuana use), and PC 4 (a measure of cigar, smokeless tobacco use and illicit drugs use) revealed significant associations with MDD (OR = 1.12, 95% CI = 1.08-1.16, OR = 1.08, 95% CI = 1.04-1.12, OR = 1.13, 95% CI = 1.07-1.18, and OR = 1.15, 95% CI = 1.09-1.21, respectively). In conclusion, PCA can be used to reduce the indicators in complex survey data. Early alcohol, tobacco and drug use prior to 18 years old were found to be associated with increased odds of adult MDD. Copyright © 2018 Elsevier Ltd. All rights reserved.
Wise, Marissa D; Little, Alison A; Holliman, Jaime Bruce; Wise, Paul H; Wang, C Jason
To determine whether Early Intervention programs have the capacity to accommodate the expected increase in referrals following the American Academy of Pediatrics' 2007 recommendation for universal screening of 18- and 24-month-old children for Autism Spectrum Disorders (ASD). We conducted a telephone survey of all state and territory early. Intervention coordinators about the demand for ASD evaluations, services, and program capacity. We used multivariate models to examine state-level factors associated with the capacity to serve children with ASD. Fifty-two of the 57 coordinators (91%) responded to the survey. Most states reported an increase in demand for ASD-related evaluations (65%) and services (58%) since 2007. In addition, 46% reported that their current capacity poses a challenge to meeting the 45-day time limit for creating the Individualized Family Service Plan. Many states reported that they have shortages of ASD-related personnel, including behavioral therapists (89%), speech-language pathologists (82%), and occupational therapists (79%). Among states that reported the number of service hours (n = 34) 44% indicated that children with ASD receive 5 or fewer weekly service hours. Multivariate models showed that states with a higher percentage of African-American and Latino children were more likely to have provider shortages whereas states with higher population densities were more likely to offer a greater number of service hours. Many Early Intervention programs may not have the capability to address the expected increase in demand for ASD services. Early Intervention programs will likely need enhanced resources to provide all children with suspected ASD with appropriate evaluations and services.
Full Text Available Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD, particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2 and 4 (TLR4, major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified, genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02. Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.
Luciano José Pereira
Full Text Available The purpose of the present study was to evaluate the relationship between psychological variables and the clinical diagnosis of temporomandbular disorders (TMD in 12-year-old adolescents. TMD pain was assessed by RDC/TMD examination (Research Diagnostic Criteria for Temporomandibular Disorders (Axis I and II. Five-hundred and fifty-eight subjects (330 girls and 228 boys were examined. Bivariate analyses were performed using the Chi-square test (χ2. The logistic regression models were adjusted estimating the Odds Ratios (OR, their 95% confidence intervals (CI, and significance levels. Only 2.19% of the boys and 8.18% of the girls presented one of the Axis I categories. All variables from axis II were related to TMD diagnosis (p < 0.001. Gender was significantly related to TMD diagnosis (p = 0.0028. The risk of TMD incidence for girls was 3.5 times higher than that for boys (Odds Ratio = 3.52, Confidence Interval 1.31-9.43. The individuals who presented the variable "characteristics of pain intensity" (CPI higher than 0 had 31 times more risk of TMD incidence (Odds Ratio = 31.361, Confidence interval 6.01-163.5. We concluded that psychological variables and female gender are important risk indicators related to TMD incidence, even in adolescents.
Yee Guan Ng
Full Text Available This cross-sectional study intends to investigate the associations of musculoskeletal disorders (MSDs among foreign labourers on a socio-economic background, occupational exposure, social lifestyle, and postures adopted during harvesting tasks. A total of 446 male respondents (263 FFB cutters; 183 FFB collectors were studied using an interview-assisted questionnaire. OWAS was used to determine the severity of awkward posture based on videos of harvesting tasks recorded for each respondent. Analysis found that increasingly educated respondents had higher risk of developing MSDs. Shorter daily work duration and longer resting duration appear to increase the risk of neck and shoulder disorders among harvesters, which may be attributable to organizational work design. Awkward posture was a particularly significant risk factor of MSDs among FFB collectors. Among the results of the study, occupational exposure, postures and certain socio-demographic backgrounds explained some, but not all, the risk factor of MSDs among harvesters. An in-depth investigation, preferably a longitudinal study investigating the dynamic of work activities and other risk factors, such as psychosocial risk factors, are recommended.
Full Text Available Introduction. Some clinicians believed that mandibular deviation leads to facial asymmetry and it also had a correlation with temporomandibular disorders (TMDs. Posteroanterior (PA cephalogram was widely reported as a regular record in treating facial asymmetry and craniofacial anomalies. The objective of this study was to analyze the relationship of menton deviation in PA cephalogram with temporomandibular disorders (TMDs symptoms. Materials and Methods. TMJ function was initially screened based on TMD-DI questionnaire. PA cephalogram of volunteer subjects with TMDs (n=37 and without TMDs (n=33 with mean age of 21.61±2.08 years was taken. The menton deviation was measured by the distance (mm from menton point to midsagittal reference (MSR horizontally, using software digitized measurement, and categorized as asymmetric if the value is greater than 3 mm. The prevalence and difference of menton deviation in both groups were evaluated by unpaired t-test. Result. The prevalence of symmetry group showed that 65.9% had no TMDs with mean of 1,815 ± 0,71 mm; in contrast, the prevalence of asymmetry group showed that 95.5% reported TMDs with mean of 3,159 ± 1,053 mm. There was a significant difference of menton deviation to TMDs (p=0.000 in subjects with and without TMDs. Conclusion. There was a significant relationship of menton deviation in PA cephalogram with TMDs based on TMD-DI index.
Tuan Leng Tay
Full Text Available Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance, and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD, hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs, and obsessive-compulsive disorder (OCD or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD, bipolar disorder (BD, schizophrenia, eating disorders and sleep disorders. Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer’s and Parkinson’s. Taking into account the recent identification of
Tay, Tuan Leng; Béchade, Catherine; D'Andrea, Ivana; St-Pierre, Marie-Kim; Henry, Mathilde S; Roumier, Anne; Tremblay, Marie-Eve
Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer's and Parkinson's). Taking into account the recent identification of microglia