Bipolar disorder is a serious mental illness. People who have it go through unusual mood changes. They go ... The down feeling is depression. The causes of bipolar disorder aren't always clear. It runs in families. ...
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Full Text Available Bipolar disorder is a common, heritable mental illness characterized by recurrent episodes of mania and depression. Despite considerable effort to elucidate the genetic underpinnings of bipolar disorder, causative genetic risk factors remain elusive. We conducted a comprehensive genomic analysis of bipolar disorder in a large Old Order Amish pedigree. Microsatellite genotypes and high-density SNP-array genotypes of 388 family members were combined with whole genome sequence data for 50 of these subjects, comprising 18 parent-child trios. This study design permitted evaluation of candidate variants within the context of haplotype structure by resolving the phase in sequenced parent-child trios and by imputation of variants into multiple unsequenced siblings. Non-parametric and parametric linkage analysis of the entire pedigree as well as on smaller clusters of families identified several nominally significant linkage peaks, each of which included dozens of predicted deleterious variants. Close inspection of exonic and regulatory variants in genes under the linkage peaks using family-based association tests revealed additional credible candidate genes for functional studies and further replication in population-based cohorts. However, despite the in-depth genomic characterization of this unique, large and multigenerational pedigree from a genetic isolate, there was no convergence of evidence implicating a particular set of risk loci or common pathways. The striking haplotype and locus heterogeneity we observed has profound implications for the design of studies of bipolar and other related disorders.
... disorder, but they think that biochemical, genetic, and environmental_factors may all be involved. It's believed this condition ... the gene or genes involved in bipolar disorder. Environmental factors may play a role in bipolar disorder. For ...
... same time, which is also known as major depressive disorder with mixed features. Bipolar Disorder and Other Illnesses Some bipolar disorder symptoms are similar to other illnesses, which can make ...
Full Text Available Bipolar disorder is a chronic disorder in which irregular course of depressive, mania or mixed episodes or a complete recovery between episodes can be observed. The studies about the effects of traumatic events on bipolar disorder showed that they had significant and long-term effects on the symptoms of the disorder. Psychosocial stress might change the neurobiology of bipolar disorder over time. The studies revealed that the traumatic events could influence not only the onset of the disorder but also the course of the disorder and in these patients the rate of suicide attempt and comorbid substance abuse might increase. Bipolar patients who had childhood trauma had an earlier onset, higher number of episodes and comorbid disorders. In this review, the relationship between childhood trauma and bipolar disorder is reviewed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2: 157-165
Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars
BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...... to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder patients...
Full Text Available Bipolar disorder is characterized by recurrent attacks, significantly disrupts the functionality of a chronic mental disorder. Although there is growing number of studies on the neurobiological basis of the disorder, the pathophysiology has not yet been clearly understood. Structural and functional imaging techniques present a better understanding of the etiology of bipolar disorder and has contributed significantly to the development of the diagnostic approach. Recent developments in brain imaging modalities have let us learn more about the underlying abnormalities in neural systems of bipolar patients. Identification of objective biomarkers would help to determine the pathophysiology of bipolar disorder, a disorder which causes significant deterioration in neurocognitive and emotional areas.
Georgios D. Kotzalidis; Elisa Ambrosi; Alessio Simonetti; Ilaria Cuomo; Antonio Del Casale; Matteo Caloro; Valeria Savoja; Chiara Rapinesi
Recent literature based on peripheral immunity findings speculated that neuroinflammation, with its connection to microglial activation, is linked to bipolar disorder. The endorsement of the neuroinflammatory hypotheses of bipolar disorder requires the demonstration of causality, which requires longitudinal studies. We aimed to review the evidence for neuroinflammation as a pathogenic mechanism of the bipolar disorder. We carried out a hyper inclusive PubMed search using all appropriate neuro...
BACKGROUND: Etiological commonalities are apparent between bipolar disorder and schizophrenia. For example, it is becoming clear that both populations show similar electrophysiological deficits in the auditory domain. Recent studies have also shown robust visual sensory processing deficits in patients with schizophrenia using the event-related potential technique, but this has not been formally tested in those with bipolar disorder. Our goal here was to assess whether early visual sensory processing in patients with bipolar disorder, as indexed by decreased amplitude of the P1 component of the visual evoked potential (VEP), would show a similar deficit to that seen in those with schizophrenia. Since the P1 deficit has already been established as an endophenotype in schizophrenia, a finding of commonality between disorders would raise the possibility that it represents a measure of common genetic liability. METHODS: We visually presented isolated-check stimuli to euthymic patients with a diagnosis of bipolar disorder and age-matched healthy controls within a simple go\\/no-go task and recorded VEPs using high-density (72-channel) electroencephalography. RESULTS: The P1 VEP amplitude was substantially reduced in patients with bipolar disorder, with an effect size of f = 0.56 (large according to Cohen\\'s criteria). LIMITATIONS: Our sample size was relatively small and as such, did not allow for an examination of potential relations between the physiologic measures and clinical measures. CONCLUSION: This reduction in P1 amplitude among patients with bipolar disorder represents a dysfunction in early visual processing that is highly similar to that found repeatedly in patients with schizophrenia and their healthy first-degree relatives. Since the P1 deficit has been related to susceptibility genes for schizophrenia, our results raise the possibility that the deficit may in fact be more broadly related to the development of psychosis and that it merits further
Collin, Guusje; van den Heuvel, Martijn P; Abramovic, Lucija; Vreeker, Annabel; de Reus, Marcel A; van Haren, Neeltje E M; Boks, Marco P M; Ophoff, Roel A; Kahn, René S
The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections--i.e., the connectome--suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected "rich club" organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, interhemispheric connections) of the brain's network. We find that bipolar I disorder patients exhibit reduced global efficiency (-4.4%, P =0.002) and that this deficit relates (r = 0.56, P brain hub connections in general, or of connections spanning brain hubs (i.e., "rich club" connections) in particular (all P > 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency in association with disruptions in interhemispheric connectivity, while the central "rich club" system appears not to be particularly affected.
Georgios D Kotzalidis
Full Text Available Recent literature based on peripheral immunity findings speculated that neuroinflammation, with its connection to microglial activation, is linked to bipolar disorder. The endorsement of the neuroinflammatory hypotheses of bipolar disorder requires the demonstration of causality, which requires longitudinal studies. We aimed to review the evidence for neuroinflammation as a pathogenic mechanism of the bipolar disorder. We carried out a hyper inclusive PubMed search using all appropriate neuroinflammation-related terms and crossed them with bipolar disorder-related terms. The search produced 310 articles and the number rose to 350 after adding articles from other search engines and reference lists. Twenty papers were included that appropriately tackled the issue of the presence (but not of its pathophysiological role of neuroinflammation in bipolar disorder. Of these, 15 were postmortem and 5 were carried out in living humans. Most articles were consistent with the presence of neuroinflammation in bipolar disorder, but factors such as treatment may mask it. All studies were cross-sectional, preventing causality to be inferred. Thus, no inference can be currently made about the role of neuroinflammation in bipolar disorder, but a link is likely. The issue remains little investigated, despite an excess of reviews on this topic.
Knott, Sarah; Forty, Liz; Craddock, Nick; Thomas, Rhys H
It is well recognized that mood disorders and epilepsy commonly co-occur. Despite this, our knowledge regarding the relationship between epilepsy and bipolar disorder is limited. Several shared features between the two disorders, such as their episodic nature and potential to run a chronic course, and the efficacy of some antiepileptic medications in the prophylaxis of both disorders, are often cited as evidence of possible shared underlying pathophysiology. The present paper aims to review the bidirectional associations between epilepsy and bipolar disorder, with a focus on epidemiological links, evidence for shared etiology, and the impact of these disorders on both the individual and wider society. Better recognition and understanding of these two complex disorders, along with an integrated clinical approach, are crucial for improved evaluation and management of comorbid epilepsy and mood disorders.
Full Text Available Berit Kerner Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA Abstract: Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a “risk” allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are
Full Text Available This paper consists of a case history and an overview of the relationship, aetiology, and treatment of comorbid bipolar disorder migraine patients. A MEDLINE literature search was used. Terms for the search were bipolar disorder bipolar depression, mania, migraine, mood stabilizer. Bipolar disorder and migraine cooccur at a relatively high rate. Bipolar II patients seem to have a higher risk of comorbid migraine than bipolar I patients have. The literature on the common roots of migraine and bipolar disorder, including both genetic and neuropathological approaches, is broadly discussed. Moreover, bipolar disorder and migraine are often combined with a variety of other affective disorders, and, furthermore, behavioural factors also play a role in the origin and course of the diseases. Approach to treatment options is also difficult. Several papers point out possible remedies, for example, valproate, topiramate, which acts on both diseases, but no first-choice treatments have been agreed upon yet.
Watson, S; Gallagher, P.; Dougall, D.; Porter, R.; Moncrieff, J; Ferrier, I N; Young, A.H.
Objective:There has been little investigation of early trauma in bipolar disorder despite evidence that stress impacts on the course of this illness. We aimed to compare the rates of childhood trauma in adults with bipolar disorder to a healthy control group, and to investigate the impact of childhood trauma on the clinical course of bipolar disorder.Methods:Retrospective assessment of childhood trauma was conducted using the Childhood Trauma Questionnaire (CTQ) in 60 outpatients with bipolar...
Maçkalı, Zeynep; Gülöksüz, Sinan; Oral, Timuçin
The relationship between creativity and bipolar disorder has been an intriguing topic since ancient times. Early studies focused on describing characteristics of creative people. From the last quarter of the twentieth century, researchers began to focus on the relationship between mood disorders and creativity. Initially, the studies were based on biographical texts and the obtained results indicated a relationship between these two concepts. The limitations of the retrospective studies led the researchers to develop systematic investigations into this area. The systematic studies that have focused on artistic creativity have examined both the prevalence of mood disorders and the creative process. In addition, a group of researchers addressed the relationship in terms of affective temperaments. Through the end of the 90's, the scope of creativity was widened and the notion of everyday creativity was proposed. The emergence of this notion led researchers to investigate the associations of the creative process in ordinary (non-artist) individuals. In this review, the descriptions of creativity and creative process are mentioned. Also, the creative process is addressed with regards to bipolar disorder. Then, the relationship between creativity and bipolar disorder are evaluated in terms of aforementioned studies (biographical, systematic, psychobiographical, affective temperaments). In addition, a new model, the "Shared Vulnerability Model" which was developed to explain the relationship between creativity and psychopathology is introduced. Finally, the methodological limitations and the suggestions for resolving these limitations are included.
Li, Yongsheng; Camarillo, Cynthia; Xu, Juan; Arana, Tania Bedard; Xiao, Yun; Zhao, Zheng; Chen, Hong; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael A.; Armas, Regina; Mendoza, Ricardo; Ontiveros, Alfonso; Nicolini, Humberto; Jerez Magaña, Alvaro Antonio; Rubin, Lewis P.; Li, Xia; Xu, Chun
Schizophrenia (SZ) and bipolar disorder (BP) are complex genetic disorders. Their appearance is also likely informed by as yet only partially described epigenetic contributions. Using a sequencing-based method for genome-wide analysis, we quantitatively compared the blood DNA methylation landscapes in SZ and BP subjects to control, both in an understudied population, Hispanics along the US-Mexico border. Remarkably, we identified thousands of differentially methylated regions for SZ and BP preferentially located in promoters 3′-UTRs and 5′-UTRs of genes. Distinct patterns of aberrant methylation of promoter sequences were located surrounding transcription start sites. In these instances, aberrant methylation occurred in CpG islands (CGIs) as well as in flanking regions as well as in CGI sparse promoters. Pathway analysis of genes displaying these distinct aberrant promoter methylation patterns showed enhancement of epigenetic changes in numerous genes previously related to psychiatric disorders and neurodevelopment. Integration of gene expression data further suggests that in SZ aberrant promoter methylation is significantly associated with altered gene transcription. In particular, we found significant associations between (1) promoter CGIs hypermethylation with gene repression and (2) CGI 3′-shore hypomethylation with increased gene expression. Finally, we constructed a specific methylation analysis platform that facilitates viewing and comparing aberrant genome methylation in human neuropsychiatric disorders. PMID:25734057
Li, Yongsheng; Camarillo, Cynthia; Xu, Juan; Arana, Tania Bedard; Xiao, Yun; Zhao, Zheng; Chen, Hong; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael A; Armas, Regina; Mendoza, Ricardo; Ontiveros, Alfonso; Nicolini, Humberto; Magaña, Alvaro Antonio Jerez; Rubin, Lewis P; Li, Xia; Xu, Chun
Schizophrenia (SZ) and bipolar disorder (BP) are complex genetic disorders. Their appearance is also likely informed by as yet only partially described epigenetic contributions. Using a sequencing-based method for genome-wide analysis, we quantitatively compared the blood DNA methylation landscapes in SZ and BP subjects to control, both in an understudied population, Hispanics along the US-Mexico border. Remarkably, we identified thousands of differentially methylated regions for SZ and BP preferentially located in promoters 3'-UTRs and 5'-UTRs of genes. Distinct patterns of aberrant methylation of promoter sequences were located surrounding transcription start sites. In these instances, aberrant methylation occurred in CpG islands (CGIs) as well as in flanking regions as well as in CGI sparse promoters. Pathway analysis of genes displaying these distinct aberrant promoter methylation patterns showed enhancement of epigenetic changes in numerous genes previously related to psychiatric disorders and neurodevelopment. Integration of gene expression data further suggests that in SZ aberrant promoter methylation is significantly associated with altered gene transcription. In particular, we found significant associations between (1) promoter CGIs hypermethylation with gene repression and (2) CGI 3'-shore hypomethylation with increased gene expression. Finally, we constructed a specific methylation analysis platform that facilitates viewing and comparing aberrant genome methylation in human neuropsychiatric disorders.
Full Text Available Schizophrenia (SZ and bipolar disorder (BP are complex genetic disorders. Their appearance is also likely informed by as yet only partially described epigenetic contributions. Using a sequencing-based method for genome-wide analysis, we quantitatively compared the blood DNA methylation landscapes in SZ and BP subjects to control, both in an understudied population, Hispanics along the US-Mexico border. Remarkably, we identified thousands of differentially methylated regions for SZ and BP preferentially located in promoters 3′-UTRs and 5′-UTRs of genes. Distinct patterns of aberrant methylation of promoter sequences were located surrounding transcription start sites. In these instances, aberrant methylation occurred in CpG islands (CGIs as well as in flanking regions as well as in CGI sparse promoters. Pathway analysis of genes displaying these distinct aberrant promoter methylation patterns showed enhancement of epigenetic changes in numerous genes previously related to psychiatric disorders and neurodevelopment. Integration of gene expression data further suggests that in SZ aberrant promoter methylation is significantly associated with altered gene transcription. In particular, we found significant associations between (1 promoter CGIs hypermethylation with gene repression and (2 CGI 3′-shore hypomethylation with increased gene expression. Finally, we constructed a specific methylation analysis platform that facilitates viewing and comparing aberrant genome methylation in human neuropsychiatric disorders.
Full Text Available The comorbidity of bipolar disorder and anxiety disorders is a well known concept. Obsessive-compulsive disorder is the most commonly seen comorbid anxiety disorder in bipolar patients. Some genetic variants, neurotransmitters especially serotonergic systems and second-messenger systems are thought to be responsible for its etiology. Bipolar disorder alters the clinical aspects of obsessive compulsive disorder and is associated with poorer outcome. The determination of comorbidity between bipolar disorder and obsessive compulsive disorder is quite important for appropriate clinical management and treatment. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 429-437
Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh
OBJECTIVE: Life expectancy in patients with bipolar disorder has been reported to be decreased by 11 to 20 years. These calculations are based on data for individuals at the age of 15 years. However, this may be misleading for patients with bipolar disorder in general as most patients have a later...... onset of illness. The aim of the present study was to calculate the remaining life expectancy for patients of different ages with a diagnosis of bipolar disorder. METHODS: Using nationwide registers of all inpatient and outpatient contacts to all psychiatric hospitals in Denmark from 1970 to 2012 we...... remaining life expectancy in bipolar disorder and that of the general population decreased with age, indicating that patients with bipolar disorder start losing life-years during early and mid-adulthood. CONCLUSIONS: Life expectancy in bipolar disorder is decreased substantially, but less so than previously...
Pedrosa, Erika; Shah, Abhishek; Tenore, Christopher; Capogna, Michael; Villa, Catalina; Guo, Xingyi; Zheng, Deyou; Lachman, Herbert M
Therapeutic concentrations of lithium salts inhibit glycogen synthase kinase 3 beta (GSK3β) and phosphoinositide (PI) signaling suggesting that abnormal activation of these pathways could be a factor in the pathophysiology of bipolar disorder (BD). Involvement of these pathways is also supported by recent genome-wide association studies (GWASs). One way investigators have investigated the molecular basis of BD and the therapeutic action of lithium is by microarray expression studies, since both GSK3β- and PI-mediated signal transduction pathways are coupled to transcriptional activation and inhibition. However, expression profiling has some limitations and investigators cannot use the approach to analyze fetal brain tissue, arguably the most relevant biological structure related to the development of genetically based psychiatric disorders. To address these shortcomings, the authors have taken a novel approach using chromatin immunoprecipitation-enriched material annealed to microarrays (ChIP-chip) targeting genes in fetal brain tissue bound by β-catenin, a transcription factor that is directly regulated by GSK3β. The promoters for 640 genes were found to be bound by β-catenin, many of which are known schizophrenia (SZ), autism spectrum disorder (ASD), and BD candidates, including CACNA1B, NRNG, SNAP29, FGFR1, PCDH9, and nine others identified in recently published GWASs and genome-wide searches for copy number variants (CNVs). The findings suggest that seemingly disparate candidate genes for SZ and BD can be incorporated into a common molecular network revolving around GSK3β/β-catenin signaling. In addition, the finding that a putative lithium-responsive pathway may influence a subgroup of SZ and ASD candidate genes could have therapeutic implications.
Watson, Stuart; Gallagher, Peter; Dougall, Dominic; Porter, Richard; Moncrieff, Joanna; Ferrier, I Nicol; Young, Allan H.
Objective: There has been little investigation of early trauma in bipolar disorder despite evidence that stress impacts on the course of this illness. We aimed to compare the rates of childhood trauma in adults with bipolar disorder to a healthy control group, and to investigate the impact of childhood trauma on the clinical course of bipolar disorder. Methods: Retrospective assessment of childhood trauma was conducted using the Childhood Trauma Questionnaire (CTQ) in 60 outpatients with bipo...
Full Text Available Comorbid endocrine and cardiovascular situations with bipolar disorder usually result from the bipolar disorder itself or as a consequence of its treatment. With habits and lifestyle, genetic tendency and side effects, this situation is becoming more striking. Subpopulations of bipolar disorders patients should be considered at high risk for diabetes mellitus. The prevalence of diabetes mellitus in bipolar disorder may be three times greater than in the general population. Comorbidity of diabetes causes a pathophysiological overlapping in the neurobiological webs of bipolar cases. Signal mechanisms of glycocorticoid/insulin and immunoinflammatory effector systems are junction points that point out the pathophysiology between bipolar disorder and general medical cases susceptible to stress. Glycogen synthetase kinase (GSK-3 is a serine/treonine kinase and inhibits the transport of glucose stimulated by insulin. It is affected in diabetes, cancer, inflammation, Alzheimer disease and bipolar disorder. Hypoglycemic effect of lithium occurs via inhibiting glycogen synthetase kinase. When comorbid with diabetes, the other disease -for example bipolar disorder, especially during its acute manic episodes-, causes a serious situation that presents its influences for a lifetime. Choosing pharmacological treatment and treatment adherence are another important interrelated areas. The aim of this article is to discuss and review the etiological, clinical and therapeutic properties of diabetes mellitus and bipolar disorder comorbidity.
... is in crisis. What do I do? Share Bipolar Disorder in Children and Teens Download PDF Download ePub ... brochure will give you more information. What is bipolar disorder? Bipolar disorder is a serious brain illness. It ...
Ben Abla, T; Ellouze, F; Amri, H; Krid, G; Zouari, A; M'Rad, M F
Bipolar and unipolar disorders share a common depressive clinical manifestation. It is important to distinguish between these two forms of depression for several reasons. First, prescribing antidepressors in monotherapy indubitably worsens the prognosis of bipolarity disorders. Second, postponing the prescription of a mood stabilizer reduces the efficacy of the treatment and multiplies the suicidal risks by two. The object of this study is to reveal the factors that distinguish between unipolar and bipolar depression. This is a retrospective study on patients' files. It includes 186 patients divided according to DSM IV criteria into two groups: patients with bipolar disorder type I or II with a recent depressive episode (123 patients) and patients with recurrent depressive disorder (63 patients). A medical record card was filled-in for every patient. It included socio-demographic data, information about the disorder, family antecedents, CGI score (global clinical impressions), physical comorbidity, substance abuse and personality disorder. In order to sort out the categorization variables, the two groups were compared using chi2 test or Fischer's test. With regard to the quantitative variables, the two groups were compared using Krostal Wallis's test or Ancova. Our study has revealed that bipolar disorder differs significantly from unipolar disorder in the following respects: bipolar disorder is prevalent among men (sex-ratio 2) while unipolar disorder is prevailing among women (sex-ratio 0.8); patients with bipolar disorder are younger than patients with unipolar disorder (38.1 +/- 5 years vs. 49.7 +/- years); the age at the onset of bipolar disorder is earlier than that of unipolar disorder (20.8 +/- 2 years vs. 38.7 +/- 5 years); family antecedents are more important in bipolar patients than in unipolar patients (51.1% vs. 33%). More importantly, bipolar disorder differs from unipolar disorder in the following aspects: The number of suicidal attempts (25.3% vs
Barde, Michael; Bellivier, Frank
Bipolar disorder is a chronic pathology whose management must lead to limit the social, professional and family impacts as well as suicidal risk. The treatment of acute episodes and prophylaxis is based on mood stabilizer treatments whose lithium is a leader. They will be chosen according to the background and history of the disease. Anti-depressants must be used with care to minimize the risk of manic episode and the induction of rapid cycles. The prognosis is not solving major episodes but avoiding major mood episodes. The management of residual symptoms (especially neuro-cognitive) is also a major challenge prognosis and justifies the implementation of adjuvant psychotherapeutic strategies.
Full Text Available Introduction: Bipolar disorder is a psychiatric condition that is also called manic-depressive disease. It causes unusual changes in mood, energy, activity levels, and the ability to carry out day-to-day tasks. In the present study, 3 sets of data were considered and analyzed: first, all papers categorized under Bipolar Disorders in Science Citation Index Expanded (SCI-E database through 2001-2011; second, papers published by the international journal of Bipolar Disorders indexed in SCI-E during a period of 11 years; and third, all papers distributed by the international journal of Bipolar Disorders indexed in MEDLINE during the period of study. Methods: The SCI-E database was used to extract all papers indexed with the topic of Bipolar Disorders as well as all papers published by The International Journal of Bipolar Disorders. Extraction of data from MEDLINE was restricted to the journals name from setting menu. The Science of Science Tool was used to map the co-authorship network of papers published by The International Journal of Bipolar Disorders through 2009-2011. Results: Analysis of data showed that the majority of publications in the subject area of bipolar disorders indexed in SCI-E were published by The International Journal of Bipolar Disorders. Although journal articles consisted of 59% of the total publication type in SCI-E, 65% of publications distributed by The Journal of Bipolar Disorders were in the form of meetingabstracts. Journal articles consisted of only 23% of the total publications. USA was the leading country regarding sharing data in the field of bipolar disorders followed by England, Canada, and Germany. Conclusion: The editorial policy of The International Journal of Bipolar Disorders has been focused on new themes and new ways of researching in the subject area of bipolar disorder. Regarding the selection of papers for indexing, the SCI-E database selects data more comprehensively than MEDLINE. The number of papers
... Is there a connection between bipolar disorder and alcoholism? Answers from Daniel K. Hall-Flavin, M.D. Bipolar disorder and alcoholism often occur together. Although the association between bipolar ...
Full Text Available Childhood and adolescent bipolar disorder diagnosis has been increasing recently. Since studies evaluating attempted suicide rates in children and adolescents have shown bipolarity to be a significant risk factor, diagnosis and treatment of bipolarity has become a very important issue. Since there is a lack of specific diagnostic criteria for especially preadolescent samples and evaluations are made mostly symptomatically, suspicions about false true diagnosis and increased prevalence rates have emerged. This situation leads to controversial data about the prevalence rates of bipolar disorder in children and adolescents. The aim of this article is to review the prevalence of childhood and adolescent bipolar disorder in community, inpatient and outpatient based samples in literature.
Full Text Available Thomas Scheidemantel,1 Irina Korobkova,2 Soham Rej,3,4 Martha Sajatovic1,2 1University Hospitals Case Medical Center, 2Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Department of Psychiatry, University of Toronto, Toronto, ON, 4Geri PARTy Research Group, Jewish General Hospital, Montreal, QC, Canada Abstract: Asenapine (Saphris® is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD. Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be
Zhao, Z; Xu, J; Chen, J; Kim, S; Reimers, M; Bacanu, S-A; Yu, H; Liu, C; Sun, J; Wang, Q; Jia, P; Xu, F; Zhang, Y; Kendler, K S; Peng, Z; Chen, X
Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental disorders with high heritability. Clinicians have long noticed the similarities of clinic symptoms between these disorders. In recent years, accumulating evidence indicates some shared genetic liabilities. However, what is shared remains elusive. In this study, we conducted whole transcriptome analysis of post-mortem brain tissues (cingulate cortex) from SCZ, BPD and control subjects, and identified differentially expressed genes in these disorders. We found 105 and 153 genes differentially expressed in SCZ and BPD, respectively. By comparing the t-test scores, we found that many of the genes differentially expressed in SCZ and BPD are concordant in their expression level (q⩽0.01, 53 genes; q⩽0.05, 213 genes; q⩽0.1, 885 genes). Using genome-wide association data from the Psychiatric Genomics Consortium, we found that these differentially and concordantly expressed genes were enriched in association signals for both SCZ (Pgenes show concordant expression and association for both SCZ and BPD. Pathway analyses of these genes indicated that they are involved in the lysosome, Fc gamma receptor-mediated phagocytosis, regulation of actin cytoskeleton pathways, along with several cancer pathways. Functional analyses of these genes revealed an interconnected pathway network centered on lysosomal function and the regulation of actin cytoskeleton. These pathways and their interacting network were principally confirmed by an independent transcriptome sequencing data set of the hippocampus. Dysregulation of lysosomal function and cytoskeleton remodeling has direct impacts on endocytosis, phagocytosis, exocytosis, vesicle trafficking, neuronal maturation and migration, neurite outgrowth and synaptic density and plasticity, and different aspects of these processes have been implicated in SCZ and BPD.
Meda, Shashwath A; Ruaño, Gualberto; Windemuth, Andreas; O'Neil, Kasey; Berwise, Clifton; Dunn, Sabra M; Boccaccio, Leah E; Narayanan, Balaji; Kocherla, Mohan; Sprooten, Emma; Keshavan, Matcheri S; Tamminga, Carol A; Sweeney, John A; Clementz, Brett A; Calhoun, Vince D; Pearlson, Godfrey D
The brain's default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 SZ probands, 300 PBP probands, 179 unaffected first-degree relatives of SZ probands (SZREL), and 206 unaffected first-degree relatives of PBP probands to identify DMNs and to test their biomarker and/or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging-genetic relationships. ICA identified three DMNs. Hypo-connectivity was observed in both patient groups in all DMNs. Similar patterns observed in SZREL were restricted to only one network. DMN connectivity also correlated with several symptom measures. Para-ICA identified five sub-DMNs that were significantly associated with five different genetic networks. Several top-ranking SNPs across these networks belonged to previously identified, well-known psychosis/mood disorder genes. Global enrichment analyses revealed processes including NMDA-related long-term potentiation, PKA, immune response signaling, axon guidance, and synaptogenesis that significantly influenced DMN modulation in psychoses. In summary, we observed both unique and shared impairments in functional connectivity across the SZ and PBP cohorts; these impairments were selectively familial only for SZREL. Genes regulating specific neurodevelopment/transmission processes primarily mediated DMN disconnectivity. The study thus identifies biological pathways related to a widely researched quantitative trait that might suggest novel, targeted drug treatments for these diseases.
José Caetano Dell'Aglio Jr.
Full Text Available This paper describes the findings of a systematic literature review aimed at providing an overview of the lifetime prevalence of bipolar disorder and bipolar spectrum disorders in population-based studies. Databases MEDLINE, ProQuest, Psychnet, and Web of Science were browsed for papers published in English between 1999 and May 2012 using the following search string: bipolar disorders OR bipolar spectrum disorders AND prevalence OR cross-sectional OR epidemiology AND population-based OR non-clinical OR community based. The search yielded a total of 434 papers, but only those published in peer-reviewed journals and with samples aged ≥ 18 years were included, resulting in a final sample of 18 papers. Results revealed rather heterogeneous findings concerning the prevalence of bipolar disorders and bipolar spectrum disorders. Lifetime prevalence of bipolar disorder ranged from 0.1 to 7.5%, whereas lifetime prevalence of bipolar spectrum disorders ranged from 2.4 to 15.1%. Differences in the rates of bipolar disorder and bipolar spectrum disorders may be related to the consideration of subthreshold criteria upon diagnosis. Differences in the prevalence of different subtypes of the disorder are discussed in light of diagnostic criteria and instruments applied.
Full Text Available From a neurobiological perspective there is no such thing as bipolar disorder. Rather, it is almost certainly the case that many somewhat similar, but subtly different, pathological conditions produce a disease state that we currently diagnose as bipolarity. This heterogeneity—reflected in the lack of synergy between our current diagnostic schema and our rapidly advancing scientific understanding of the condition—limits attempts to articulate an integrated perspective on bipolar disorder. However, despite these challenges, scientific findings in recent years are beginning to offer a provisional unified field theory of the disease. This theory sees bipolar disorder as a suite of related neurodevelopmental conditions with interconnected functional abnormalities that often appear early in life and worsen over time. In addition to accelerated loss of volume in brain areas known to be essential for mood regulation and cognitive function, consistent findings have emerged at a cellular level, providing evidence that bipolar disorder is reliably associated with dysregulation of glial-neuronal interactions. Among these glial elements are microglia—the brain’s primary immune elements, which appear to be overactive in the context of bipolarity. Multiple studies now indicate that inflammation is also increased in the periphery of the body in both the depressive and manic phases of the illness, with at least some return to normality in the euthymic state. These findings are consistent with changes in the HPA axis, which are known to drive inflammatory activation. In summary, the very fact that no single gene, pathway or brain abnormality is likely to ever account for the condition is itself an extremely important first step in better articulating an integrated perspective on both its ontological status and pathogenesis. Whether this perspective will translate into the discovery of innumerable more homogeneous forms of bipolarity is one of the great
Simeonova, Diana I; Chang, Kiki D; Strong, Connie; Ketter, Terence A
Studies have demonstrated relationships between creativity and bipolar disorder (BD) in individuals, and suggested familial transmission of both creativity and BD. However, to date, there have been no studies specifically examining creativity in offspring of bipolar parents and clarifying mechanisms of intergenerational transmission of creativity. We compared creativity in bipolar parents and their offspring with BD and bipolar offspring with attention-deficit/hyperactivity disorder (ADHD) with healthy control adults and their children. 40 adults with BD, 20 bipolar offspring with BD, 20 bipolar offspring with ADHD, and 18 healthy control parents and their healthy control children completed the Barron-Welsh Art Scale (BWAS), an objective measure of creativity. Adults with BD compared to controls scored significantly (120%) higher on the BWAS Dislike subscale, and non-significantly (32%) higher on the BWAS Total scale. Mean BWAS Dislike subscale scores were also significantly higher in offspring with BD (107% higher) and offspring with ADHD (91% higher) than in healthy control children. Compared to healthy control children, offspring with BD had 67% higher and offspring with ADHD had 40% higher BWAS Total scores, but these differences failed to reach statistical significance when adjusted for age. In the bipolar offspring with BD, BWAS Total scores were negatively correlated with duration of illness. The results of this study support an association between BD and creativity and contribute to a better understanding of possible mechanisms of transmission of creativity in families with genetic susceptibility for BD. This is the first study to show that children with and at high risk for BD have higher creativity than healthy control children. The finding in children and in adults was related to an enhanced ability to experience and express dislike of simple and symmetric images. This could reflect increased access to negative affect, which could yield both benefits
Bipolar disorder is a mental disorder with chronic and remitting course. The disorder is related to high mortality and severely impairs everyday functioning. Therefore a scientifically sound and practical approach to treatment is needed. Making a long-term treatment plan usually also demands some creativity. The patient is interested in a number of issues, from the choice of therapy in acute phases to long-term treatment. Usual questions are how long shall I take the medications, do I really need all those pills or can we decrease the dosage of some drugs? This paper discussed the above mentioned questions in light of latest publications in this field.
Full Text Available To review the data with respect to prevalence and risk factors of metabolic syndrome (MetS in bipolar disorder patients. Electronic searches were done in PUBMED, Google Scholar and Science direct. From 2004 to June 2011, 34 articles were found which reported on the prevalence of MetS. The sample size of these studies varied from 15 to 822 patients, and the rates of MetS vary widely from 16.7% to 67% across different studies. None of the sociodemographic variable has emerged as a consistent risk factor for MetS. Among the clinical variables longer duration of illness, bipolar disorder- I, with greater number of lifetime depressive and manic episodes, and with more severe and difficult-to-treat index affective episode, with depression at onset and during acute episodes, lower in severity of mania during the index episode, later age of onset at first manic episode, later age at first treatment for the first treatment for both phases, less healthy diet as rated by patients themselves, absence of physical activity and family history of diabetes mellitus have been reported as clinical risk factors of MetS. Data suggests that metabolic syndrome is fairly prevalent in bipolar disorder patients.
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.
Pacchiarotti, Isabella; Bond, David J.; Baldessarini, Ross J.; Nolen, Willem A.; Grunze, Heinz; Licht, Rasmus W.; Post, Robert M.; Berk, Michael; Goodwin, Guy M.; Sachs, Gary S.; Tondo, Leonardo; Findling, Robert L.; Youngstrom, Eric A.; Tohen, Mauricio; Undurraga, Juan; Gonzalez-Pinto, Ana; Goldberg, Joseph F.; Yildiz, Aysegul; Altshuler, Lori L.; Calabrese, Joseph R.; Mitchell, Philip B.; Thase, Michael E.; Koukopoulos, Athanasios; Colom, Francesc; Frye, Mark A.; Malhi, Gin S.; Fountoulakis, Konstantinos N.; Vazquez, Gustavo; Perlis, Roy H.; Ketter, Terence A.; Cassidy, Frederick; Akiskal, Hagop; Azorin, Jean-Michel; Valenti, Marc; Mazzei, Diego Hidalgo; Lafer, Beny; Kato, Tadafumi; Mazzarini, Lorenzo; Martinez-Aran, Anabel; Parker, Gordon; Souery, Daniel; Ozerdem, Aysegul; McElroy, Susan L.; Girardi, Paolo; Bauer, Michael; Yatham, Lakshmi N.; Zarate, Carlos A.; Nierenberg, Andrew A.; Birmaher, Boris; Kanba, Shigenobu; El-Mallakh, Rif S.; Serretti, Alessandro; Rihmer, Zoltan; Young, Allan H.; Kotzalidis, Georgios D.; MacQueen, Glenda M.; Bowden, Charles L.; Ghaemi, S. Nassir; Lopez-Jaramillo, Carlos; Rybakowski, Janusz; Ha, Kyooseob; Perugi, Giulio; Kasper, Siegfried; Amsterdam, Jay D.; Hirschfeld, Robert M.; Kapczinski, Flavio; Vieta, Eduard
Objective: The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations
Full Text Available New high-throughput, population-based methods and next-generation sequencing capabilities hold great promise in the quest for common and rare variant discovery and in the search for "missing heritability." However, the optimal analytic strategies for approaching such data are still actively debated, representing the latest rate-limiting step in genetic progress. Since it is likely a majority of common variants of modest effect have been identified through the application of tagSNP-based microarray platforms (i.e., GWAS, alternative approaches robust to detection of low-frequency (1-5% MAF and rare (<1% variants are of great importance. Of direct relevance, we have available an accumulated wealth of linkage data collected through traditional genetic methods over several decades, the full value of which has not been exhausted. To that end, we compare results from two different linkage meta-analysis methods--GSMA and MSP--applied to the same set of 13 bipolar disorder and 16 schizophrenia GWLS datasets. Interestingly, we find that the two methods implicate distinct, largely non-overlapping, genomic regions. Furthermore, based on the statistical methods themselves and our contextualization of these results within the larger genetic literatures, our findings suggest, for each disorder, distinct genetic architectures may reside within disparate genomic regions. Thus, comparative linkage meta-analysis (CLMA may be used to optimize low-frequency and rare variant discovery in the modern genomic era.
Zeynep Namli; Gonca Karakus; Lut Tamam; Mehmet Emin Demirkol
In the clinical course of bipolar disorder, there is a reduction in sexual will during depressive episodes and inappopriate sexual experiences and hypersexuality occurs during manic episodes. Up to now, studies focused on sexual side effects of drugs. Sexual violence, sexually transmitted diseases, contraception methods, unplanned pregnancies need to be assessed carefully in bipolar disorder patients. This review focused on sexuality and sexual dysfunctions in the course of bipolar disorder. ...
Senokossoff, Gwyn W.; Stoddard, Kim
The authors focused on one parent's struggles in finding a diagnosis and intervention for a child who had bipolar disorder. The authors explain the process of identification, diagnosis, and intervention of a child who had bipolar disorder. In addition to the personal story, the authors provide information on the disorder and outline strategies…
Boeira, Manuela V; Berni, Gabriela de Á; Passos, Ives C; Kauer-Sant'Anna, Márcia; Kapczinski, Flávio
Family history and traumatic experiences are factors linked to bipolar disorder. It is known that the lifetime risk of bipolar disorder in relatives of a bipolar proband are 5-10% for first degree relatives and 40-70% for monozygotic co-twins. It is also known that patients with early childhood trauma present earlier onset of bipolar disorder, increased number of manic episodes, and more suicide attempts. We have recently reported that childhood trauma partly mediates the effect of family history on bipolar disorder diagnosis. In light of these findings from the scientific literature, we reviewed the work of British writer Virginia Woolf, who allegedly suffered from bipolar disorder. Her disorder was strongly related to her family background. Moreover, Virginia Woolf was sexually molested by her half siblings for nine years. Her bipolar disorder symptoms presented a pernicious course, associated with hospitalizations, suicidal behavioral, and functional impairment. The concept of neuroprogression has been used to explain the clinical deterioration that takes places in a subgroup of bipolar disorder patients. The examination of Virgina Woolf's biography and art can provide clinicians with important insights about the course of bipolar disorder.
Manuela V. Boeira
Full Text Available Family history and traumatic experiences are factors linked to bipolar disorder. It is known that the lifetime risk of bipolar disorder in relatives of a bipolar proband are 5-10% for first degree relatives and 40-70% for monozygotic co-twins. It is also known that patients with early childhood trauma present earlier onset of bipolar disorder, increased number of manic episodes, and more suicide attempts. We have recently reported that childhood trauma partly mediates the effect of family history on bipolar disorder diagnosis. In light of these findings from the scientific literature, we reviewed the work of British writer Virginia Woolf, who allegedly suffered from bipolar disorder. Her disorder was strongly related to her family background. Moreover, Virginia Woolf was sexually molested by her half siblings for nine years. Her bipolar disorder symptoms presented a pernicious course, associated with hospitalizations, suicidal behavioral, and functional impairment. The concept of neuroprogression has been used to explain the clinical deterioration that takes places in a subgroup of bipolar disorder patients. The examination of Virgina Woolf’s biography and art can provide clinicians with important insights about the course of bipolar disorder.
Axelson, David A.; Birmaher, Boris; Strober, Michael A.; Goldstein, Benjamin I.; Ha, Wonho; Gill, Mary Kay; Goldstein, Tina R.; Yen, Shirley; Hower, Heather; Hunt, Jeffrey I.; Liao, Fangzi; Iyengar, Satish; Dickstein, Daniel; Kim, Eunice; Ryan, Neal D.; Frankel, Erica; Keller, Martin B.
Objective: To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow-up and to identify factors associated with conversion. Method: Subjects were 140 children and adolescents…
Full Text Available Background/Aim. Bipolar affective disorder is mental disorder with polygenic type of heredity. Heritability - relation between genetic and environmental variance is used to estimate the level of influence of genetic variance to phenotype variance. Study results show decreasing trend in the value of heritability of bipolar affective disorder, thus indicating that this disorder is a complex behavioral threshold characteristic. Therefore, the aim of this study was to estimate the contribution of genetic variance to phenotype variance of bipolar affective disorder, i.e. to estimate heritability of this disorder. Methods. By the use of a questionnaire, 80 patients with over crossed threshold for bipolar affective disorder were asked for functional information about the members of their families belonging to the first degree of relation (fathers, mothers and full- sibs. By using ”Applet for calculating heritability for threshold traits (disease“, and regression analysis, heritability of bipolar affective disorder as well as its statistical significance, were estimated (χ2 test. Results. Heritability and relationship of genetic and environmental variance of bipolar affective disorder is 0.2 with statistically significant difference from zero (p < 0.001. Conclusion. The estimated contribution of genetic variance to phenotype variance of bipolar affective disorder is low being 20%, while the contribution of environmental variance is 80%. This result contributes to the understanding of bipolar affective disorder as a complex behavioral threshold trait.
Rodrigues, Aline André
Full Text Available In bipolar disorder illness progression has been associated with a higher number of mood episodes and hospitalizations, poorer response to treatment, and more severe cognitive and functional impairment. This supports the notion of the use of staging models in this illness. The value of staging models has long been recognized in many medical and malignant conditions. Staging models rely on the fact that different interventions may suit different stages of the disorder, and that better outcomes can be obtained if interventions are implemented earlier in the course of illness. Thus, treatment planning would benefit from the assessment of cognition, functioning and comorbidities. Staging may offer a means to refine treatment options, and most importantly, to establish a more precise diagnosis. Moreover, staging could have utility as course specifier and may guide treatment planning and better information to patients and their family members of what could be expected in terms of prognosis. The present study reviews the clinical and biological basis of the concept of illness progression in bipolar disorder.
Vedel Kessing, Lars; Vradi, Eleni; Andersen, Per Kragh
BACKGROUND: The diagnostic stability of pediatric bipolar disorder has not been investigated previously. The aim was to investigate the diagnostic stability of the ICD-10 diagnosis of pediatric mania/bipolar disorder.METHODS: All patients below 19 years of age who got a diagnosis of mania/bipolar...... disorder at least once in a period from 1994 to 2012 at psychiatric inpatient or outpatient contact in Denmark were identified in a nationwide register.RESULTS: Totally, 354 children and adolescents got a diagnosis of mania/bipolar disorder at least once; a minority, 144 patients (40.7%) got the diagnosis...... at the first contact whereas the remaining patients (210; 59.3%) got the diagnosis at later contacts before age 19. For the latter patients, the median time elapsed from first treatment contact with the psychiatric service system to the first diagnosis with a manic episode/bipolar disorder was nearly 1 year...
Obradović Tanja; Veličković Ružica; Timotijević Ivana; Anđelković Marko
Background/Aim. Bipolar affective disorder is mental disorder with polygenic type of heredity. Heritability - relation between genetic and environmental variance is used to estimate the level of influence of genetic variance to phenotype variance. Study results show decreasing trend in the value of heritability of bipolar affective disorder, thus indicating that this disorder is a complex behavioral threshold characteristic. Therefore, the aim of this study was to estimate the contribut...
Full Text Available Abstract Background Bipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, RAR-related orphan receptors alpha (RORA and beta (RORB, was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms (SNPs in RORA and RORB. Methods We genotyped 355 RORA and RORB SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching. Results We report that four intronic RORB SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three RORB haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any RORA SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any RORA or RORB SNPs. Conclusion Our findings suggest that clock genes in
Simon M McCrea
Full Text Available Simon M McCreaDepartments of Neurology and Neuroophthalmology, University of British Columbia, 2550 Willow Street, Vancouver, British Columbia, Canada V5Z 3N9Abstract: Recent studies have suggested that some variants of bipolar disorder (BD may be due to hyperconnectivity between orbitofrontal (OFC and temporal pole (TP structures in the dominant hemisphere. Some initial MRI studies noticed that there were corpus callosum abnormalities within specific regional areas and it was hypothesized that developmentally this could result in functional or effective connectivity changes within the orbitofrontal-basal ganglia-thalamocortical circuits. Recent diffusion tensor imaging (DTI white matter fiber tractography studies may well be superior to region of interest (ROI DTI in understanding BD. A “ventral semantic stream” has been discovered connecting the TP and OFC through the uncinate and inferior longitudinal fasciculi and the elusive TP is known to be involved in theory of mind and complex narrative understanding tasks. The OFC is involved in abstract valuation in goal and sub-goal structures and the TP may be critical in binding semantic memory with person–emotion linkages associated with narrative. BD patients have relative attenuation of performance on visuoconstructional praxis consistent with an atypical localization of cognitive functions. Multiple lines of evidence suggest that some BD alleles are being selected for which could explain the enhanced creativity in higher-ability probands. Associations between ROI’s that are not normally connected could explain the higher incidence of artistic aptitude, writing ability, and scientific achievements among some mood disorder subjects.Keywords: bipolar disorder, diffusion tensor imaging, white matter tractography, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, mood dysphoria, creativity, ventral semantic stream, writing ability, artistic aptitude
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It has been estimated that the heritable component of bipolar disorder ranges between 80 and 90%. However, even genome-wide association studies explain only a fraction of phenotypic variability not resolving the problem of "lost heritability". Although direct evidence for epigenetic dysfunction in bipolar disorder is still limited, methodological technologies in epigenomic profiling have advanced, offering even single cell analysing and resolving the problem of cell heterogeneity in epigenetics research. Gene overlapping with other mental disorders represents another problem in identifying potential susceptibility genes in bipolar disorder. Better understanding of the interplay between multiple environmental and genetic factors involved in the patogenesis of bipolar disorder could provide relevant information for treatment of patients with this complex disorder. Future studies on the role of these factors in psychopathological conditions, subphenotypes and endophenotypes may greatly benefit by using more precise clinical data and a combined approach with multiple research tools incorporated into a single study.
Recent studies provide considerable evidence that schizophrenia and bipolar disorder may share overlapping etiologic determinants. Identifying disease-related genetic effects is a major focus in schizophrenia and bipolar disorder research, with implications for clarifying diagnosis and developing specific treatments for various impairments in these 2 disorders. Efforts have been multifaceted, with the ultimate goal of describing causal paths from specific genetic variants, to changes in neuro...
Full Text Available In the clinical course of bipolar disorder, there is a reduction in sexual will during depressive episodes and inappopriate sexual experiences and hypersexuality occurs during manic episodes. Up to now, studies focused on sexual side effects of drugs. Sexual violence, sexually transmitted diseases, contraception methods, unplanned pregnancies need to be assessed carefully in bipolar disorder patients. This review focused on sexuality and sexual dysfunctions in the course of bipolar disorder. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(4.000: 309-320
Harvey, Allison G; Kaplan, Katherine A; Soehner, Adriane M
Bipolar disorder is a severe and chronic disorder, ranked in the top 10 leading causes of disability worldwide. Sleep disturbances are strongly coupled with interepisode dysfunction and symptom worsening in bipolar disorder. Experimental studies suggest that sleep deprivation can trigger manic relapse. There is evidence that sleep deprivation can have an adverse impact on emotion regulation the following day. The clinical management of the sleep disturbances experienced by bipolar patients, including insomnia, hypersomnia delayed sleep phase, and irregular sleep-wake schedule, may include medication approaches, psychological interventions, light therapies and sleep deprivation.
Izabela Guimarães Barbosa
Full Text Available OBJETIVO: Pesquisas recentes têm implicado fatores imunes na patogênese de diversos transtornos neuropsiquiátricos. O objetivo do presente trabalho é revisar os trabalhos que investigaram a associação entre transtorno bipolar e alterações em parâmetros imunes. MÉTODOS: Artigos que incluíam as palavras-chave: "bipolar disorder", "mania", "immunology", "cytokines", "chemokines", "interleukins", "interferon" e "tumor necrosis factor" foram selecionados em uma revisão sistemática da literatura. As bases de dados avaliadas foram MedLine e Scopus, entre os anos de 1980 e 2008. RESULTADOS: Foram identificados 28 trabalhos que estudaram alterações imunes em pacientes com transtorno bipolar. Seis artigos investigaram genes relacionados à resposta imune; cinco, autoanticorpos; quatro, populações leucocitárias; 13, citocinas e/ou moléculas relacionadas à resposta imune e seis, leucócitos de pacientes in vitro. CONCLUSÕES: Embora haja evidências na literatura correlacionando o transtorno bipolar a alterações imunes, os dados não são conclusivos. O transtorno bipolar parece estar associado a níveis mais elevados de autoanticorpos circulantes, assim como à tendência à ativação imune com produção de citocinas pró-inflamatórias e redução de parâmetros anti-inflamatórios.OBJECTIVE: Emerging research has implicated immune factors in the pathogenesis of a variety of neuropsychiatric disorders. The objective of the present paper is to review the studies that investigated the association between bipolar disorder and immune parameters. METHODS: Papers that included the keywords "bipolar to disorder", "mania", "immunology", "cytokines", "chemokines", "interleukins", "interferon" and "tumor necrosis factor" were selected in a systematic review of the literature. The evaluated databases were MedLine and Scopus in the period between 1980 and 2008. RESULTS: Twenty eight works were found. Six studies investigated immune response
McCrea, Simon M
Recent studies have suggested that some variants of bipolar disorder (BD) may be due to hyperconnectivity between orbitofrontal (OFC) and temporal pole (TP) structures in the dominant hemisphere. Some initial MRI studies noticed that there were corpus callosum abnormalities within specific regional areas and it was hypothesized that developmentally this could result in functional or effective connectivity changes within the orbitofrontal-basal ganglia-thalamocortical circuits. Recent diffusion tensor imaging (DTI) white matter fiber tractography studies may well be superior to region of interest (ROI) DTI in understanding BD. A "ventral semantic stream" has been discovered connecting the TP and OFC through the uncinate and inferior longitudinal fasciculi and the elusive TP is known to be involved in theory of mind and complex narrative understanding tasks. The OFC is involved in abstract valuation in goal and sub-goal structures and the TP may be critical in binding semantic memory with person-emotion linkages associated with narrative. BD patients have relative attenuation of performance on visuoconstructional praxis consistent with an atypical localization of cognitive functions. Multiple lines of evidence suggest that some BD alleles are being selected for which could explain the enhanced creativity in higher-ability probands. Associations between ROI's that are not normally connected could explain the higher incidence of artistic aptitude, writing ability, and scientific achievements among some mood disorder subjects.
Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh
Studies from the USA suggest that rates of pediatric bipolar disorder have increased since the mid-90s, but no study outside the USA has been published on the rates of pediatric bipolar disorder. Further, it is unclear whether an increase in rates reflects a true increase in the illness or more...... diagnostic attention. Using nationwide registers of all inpatients and outpatients contacts to all psychiatric hospitals in Denmark, we investigated (1) gender-specific rates of incident pediatric mania/bipolar disorder during a period from 1995 to 2012, (2) whether age and other characteristics...... for pediatric mania/bipolar disorder changed during the calendar period (1995 to 2003 versus 2004 to 2012), and (3) whether the diagnosis is more often made at first psychiatric contact in recent time compared to earlier according to gender. Totally, 346 patients got a main diagnosis of a manic episode (F30...
Quilty, Lena Catherine; Sellbom, Martin; Tackett, Jennifer Lee; Bagby, Robert Michael
The purpose of the current investigation was to examine the personality predictors of bipolar disorder symptoms, conceptualized as one-dimensional (bipolarity) or two-dimensional (mania and depression). A psychiatric sample (N=370; 45% women; mean age 39.50 years) completed the Revised NEO Personality Inventory and the Minnesota Multiphasic Personality Inventory -2. A model in which bipolar symptoms were represented as a single dimension provided a good fit to the data. This dimension was predicted by Neuroticism and (negative) Agreeableness. A model in which bipolar symptoms were represented as two separate dimensions of mania and depression also provided a good fit to the data. Depression was associated with Neuroticism and (negative) Extraversion, whereas mania was associated with Neuroticism, Extraversion and (negative) Agreeableness. Symptoms of bipolar disorder can be usefully understood in terms of two dimensions of mania and depression, which have distinct personality correlates.
Full Text Available Alexandra K Gold,1 Louisa G Sylvia,1,2 1Department of Psychiatry, Massachusetts General Hospital, 2Harvard Medical School, Boston, MA, USA Abstract: Bipolar disorder is a serious mental illness characterized by alternating periods of elevated and depressed mood. Sleep disturbances in bipolar disorder are present during all stages of the condition and exert a negative impact on overall course, quality of life, and treatment outcomes. We examine the partnership between circadian system (process C functioning and sleep–wake homeostasis (process S on optimal sleep functioning and explore the role of disruptions in both systems on sleep disturbances in bipolar disorder. A convergence of evidence suggests that sleep problems in bipolar disorder result from dysregulation across both process C and process S systems. Biomarkers of depressive episodes include heightened fragmentation of rapid eye movement (REM sleep, reduced REM latency, increased REM density, and a greater percentage of awakenings, while biomarkers of manic episodes include reduced REM latency, greater percentage of stage I sleep, increased REM density, discontinuous sleep patterns, shortened total sleep time, and a greater time awake in bed. These findings highlight the importance of targeting novel treatments for sleep disturbance in bipolar disorder. Keywords: bipolar disorder, circadian rhythms, sleep–wake homeostasis
Xiaohan Hu; Qiang Liu; Zhao Zhang; Zhiqiang Li; Shilin Wang; Lin He; Yongyong Shi
@@ Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study (GWAS) of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium's (WTCCC)GWAS data of bipolar disorder (BPD) with 500K SNPs.
Full Text Available Abstract Depression in bipolar disorder has long been thought to be a state characterized by mental inactivity. However, recent research demonstrates that patients with bipolar disorder engage in rumination, a form of self-focused repetitive cognitive activity, in depressed as well as in manic states. While rumination has long been associated with depressed states in major depressive disorder, the finding that patients with bipolar disorder ruminate in manic states is unique to bipolar disorder and challenges explanations put forward for why people ruminate. We review the research on rumination in bipolar disorder and propose that rumination in bipolar disorder, in both manic and depressed states, reflects executive dysfunction. We also review the neurobiology of bipolar disorder and recent neuroimaging studies of rumination, which is consistent with our hypothesis that the tendency to ruminate reflects executive dysfunction in bipolar disorder. Finally, we relate the neurobiology of rumination to the neurobiology of emotion regulation, which is disrupted in bipolar disorder.
Monteith, Scott; Glenn, Tasha; Geddes, John; Whybrow, Peter C; Bauer, Michael
The delivery of psychiatric care is changing with a new emphasis on integrated care, preventative measures, population health, and the biological basis of disease. Fundamental to this transformation are big data and advances in the ability to analyze these data. The impact of big data on the routine treatment of bipolar disorder today and in the near future is discussed, with examples that relate to health policy, the discovery of new associations, and the study of rare events. The primary sources of big data today are electronic medical records (EMR), claims, and registry data from providers and payers. In the near future, data created by patients from active monitoring, passive monitoring of Internet and smartphone activities, and from sensors may be integrated with the EMR. Diverse data sources from outside of medicine, such as government financial data, will be linked for research. Over the long term, genetic and imaging data will be integrated with the EMR, and there will be more emphasis on predictive models. Many technical challenges remain when analyzing big data that relates to size, heterogeneity, complexity, and unstructured text data in the EMR. Human judgement and subject matter expertise are critical parts of big data analysis, and the active participation of psychiatrists is needed throughout the analytical process.
... html Kids With Bipolar Disorder More Likely to Abuse Drugs, Alcohol: Study And those who also have conduct disorder ... with bipolar disorder, the risk that they will abuse alcohol and drugs may increase as they get older, ...
Christensen, Ellen Margrethe; Larsen, Jens Knud; Gjerris, Annette
In bipolar disorder, the factors provoking a new episode are unknown. As a seasonal variation has been noticed, it has been suggested that weather conditions may play a role. The aim of the study was to elucidate whether meteorological parameters influence the development of new bipolar phases....... A group of patients with at least three previous hospitalizations for bipolar disorder was examined every 3 months for up to 3 years. At each examination an evaluation of the affective phase was made according to the Hamilton Depression Scale (HAM-D(17)), and the Bech-Rafaelsen Mania Rating Scale (MAS......). In the same period, daily recordings from the Danish Meteorological Institute were received. We found no correlations between onset of bipolar episodes [defined as MAS score of 11 or more (mania) and as HAM-D(17) score of 12 or more (depression)] and any meteorological parameters. We found a statistical...
Kontis, D; Theochari, I; Tsalta, E
Dementia and bipolar disorder have been traditionally considered two separate clinical entities. However, recent preclinical and clinical data in elderly people suggest that they are in fact related. Several theories have been put forward to interpret their relationship which could be summed up as follows: (1) Dementia could increase the risk for the emergence of bipolar symptoms, or (2) conversely, bipolar disorder might be associated with heightened risk for developing pseudodementia or dementia. (3) Alternatively, dementia, other brain diseases or drugs affecting brain function could lead to the combination of symptoms of dementia and bipolar disorder in elderly individuals. The two disorders demonstrate similarities with respect to their clinical expression (agitation, psychotic, mood and cognitive symptoms) and structural brain neuroimaging (enlarged lateral ventricles and white matter hyperintensities using magnetic resonance imaging-MRI). Despite the above similarities, the two disorders also have important differences. As expected, cognitive symptoms prevail in dementia and mood symptoms in bipolar disorder. In dementia but not in bipolar disorder there is evidence that brain structural abnormalities are diffuse and hippocampal volumes are smaller. Dementia and bipolar disorder present different abnormalities in functional brain neuroimaging. The pattern of "ventral" hyperactivity and "dorsal" hypoactivity in brain emotional circuits at rest is revealed in bipolar disorder but not dementia. With respect to their treatment, acetylcholinesterase inhibitors and memantine are indicated against cognitive symptoms in dementia and also improve behavioural and psychological symptoms appearing during the course of dementia. Lithium, anticonvulsants, antipsychotics and antidepressants are effective in the management of the acute episodes of bipolar disorder of younger adults, but there are not yet evidence-based data in elderly bipolar patients. It is likely that the
Full Text Available Stigma is a serious impediment to the well-being of those who experience it. Many family- caregivers are challenged by the stereotypes and prejudice that result from misconceptions about bipolar disorder.The purpose of this study was to explore the stigma experienced by family caregivers of patients with bipolar disorder.This was a qualitative and phenomenological study. In this study, we selected the family caregivers of patients with bipolar disorder in a psychiatric hospital (Iran using purposive sampling in 2011. By reaching data saturation, the number of participant was 12. Data were gathered through in-depth interviews and analyzed by the "Collaizi" method.Stigma was a pervasive concern to almost all participants. Family caregivers of patients with Bipolar disorders reported feelings and experiences of stigma and were most affected by them. Analysis of the interviews revealed 3 themes: Negative judgment, Shame, Stigmatization and Social Isolation.For a person with bipolar disorder, this illness is associated with the following problems: worse recovery, difficulty accessing health services, receiving poor treatment and support, and difficulty gaining community acceptance. Rejection of people with mental illness might also affect their family caregivers at various levels.
Faurholt-Jepsen, Maria; Kessing, Lars Vedel; Munkholm, Klaus
BACKGROUND: Heart rate variability (HRV) has been suggested reduced in bipolar disorder (BD) compared with healthy individuals (HC). This meta-analysis investigated: HRV differences in BD compared with HC, major depressive disorder or schizophrenia; HRV differences between affective states; HRV...
Full Text Available Sirijit Suttajit,1 Suchat Paholpak,2 Somrak Choovanicvong,3 Khanogwan Kittiwattanagul,4 Wetid Pratoomsri,5 Manit Srisurapanont1On behalf of the Thai Bipolar Registry Group1Department of Psychiatry, Chiang Mai University, Chiang Mai, 2Department of Psychiatry, Khon Kaen University, Khon Kaen, 3Srithanya Hospital, Nonthaburi, 4Khon Kaen Rajanagarindra Psychiatric Hospital, Khon Kaen, 5Chachoengsao Hospital, Chachoengsao, ThailandBackground: The Thai Bipolar Disorder Registry was a prospective, multisite, naturalistic study conducted in 24 hospitals across Thailand. This study aimed to examine the correlates of current suicide risk in Thai patients with bipolar I disorder.Methods: Participants were adult inpatients or outpatients with bipolar disorder, based on the Diagnosis and Statistical Manual of Mental Disorders, fourth edition. All were assessed by using the Mini International Neuropsychiatric Interview (MINI, version 5. The severity of current suicide risk was determined by using the total score of the MINI suicidality module. Mood symptoms were assessed by using the Young Mania Rating Scale and the Montgomery Asberg Depression Rating Scale.Results: The data of 383 bipolar I disorder patients were included in the analyses. Of these, 363 (94.8% were outpatients. The mean (standard deviation of the MINI suicide risk score was 1.88 (5.0. The demographic/clinical variables significantly associated with the MINI suicide risk scores included age, number of overall previous episodes, the Young Mania Rating Scale score, the Montgomery Asberg Depression Rating Scale scores, and the Clinical Global Impression Severity of Illness Scale for Bipolar Disorder mania score, depression score, and overall score. The variables affecting the differences of suicide risk scores between or among groups were type of first mood episode, a history of rapid cycling, anxiety disorders, and alcohol use disorders. The stepwise multiple linear regression model revealed
Shain, Benjamin N
Pediatric bipolar disorder, once thought rare, has gone through stages of conceptualization. DSM criteria were reinterpreted such that children and adolescents, particularly those with ADHD, were commonly diagnosed with bipolar disorder and thought to be atypical by adult standards. Research criteria separated pediatric bipolar patients into 3 phenotypes, including a research diagnosis of "severe mood dysregulation." DSM-5 largely maintained previous criteria for bipolar disorder at all ages and created a new diagnosis called "disruptive mood dysregulation disorder," categorized as a depressive disorder, for persistently angry or irritable patients with symptoms of childhood onset. However, the controversy regarding the diagnosis of pediatric bipolar disorder continues. Progress has been made in the classification of children and adolescents with mood symptoms who are predominantly irritable or angry, but lack of clarity remains regarding classification of children and adolescents with "symptoms characteristic of bipolar disorder" who do not meet criteria for bipolar I disorder, bipolar II disorder, or cyclothymia.
Hasler, Gregor; Wolf, Andreas
In bipolar disorders, there are unclear diagnostic boundaries with unipolar depression and schizophrenia, inconsistency of treatment guidelines, relatively long trial-and-error phases of treatment optimization, and increasing use of complex combination therapies lacking empirical evidence. These suggest that the current definition of bipolar disorders based on clinical symptoms reflects a clinically and etiologically heterogeneous entity. Stratification of treatments for bipolar disorders based on biomarkers and improved clinical markers are greatly needed to increase the efficacy of currently available treatments and improve the chances of developing novel therapeutic approaches. This review provides a theoretical framework to identify biomarkers and summarizes the most promising markers for stratification regarding beneficial and adverse treatment effects. State and stage specifiers, neuropsychological tests, neuroimaging, and genetic and epigenetic biomarkers will be discussed with respect to their ability to predict the response to specific pharmacological and psychosocial psychotherapies for bipolar disorders. To date, the most reliable markers are derived from psychopathology and history-taking, while no biomarker has been found that reliably predicts individual treatment responses. This review underlines both the importance of clinical diagnostic skills and the need for biological research to identify markers that will allow the targeting of treatment specifically to sub-populations of bipolar patients who are more likely to benefit from a specific treatment and less likely to develop adverse reactions.
Full Text Available Bipolar disorder is a common, complex psychiatric disorder characterized by mania and depression. The disease aggregates in families, but despite much effort, it has been difficult to delineate the basic genetic model or identify specific genetic risk factors. Single gene Mendelian transmission and common variant hypotheses, but also multivariate threshold models and oligogenic quasi-Mendelian modes of inheritance have dominated the discussion at times. Almost complete sequence information of the human genome and falling sequencing costs now offer the opportunity to test these models in families in which the disorder is transmitted over several generations. Exome-wide sequencing studies have revealed an astonishing number of rare and potentially damaging mutations in brain expressed genes that could have contributed to the disease manifestation. However, the statistical analysis of these data has been challenging, because genetic risk factors displayed a high degree of dissimilarity across families. This scenario is not unique to bipolar disorder, but similar results have also been found in schizophrenia, a potentially related psychiatric disorder. Recently, our group has published data which supported an oligogenic genetic model of transmission in a family with bipolar disorder. In this family, three affected siblings shared rare, damaging mutations in multiple genes, which were linked to stress response pathways. These pathways are also the target for drugs frequently used to treat bipolar disorder. This article discusses these findings in the context of previously proclaimed disease models and suggests future research directions, including biological confirmation and phenotype stratification as an approach to disease heterogeneity.
Hirschfeld, Robert M.A.
Bipolar disorder is frequently encountered in primary care settings, often in the form of poor response to treatment for depression. Although lifetime prevalence of bipolar I disorder is 1%, the prevalence of bipolar spectrum disorders (e.g., bipolar I, bipolar II, and cyclothymia) is much higher, especially among patients with depression. The consequences of misdiagnosis can be devastating. One way to improve recognition of bipolar spectrum disorders is to screen for them. The Mood Disorder ...
Alexandre Martins Valença
Full Text Available Os autores relatam o caso de uma mulher que cometeu delito de assalto e foi avaliada em perícia psiquiátrica para análise da responsabilidade penal. Conclui-se que ela apresentava doença mental, na forma de transtorno bipolar, daí ser inimputável. A avaliação da responsabilidade penal é de extrema importância, para que se possam aplicar medidas de segurança ou sanções penais e correcionais adequadas a cada caso.The authors report a case of a woman who committed the crime of assault and was evaluated in penal imputability exam to assess criminal responsibility. It was concluded that she had a mental illness, bipolar disorder, being inimputable. The evaluation of penal responsibility is extremely important, in order to apply adequate involuntary commitment or correctional and penal sanctions to each case.
Severance, E.G.; Dupont, D.; Dickerson, F.B.; Stallings, C.R.; Origoni, A.E.; Krivogorsky, B.; Yang, S.; Haasnoot, W.; Yolken, R.H.
Objectives: Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized differe
Demant, Kirsa M; Vinberg, Maj; Kessing, Lars V
Cognitive dysfunction is prevalent in bipolar disorder (BD). However, the evidence regarding the association between subjective cognitive complaints, objective cognitive performance and psychosocial function is sparse and inconsistent. Seventy seven patients with bipolar disorder who presented...
Munkholm, Klaus; Braüner, Julie Vestergaard; Kessing, Lars Vedel
Bipolar disorder may be associated with peripheral immune system dysfunction; however, results in individual studies are conflicting. Our aim was to systematically review evidence of peripheral cytokine alterations in bipolar disorder integrating findings from various affective states....
Tânia M.S. Novaretti
Full Text Available ABSTRACT Parkinson's disease is a neurodegenerative disorder predominantly resulting from dopamine depletion in the substantia nigra pars compacta. Some psychiatric disorders may have dopaminergic dysfunction as their substrate. We describe a well-documented case of Parkinson's disease associated with Bipolar Disorder. Although there is some knowledge about the association between these diseases, little is known about its pathophysiology and correlation. We believe that among various hypotheses, many neurotransmitters are linked to this pathophysiology.
Goldstein, Benjamin I.; Shamseddeen, Wael; Axelson, David A.; Kalas, Cathy; Monk, Kelly; Brent, David A.; Kupfer, David J.; Birmaher, Boris
Objective: Despite increased risk, most offspring of parents with bipolar disorder (BP) do not manifest BP. The identification of risk factors for BP among offspring could improve preventive and treatment strategies. We examined this topic in the Pittsburgh Bipolar Offspring Study (BIOS). Method: Subjects included 388 offspring, ages 7-17 years,…
Full Text Available In 1975 Fieve and Dunner made the distinction between hypomania and mania as hypomania does not usually cause social and occupational impair-ment and hospitalization is not needed, moreover patients do not experience psychosis. Bipolar disorder type I is defined by the presence of manic and depressive episodes and differs from Bipolar disorder type II characterized with hipomanic and depressive episodes. Bipolar disorder type I and II do not differ in their depressive episodes. It is still point of contention whether bipolar type II is a variant of bipolar disorder type I or is positioned on the spectrum between bipolar type I and unipolar disorder. Even there are some similarities in characteristics of depressive episodes and outcome features of different bipolar disorder subtypes, there are differences that can be useful in differential diagnosis and treatment. This paper aims to focus on those differences between bipolar disorder type I and II.
Sullivan, Aimee E.; Judd, Charles M.; Axelson, David A.; Miklowitz, David J.
The symptoms of bipolar disorder affect and are affected by the functioning of family environments. Little is known, however, about the stability of family functioning among youth with bipolar disorder as they cycle in and out of mood episodes. This study examined family functioning and its relationship to symptoms of adolescent bipolar disorder,…
Full Text Available Abstract Background and objective Asperger's Syndrome (AS is a pervasive developmental disorder that is sometimes unrecognized, especially in the adult psychiatric setting. On the other hand, in patients with an AS diagnosis, comorbid psychiatric disorders may be unrecognized in the juvenile setting. The aim of the paper is to show and discuss some troublesome and complex problems of the management of patients with AS and comorbid Bipolar Disorder (BD. Methods The paper describes three patients affected by AS and bipolar spectrum disorders. Results and conclusion Mood stabilizers and 2nd generation antipsychotics were effective in the treatment of these AS patients with comorbid BD, while the use of antidepressants was associated with worsening of the mood disorder. It is of importance to recognize both the psychiatric diagnoses in order to arrange an exhaustive therapeutic program and to define specific and realistic goals of treatment.
Dallaspezia, Sara; Benedetti, Francesco
Multiple lines of evidence suggest that psychopathological symptoms of bipolar disorder arise in part from a malfunction of the circadian system, linking the disease with an abnormal internal timing. Alterations in circadian rhythms and sleep are core elements in the disorders, characterizing both mania and depression and having recently been shown during euthymia. Several human genetic studies have implicated specific genes that make up the genesis of circadian rhythms in the manifestation of mood disorders with polymorphisms in molecular clock genes not only showing an association with the disorder but having also been linked to its phenotypic particularities. Many medications used to treat the disorder, such as antidepressant and mood stabilizers, affect the circadian clock. Finally, circadian rhythms and sleep researches have been the starting point of the developing of chronobiological therapies. These interventions are safe, rapid and effective and they should be considered first-line strategies for bipolar depression.
Rajkumar, A.P.; Christensen, Jane H.; Mattheisen, Manuel
OBJECTIVES: Breakpoints of chromosomal abnormalities facilitate identification of novel candidate genes for psychiatric disorders. Genome-wide significant evidence supports the linkage between chromosome 17q25.3 and bipolar disorder (BD). Co-segregation of translocation t(9;17)(q33.2;q25.......3) with psychiatric disorders has been reported. We aimed to narrow down these chromosomal breakpoint regions and to investigate the associations between single nucleotide polymorphisms within these regions and BD as well as schizophrenia (SZ) in large genome-wide association study samples. METHODS: We cross......,856) data. Genetic associations between these disorders and single nucleotide polymorphisms within these breakpoint regions were analysed by BioQ, FORGE, and RegulomeDB programmes. RESULTS: Four protein-coding genes [coding for (endonuclease V (ENDOV), neuronal pentraxin I (NPTX1), ring finger protein 213...
Vöhringer, Paul A; Perlis, Roy H
Rates of misdiagnosis between major depressive disorder and bipolar disorder have been reported to be substantial, and the consequence of such misdiagnosis is likely to be a delay in achieving effective control of symptoms, in some cases spanning many years. Particularly in the midst of a depressive episode, or early in the illness course, it may be challenging to distinguish the 2 mood disorders purely on the basis of cross-sectional features. To date, no useful biological markers have been reliably shown to distinguish between bipolar disorder and major depressive disorder.
Wilson, Lynere; Crowe, Marie; Scott, Anne; Lacey, Cameron
Psychoeducation has become a common intervention within mental health settings. It aims to increase people's ability to manage a life with a long-term illness. For people with bipolar disorder, psychoeducation is one of a range of psychosocial interventions now considered part of contemporary mental health practice. It has taken on a 'common sense' status that results in little critique of psychoeducation practices. Using a published manual on psychoeducation and bipolar disorder as its data, Foucauldian discourse analysis was used in the present study for a critical perspective on psychoeducation in order to explore the taken-for-granted assumptions on which it is based. It identifies that the text produces three key subject positions for people with bipolar disorder. To practice self-management, a person must: (i) accept and recognize the authority of psychiatry to know them; (ii) come to see that they can moderate themselves; and (iii) see themselves as able to undertake a reflexive process of self-examination and change. These findings highlight the circular and discursive quality to the construct of insight that is central to how psychoeducation is practiced. Using Foucault's construct of pastoral power, it also draws attention to the asymmetrical nature of power relations between the clinician and the person with bipolar disorder. An effect of the use of medical discourse in psychoeducation is to limit its ability to work with ambivalence and contradiction. A critical approach to psychotherapy and education offers an alternate paradigm on which to basis psychoeducation practices.
Miskowiak, Kamilla W; Carvalho, André F; Vieta, Eduard
Cognitive dysfunction is an emerging treatment target in bipolar disorder (BD). Several trials have assessed the efficacy of novel pharmacological and psychological treatments on cognition in BD but the findings are contradictory and unclear. A systematic search following the PRISMA guidelines...
Carvalho, A F; Köhler, C A; Fernandes, B S
BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed...
Morsel, A.M.; Temmerman, A.; Sabbe, B.G.C.; Hulstijn, W.; Morrens, M.
Background/Aims: In addition to affective and cognitive symptomatology, psychomotor deficits are known to be present in bipolar disorder (BD). Psychomotor functioning includes all of the processes necessary for completing a movement, from planning to initiation and execution. While these psychomotor
Kaufman, Kenneth R
This brief historical overview of bipolar disorder addresses diagnosis, treatment, cost, creativity, suicide, and stigma with a review of the literature. This served as the introduction to the 27th Annual Scientific Meeting of the American Academy of Clinical Psychiatrists (51 references).
Sajatovic, Martha; Strejilevich, Sergio A; Gildengers, Ariel G
OBJECTIVES: In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). METHODS...
Dernovšek, Mojca Zvezdana; Frangeš, Tadeja
Bipolar disorder is very prevalent in general population. According to Diagnostic and statistical manual ofmental disorders, fourth revision - DSM-IV, four types ofbipolar disorder are distinguished: bipolar disorder 1, bipolar disorder II, cyclothymia, and other types (not specified otherwise). Etiology of disorder is multifactorial with overlap between genetic, environmental"and neurobiological factors. Due to complexity of clinical features it represents diagnostical and therapeutical chal...
Many bipolar disorder patients exhibit mixed affective states, which portend a generally more severe illness course and treatment resistance. In the previous renditions of Diagnostic and Statistical Manual mixed states were narrowly defined in the context of bipolar I disorder, but with the advent of DSM-5 the term "mixed episode" was dropped and replaced by "mixed features" specifier which could be broadly applied to manic, hypomanic and depressive episodes in both the bipolar spectrum and major depressive disorders. This paradigm shift reflected their significance in the prognosis and overall management of mood disorders, so that the clinicians should thoroughly familiarize themselves with the contemporary notions surrounding these conditions. The purpose of this manuscript is to bring to light the current conceptualizations regarding the etiology, pathogenesis and treatment of mixed states. To achieve this goal, in June 2016 an extensive literature search was undertaken using the PubMed database. Some exploratory terms utilized included "mixed states", "mixed episodes", "switching", "rapid cycling" cross referenced with "bipolar disorder". Focusing on the most relevant and up to date studies, it was revealed that mixed states result from genetic susceptibility in the circadian and dopamine neurotransmission apparatuses and disturbance in the intricate catecholamine-acetylcholine neurotransmission balance which leads to mood fluctuations. The management of mixed states is challenging with atypical antipsychotics, newer anticonvulsants and electroconvulsive therapy emerging as the foremost treatment options. In conclusion, while progress has been made in the neurobiological understanding of mixed states, the currently available therapeutic modalities have only shown limited effectiveness.
Ludwig, B; Dwivedi, Y
In recent years, numerous studies of gene regulation mechanisms have emerged in neuroscience. Epigenetic modifications, described as heritable but reversible changes, include DNA methylation, DNA hydroxymethylation, histone modifications and noncoding RNAs. The pathogenesis of psychiatric disorders, such as bipolar disorder, may be ascribed to a complex gene–environment interaction (G × E) model, linking the genome, environmental factors and epigenetic marks. Both the high complexity and the high heritability of bipolar disorder make it a compelling candidate for neurobiological analyses beyond DNA sequencing. Questions that are being raised in this review are the precise phenotype of the disorder in question, and also the trait versus state debate and how these concepts are being implemented in a variety of study designs. PMID:27480490
Full Text Available Abstract Background Nearly all information processing during cognitive processing takes place during periods of sustained attention. Sustained attention deficit is among the most commonly reported impairments in bipolar disorder (BP. The majority of previous studies have only focused on bipolar I disorder (BP I, owing to underdiagnosis or misdiagnosis of bipolar II disorder (BP II. With the refinement of the bipolar spectrum paradigm, the goal of this study was to compare the sustained attention of interepisode patients with BP I to those with BP II. Methods In all, 51 interepisode BP patients (22 with BP I and 29 with BP II and 20 healthy controls participated in this study. The severity of psychiatric symptoms was assessed by the 17-item Hamilton Depression Rating Scale and the Young Mania Rating Scale. All participants undertook Conners' Continuous Performance Test II (CPT-II to evaluate sustained attention. Results After controlling for the severity of symptoms, age and years of education, BP I patients had a significantly longer reaction times (F(2,68 = 7.648, P = 0.001, worse detectability (d' values (F(2,68 = 6.313, P = 0.003 and more commission errors (F(2,68 = 6.182, P = 0.004 than BP II patients and healthy controls. BP II patients and controls scored significantly higher than BP I patients for d' (F = 6.313, P = 0.003. No significant difference was found among the three groups in omission errors and no significant correlations were observed between CPT-II performance and clinical characteristics in the three groups. Conclusions These findings suggested that impairments in sustained attention might be more representative of BP I than BP II after controlling for the severity of symptoms, age, years of education and reaction time on the attentional test. A longitudinal follow-up study design with a larger sample size might be needed to provide more information on chronological sustained attention deficit in BP patients, and to illustrate
Serra, Giulia; Demontis, Francesca; Serra, Francesca; De Chiara, Lavinia; Spoto, Andrea; Girardi, Paolo; Vidotto, Giulio; Serra, Gino
We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer’s dementia, is an effective treatment for acute mania and for the prevention of manic/hypomanic and depressive recurrences of manic-depressive illness. Lithium remains the first line for the treatment and prophylaxis of bipolar disorders, but currently available treatment alternatives for lithium resistant patients are of limited and/or questionable efficacy. Thus, research and development of more effective mood stabilizer drugs is a leading challenge for modern psychopharmacology. We have demonstrated that 21 d administration of imipramine causes a behavioural syndrome similar to a cycle of bipolar disorder, i.e., a mania followed by a depression, in rats. Indeed, such treatment causes a behavioural supersensitivity to dopamine D2 receptor agonists associated with an increase sexual activity and aggressivity (mania). The dopamine receptor sensitization is followed, after imipramine discontinuation, by an opposite phenomenon (dopamine receptor desensitization) and an increased immobility time (depression) in the forced swimming test of depression. Memantine blocks the development of the supersensitivity and the ensuing desensitization associated with the depressive like behavior. On the basis of these observations we have suggested the use of memantine in the treatment of mania and in the prophylaxis of bipolar disorders. To test this hypothesis we performed several naturalistic studies that showed an acute antimanic effect and a long-lasting and progressive mood-stabilizing action (at least 3 years), without clinically relevant side effects. To confirm the observations of our naturalistic trials we are now performing a randomized controlled clinical trial. Finally we described the studies reporting the efficacy of memantine in manic-like symptoms occurring in psychiatric disorders other than bipolar. Limitations: A randomized controlled
Christensen, Ellen Margrethe; Larsen, Jens Knud; Gjerris, Annette;
. A group of patients with at least three previous hospitalizations for bipolar disorder was examined every 3 months for up to 3 years. At each examination an evaluation of the affective phase was made according to the Hamilton Depression Scale (HAM-D(17)), and the Bech-Rafaelsen Mania Rating Scale (MAS......). In the same period, daily recordings from the Danish Meteorological Institute were received. We found no correlations between onset of bipolar episodes [defined as MAS score of 11 or more (mania) and as HAM-D(17) score of 12 or more (depression)] and any meteorological parameters. We found a statistical...
Full Text Available Aim of the study. Study aims were to compare neuropsychological functioning of depressed bipolar patients and healthy controls and to estimate relationship between severity of depressive symptoms and cognitive functioning. Method. Cognitive functions were examined in 30 depressed bipolar patients aged 18-68 (M=45,6, SD=12,6; 18 women and 12 men who fulfilled ICD-10 criteria for depressive episode (Hamilton Depression Rating Scale score ≥11. The comparison group consisted of 30 healthy subjects aged 23-71 (M=46, 20 women and 10 men matched in age, years of education and gender to bipolar group. A neuropsychological battery assessed executive functions and working memory. Results. The bipolar patients in depression revealed neuropsychological deficits in working memory and some aspects of executive functions in comparison to healthy group. Only in WCST test both groups received similar results. Neuropsychological functioning seems to be independent of the severity of depressive symptoms. Discussion. Different aspects of working memory and executive functions are impaired in depression period of bipolar disorder and they seem independent of the severity of depressive symptoms. These results are consistent with previous reports. Conclusions. In patients with bipolar depression cognitive assessment should be taken into account in the diagnosis and the disturbances in executive functions and working memory should be treated with neuropsychological rehabilitation and / or pharmacotherapy.
Anticonvulsant Drugs for Nerve Pain, Bipolar Disorder &Fibromyalgia: Choosing What’sRight for You What are anticonvulsant drugs? Anticonvulsants are drugs used to treat seizures. They are also used to treat bipolar ...
Antila, Mervi; Tuulio-Henriksson, Annamari; Kieseppä, Tuula; Soronen, Pia; Palo, Outi M; Paunio, Tiina; Haukka, Jari; Partonen, Timo; Lönnqvist, Jouko
Bipolar disorder is highly heritable. Cognitive dysfunctions often observed in bipolar patients and their unaffected relatives implicate that these impairments may be associated with genetic predisposition to bipolar disorder and thus fulfill the criteria of a valid endophenotype for the disorder. However, the most fundamental criterion, their heritability, has not been directly studied in any bipolar population. This population-based study estimated the heritability of cognitive functions in bipolar disorder. A comprehensive neuropsychological test battery and the Structured Clinical Interview for DSM-IV were administered to a population-based sample of 110 individuals from 52 families with bipolar disorder. Heritability of cognitive functions as assessed with neuropsychological test scores were estimated using the Solar package. Significant additive heritabilities were found in verbal ability, executive functioning, and psychomotor processing speed. Genetic contribution was low to verbal learning functions. High heritability, in executive functioning and psychomotor processing speed suggest that these may be valid endophenotypic traits for genetic studies of bipolar disorder.
Full Text Available Miroslav Hajda,1 Jan Prasko,1 Klara Latalova,1 Radovan Hruby,2 Marie Ociskova,1 Michaela Holubova,1,3 Dana Kamaradova,1 Barbora Mainerova1 1Department of Psychiatry, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic; 2Outpatient Psychiatric Department, Martin, Slovak Republic; 3Department of Psychiatry, Regional Hospital Liberec, Liberec, Czech Republic Background: Bipolar disorder (BD is a serious mental illness with adverse impact on the lives of the patients and their caregivers. BD is associated with many limitations in personal and interpersonal functioning and restricts the patients’ ability to use their potential capabilities fully. Bipolar patients long to live meaningful lives, but this goal is hard to achieve for those with poor insight. With progress and humanization of society, the issue of patients’ needs became an important topic. The objective of the paper is to provide the up-to-date data on the unmet needs of BD patients and their caregivers. Methods: A systematic computerized examination of MEDLINE publications from 1970 to 2015, via the keywords “bipolar disorder”, “mania”, “bipolar depression”, and “unmet needs”, was performed. Results: Patients’ needs may differ in various stages of the disorder and may have different origin and goals. Thus, we divided them into five groups relating to their nature: those connected with symptoms, treatment, quality of life, family, and pharmacotherapy. We suggested several implications of these needs for pharmacotherapy and psychotherapy. Conclusion: Trying to follow patients’ needs may be a crucial point in the treatment of BD patients. However, many needs remain unmet due to both medical and social factors. Keywords: bipolar disorder, unmet needs, stigma, treatment, medication, quality of life, family, psychotherapy
Wilens, Timothy E.; Biederman, Joseph; Kwon, Anne; Ditterline, Jeffrey; Forkner, Peter; Moore, Hadley; Swezey, Allison; Snyder, Lindsey; Henin, Aude; Wozniak, Janet; Faraone, Stephen V.
Objective: Previous work in adults and youths has suggested that juvenile onset bipolar disorder (BPD) is associated with an elevated risk of substance use disorders (SUD). Considering the public health importance of this issue, the authors now report on a controlled study of adolescents with and without BPD to evaluate the risk of SUD. Method:…
Arias, Francisco; Szerman, Nestor; Vega, Pablo; Mesías, Beatriz; Basurte, Ignacio; Rentero, David
Given its prevalence and impact on public health, the comorbidity of bipolar and substance use disorders is one of the most relevant of dual diagnoses. The objective was to evaluate the characteristics of patients from community mental health and substance abuse centres in Madrid. The sample consisted of 837 outpatients from mental health and substance abuse centres. We used the Mini International Neuropsychiatric Interview (MINI) and Personality Disorder Questionnaire (PDQ4+) to evaluate axis I and II disorders. Of these patients, 174 had a lifetime bipolar disorder, 83 had bipolar disorder type I and 91 had type II. Most patients had dual pathology. Of the 208 participants from the mental health centres, 21 had bipolar disorder and 13 (61.9%) were considered dually-diagnosed patients, while 33.2% of non-bipolar patients had a dual diagnoses (p = 0.03). Of the 629 participants from the substance abuse centres, 153 patients (24.3%) had a bipolar diagnosis. Bipolar dual patients had higher rates of alcohol and cocaine dependence than non-bipolar patients. Moreover, age at onset of alcohol use was earlier in bipolar duallydiagnosed patients than in other alcoholics. Bipolar dually-diagnosed patients had higher personality and anxiety disorder comorbidities and greater suicide risk. Thus, alcohol and cocaine are the drugs most associated with bipolar disorder. Given the nature of the study, the type of relationship between these disorders cannot be determined.
Yu, Hao; Bi, Wenjian; Liu, Chenxing; Zhao, Yanlong; Zhang, Dai; Yue, Weihua
Schizophrenia (SZ) and bipolar disorder (BD) are both severe neuropsychiatric disorders with a strong and potential overlapping genetic background. Multiple lines of evidence, including genetic studies, gene expression studies and neuroimaging studies, have suggested that both disorders are closely related to myelin and oligodendrocyte dysfunctions. In the current study, we hypothesized that the holistic effect of the myelin-related pathway contributes to the genetic susceptibility to both SZ and BD. We extracted pathway data from the canonical pathway database, Gene Ontology (GO), and selected a 'compiled' pathway based on previous literature. We then performed hypothesis-driven pathway analysis on GWAS data from the Psychiatric Genomics Consortium (PGC). As a result, we identified three myelin-related pathways with a joint effect significantly associated with both disorders: 'Myelin sheath' pathway (P(SZ) = 2.45E-7, P(BD) = 1.22E-3), 'Myelination' pathway (P(SZ) = 2.10E-4, P(BD) = 2.53E-24), and 'Compiled' pathway (P(SZ) = 4.57E-8, P(BD) = 2.61E-9). In comparing the SNPs and genes in these three pathways across the two diseases, we identified a substantial overlap in nominally associated SNPs and genes, which could be susceptibility SNPs and genes for both disorders. From these observations, we propose that myelin-related pathways may be involved in the etiologies of both SZ and BD.
Calabrese, Joseph R
Recent studies have reported lifetime prevalence estimates of 1.0% for bipolar I disorder, 1.1% for bipolar II disorder, and 2.4% to 4.7% for subthreshold bipolar disorder, illustrating the need for consensus definitions of bipolar spectrum disorders. These definitions will aid researchers in studying viable treatments options, as well as help clinicians in the differential diagnosis of patients. Broader definitions of bipolar spectrum disorders would also allow clinicians to more accurately diagnose patients, rather than placing them in the catchall category of bipolar disorder not otherwise specified. Bipolar symptoms that are currently labeled as subthreshold symptoms are becoming increasingly recognized as having relevant clinical implications. Despite diagnostic controversy, screening for the presence of mania in patients who present with depressive symptoms is a critical step in the appropriate treatment of bipolar spectrum disorders. Identifying the early onset of bipolar symptoms as manifested in prodromal disorders such as childhood major depressive disorder and attention-deficit/hyperactivity disorder is also important for possible early intervention and improved outcomes.
Quattlebaum, Patricia D.; Grier, Betsy C.; Klubnik, Cynthia
In the United States, bipolar disorder is an increasingly common diagnosis in children, and these children can present with severe behavior problems and emotionality. Many studies have documented the frequent coexistence of behavior disorders and speech-language disorders. Like other children with behavior disorders, children with bipolar disorder…
Fábio Gomes de Matos e Souza
Full Text Available O transtorno bipolar é um quadro complexo caracterizado por episódios de depressão, mania ou hipomania e fases assintomáticas. O tratamento visa ao controle de episódios agudos e prevenção de novos episódios. O tratamento farmacológico iniciou-se com o lítio. Até o momento, o lítio permanece como o tratamento com mais evidências favoráveis na fase de manutenção. Outros tratamentos demonstram eficácia nessa fase, como o valproato, a carbamazepina e os antipsicóticos atípicos. Dos antipsicóticos atípicos o mais estudado nesta fase do tratamento é a olanzapina. Mais estudos prospectivos são necessários para confirmar a ação profilática de novos agentes.Bipolar disorder is a complex disorder characterized by depression episodes, mania or hypomania and asymptomatic phases. The treatment aims at the control of acute episodes and prevention of new episodes. The pharmacological treatment was inaugurated with lithium. Until the moment, lithium remains as the treatment with more favorable evidences in the maintenance phase. Other treatments demonstrate efficacy in this phase, as valproate, carbamazepine and atypical antipsychotics. Of the atypical antipsychotics, the most studied in this phase of treatment is olanzapine. More prospective studies are necessary to confirm prophylactic action of new agents.
Cardno, Alastair G; Owen, Michael J
There is substantial evidence for partial overlap of genetic influences on schizophrenia and bipolar disorder, with family, twin, and adoption studies showing a genetic correlation between the disorders of around 0.6. Results of genome-wide association studies are consistent with commonly occurring genetic risk variants, contributing to both the shared and nonshared aspects, while studies of large, rare chromosomal structural variants, particularly copy number variants, show a stronger influence on schizophrenia than bipolar disorder to date. Schizoaffective disorder has been less investigated but shows substantial familial overlap with both schizophrenia and bipolar disorder. A twin analysis is consistent with genetic influences on schizoaffective episodes being entirely shared with genetic influences on schizophrenic and manic episodes, while association studies suggest the possibility of some relatively specific genetic influences on broadly defined schizoaffective disorder, bipolar subtype. Further insights into genetic relationships between these disorders are expected as studies continue to increase in sample size and in technical and analytical sophistication, information on phenotypes beyond clinical diagnoses are increasingly incorporated, and approaches such as next-generation sequencing identify additional types of genetic risk variant.
Full Text Available Objective: The efficacy of atypical antipsychotics including olanzapine in acute treatment of manic episode has been established, whereas its role in maintenance treatment is not clear. Materials and Methods: Thirteen patients of bipolar disorder who were on regular treatment with mood stabilizer and subsequently relapsed into mania or depressive episode after discontinuation of olanzapine were studied for various socio-demographic and clinical factors using retrospective chart review. Results: There was no correlation found between the period of tapering olanzapine, time to recurrence of episode after discontinuation, and the dosage of olanzapine at the time of discontinuation. The predominant early signs of relapse after discontinuation of olanzapine included sleep disturbance (72.7%, lack of insight for change in behavior (72.7%, irritability (54.5%, and elevated mood (45.5%. Conclusion: Mood stabilizer alone as a maintenance therapy of bipolar disorder may be inadequate for long-term management. A low dose of olanzapine along with mood stabilizers might be useful for prevention of recurrence in bipolar disorder.
Mason, Brittany L; Brown, E Sherwood; Croarkin, Paul E
Mood is the changing expression of emotion and can be described as a spectrum. The outermost ends of this spectrum highlight two states, the lowest low, melancholia, and the highest high, mania. These mood extremes have been documented repeatedly in human history, being first systematically described by Hippocrates. Nineteenth century contemporaries Falret and Baillarger described two forms of an extreme mood disorder, with the validity and accuracy of both debated. Regardless, the concept of a cycling mood disease was accepted before the end of the 19th century. Kraepelin then described "manic depressive insanity" and presented his description of a full spectrum of mood dysfunction which could be exhibited through single episodes of mania or depression or a complement of many episodes of each. It was this concept which was incorporated into the first DSM and carried out until DSM-III, in which the description of episodic mood dysfunction was used to build a diagnosis of bipolar disorder. Criticism of this approach is explored through discussion of the bipolar spectrum concept and some recent examinations of the clinical validity of these DSM diagnoses are presented. The concept of bipolar disorder in children is also explored.
Brittany L. Mason
Full Text Available Mood is the changing expression of emotion and can be described as a spectrum. The outermost ends of this spectrum highlight two states, the lowest low, melancholia, and the highest high, mania. These mood extremes have been documented repeatedly in human history, being first systematically described by Hippocrates. Nineteenth century contemporaries Falret and Baillarger described two forms of an extreme mood disorder, with the validity and accuracy of both debated. Regardless, the concept of a cycling mood disease was accepted before the end of the 19th century. Kraepelin then described “manic depressive insanity” and presented his description of a full spectrum of mood dysfunction which could be exhibited through single episodes of mania or depression or a complement of many episodes of each. It was this concept which was incorporated into the first DSM and carried out until DSM-III, in which the description of episodic mood dysfunction was used to build a diagnosis of bipolar disorder. Criticism of this approach is explored through discussion of the bipolar spectrum concept and some recent examinations of the clinical validity of these DSM diagnoses are presented. The concept of bipolar disorder in children is also explored.
S Gh Mousavi
Full Text Available Background: Despite the effectiveness of pharmacotherapy in acute phase of bipolar mood disorder, patients often experience relapses or recurrent episodes. Hospitalization of patients need a great deal of financial and humanistic resources which can be saved through understanding more about the rate of relapse and factors affecting this rate. Methods: In a descriptive analytical study, 380 patients with bipolar disorder who were hospitalized in psychiatric emergency ward of Noor hospital, Isfahan, Iran, were followed. Each patient was considered for; the frequency of relapse and recurrence, kind of pharmachotherapy, presence of psychotherapeutic treatments, frequency of visits by psychiatrist and the rank of present episode. Results: The overall prevalence of recurrence was 42.2%. Recurrence was lower in patients using lithium carbonate or sodium valproate or combined therapy (about 40%, compared to those using carbamazepine (80%. Recurrence was higher in patients treated with only pharmacotherapy (44.5% compared to those treated with both pharmacotherapy and psychotherapy (22.2%. Patients who were visited monthy by psychiatrist had lower rate of recurrence compared to those who had irregular visits. Conclusion: The higher rate of recurrence observed in carbamazepine therapy may be due to its adverse reactions and consequently poor compliance to this drug. Lower rates of recurrence with psychotherapy and regular visits may be related to the preventive effects of these procedures and especially to the effective management of stress. Keywords: Bipolar Mood Disorder, Recurrence, Relapse.
Mason, Brittany L.; Brown, E. Sherwood; Croarkin, Paul E.
Mood is the changing expression of emotion and can be described as a spectrum. The outermost ends of this spectrum highlight two states, the lowest low, melancholia, and the highest high, mania. These mood extremes have been documented repeatedly in human history, being first systematically described by Hippocrates. Nineteenth century contemporaries Falret and Baillarger described two forms of an extreme mood disorder, with the validity and accuracy of both debated. Regardless, the concept of a cycling mood disease was accepted before the end of the 19th century. Kraepelin then described “manic depressive insanity” and presented his description of a full spectrum of mood dysfunction which could be exhibited through single episodes of mania or depression or a complement of many episodes of each. It was this concept which was incorporated into the first DSM and carried out until DSM-III, in which the description of episodic mood dysfunction was used to build a diagnosis of bipolar disorder. Criticism of this approach is explored through discussion of the bipolar spectrum concept and some recent examinations of the clinical validity of these DSM diagnoses are presented. The concept of bipolar disorder in children is also explored. PMID:27429010
An early recognition of bipolar disorders may have an important impact on the prognosis of this disorder according to different mechanisms. Bipolar disorder is nevertheless not easy to detect, the diagnosis being correctly proposed after, in average more than a couple of Years and three different doctors assessments. A short delay before introducing the relevant treatment should help avoiding inappropriate treatments (prescribing, for example, neuroleptics for long periods, antidepressive drugs each time depressive symptoms occurs, absence of treatment despite mood disorders), with their associated negative impact such as mood-switching, rapid cycling or presence of chronic side-effects stigmates. Furthermore, non-treated mood disorders in bipolar disorder are longer, more stigmatizing and may be associated with an increased risk of suicidal behaviour and mortality. Lastly, compliance, an important factor regarding the long term prognosis of bipolar disorder, should be improved when there is a short delay between correct diagnosis and treatment and onset of the disorder. We therefore propose to review the literature for the different pitfalls involved in the diagnosis of bipolar disorder. Non-bipolar mood-disorders are frequently quoted as one of the alternative diagnosis. Hyperthymic temperament, side-effects of prescribed treatments and organic comorbid disorders may be involved. Bipolar disorders have a sex-ratio closer to 1 (men are thus more frequently of the bipolar type in mood-disorders), with earlier age at onset, and more frequent family history of suicidal attempts and bipolar disorder. Schizo-affective disorders are also a major concern regarding the diagnosis of bipolar disorder. This is explained by flat affects sometimes close to anhedonia, presence of a schizoïd personality in bipolar disorder, persecutive hostility that can be considered to be related to irritability rather than a schizophrenic symptom. Rapid cycling, mixed episodes and short
Alexandro de Borja Gonçalves Guerra
Full Text Available Diferenças sexuais, descritas em vários transtornos psiquiátricos, também parecem estar presentes no transtorno afetivo bipolar (TAB. A prevalência do TAB tipo I se distribui igualmente entre mulheres e homens. Mulheres parecem estar sujeitas a um risco maior de ciclagem rápida e mania mista, condições que fariam do TAB um transtorno com curso mais prejudicial no sexo feminino. Uma diátese depressiva mais marcante, uso excessivo de antidepressivos e diferenças hormonais surgem como hipóteses para explicar essas diferenças fenomenológicas, apesar das quais, mulheres e homens parecem responder igualmente ao tratamento medicamentoso. A indicação de anticonvulsivantes como primeira escolha em mulheres é controversa, a não ser para o tratamento da mania mista e, talvez, da ciclagem rápida. O tratamento do TAB na gravidez deve levar em conta tanto os riscos de exposição aos medicamentos quanto à doença materna. A profilaxia do TAB no puerpério está fortemente indicada em decorrência do grande risco de recorrência da doença nesse período. Embora, de modo geral, as medicações psicotrópicas estejam contra-indicadas durante a amamentação, entre os estabilizadores do humor, a carbamazepina e o valproato são mais seguros do que o lítio. Mais estudos são necessários para a confirmação das diferenças de curso do TAB entre mulheres e homens e a investigação de possíveis diferenças na efetividade dos tratamentos.Gender differences, described in several psychiatric disorders, seem to be also present in bipolar disorder (BD. The prevalence of bipolar I disorder is equally distributed between women and men. Women seem to be at higher risk for rapid cycling and mixed mania, conditions that could make BD a disorder with a more severe course in the female sex. A marked depressive diathesis among women, greatest use of antidepressants and hormonal differences have been mentioned as hypotheses to explain these
Letícia Czepielewski; Ledo Daruy Filho; Elisa Brietzke; Rodrigo Grassi-Oliveira
OBJECTIVE: Summarize data on metabolic syndrome (MS) in bipolar disorder (BD). METHODS: A systematic review of the literature was conducted using the Medline, Embase and PsycInfo databases, using the keywords "metabolic syndrome", "insulin resistance" and "metabolic X syndrome" and cross-referencing them with "bipolar disorder" or "mania". The following types of publications were candidates for review: (i) clinical trials, (ii) studies involving patients diagnosed with bipolar disorder or (ii...
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…
McElroy, Susan L.; Frye, Mark A.; Hellemann, Gerhard; Altshuler, Lori; Leverich, Gabriele S.; Suppes, Trisha; Keck, Paul E.; Nolen, Willem A.; Kupka, Ralph; Post, Robert M.
Objective: Relatively little is known about the co-occurrence of bipolar and eating disorders. We therefore assessed the prevalence and clinical correlates of eating disorders in 875 patients with bipolar disorder. Method: 875 outpatients with DSM-IV bipolar I or II disorder were evaluated with stru
Regeer, Eline Janet
Bipolar disorder, or manic-depressive illness, is a mood disorder in which episodes of mania, hypomania and depression occur in alternation with intervals of normal mood. Bipolar disorder is typically a recurrent illness and may have serious consequences such as poor social and occupational function
Bogarapu, S; Bishop, J R; Krueger, C D; Pavuluri, M N
The increasing number and availability of various complementary and alternative medicines (CAM) has resulted in an exponentially growing utilization of these products for everything from minor aches and pains to the treatment of mental illness. Difficulties in treating mental illnesses in children, averseness to having children take psychiatric medications, and stigma all drive patients and their families to research alternative treatments. As a result, there has been an increased utilization of CAM in psychiatry, particularly for hard to treat conditions like pediatric BD. It is important for the health care providers to be aware of the alternative treatments by some of their patients. A review of studies investigating the utility of complementary and alternative medicines in bipolar patients was conducted and selected studies were included. Omega-3 fatty acids and lecithin/ choline have preliminary data indicating potential utility in the CAM treatment for bipolar disorder while S-adenosyl methionine (SAM-e) and inositol have some data supporting their efficacy in the treatment of depressive symptoms. Some data for CAM suggest they may be useful adjunctive treatments but only little data are available to support their use as stand-alone therapy. Thus, the conventional medicines remain the first choice in pediatric bipolar management. Healthcare providers need to routinely inquire about the utilization of these treatments by their patients and become familiar with the risks and benefits involved with their use in children.
Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A
Cognitive impairment is a core feature of schizophrenia (SZ) and bipolar disorder (BD). A neurocognitive profile characterized by widespread cognitive deficits across multiple domains in the context of substantial intellectual impairment, which appears to antedate illness onset, is a replicated...... deterioration in either SZ or BD, some findings point to more severe cognitive deficits in patients with early illness onset across both disorders. A compromised pattern of cognitive functioning in individuals at familiar and/or clinical risk to psychosis as well as in first-degree relatives of BD patients...... suggests that early neurodevelopmental factors may play a role in the emergence of cognitive deficits in both disorders. Premorbid intellectual impairment in SZ and at least in a subgroup of patients with BD may be related to a shared genetically determined influence on neurodevelopment....
Full Text Available Studies have suggested that chronic inflammation plays an essential role in the pathophysiology of both rheumatoid arthritis (RA and bipolar disorder. The most common clinical features associated with RA are anxiety and depression. The risk of bipolar disorder among patients with RA has not been characterized adequately.To determine the association between RA and the subsequent development of bipolar disorder and examine the risk factors for bipolar disorder among patients with RA.We identified patients who were diagnosed with RA in the Taiwan National Health Insurance Research Database. A comparison cohort was created by matching patients without RA with those with RA according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts.The RA cohort consisted of 2,570 patients, and the comparison cohort consisted of 2,570 matched control patients without RA. The incidence of bipolar disorder (incidence rate ratio = 2.13, 95% confidence interval [CI] = 1.12-4.24, P = .013 was higher among patients with RA than among control patients. Multivariate, matched regression models revealed that asthma (hazard ratio [HR] = 2.76, 95% CI 1.27-5.96, P = .010, liver cirrhosis (HR = 3.81, 95% CI = 1.04-14.02, P = .044, and alcohol use disorders (HR = 5.29, 95% CI = 1.71-16.37, P = .004 were independent risk factors for the development of bipolar disorder among patients with RA.RA might increase the incidence of bipolar disorder development. Based on our data, we suggest that, following RA diagnosis, greater attention be focused on women with asthma, liver cirrhosis, and alcohol use disorder. Prospective clinical studies of the relationship between RA and bipolar disorder are warranted.
RACHEL JANE LIEBERT
Full Text Available This essay is at once a critical analysis, an experiment in form, and – with some irony – a cautionary tale. Triggered by the inclusion of prodromal diagnoses in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, and the recent call by the United States’ (U.S. Obama administration for increased mental health screening, I argue that shifts toward identifying and intervening on one’s potential madness, or risk, circulate with/in the contemporary U.S. climate of intensified discipline and terror, and use Bipolar Disorder as a site to critically explore how and with what implications this circulation occurs. Specifically, I weave Massumi’s ‘political ontology of threat’ with the narrative of a woman diagnosed with Bipolar Disorder in order to trace the pre-emptive politics and affective logic of a risk-based approach to madness. I contend that the diagnosing and drugging of potential is a self-perpetuating loop that is personally and politically harmful, and consider alternatives to this burgeoning practice.
a current AD while 38 (9% had a substance use disorder (SUD. The univariate analysis revealed 13 significant risks for current AD comorbidity, which the multivariate analysis narrowed to age at first diagnosis of BD (odds ratio =0.95, P<0.01, family history of SUD (odds ratio =2.18, P=0.02, and having a higher current MADRS score (odds ratio =1.11, P<0.01. Conclusion: A diagnosis of AD comorbid with BD is suggested by early-age onset of BD together with a higher MADRS score and a family history of SUD. The likelihood of AD comorbidity decreases by 5% with each passing year; early-age onset of BD is a risk while later age onset is protective. Our results underscore how SUD within the family significantly contributes to the risk of an AD comorbidity. Keywords: bipolar disorders, risk, protect, anxiety, comorbid, Thai
Fagiolini, Andrea; Frank, Ellen; Axelson, David A; Birmaher, Boris; Cheng, Yu; Curet, David E; Friedman, Edward S; Gildengers, Ariel G; Goldstein, Tina; Grochocinski, Victoria J; Houck, Patricia R; Stofko, Mary G; Thase, Michael E; Thompson, Wesley K; Turkin, Scott R; Kupfer, David J
Introduction We developed models of Specialized Care for Bipolar Disorder (SCBD) and a psychosocial treatment [Enhanced Clinical Intervention (ECI)] that is delivered in combination with SCBD. We investigated whether SCBD and ECI + SCBD are able to improve outcomes and reduce health disparities for young and elderly individuals, African Americans, and rural residents with bipolar disorder. Method Subjects were 463 individuals with bipolar disorder, type I, II, or not otherwise specified, or schizoaffective disorder, bipolar type, randomly assigned to SCBD or ECI + SCBD and followed longitudinally for a period of one to three years at four clinical sites. Results Both treatment groups significantly improved over time, with no significant differences based on age, race, or place of residence, except for significantly greater improvement among elderly versus adult subjects. Improvement in quality of life was greater in the ECI + SCBD group. Of the 299 participants who were symptomatic at study entry, 213 achieved recovery within 24 months, during which 86 of the 213 subjects developed a new episode. No significant difference was found for race, place of residence, or age between the participants who experienced a recurrence and those who did not. However, the adolescent patients were less likely than the adult and elderly patients to experience a recurrence. Conclusion This study demonstrated the effectiveness of SCBD and the additional benefit of ECI independent of age, race, or place of residence. It also demonstrated that new mood episodes are frequent in individuals with bipolar disorder who achieve recovery and are likely to occur in spite of specialized, guideline-based treatments. PMID:19500091
Many bipolar disorder patients exhibit mixed affective states, which portend a generally more severe illness course and treatment resistance. In the previous renditions of Diagnostic and Statistical Manual mixed states were narrowly defined in the context of bipolar I disorder, but with the advent of DSM-5 the term “mixed episode” was dropped and replaced by “mixed features” specifier which could be broadly applied to manic, hypomanic and depressive episodes in both the bipolar spectrum and major depressive disorders. This paradigm shift reflected their significance in the prognosis and overall management of mood disorders, so that the clinicians should thoroughly familiarize themselves with the contemporary notions surrounding these conditions. The purpose of this manuscript is to bring to light the current conceptualizations regarding the etiology, pathogenesis and treatment of mixed states. To achieve this goal, in June 2016 an extensive literature search was undertaken using the PubMed database. Some exploratory terms utilized included “mixed states”, “mixed episodes”, “switching”, “rapid cycling” cross referenced with “bipolar disorder”. Focusing on the most relevant and up to date studies, it was revealed that mixed states result from genetic susceptibility in the circadian and dopamine neurotransmission apparatuses and disturbance in the intricate catecholamine-acetylcholine neurotransmission balance which leads to mood fluctuations. The management of mixed states is challenging with atypical antipsychotics, newer anticonvulsants and electroconvulsive therapy emerging as the foremost treatment options. In conclusion, while progress has been made in the neurobiological understanding of mixed states, the currently available therapeutic modalities have only shown limited effectiveness. PMID:28184334
Power, R.A.; Steinberg, S.; Bjornsdottir, G.; Rietveld, C.A.; Abdellaoui, A.; Nivard, M.M.; Johannesson, M.; Galesloot, T.E.; Hottenga, J.J.; Willemsen, G.; Cesarini, D.; Benjamin, D.J.; Magnusson, P.K.; Ullen, F.; Tiemeier, H.; Hofman, A.; Rooij, F.J. van; Walters, G.B.; Sigurdsson, E.; Thorgeirsson, T.E.; Ingason, A.; Helgason, A.; Kong, A.; Kiemeney, B.; Koellinger, P.; Boomsma, D.I.; Gudbjartsson, D.; Stefansson, H.; Stefansson, K.
We tested whether polygenic risk scores for schizophrenia and bipolar disorder would predict creativity. Higher scores were associated with artistic society membership or creative profession in both Icelandic (P = 5.2 x 10(-6) and 3.8 x 10(-6) for schizophrenia and bipolar disorder scores, respectiv
Hatchett, Gregory T.
In the past decade, there has been a proliferation in the number of children and adolescents diagnosed with bipolar disorder. Except in rare cases, the young people who receive this diagnosis do not meet the strict diagnostic criteria for bipolar disorder I or II in the DSM-IV-TR. Many pediatric psychiatrists insist there are important development…
Wang, Fei; Kalmar, Jessica H.; Womer, Fay Y.; Edmiston, Erin E.; Chepenik, Lara G.; Chen, Rachel; Spencer, Linda; Blumberg, Hilary P.
The olfactocentric paralimbic cortex plays a critical role in the regulation of emotional and neurovegetative functions that are disrupted in core features of bipolar disorder. Adolescence is thought to be a critical period in both the maturation of the olfactocentric paralimbic cortex and in the emergence of bipolar disorder pathology. Together,…
Sørensen, Holger Jelling; Sæbye, Ditte; Urfer-Parnas, Annick
Registry-based studies have found no or weak associations between premorbid intelligence and the broad entity of affective spectrum disorder, but none of the studies compared bipolar/unipolar subgroups.......Registry-based studies have found no or weak associations between premorbid intelligence and the broad entity of affective spectrum disorder, but none of the studies compared bipolar/unipolar subgroups....
Kulak, Anita; Steullet, Pascal; Cabungcal, Jan-Harry
Abstract Significance: Schizophrenia (SZ) and bipolar disorder (BD) are classified as two distinct diseases. However, accumulating evidence shows that both disorders share genetic, pathological, and epidemiological characteristics. Based on genetic and functional findings, redox dysregulation due...
Munkholm, Klaus; Vinberg, Maj; Berk, Michael
Munkholm K, Vinberg M, Berk M, Kessing LV. State-related alterations of gene expression in bipolar disorder: a systematic review. Bipolar Disord 2012: 14: 684-696. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Alterations in gene expression in bipolar disorder...... vulnerability pathways. This review therefore evaluated the evidence for whether gene expression in bipolar disorder is state or trait related. Methods: A systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline for reporting systematic reviews, based...... on comprehensive database searches for studies on gene expression in patients with bipolar disorder in specific mood states, was conducted. We searched Medline, Embase, PsycINFO, and The Cochrane Library, supplemented by manually searching reference lists from retrieved publications. Results: A total of 17...
Kaufman, Kenneth R; Struck, Peter J
Antiepileptic drugs are effective psychotropics, especially for bipolar disorder, which leads to their use off-label in treatment-refractory cases. A recent publication suggests that rufinamide may be beneficial adjunctively for bipolar disorder with comorbid psychopathology. This report addresses two negative cases with significant psychiatric adverse effects: increased depression, agitation, and activation of suicidal ideation. These findings suggest that adjunctive rufinamide may lead to increased suicidal ideation in patients with treatment-refractory bipolar disorder. Secondary to the course of severe bipolar disorder, rufinamide cannot be specifically implicated; however, clinicians should be aware of this potential significant adverse effect and monitor high-risk patients. Further studies are required to address rufinamide treatment efficacy and severity of adverse effects in patients with bipolar disorder.
Ladouceur, Cecile D.; Almeida, Jorge R. C.; Birmaher, Boris; Axelson, David A.; Nau, Sharon; Kalas, Catherine; Monk, Kelly; Kupfer, David J.; Phillips, Mary L.
A study is conducted to examine the extent to which bipolar disorder (BD) is associated with gray matter volume abnormalities in brain regions in healthy bipolar offspring relative to age-matched controls. Results show increased gray matter volume in the parahippocampus/hippocampus in healthy offspring at genetic risk for BD.
Francisco Lotufo Neto
Full Text Available Descrição dos objetivos e principais técnicas da terapia comportamental cognitiva usadas para a psicoterapia das pessoas com transtorno bipolar.Objectives and main techniques of cognitive behavior therapy for the treatment of bipolar disorder patients are described.
It has recently become evident that bipolar disorder exists in children and adolescents. The criteria for making the diagnosis of juvenile bipolar disorder (JBD) are in the process of being proposed for the fifth edition of the Diagnostic and Statistical Manual (DSM-V). In adults, a criterion for bipolar disorder is excessive involvement in pleasurable activities including hypersexuality. Recently, some clinicians and researchers have suggested that hypersexuality be included as a criterion for JBD as well. Although abnormal sexuality has been reported to be present in some youth thought to have JBD, the reason for this association is not yet clear. Hypersexuality may be primary and intrinsic to bipolar disorder in youth, secondary and associated with it as the result of psychosocial influences or psychodynamic factors, or due to general aggression and disruptive behavior. Not only have developmental psychosocial factors that may influence sexuality in children and adolescence not been fully investigated, but psychodynamic influences have been omitted from modern etiological constructs as well. This report discusses the importance of psychosocial and psychodynamic influences on the sexual experience and activity of bipolar children. It is proposed that a developmental, psychodynamically informed model is helpful in understanding sexuality in children and adolescents with bipolar disorder. It is also suggested that assessment of psychosocial and psychodynamic influences on the sexuality of bipolar children is necessary in order to adequately assess whether hypersexuality should be a criterion of bipolar disorder in youth.
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......-response to lithium compared with the rate for patients starting lithium later (adjusted analyses: first v. later contact: Pbipolar disorder: P
Meinhard, Ninja; Kessing, Lars Vedel; Vinberg, Maj
BACKGROUND: It appears that the female reproductive events and hormonal treatments may impact the course of bipolar disorder in women. In particular, childbirth is known to be associated with onset of affective episodes in women with bipolar disorder. During the female reproductive events the sex...... hormones, e.g. estrogen, are fluctuating and particularly postpartum there is a steep fall in the levels of serum estrogen. The role of estrogen in women with bipolar disorder is, however, not fully understood. AIM: The main objective of this review is to evaluate the possible relation between serum...... estrogen levels and women with bipolar disorder including studies of the anti manic effects of the selective estrogen receptor modulator tamoxifen. METHOD: A systematically literature search on PubMed was conducted: two studies regarding the connection between serum estrogen levels and women with bipolar...
Sigitova, Ekaterina; Fišar, Zdeněk; Hroudová, Jana; Cikánková, Tereza; Raboch, Jiří
The most common mood disorders are major depressive disorders and bipolar disorders (BD). The pathophysiology of BD is complex, multifactorial, and not fully understood. Creation of new hypotheses in the field gives impetus for studies and for finding new biomarkers for BD. Conversely, new biomarkers facilitate not only diagnosis of a disorder and monitoring of biological effects of treatment, but also formulation of new hypotheses about the causes and pathophysiology of the BD. BD is characterized by multiple associations between disturbed brain development, neuroplasticity, and chronobiology, caused by: genetic and environmental factors; defects in apoptotic, immune-inflammatory, neurotransmitter, neurotrophin, and calcium-signaling pathways; oxidative and nitrosative stress; cellular bioenergetics; and membrane or vesicular transport. Current biological hypotheses of BD are summarized, including related pathophysiological processes and key biomarkers, which have been associated with changes in genetics, systems of neurotransmitter and neurotrophic factors, neuroinflammation, autoimmunity, cytokines, stress axis activity, chronobiology, oxidative stress, and mitochondrial dysfunctions. Here we also discuss the therapeutic hypotheses and mechanisms of the switch between depressive and manic state.
Johnson, Sheri L; Moezpoor, Michelle; Murray, Greg; Hole, Rachelle; Barnes, Steven J; Michalak, Erin E
Bipolar disorder (BD) has been related to heightened creativity, yet core questions remain unaddressed about this association. We used qualitative methods to investigate how highly creative individuals with BD understand the role of symptoms and treatment in their creativity, and possible mechanisms underpinning this link. Twenty-two individuals self-identified as highly creative and living with BD took part in focus groups and completed quantitative measures of symptoms, quality of life (QoL), and creativity. Using thematic analysis, five themes emerged: the pros and cons of mania for creativity, benefits of altered thinking, the relationship between creativity and medication, creativity as central to one's identity, and creativity's importance in stigma reduction and treatment. Despite reliance on a small sample who self-identified as having BD, findings shed light on previously mixed results regarding the influence of mania and treatment and suggest new directions for the study of mechanisms driving the creative advantage in BD.
Holmes, Emily A; Geddes, John R; Colom, Francesc; Goodwin, Guy M
Cognitions in the form of mental images have a more powerful impact on emotion than their verbal counterparts. This review synthesizes the cognitive science of imagery and emotion with transdiagnostic clinical research, yielding novel predictions for the basis of emotional volatility in bipolar disorder. Anxiety is extremely common in patients with bipolar disorder and is associated with increased dysfunction and suicidality, yet it is poorly understood and rarely treated. Mental imagery is a neglected aspect of bipolar anxiety although in anxiety disorders such as posttraumatic stress disorder and social phobia focusing on imagery has been crucial for the development of cognitive behavior therapy (CBT). In this review we present a cognitive model of imagery and emotion applied to bipolar disorder. Within this model mental imagery amplifies emotion, drawing on Clark's cyclical panic model [(1986). A cognitive approach to panic. Behaviour Research and Therapy, 24, 461-470]. We (1) emphasise imagery's amplification of anxiety (cycle one); (2) suggest that imagery amplifies the defining (hypo-) mania of bipolar disorder (cycle two), whereby the overly positive misinterpretation of triggers leads to mood elevation (escalated by imagery), increasing associated beliefs, goals, and action likelihood (all strengthened by imagery). Imagery suggests a unifying explanation for key unexplained features of bipolar disorder: ubiquitous anxiety, mood instability and creativity. Introducing imagery has novel implications for bipolar treatment innovation--an area where CBT improvements are much-needed.
Hélio Anderson Tonelli
Full Text Available OBJETIVO: O transtorno afetivo bipolar está associado ao comprometimento funcional persistente. Apesar de muitas pesquisas demonstrarem que bipolares podem apresentar déficits cognitivos, um número menor de trabalhos avaliou o papel de prejuízos no processamento cognitivo social, a Teoria da Mente (relacionado à capacidade de inferir estados mentais, no aparecimento de sintomas e complicações sociais em bipolares. O objetivo deste trabalho é o de revisar sistemática e criticamente a literatura sobre possíveis alterações do processamento Teoria da Mente no transtorno afetivo bipolar. MÉTODO: Foi realizada uma busca na base de dados Medline por trabalhos publicados em língua inglesa, alemã, espanhola ou portuguesa nos últimos 20 anos, utilizando a frase de busca "Bipolar Disorder"[Mesh] AND "Theory of Mind". Foram procurados por estudos clínicos envolvendo indivíduos bipolares e que empregaram uma ou mais tarefas cognitivas desenvolvidas para a avaliação de habilidades Teoria da Mente. Foram excluídos os relatos de caso e cartas ao editor. A busca inicial resultou em cinco artigos, sendo selecionados quatro. Outros quatro foram também selecionados a partir da leitura dos artigos acima. DISCUSSÃO: Os artigos selecionados avaliaram populações de bipolares adultos e pediátricos, incluindo indivíduos eutímicos, maníacos e deprimidos. A maioria dos trabalhos avaliados sugere que existam prejuízos no processamento Teoria da Mente em portadores de transtorno afetivo bipolar e que estes podem estar por trás dos sintomas e dos déficits funcionais do transtorno afetivo bipolar. CONCLUSÃO: Pesquisas futuras a respeito do tema em questão poderão esclarecer muito acerca do papel das alterações sociocognitivas no surgimento dos sintomas do transtorno afetivo bipolar, bem como ajudar no desenvolvimento de estratégias preventivas e terapêuticas do mesmo.OBJECTIVE: Bipolar disorder is associated to persistent functional
Okkels, Niels; Trabjerg, Betina; Arendt, Mikkel
OBJECTIVE: Traumatic stress disorders are prevalent in patients with schizophrenia and bipolar disorder. However, there is a lack of prospective longitudinal studies investigating the risk of severe mental illness for people diagnosed with traumatic stress disorders. We aimed to assess if patients...... with acute stress reaction (ASR) or post-traumatic stress disorder (PTSD) are at increased risk of schizophrenia spectrum disorders or bipolar disorder. METHODS: We performed a prospective cohort study covering the entire Danish population including information on inpatient and outpatient mental hospitals...... over 2 decades. Predictors were in- or outpatient diagnoses of ASR or PTSD. We calculated incidence rate ratios (IRR) with 95% CIs of schizophrenia, schizophrenia spectrum disorder, and bipolar disorder. RESULTS: Persons with a traumatic stress disorder had a significantly increased risk...
Suppes, T; Chisholm, KA; Dhavale, D; Frye, MA; Atshuler, LL; McElroy, SL; Keck, PE; Nolen, WA; Kupka, R; Denicoff, KD; Leverich, GS; Rush, AJ; Post, RM
Objectives: Anticonvulsants have provided major treatment advances for patients with bipolar disorder. Many of these drugs, including several with proven efficacy in bipolar mania or depression, enhance the activity of the gamma-amino butyric acid (GABA) neurotransmitter system. A new anticonvulsant
Suicide rates of bipolar patients are among the highest of any psychiatric disorder, and improved identification of risk factors for attempted and completed suicide translates into improved clinical outcome. Factors that may be predictive of suicidality in an exclusively bipolar population are examined. White race, family suicide history, and…
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.
Full Text Available Neuroinflammation has been proposed as a strong biological factor underlying the development of neuropsychiatric diseases. A role for dysregulation of the immune system was initially suggested in depressive disorders and subsequently extended to other illnesses, including bipolar disorder (BD. Indeed, there is growing evidence confirming the presence of a generalized pro-inflammatory state in BD patients, involving alterations in cytokine, acute-phase proteins, and complement factor secretion, white blood cell differentiation, microglial activation, arachidonic acid signaling pathways, and increased oxidative stress markers. Medications commonly used to treat BD, such as lithium, antiepileptics and antipsychotics, show some immunoregulatory activity both in vitro and in vivo. The aim of our study was to review the role of different inflammatory mechanisms, specifically in the development of excitatory symptoms, via a systematic PubMed search of the literature. Despite the high variability of results among studies, we found evidence indicating specific alterations of the inflammatory response during manic and mixed states of BD. These findings may help to clarify some of the complex mechanisms underlying the development of excitatory symptoms and suggest a potential role for drugs targeting the inflammatory system as new therapeutic options.
Koefoed, Pernille; Andreassen, Ole A; Bennike, Bente
of complex diseases, it may be useful to look at combinations of genotypes. Genes related to signal transmission, e.g., ion channel genes, may be of interest in this respect in the context of bipolar disorder. In the present study, we analysed 803 SNPs in 55 genes related to aspects of signal transmission...... and calculated all combinations of three genotypes from the 3×803 SNP genotypes for 1355 controls and 607 patients with bipolar disorder. Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC...... in the clusters in the two datasets. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder....
Jensen, Johan Høy; Knorr, Ulla; Vinberg, Maj
BACKGROUND: Neurocognitive impairment in remitted patients with bipolar disorder contributes to functional disabilities. However, the pattern and impact of these deficits are unclear. METHODS: We pooled data from 193 fully or partially remitted patients with bipolar disorder and 110 healthy...... controls. Hierarchical cluster analysis was conducted to determine whether there are discrete neurocognitive subgroups in bipolar disorder. The pattern of the cognitive deficits and the characteristics of patients in these neurocognitive subgroups were examined with analyses of covariance and least...... was cross-sectional which limits inferences regarding the causality of the findings. CONCLUSION: Globally and selectively impaired bipolar disorder patients displayed more functional disabilities than those who were cognitively intact. The present findings highlight a clinical need to systematically screen...
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....
Faurholt-Jepsen, M.; Busk, Jonas; Frost, M.
Changes in speech have been suggested as sensitive and valid measures of depression and mania in bipolar disorder. The present study aimed at investigating (1) voice features collected during phone calls as objective markers of affective states in bipolar disorder and (2) if combining voice...... features, automatically generated objective smartphone data on behavioral activities and electronic self-monitored data were collected from 28 outpatients with bipolar disorder in naturalistic settings on a daily basis during a period of 12 weeks. Depressive and manic symptoms were assessed using...... and electronic self-monitored data increased the accuracy, sensitivity and specificity of classification of affective states slightly. Voice features collected in naturalistic settings using smartphones may be used as objective state markers in patients with bipolar disorder....
Schaffer, Ayal; Isometsä, Erkki T; Tondo, Leonardo
the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles...... significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use...
Mellerup, Erling; Andreassen, Ole; Bennike, Bente
Complex diseases may be associated with combinations of changes in DNA, where the single change has little impact alone. In a previous study of patients with bipolar disorder and controls combinations of SNP genotypes were analyzed, and four large clusters of combinations were found...... to be significantly associated with bipolar disorder. It has now been found that these clusters may be connected to clinical data....
Kessing, L. V.; Andersen, P. K.
) the risk of recurrence of episodes, (ii) probability of recovery from episodes, (iii) severity of episodes, (iv) the threshold for developing episodes, and (v) progression of cognitive deficits in unipolar and bipolar disorders. Method: A systematic review comprising an extensive literature search...... severity of episodes, (iv) decreasing threshold for developing episodes, and (v) increasing risk of developing dementia. Conclusion: Although the course of illness is heterogeneous, there is evidence for clinical progression of unipolar and bipolar disorders....
Henry, Chantal; Phillips, Mary; Leibenluft, Ellen; M'Bailara, Katia; Houenou, Josselin; Leboyer, Marion
Background assessment of emotional reactivity, defined as rapid emotional responses to salient environmental events, has been neglected in mood disorders. This article reviews data showing the relevance of using emotional reactivity to better characterize bipolar mood episodes. Method We reviewed clinical data on emotional reactivity during all phases of bipolar disorders (euthymic, manic, mixed and depressive states) and brain-imaging, neurochemical, genetic studies related to emotional reac...
STRAKOWSKI, STEPHEN M.; FLECK, DAVID E.; MAJ, MARIO
There is considerable debate over whether bipolar and related disorders that share common signs and symptoms, but are currently defined as distinct clinical entities in DSM-IV and ICD-10, may be better characterized as falling within a more broadly defined “bipolar spectrum”. With a spectrum view in mind, the possibility of broadening the diagnosis of bipolar disorder has been proposed. This paper discusses some of the rationale for an expanded diagnostic scheme from both clinical and research perspectives in light of potential drawbacks. The ultimate goal of broadening the diagnosis of bipolar disorder is to help identify a common etiopathogenesis for these conditions to better guide treatment. To help achieve this goal, bipolar researchers have increasingly expanded their patient populations to identify objective biological or endophenotypic markers that transcend phenomenological observation. Although this approach has and will likely continue to produce beneficial results, the upcoming DSM-IV and ICD-10 revisions will place increasing scrutiny on psychiatry’s diagnostic classification systems and pressure to re-evaluate our conceptions of bipolar disorder. However, until research findings can provide consistent and converging evidence as to the validity of a broader diagnostic conception, clinical expansion to a dimensional bipolar spectrum should be considered with caution. PMID:21991268
Full Text Available In 2013, a version of the Diagnostic and Statistical Manual of Mental Disorders (DSM, having number 5, was published. The DSM is a textbook which aims to present diagnostic criteria for each psychiatric disorder recognized by the U.S. healthcare system. The DSM-5 comprises the most updated diagnostic criteria of psychiatric disorders as well as their description, and provides a common language for clinicians to communicate about the patients. Diagnostic criteria of the DSM-5 have been popular all over the world, including countries where the ICD-10 classification is obligatory, and are widely used for clinical and neurobiological research in psychiatry. In this article, two chapters of the DSM-5 pertained to mood (affective disorders are presented, such as “Bipolar and related disorders” and “Depressive disorders” replacing the chapter titled “Mood disorders” in the previous version of DSM-IV. The aim of this article is to discuss a structure of new classification, to point out differences compared with previous version (DSM-IV. New diagnostic categories, such as e.g. disruptive mood dysregulation disorder or premenstrual dysphoric disorder were depicted as well as some elements of dimensional approach to mood disorders were presented.
Ford, Brett Q; Mauss, Iris B; Gruber, June
Although people who experience happiness tend to have better psychological health, people who value happiness to an extreme tend to have worse psychological health, including more depression. We propose that the extreme valuing of happiness may be a general risk factor for mood disturbances, both depressive and manic. To test this hypothesis, we examined the relationship between the extreme valuing of happiness and risk for, diagnosis of, and illness course for bipolar disorder (BD). Supporting our hypothesis, the extreme valuing of happiness was associated with a measure of increased risk for developing BD (Studies 1 and 2), increased likelihood of past diagnosis of BD (Studies 2 and 3), and worse prospective illness course in BD (Study 3), even when controlling for current mood symptoms (Studies 1-3). These findings indicate that the extreme valuing of happiness is associated with and even predicts BD. Taken together with previous evidence, these findings suggest that the extreme valuing of happiness is a general risk factor for mood disturbances. More broadly, what emotions people strive to feel may play a critical role in psychological health.
Atmaca, Murad; Ozler, Sinan; Topuz, Mehtap; Goldstein, Sam
Objective: There is a dearth of literature on patients erroneously diagnosed and treated for bipolar disorder. Method: The authors report a case of an adult with attention deficit hyperactivity disorder erroneously diagnosed and treated for bipolar disorder for 6 years. At that point, methylphenidate was initiated. The patient was judged to be a…
Full Text Available Bipolar disorders and addictions constitute reciprocal risk factors and are best considered under a unitary perspective. The concepts of allostasis and allostatic load may contribute to the understanding of the complex relationships between bipolar disorder and addictive behaviors. Allostasis entails the safeguarding of reward function stability by recruitment of changes in the reward and stress system neurocircuitry and it may help to elucidate neurobiological underpinnings of vulnerability to addiction in bipolar patients. Conceptualizing bipolar disorder as an illness involving the cumulative build-up of allostatic states, we hypothesize a progressive dysregulation of reward circuits clinically expressed as negative affective states (i.e. anhedonia. Such negative affective states may render bipolar disorder patients more vulnerable to drug addiction, fostering a very rapid transition from occasional drug use to addiction, through mechanisms of negative reinforcement. The resulting addictive behavior-related allostatic loads, in turn, may contribute to illness progression. This framework could have a heuristic value to enhance research on pathophysiology and treatment of bipolar disorder and addiction comorbidity.
João Pedro Ribeiro
Full Text Available Anxiety disorders have been described as features of Bipolar Disorder (BD, and Obsessive-compulsive-bipolar disorder (OCBD may occur in as many as 56% of obsessive-compulsive patients. Mania in Obsessive-Compulsive Disorder (OCD can occur either as an independent comorbidity or as a result of an antidepressant-induced switch. We report the case of a 38-year-old male with a 3 year diagnosis of OCD treated with antidepressants, admitted due to a manic episode, and describe diagnostic and treatment challenges of this comorbidity.
Evans, Simon J; Bassis, Christine M; Hein, Robert; Assari, Shervin; Flowers, Stephanie A; Kelly, Marisa B; Young, Vince B; Ellingrod, Vicky E; McInnis, Melvin G
The gut microbiome is emerging as an important factor in regulating mental health yet it remains unclear what the target should be for psychiatric treatment. We aimed to elucidate the complement of the gut-microbiome community for individuals with bipolar disorder relative to controls; and test for relationships with burden of disease measures. We compared the stool microbiome from individuals with bipolar disorder (n = 115) and control subjects (n = 64) using 16S ribosomal RNA (rRNA) gene sequence analysis. Analysis of molecular variance (AMOVA) revealed global community case-control differences (AMOVA p = 0.047). Operational Taxonomical Unit (OTU) level analysis revealed significantly decreased fractional representation (p bipolar disorder, the fractional representation of Faecalibacterium associated with better self-reported health outcomes based on the Short Form Health Survey (SF12); the Patient Health Questionnaire (PHQ9); the Pittsburg Sleep Quality Index (PSQI); the Generalized Anxiety Disorder scale (GAD7); and the Altman Mania Rating Scale (ASRM), independent of covariates. This study provides the first detailed analysis of the gut microbiome relationships with multiple psychiatric domains from a bipolar population. The data support the hypothesis that targeting the microbiome may be an effective treatment paradigm for bipolar disorder.
Swann, Alan C
The combination of depression and activation presents clinical and diagnostic challenges. It can occur, in either bipolar disorder or major depressive disorder, as increased agitation as a dimension of depression. What is called agitation can consist of expressions of painful inner tension or as disinhibited goal-directed behavior and thought. In bipolar disorder, elements of depression can be combined with those of mania. In this case, the agitation, in addition to increased motor activity and painful inner tension, must include symptoms of mania that are related to goal-directed behavior or manic cognition. These diagnostic considerations are important, as activated depression potentially carries increased behavioral risk, especially for suicidal behavior, and optimal treatments for depressive episodes differ between bipolar disorder and major depressive disorder.
Full Text Available Rona Jeannie Roberts,1 Lillian Jan Findlay,2 Peggy L El-Mallakh,2 Rif S El-Mallakh1 1Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, 2School of Nursing, University of Kentucky, Lexington, KY, USA Abstract: Schizophrenia and bipolar disorder are severe psychiatric disorders that are frequently associated with persistent symptoms and significant dysfunction. While there are a multitude of psychopharmacologic agents are available for treatment of these illnesses, suboptimal response and significant adverse consequences limit their utility. Cariprazine is a new, novel antipsychotic medication with dopamine D2 and D3 partial agonist effects. Its safety and efficacy have been investigated in acute psychosis of schizophrenia, bipolar mania, bipolar depression, and unipolar depression. Efficacy has been demonstrated in schizophrenia and mania. It is unclear if cariprazine is effective in depression associated with unipolar or bipolar illness. Adverse consequences include extrapyramidal symptoms including akathisia, and various gastrointestinal symptoms. The US Food and Drug Administration (FDA has recently approved cariprazine. This review will provide clinicians with basic information regarding the research program of cariprazine. Keywords: cariprazine, dopamine D3 receptor, dopamine D2 receptor, bipolar disorder, mania, bipolar depression, schizophrenia
Gokben Hizli Sayar
Full Text Available Interpersonal Social Rhythm Therapy is a psychotherapy modality that helps the patient recognize the relationship between disruptions in social rhythms and the onset of previous episodes of psychiatric disorders. It uses psychoeducation and behavioral techniques to maintain social rhythm and sleep/wake regularity. It is closely related to and ldquo;social zeitgeber theory and rdquo; that emphasizes the importance that social rhythm regularity may play in synchronization of circadian rhythms in individuals with or at risk for bipolar spectrum disorders. Interpersonal and social rhythm therapy have been shown to stabilize social rhythms and enhance course and outcome in bipolar disorder. This review focuses on the theoretical principles and the basic steps of interpersonal and social rhythm therapy as a psychotherapy approach in bipolar disorder. PubMed, Scopus, Google Scholar databases were searched without temporal restriction. Search terms included interpersonal social rhythm therapy, bipolar, mood disorders. Abstracts were reviewed for relevance, and randomized controlled trials of interpersonal and social rhythm therapy in bipolar disorder selected. These researches also summarized on the final part of this review. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 438-446
Hahn, Changtae; Lim, Hyun Kook; Lee, Chang Uk
In recent years, there has been an increasing interest in late-onset mental disorders. Among them, geriatric schizophrenia and bipolar disorder are significant health care risks and major causes of disability. We discussed whether late-onset schizophrenia (LOS) and late-onset bipolar (LOB) disorder can be a separate entity from early-onset schizophrenia (EOS) and early-onset bipolar (EOB) disorder in a subset of late-life schizophrenia or late-life bipolar disorder through neuroimaging studies. A literature search for imaging studies of LOS or LOB was performed in the PubMed database. Search terms used were "(imaging OR MRI OR CT OR SPECT OR DTI OR PET OR fMRI) AND (schizophrenia or bipolar disorder) AND late onset." Articles that were published in English before October 2013 were included. There were a few neuroimaging studies assessing whether LOS and LOB had different disease-specific neural substrates compared with EOS and EOB. These researches mainly observed volumetric differences in specific brain regions, white matter hyperintensities, diffusion tensor imaging, or functional neuroimaging to explore the differences between LOS and LOB and EOS and EOB. The aim of this review was to highlight the neural substrates involved in LOS and LOB through neuroimaging studies. The exploration of neuroanatomical markers may be the key to the understanding of underlying neurobiology in LOS and LOB.
Kupka, Ralph W.; Altshuler, Lori L.; Nolen, Willem A.; Suppes, Trisha; Luckenbaugh, David A.; Leverich, Gabriele S.; Frye, Mark A.; Keck, Paul E.; McElroy, Susan L.; Grunze, Heinz; Post, Robert M.
Objectives: To assess the proportion of time spent in mania, depression and euthymia in a large cohort of bipolar subjects studied longitudinally, and to investigate depression/mania ratios in patients with bipolar I versus bipolar II disorder. Methods: Clinician-adjusted self-ratings of mood were c
Altamura, Mario; Padalino, Flavia A; Stella, Eleonora; Balzotti, Angela; Bellomo, Antonello; Palumbo, Rocco; Di Domenico, Alberto; Mammarella, Nicola; Fairfield, Beth
Emotional face recognition is impaired in bipolar disorder, but it is not clear whether this is specific for the illness. Here, we investigated how aging and bipolar disorder influence dynamic emotional face recognition. Twenty older adults, 16 bipolar patients, and 20 control subjects performed a dynamic affective facial recognition task and a subsequent rating task. Participants pressed a key as soon as they were able to discriminate whether the neutral face was assuming a happy or angry facial expression and then rated the intensity of each facial expression. Results showed that older adults recognized happy expressions faster, whereas bipolar patients recognized angry expressions faster. Furthermore, both groups rated emotional faces more intensely than did the control subjects. This study is one of the first to compare how aging and clinical conditions influence emotional facial recognition and underlines the need to consider the role of specific and common factors in emotional face recognition.
Kerri L. Kim
Full Text Available Pediatric bipolar disorder (BD rates have notably increased over the past three decades. Given the significant morbidity and mortality associated with BD, efforts are needed to identify factors useful in earlier detection to help address this serious public health concern. Sleep is particularly important to consider given the sequelae of disrupted sleep on normative functioning and that sleep is included in diagnostic criteria for both Major Depressive and Manic Episodes. Here, we examine one component of sleep—i.e., circadian phase preference with the behavioral construct of morningness/eveningness (M/E. In comparing 30 BD and 45 typically developing control (TDC participants, ages 7–17 years, on the Morningness-Eveningness Scale for Children (MESC, no between-group differences emerged. Similar results were found when comparing three groups (BD−ADHD; BD+ADHD; TDC. Consistent with data available on circadian phase preference in adults with BD, however, we found that BD adolescents, ages 13 years and older, endorsed significantly greater eveningness compared to their TDC peers. While the current findings are limited by reliance on subjective report and the high-rate of comorbid ADHD among the BD group, this finding that BD teens demonstrate an exaggerated shift towards eveningness than would be developmentally expected is important. Future studies should compare the circadian rhythms across the lifespan for individuals diagnosed with BD, as well as identify the point at which BD youth part ways with their healthy peers in terms of phase preference. In addition, given our BD sample was overall euthymic, it may be that M/E is more state vs. trait specific in latency age youth. Further work would benefit from assessing circadian functioning using a combination of rating forms and laboratory-based measures. Improved understanding of sleep in BD may identify behavioral targets for inclusion in prevention and intervention protocols.
Parsian, A.; Todd, R.D. [Washington Univ. School of Medicine, St. Louis, MO (United States)
From family, adoption, and twin studies it is clear that genetic factors play an important role in the etiology of bipolar disorder (McGuffin and Katz: The Biology of Depression, Gaskell, London, 1986). Recently Yoneda et al. reported an association between an allele (A4) of a VNTR marker (DXYS20) for the pseudoautosomal region and bipolar disorder in a Japanese population. In order to test for this association in a Caucasian population, we have typed a sample of 52 subjects with bipolar disorder and 61 normal controls. The bipolar subjects are probands of multiple incidence families. The normal controls are an epidemiologically ascertained sample of middle-aged, unrelated individuals. The two groups were matched for sex and ethnic background. There were no significant differences in the allele or genotype frequencies of DXYS20 between the two groups. In particular, there was no significant difference in the frequency of the A4 allele in normal controls and bipolar patients (0.377 vs. 0.317, respectively). The prevalence of the A4 allele in bipolar patients and normal controls was 0.567 and 0.622, respectively. We were not able to replicate the results of the 1992 Yoneda et al. study. 15 refs., 2 tabs.
Du Rocher Schudlich, Tina D.; Youngstrom, Eric A.; Calabrese, Joseph R.; Findling, Robert L.
Investigated the association between family functioning and conflict and their links with mood disorder in parents and with children's risk for bipolar disorder. Participants were 272 families with a child between the ages of 5-17 years. Parents' history of psychiatric diagnoses and children's current diagnoses were obtained via semi-structured…
Savitz, Jonathan; Solms, Mark; Ramesar, Rajkumar
Data from the imaging literature have led to suggestions that permanent structural brain changes may be associated with bipolar disorder. Individuals diagnosed with bipolar disorder display deficits on a range of neuropsychological tasks in both the acute and euthymic phases of illness, and correlations between experienced number of affective episodes and task performance are commonly reported. These findings have renewed interest in the neuropsychological profile of individuals with bipolar disorder, with deficits of attention, learning and memory, and executive function, asserted to be present. This paper critically reviews five different potential causes of neurocognitive dysfunction in bipolar disorder: (i) iatrogenic, (ii) acute functional changes associated with depression or mania, (iii) permanent structural lesions of a neurodegenerative origin, (iv) permanent structural lesions that are neurodevelopmental in origin, and (v) permanent functional changes that are most likely genetic in origin. Although the potential cognitive effects of residual symptomatology and long-term medication use cannot be entirely excluded, we conclude that functional changes associated with genetically driven population variation in critical neural networks underpin both the neurocognitive and affective symptoms of bipolar disorder. The philosophical implications of this conclusion for neuropsychology are briefly discussed.
Full Text Available Despite evidence that exercise has been found to be effective in the treatment of depression, it is unclear whether these data can be extrapolated to bipolar disorder. Available evidence for bipolar disorder is scant, with no existing randomised controlled trials having tested the impact of exercise on depressive, manic or hypomanic symptomatology. Although exercise is often recommended in bipolar disorder, this is based on extrapolation from the unipolar literature, theory and clinical expertise and not empirical evidence. In addition, there are currently no available empirical data on program variables, with practical implications on frequency, intensity and type of exercise derived from unipolar depression studies. The aim of the current paper is to explore the relationship between exercise and bipolar disorder and potential mechanistic pathways. Given the high rate of medical co-morbidities experienced by people with bipolar disorder, it is possible that exercise is a potentially useful and important intervention with regard to general health benefits; however, further research is required to elucidate the impact of exercise on mood symptomology.
Belli, Hasan; Ural, Cenk; Akbudak, Mahir
In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders. In this context, common phenomenology between borderline personality and bipolar disorders and differential features of clinical diagnosis will be reviewed in line with the literature. Both disorders can demonstrate common features in the diagnostic aspect, and can overlap phenomenologically. Concomitance rate of both disorders is quite high. In order to differentiate these two disorders from each other, quality of mood fluctuations, impulsivity types and linear progression of disorders should be carefully considered. There are various studies in mood stabilizer use, like lithium, carbamazepine, oxcarbazepine, sodium valproate and lamotrigine, in the treatment of borderline personality disorder. Moreover, there are also studies, which have revealed efficacies of risperidone, olanzapine and quetiapine as atypical antipsychotics. It is not easy to differentiate borderline personality disorder from the bipolar disorders. An intensively careful evaluation should be performed. This differentiation may be helpful also for the treatment. There are many studies about efficacy of valproate and lamotrigine in treatment of borderline personality disorder. However, findings related to other mood stabilizers are inadequate. Olanzapine and quetiapine are reported to be more effective among atypical antipsychotics. No drug is approved for the treatment of borderline personality disorder by the entitled authorities, yet. Psychotherapeutic approaches have preserved their significant places in treatment of borderline personality disorder. Moreover, symptom based approach is recommended in use of mood stabilizers and atypical antipsychotics.
Dunner, D L
In this paper, we review the process for inclusion of rapid cycling as a course modifier to bipolar disorders in DSM-IV. This process involved definition of bipolar II disorder, delineating the duration of manic episode for bipolar I disorder, and clarification of the diagnosis of cyclothymic disorder and mixed mania.
In treating bipolar disorder, specific psychotherapies in adjunct to pharmacotherapy have been shown to be effective in preventing new episodes and treating depressive episodes. Among those, interpersonal and social rhythm therapy (IPSRT) developed by Frank, amalgamation of interpersonal psychotherapy (IPT) with behavioral therapy focused on social rhythm has been shown to be an efficacious adjunct to mediation in preventing new episodes in bipolar I patients and in treating depression in bipolar I arid II disorder. IPSRT has also been shown to enhance total functioning, relationship functioning and life satisfaction among patients with bipolar disorder, even after pretreatment functioning and concurrent depression were covaried. IPSRT was designed to directly address the major pathways to recurrence in bipolar disorder, namely medication nonadherence, stressful life events, and disruptions in social rhythms. IPT, originated by Klerman et al., is a strategic time-limited psychotherapy focused on one or two of four current interpersonal problem areas (ie, grief, interpersonal role disputes, role transitions, and interpersonal dificits). In IPSRT, the fifth problem area "grief for the lost healthy self" has been added in order to promote acceptance of the diagnosis and the need for life-long treatment. Social rhythm therapy is a behavioral approach aiming at increasing regularity of social rhythms using the Social Rhythm Metric (SRM), a chart to record daily social activities including how stimulating they were, developed from observation that disruptions in social rhythms often trigger affective episodes in patients with bipolar disorder. IPSRT also appears to be a promising intervention for a subset of individuals with bipolar II depression as monotherapy for the acute treatment.
Full Text Available Introduction: The diagnosis of Bipolar Disorder (BD in youths has been controversial, especially for the subtype BD Not Otherwise Specified (BD-NOS. In spite of growing evidence that sleep is a core feature of BD, few studies characterize and compare sleep disturbances in youth with BD type I (BD-I and BD-NOS. Sleep disturbances are frequently reported in clinical descriptions of children and adolescents with BD, however the reporting of the frequency and characteristics of sleep symptoms in youth with BD NOS and BD I during episodes remain poor. This study compares symptom of sleep disturbance as occurring in manic and depressive episodes in BD I and BD NOS youth using KSADS-PL interview data. The study also addresses whether symptoms of sleep disturbance vary in different age groups. Material and Methods: The sample consisted of 70 children and adolescent outpatients at an urban specialty clinic (42M/28F, 10.8±3.6 years old including 24 BP-I and 46 BP-NOS assessed using K-SADS-PL-parent interview. Results: Sleep disturbances including insomnia and decreased need for sleep were reported by 84.3% of the sample. Enuresis was diagnosed in 27% of sample. There were no significant differences in frequency of sleep symptoms between BD-I and BD-NOS. Regardless of BD subtype, current functioning was negatively correlated with decreased need for sleep but not insomnia, and regardless of BD subtype. Conclusion: The majority of youth with BD presents with sleep symptoms during mood episodes. BD NOS presents with the same proportion of sleep symptoms as BD I in our sample.
Swann, Alan C; Lijffijt, Marijn; Lane, Scott D; Steinberg, Joel L; Acas, Michelle D; Cox, Blake; Moeller, F Gerard
Early responses to stimuli can be measured by sensory evoked potentials (EP) using repeated identical stimuli, S1 and S2. Response to S1 may represent efficient stimulus detection, while suppression of response to S2 may represent inhibition. Early responses to stimuli may be related to impulsivity. We compared EP reflecting stimulus detection and inhibition in bipolar disorder and healthy controls, and investigated relationships to impulsivity. Subjects were 48 healthy controls without family histories of mood disorder and 48 with bipolar disorder. EP were measured as latencies and amplitudes for auditory P50 (pre-attentional), N100 (initial direction of attention) and P200 (initial conscious awareness), using a paired-click paradigm, with identical stimuli 0.5 s apart. Impulsivity was measured by questionnaire and by laboratory tests for inability to suppress responses to stimuli or to delay response for a reward. Analyses used general linear models. S1 amplitudes for P50, N100, and P200, and gating of N100 and P200, were lower in bipolar disorder than in controls. P50 S1 amplitude correlated with accurate laboratory-task responding, and S2 amplitude correlated with impulsive task performance and fast reaction times, in bipolar disorder. N100 and P200 EP did not correlate with impulsivity. These findings were independent of symptoms, treatment, or substance-use history. EPs were not related to questionnaire-measured or reward-based impulsivity. Bipolar I disorder is characterized by reduced pre-attentional and early attentional stimulus registration relative to controls. Within bipolar disorder, rapid-response impulsivity correlates with impaired pre-attentional response suppression. These results imply specific relationships between ERP-measured response inhibition and rapid-response impulsivity.
Full Text Available BACKGROUND: Mitochondria provide most of the energy for brain cells by the process of oxidative phosphorylation. Mitochondrial abnormalities and deficiencies in oxidative phosphorylation have been reported in individuals with schizophrenia (SZ, bipolar disorder (BD, and major depressive disorder (MDD in transcriptomic, proteomic, and metabolomic studies. Several mutations in mitochondrial DNA (mtDNA sequence have been reported in SZ and BD patients. METHODOLOGY/PRINCIPAL FINDINGS: Dorsolateral prefrontal cortex (DLPFC from a cohort of 77 SZ, BD, and MDD subjects and age-matched controls (C was studied for mtDNA sequence variations and heteroplasmy levels using Affymetrix mtDNA resequencing arrays. Heteroplasmy levels by microarray were compared to levels obtained with SNaPshot and allele specific real-time PCR. This study examined the association between brain pH and mtDNA alleles. The microarray resequencing of mtDNA was 100% concordant with conventional sequencing results for 103 mtDNA variants. The rate of synonymous base pair substitutions in the coding regions of the mtDNA genome was 22% higher (p = 0.0017 in DLPFC of individuals with SZ compared to controls. The association of brain pH and super haplogroup (U, K, UK was significant (p = 0.004 and independent of postmortem interval time. CONCLUSIONS: Focusing on haplogroup and individual susceptibility factors in psychiatric disorders by considering mtDNA variants may lead to innovative treatments to improve mitochondrial health and brain function.
Bowen, T; Kirov, G; Gill, M; Spurlock, G; Vallada, H P; Murray, R M; McGuffin, P; Collier, D A; Owen, M J; Craddock, N
Evidence consistent with the existence of genetic linkage between bipolar disorder and three regions on chromosome 18, the pericentromeric region, 18q21, and 18q22-q23 have been reported. Some analyses indicated greater evidence for linkage in pedigrees in which paternal transmission of disease occurs. We have undertaken linkage analyses using 12 highly polymorphic markers spanning these three regions of interest in a sample of 48 U.K. bipolar pedigrees. The sample comprises predominantly nuclear families and includes 118 subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM IV) bipolar I disorder and 147 subjects with broadly defined phenotype. Our data do not provide support for linkage using either parametric or nonparametric analyses. Evidence for linkage was not significantly increased by analyses that allowed for heterogeneity nor by analysing the subset of pedigrees consistent with paternal transmission.
Harrison, Paul J
Bipolar disorder is a serious psychiatric disorder, with a high heritability and unknown pathogenesis. Recent genome-wide association studies have identified the first loci, implicating genes such as CACNA1C and ANK3. The genes highlight several pathways, notably calcium signalling, as being of importance. Molecular studies suggest that the risk variants impact on gene regulation and expression. Preliminary studies using reprogrammed patient-derived cells report alterations in the transcriptome and in cellular adhesion and differentiation. Mouse models show that genes involved in circadian biology, acting via dopaminergic effects, reproduce aspects of the bipolar phenotype. These findings together represent significant advances in identification of the genetic and molecular basis of bipolar disorder, yet we are still far from an integrated, evidence-based understanding of its aetiopathogenesis.
Waheed K. Bajwa
Full Text Available Catatonia, while not a rare occurrence in bipolar disorder, has not been widely discussed in the literature. We present a case of a married Caucasian male with a history of bipolar disorder, exhibiting catatonia and experiencing difficulty in day-to-day functioning. He demonstrated impairment in cognition and an inability to organize simple activities of daily life. After exhausting a number of options for medical management, including benzodiazepines, atypical antipsychotics, and amantadine, he only displayed significant clinical improvement with the addition of a stimulant, methylphenidate. In time, the patient saw a complete return to normal functioning. The use of stimulants for catatonia in bipolar disorder may be an interesting and effective option for treatment. While this is not the first time this treatment has been suggested, there is very little data in support of it; our case confirms the discoveries of previous case reports.
Jönsson, Erik G; Larsson, Kristina; Vares, Maria
disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences....... The present Scandinavian results do not verify previous associations between the putative functional MTHFR gene polymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism......Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single gene polymorphisms (SNPs; C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar...
Conell, Jörn; Bauer, Rita; Glenn, Tasha
BACKGROUND: Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information. METHODS: A 39 question, paper......-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating...... equations to account for correlated data. RESULTS: 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general...
Jönsson, Erik G; Larsson, Kristina; Vares, Maria;
Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single gene polymorphisms (SNPs; C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar....... The present Scandinavian results do not verify previous associations between the putative functional MTHFR gene polymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism...... disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences...
Full Text Available Anomalous perception has been investigated extensively in schizophrenia, but it is unclear whether these impairments are specific to schizophrenia or extend to other psychotic disorders. Recent studies of visual context processing in schizophrenia (Tibber et al., 2013; Yang et al., 2013 point to circumscribed, task-specific abnormalities. Here we examined visual contextual processing across a comprehensive set of visual tasks in individuals with bipolar disorder and compared their performance with that of our previously published results from schizophrenia and healthy participants tested on those same tasks. We quantified the degree to which the surrounding visual context alters a center stimulus’ appearance for brightness, size, contrast, orientation and motion. Across these tasks, healthy participants showed robust contextual effects, as indicated by pronounced misperceptions of the center stimuli. Participants with bipolar disorder showed contextual effects similar in magnitude to those found in healthy participants on all tasks. This result differs from what we found in schizophrenia participants (Yang et al., 2013 who showed weakened contextual modulations of contrast but intact contextual modulations of perceived luminance and size. Yet in schizophrenia participants, the magnitude of the contrast illusion did not correlate with symptom measures. Performance on the contrast task by the bipolar disorder group also could not be distinguished from that of the schizophrenia group, and this may be attributed to the result that bipolar patients who presented with greater manic symptoms showed weaker contrast modulation. Thus, contrast gain control may be modulated by clinical state in bipolar disorder. Stronger motion and orientation context effects correlated with worse clinical symptoms across both patient groups and especially in schizophrenia participants. These results highlight the complexity of visual context processing in schizophrenia
Full Text Available Annemiek Dols,1 Welmoed Krudop,2 Christiane Möller,2 Kenneth Shulman,3 Martha Sajatovic,4 Yolande AL Pijnenburg2 1Department of Old Age Psychiatry, GGZInGeest, 2Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, the Netherlands; 3Department of Geriatric Psychiatry, Sunnybrook Health Science Centre, Faculty of Medicine, University of Toronto, Toronto, Canada; 4Department of Psychiatry and Neurology, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA Objectives: Although bipolar disorder has been understood classically as a cyclic disease with full recovery between mood episodes, in the last decade, evidence has accumulated supporting progressive features. The clinical picture of advanced or end-stage bipolar disorder is heterogeneous with possible deficits in cognition and behavior, as illustrated by our case series.Cases: From our neuropsychiatric outpatient clinic, we describe four cases with bipolar disorder gradually developing a clinical syndrome, including apathy, disinhibition, loss of empathy, stereotypical behavior, and compulsiveness, fulfilling the criteria for possible behavioral variant frontotemporal dementia. All cases were diagnosed with bipolar 1 disorder at least 10 years before the onset of the current symptoms, which were not due to recent mood episodes or switches of medication. In all cases, 3–7 years of follow-up yielded no progression. Repeated neuroimaging was within normal limits. Cerebrospinal fluid biomarker studies were not supportive of underlying neurodegenerative pathology. C9orf72 mutation status was negative in all cases.Conclusion: Symptoms fitting the criteria for possible behavioral variant frontotemporal dementia may be present in end-stage of bipolar disorder. An alternative neurodegenerative nature seems unlikely based on repeated normal neuroimaging and the absence of clinical
van der Schot, A.C.
The focus of this thesis is twofold. The first part will discuss the structural brain abnormalities and schoolperformance associated with bipolar disorder and the influence of genetic and/or environmental factors to this association. It is part of a large twin study investigating several potential b
van der Werf - Eldering, Marieke; van der Meer, Lisette; Burger, Huibert; Holthausen, Esther; Nolen, W.A.; Aleman, Andre
Objective: To investigate the multifactorial relationship between illness insight, cognitive and emotional processes, and illness characteristics in bipolar disorder patients. Methods: Data from 85 euthymic or mildly to moderately depressed bipolar disorder patients were evaluated. Insight was measu
Full Text Available Introduction: Cognitive performance in patients with schizophrenia and Bipolar I disorder seems to be different from the normal individuals, that these defects affect their treatment results. Therefore, this study aimed to compare executive function and behavioral inhibition within patients suffering from schizophrenia, bipolar type I as well as a normal group. Methods: In this descriptive-comparative study, out of all patients hospitalized in daily psychiatric clinic in Najafabad in 2014 due to these disorders, 20 schizophrenia and 20 bipolar type I as well as 20 normal individuals were selected via the convinience sampling. All the study participants completed the computerizing tests including Tower of London and Go-No Go. The study data were analyzed utilizing SPSS software (ver 22 via MANOVA. Results: The study findings revealed a significant difference between the two patient groups and the normal group in regard with executive function and behavioral inhibition (p<0.05, whereas no differences were detected between schizophrenics and bipolar patient groups. Furthermore, patients suffering from schizophrenia and bipolar I mood disorder demonstrated significantly poor performance in cognitive function and behavioral inhibition compared to the normal group. Conclusion: The present study results can be significantly applied in pathology and therapy of these disorders, so as recognizing the inability of such patients can be effective in developing cognitive rehabilitation programs in these patients.
Correard, N; Elissalde, S N; Azorin, J-M; Fakra, E; Belzeaux, R
Diseases with complex determinism, bipolar disorders, involve at the same time environmental and genetic factors of vulnerability. The characterization of these vulnerabilities would allow a better knowledge of their etiology and envisage the development of therapeutics, more specialized, even preventive. The research in genetic psychiatry allowed to highlight endophenotype candidates associated to bipolar disorders. They are endogenous clinical or biological features, biologically more elementary than phenotypes and more directly bound to the physiological consequences of genes and their polymorphisms. Targeting some of them with specific psychotherapy and psychosocial interventions could reduce the consequences of their expression and so have an action on the course of the disease and also preventive.
Kawahara, Kazuhiro; Jono, Tadashi; Nishi, Yoshitomo; Ushijima, Hirokage; Ikeda, Manabu
Klinefelter syndrome (KS) is widely associated with cognitive impairment and language problems. KS patients may also exhibit psychiatric symptoms. We present the case of an 18-year-old man with KS who experienced rapidly repeating relapses of manic episodes. He was unresponsive to the usual pharmacotherapies for bipolar disorders such as mood stabilizers and second-generation antipsychotics. Mood was eventually improved with testosterone therapy in addition to pharmacotherapy, with no relapse of manic episodes for 3 years after discharge. Testosterone therapy may prevent relapsing manic episodes of bipolar disorder in patients with KS.
Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh
OBJECTIVES: The aim of the present study was to describe prescription patterns and changes in these patterns over the last decade for patients diagnosed with bipolar disorder in mental healthcare, using population-based and nationwide data, and to relate the findings to recommendations from...... international guidelines. METHODS: A population-based, nationwide study was carried out. It included register-based longitudinal data on all patients with a first-ever contact with mental healthcare with a diagnosis of mania/bipolar disorder from the entire Danish population, and all prescription data...
Nono Dueyou Buckjohn, C., E-mail: firstname.lastname@example.org [Laboratoire de Mecanique, Departement de Physique, Faculte des Sciences, Universite de Yaounde I, B.P. 812 Yaounde (Cameroon); Siewe Siewe, M., E-mail: email@example.com [Laboratoire de Mecanique, Departement de Physique, Faculte des Sciences, Universite de Yaounde I, B.P. 812 Yaounde (Cameroon); Tchawoua, C., E-mail: firstname.lastname@example.org [Laboratoire de Mecanique, Departement de Physique, Faculte des Sciences, Universite de Yaounde I, B.P. 812 Yaounde (Cameroon); Kofane, T.C., E-mail: email@example.com [Laboratoire de Mecanique, Departement de Physique, Faculte des Sciences, Universite de Yaounde I, B.P. 812 Yaounde (Cameroon)
In this Letter, we use a synchronization scheme on two bipolar disorder models consisting of a strong nonlinear system with multiplicative excitation and a nonlinear oscillator without parametric harmonic forcing. The stability condition following our control function is analytically demonstrated using the Lyapunov theory and Routh-Hurwitz criteria, we then have the condition for the existence of a feedback gain matrix. A convenient demonstration of the accuracy of the method is complemented by the numerical simulations from which we illustrate the synchronized dynamics between the two non-identical bipolar disorder patients.
Power, Robert A.; Steinberg, Stacy; Bjornsdottir, Gyda; Rietveld, Cornelius A.; Abdellaoui, Abdel; Nivard, Michel M; Johannesson, Magnus; Galesloot, Tessel E.; Hottenga, Jouke J.; Willemsen, Gonneke; Cesarini, David; Benjamin, Daniel J.; Magnusson, Patrik K. E.; Ullén, Fredrik; Tiemeier, Henning
To access publisher's full text version of this article click on the hyperlink at the bottom of the page We tested whether polygenic risk scores for schizophrenia and bipolar disorder would predict creativity. Higher scores were associated with artistic society membership or creative profession in both Icelandic (P = 5.2 × 10(-6) and 3.8 × 10(-6) for schizophrenia and bipolar disorder scores, respectively) and replication cohorts (P = 0.0021 and 0.00086). This could not be accounted for by...
Power, Robert A; Steinberg, Stacy; Bjornsdottir, Gyda; Rietveld, Cornelius A; Abdellaoui, Abdel; Nivard, Michel M; Johannesson, Magnus; Galesloot, Tessel E; Hottenga, Jouke J; Willemsen, Gonneke; Cesarini, David; Benjamin, Daniel J; Magnusson, Patrik K E; Ullén, Fredrik; Tiemeier, Henning; Hofman, Albert; van Rooij, Frank J A; Walters, G Bragi; Sigurdsson, Engilbert; Thorgeirsson, Thorgeir E; Ingason, Andres; Helgason, Agnar; Kong, Augustine; Kiemeney, Lambertus A; Koellinger, Philipp; Boomsma, Dorret I; Gudbjartsson, Daniel; Stefansson, Hreinn; Stefansson, Kari
We tested whether polygenic risk scores for schizophrenia and bipolar disorder would predict creativity. Higher scores were associated with artistic society membership or creative profession in both Icelandic (P = 5.2 × 10(-6) and 3.8 × 10(-6) for schizophrenia and bipolar disorder scores, respectively) and replication cohorts (P = 0.0021 and 0.00086). This could not be accounted for by increased relatedness between creative individuals and those with psychoses, indicating that creativity and psychosis share genetic roots.
Ali Reza Shafiee-Kandjani
Full Text Available "n Objective: Patients with bipolar mood disorder constitute a relatively large number of individuals hospitalized in psychiatric hospitals. This disorder is highly co-morbid with other psychiatric disorders and may effect their clinical course. The goal of this study was to determine the co-occurrence rate of anxiety disorders and substance abuse with bipolar mood disorders and their impact on clinical course. "n Methods: 153 bipolar patients (type I were selected among the hospitalized patients at Razi Psychiatric Hospital in Tabriz, Iran, from September 2007 to October 2008 through convenience sampling method. The participants were evaluated by a structured clinical interview based on DSM-IV criteria (SCID, Hamilton Rating Scale for Depression (HRSD and Young Mania Rating Scale (YMRS. Results: Co-morbidity of anxiety disorders was 43% . Occurrence of anxiety disorders was 26% for obsessive-compulsive disorder, 24.8% for generalized anxiety disorder, 3.9% for phobia and 2% for panic disorder. Co-morbidity of substance abuse was 7.2% and the highest occurrence of substance abuse was 5.2% for alcoholism and 3.9% for opium. No significant difference was observed between the severity of disease and duration of hospitalization in bipolar patients with or without anxiety disorder. The severity of disease and duration of hospitalization in bipolar patients with substance abuse was higher compared to bipolar patients without substance abuse (P<0.05. "nConclusions: This study suggests that there is a high co-morbidity between anxiety disorders and substance abuse with bipolar disorder. Further, this study suggests that co-occurrence of substance abuse disorder with bipolar disorder increases the severity of the disease and duration of hospitalization.
Full Text Available Satoshi Ueda,1 Takeshi Sakayori,1 Ataru Omori,2 Hajime Fukuta,3 Takashi Kobayashi,3 Kousuke Ishizaka,1 Tomoyuki Saijo,4 Yoshiro Okubo1 1Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan; 2Tamachuo Hospital, Tokyo, Japan; 3Kurumegaoka Hospital, Tokyo, Japan; 4Saijo Clinic, Tokyo, Japan Abstract: Neuroleptics can induce not only physical adverse effects but also mental effects that produce deficit status in thought, affect, cognition, and behavior. This condition is known as neuroleptic-induced deficit syndrome (NIDS, which includes apathy, lack of initiative, anhedonia, indifference, blunted affect, and reduced insight into disease. Although this old concept now appears almost forgotten, neuroleptics, whether typical or atypical, can make depression or bipolar disorder resemble other more refractory conditions, readily leading to mistaken diagnosis and inappropriate treatment. The authors describe three cases of NIDS superimposed on depressive phase in bipolar disorder with psychosis, where the attending psychiatrist’s failure to recognize NIDS prevented patients from receiving effective treatment and achieving remission. All cases achieved remission after reduction of neuroleptics and intensive therapy, including electroconvulsive therapy, for bipolar depression. The concept of NIDS was originally introduced for schizophrenia, and it has rarely been highlighted in other diseases. In recent years, however, atypical antipsychotics are being more often administered to patients with bipolar disorder. Psychiatrists, therefore, should also remember and exercise caution regarding NIDS in the pharmacotherapy of bipolar disorder with and without psychosis. The authors believe that the concept of NIDS needs to be reappraised in current psychiatry. Keywords: neuroleptic-induced deficit syndrome (NIDS, bipolar disorder, psychosis, atypical antipsychotics, electroconvulsive therapy
Venkataraman, Meenakshi; Ackerson, Barry J.
Bipolar disorder is a severe form of mental illness with a primary disruption in mood. With fluctuating phases of mania and depression, bipolar disorder can have a serious impact on all activities of daily living, including parenting. Ten mothers with bipolar disorder were interviewed to understand their strengths, challenges, and service needs in…
Full Text Available Nizar El-KhaliliAlpine Clinic, Lafayette, IN, USAAbstract: The atypical antipsychotic quetiapine fumarate is available both as an immediate release (IR and as an extended release (XR formulation allowing flexibility of dosing for individual patients. Approved uses of quetiapine XR include the treatment of schizophrenia (including maintenance therapy for prevention of relapse, the treatment of bipolar disorder (manic and depressive episodes, and the prevention of recurrence in patients with bipolar disorder who respond to quetiapine XR. This narrative review provides an update on quetiapine XR in these indications. The pharmacological profile of quetiapine, including a moderate affinity for dopamine D2 receptors and higher affinity for serotonin 5-hydroxytryptophan (5-HT2A receptors, may explain its broad efficacy and low propensity for extrapyramidal symptoms (EPS. The XR formulation has similar bioavailability but prolonged plasma levels compared with the IR formulation, allowing for less frequent (once-daily dosing. Clinical studies have confirmed the efficacy of quetiapine XR in relieving the acute symptoms of schizophrenia during short-term trials, and reducing the risk for relapse in long-term studies. Direct switching from the IR formulation to the same dose of the XR formulation did not reveal any loss of efficacy or tolerability issues, and switching patients to quetiapine XR from conventional or other atypical antipsychotics (for reasons of insufficient efficacy or tolerability also proved to be beneficial and generally well tolerated. In bipolar disorder, quetiapine XR has also proven effective in relieving acute depressive and manic symptoms. Adverse events with quetiapine XR in patients with either schizophrenia or bipolar disorder are similar to those associated with the IR formulation, the most common being sedation, dry mouth, somnolence, dizziness, and headache. The low propensity for EPS is maintained with the XR formulation
Fabiano A. Gomes
Full Text Available Objective: Bipolar disorder (BD is associated with significant morbidity and mortality due to comorbid general medical conditions, particularly cardiovascular disease. This study is the first report of the Brazilian Research Network in Bipolar Disorder (BRN-BD that aims to evaluate the prevalence and clinical correlates of cardiovascular risk factors among Brazilian patients with BD. Methods: A cross-sectional study of 159 patients with DSM-IV BD, 18 years or older, consecutively recruited from the Bipolar Research Program (PROMAN in São Paulo and the Bipolar Disorder Program (PROTAHBI in Porto Alegre. Clinical, demographic, anthropometric, and metabolic variables were systematically assessed. Results: High rates of smoking (27%, physical inactivity (64.9%, alcohol use disorders (20.8%, elevated fasting glucose (26.4%, diabetes (13.2%, hypertension (38.4%, hypertriglyceridemia (25.8%, low HDL-cholesterol (27.7%, general (38.4% and abdominal obesity (59.1% were found in the sample. Male patients were more likely to have alcohol use disorders, diabetes, and hypertriglyceridemia, whereas female patients showed higher prevalence of abdominal obesity. Variables such as medication use pattern, alcohol use disorder, and physical activity were associated with selected cardiovascular risk factors in the multivariable analysis. Conclusion: This report of the BRN-BD provides new data regarding prevalence rates and associated cardiovascular risk factors in Brazilian outpatients with BD. There is a need for increasing both awareness and recognition about metabolic and cardiovascular diseases in this patient population.
Ravindra Neelakanthappa Munoli
Full Text Available Background: Bipolar disorder is a relatively common, long-term, and disabling psychiatric illness that is associated with high levels of functional impairment, morbidity, mortality, and an increased risk of suicide. Psychiatric co-morbidity in bipolar disorder ranges from 57.3% to 74.3%, whereas medical co-morbidity varies from 2.7-70%. Indian scenario in this aspect is not clear. Materials and Methods: The objective was to ascertain the prevalence of physical and psychiatric co-morbidities in patients attending a tertiary care center over a period of 1 year and its relationship with socio-demographic and clinical variables. One hundred and twenty-five case record files were included in the review. OPCRIT software was used for re-establishing the diagnosis of bipolar disorder, which yielded 120 cases. A semi-structured pro-forma, specifically designed for the study, was used to collect the socio-demographic and clinical details. Results: Co-morbid psychiatric disorders were found in 52 (43.3% of the sample, whereas co-morbid physical illness was present in 77 (64.2% patients. The most common psychiatric disorder associated was substance use disorder (27.5%, whereas co-morbid cardiovascular disorder was the most frequent physical diagnosis in the sample (20%. Discussion: The prevalence of co-morbid psychiatric disorders in bipolar patients was lower than that reported in western literature. It could be related to retrospective nature of study or reflect true lower prevalence rates. Also, certain disorders such as eating disorders were absent in our sample, and migraine diagnosis was very infrequent.
Full Text Available Aim: The subject of the research presented in this paper was to analyze the relationships between bipolar disorder (BD and the profile of moral reasoning according to the concept of James Rest. Material and methods: 86 persons took part in the research, including 43 bipolar patients and 43 healthy individuals. To measure the severity of depression and mania symptoms the following scales were used: Hamilton Rating Scale for Depression (HAM-D, Montgomery-Asberg Depression Rating Scale (MADRS and Young Rating Scale for Mania (YMRS. Profile of moral reasoning was defined on the basis of the results obtained in the Defining Issue Test (DIT by James Rest. Results: Statistical analysis showed that there is a relationship between bipolar disorder (and its phases and the profile of moral reasoning: bipolar patients significantly less often than healthy individuals chose answers indicating the postconventional thinking (p=0,000 – and more often – answers indicating stage 3 and those belonging to the anti-institutional thinking index (p=0,000. There was also a relationship shown between the development of moral reasoning and the phase of bipolar disorder: patients in mania less often than per- sons in euthymia chose answers indicating the final stage of moral thinking (p=0,050. There were no significant differences between the results of patients with a depressive episode and the results of patients in mania and between the results of patients with a depressive episode and the results of patients in euthymia. Conclusions: The results suggest that the psychological state of the individual may have an impact on the process of moral reasoning – bipolar disorder may to some extent influence the way of thinking about moral dilemmas. The collected data also seem to emphasize the specificity of the manic phase which is especially worth exploration when conducting further studies.
Pfeifer, Jonathan C.; Welge, Jeffrey; Strakowski. Stephen M.; Adler, Caleb M.; Delbello, Melissa P.
The size of amygdala of bipolar youths and adults is investigated using neuroimaging studies. Findings showed that smaller volumes of amygdala were observed in youths with bipolar youths compared with children and adolescents without bipolar disorder. The structural amygdala abnormalities in bipolar youths are examined further.
Alice Aita Cacilhas
Full Text Available OBJECTIVE: Although bipolar disorder is a major contributor to functional impairment worldwide, an independent impact of bipolar disorder and ageing on functioning has yet to be demonstrated. The objective of the present study was to evaluate the effect of bipolar disorder on age-related functional status using matched controls as a standard. METHOD: One-hundred patients with bipolar disorder and matched controls were evaluated for disability. Age-related effects controlled for confounders were cross-sectionally evaluated. RESULTS: Patients were significantly more impaired than controls. Regression showed effects for aging in both groups. The effect, size, however, was significantly stronger in patients. CONCLUSION: Bipolar disorder was an important effect modifier of the age impact on functioning. While a longitudinal design is needed to effectively demonstrate this different impact, this study further depicts bipolar disorder as a chronic and progressively impairing illness.OBJETIVO: O transtorno bipolar é responsável por importante parcela do prejuízo funcional ao redor do mundo. Um efeito independente do transtorno bipolar e da idade no funcionamento ainda não foi demonstrado. O presente estudo tem o objetivo de avaliar o efeito do transtorno bipolar no prejuízo funcional relacionado à idade, com controles pareados como padrão. MÉTODO: Cem pacientes com transtorno bipolar e controles pareados foram avaliados para incapacidade. Efeitos relacionados à idade, com controle para confundidores, foram investigados. RESULTADOS: Pacientes tiveram significativamente mais prejuízo que controles. A regressão mostrou efeito para a idade em ambos os grupos, e o efeito foi significativamente mais forte nos pacientes. CONCLUSÃO: O transtorno bipolar foi um importante modificador de efeito no impacto da idade no funcionamento. Enquanto um desenho de estudo longitudinal é necessário para efetivamente demonstrar este impacto diferencial, este
Four children from three families in which the mother had a bipolar disorder were interviewed to understand their perspectives on their mothers' parenting. Children identified strengths in their mother's parenting, such as helping them with homework and moods and providing for their wants. They also identified challenges, such as mothers sleeping…
Jacoby, Anne Sophie; Faurholt-Jepsen, Maria; Vinberg, Maj;
Bipolar disorder is a great challenge to patients, relatives and clinicians, and there is a need for development of new methods to identify prodromal symptoms of affective episodes in order to provide efficient preventive medical and behavioural intervention. Clinical trials prove that electronic...
Singh, Manpreet K.; Chang, Kiki D.; Kelley, Ryan G.; Cui, Xu; Sherdell, Lindsey; Howe, Meghan E.; Gotlib, Ian H.; Reiss, Allan L.
Objective: Bipolar disorder (BD) is a debilitating psychiatric condition that commonly begins in adolescence, a developmental period that has been associated with increased reward seeking. Because youth with BD are especially vulnerable to negative risk-taking behaviors, understanding the neural mechanisms by which dysregulated affect interacts…
Siegel, Rebecca S.; Freeman, Andrew J.; La Greca, Annette M.; Youngstrom, Eric A.
Background: Pediatric bipolar disorder (PBD) is associated with psychosocial impairment, but few studies have examined peer relationship functioning and PBD. Adolescence is a crucial developmental period when peers become increasingly salient. Objective: This study compared perceived friendship quality and peer victimization in adolescents with…
Serrano, Eduardo; Ezpeleta, Lourdes; Castro-Fornieles, Josefina
Objective: To assess the comorbidity of bipolar disorder (BPD) in children with ADHD and to study the psychopathological profile of ADHD children with and without mania. Method: A total of 100 children with ADHD were assessed with a semistructured diagnostic interview and questionnaires of mania, ADHD, and general psychopathology. Results: 8% of…
Whitney, Jane; Joormann, Jutta; Gotlib, Ian H.; Kelley, Ryan G.; Acquaye, Tenah; Howe, Meghan; Chang, Kiki D.; Singh, Manpreet K.
Background: Cognitive models of bipolar I disorder (BD) may aid in identification of children who are especially vulnerable to chronic mood dysregulation. Information-processing biases related to memory and attention likely play a role in the development and persistence of BD among adolescents; however, these biases have not been extensively…
Ohgidani, Masahiro; Kato, Takahiro A.; Haraguchi, Yoshinori; Matsushima, Toshio; Mizoguchi, Yoshito; Murakawa-Hirachi, Toru; Sagata, Noriaki; Monji, Akira; Kanba, Shigenobu
The pathophysiology of bipolar disorder, especially the underlying mechanisms of the bipolarity between manic and depressive states, has yet to be clarified. Microglia, immune cells in the brain, play important roles in the process of brain inflammation, and recent positron emission tomography studies have indicated microglial overactivation in the brain of patients with bipolar disorder. We have recently developed a technique to induced microglia-like (iMG) cells from peripheral blood (monocytes). We introduce a novel translational approach focusing on bipolar disorder using this iMG technique. We hypothesize that immunological conditional changes in microglia may contribute to the shift between manic and depressive states, and thus we herein analyzed gene profiling patterns of iMG cells from three patients with rapid cycling bipolar disorder during both manic and depressive states, respectively. We revealed that the gene profiling patterns are different between manic and depressive states. The profiling pattern of case 1 showed that M1 microglia is dominant in the manic state compared to the depressive state. However, the patterns of cases 2 and 3 were not consistent with the pattern of case 1. CD206, a mannose receptor known as a typical M2 marker, was significantly downregulated in the manic state among all three patients. This is the first report to indicate the importance of shifting microglial M1/M2 characteristics, especially the CD206 gene expression pattern between depressive and manic states. Further translational studies are needed to dig up the microglial roles in the underlying biological mechanisms of bipolar disorder. PMID:28119691
Johnson, Sheri L.; Murray, Greg; Fredrickson, Barbara; Youngstrom, Eric A.; Hinshaw, Stephen; Bass, Julie Malbrancq; Deckersbach, Thilo; Schooler, Jonathan; Salloum, Ihsan
Substantial literature has linked bipolar disorder with creative accomplishment. Much of the thinking in this area has been inspired by biographical accounts of poets, musicians, and other highly accomplished groups, which frequently document signs of bipolar disorder in these samples. A smaller literature has examined quantitative measures of creativity among people with bipolar disorder or at risk for the disorder. In this paper, we provide a critical review of such evidence. We then consider putative mechanisms related to the link of bipolar disorder with creativity, by drawing on literature outside of bipolar disorder on personality, motivational, and affective predictors of creativity. Because so little research has directly evaluated whether these factors could help explain the elevations of creativity in bipolar disorder, we conclude with an agenda for future research on the theoretically and clinically compelling topic of creativity in bipolar disorder. PMID:22088366
Johnson, Sheri L; Murray, Greg; Fredrickson, Barbara; Youngstrom, Eric A; Hinshaw, Stephen; Bass, Julie Malbrancq; Deckersbach, Thilo; Schooler, Jonathan; Salloum, Ihsan
Substantial literature has linked bipolar disorder with creative accomplishment. Much of the thinking in this area has been inspired by biographical accounts of poets, musicians, and other highly accomplished groups, which frequently document signs of bipolar disorder in these samples. A smaller literature has examined quantitative measures of creativity among people with bipolar disorder or at risk for the disorder. In this paper, we provide a critical review of such evidence. We then consider putative mechanisms related to the link of bipolar disorder with creativity, by drawing on literature outside of bipolar disorder on personality, motivational, and affective predictors of creativity. Because so little research has directly evaluated whether these factors could help explain the elevations of creativity in bipolar disorder, we conclude with an agenda for future research on the theoretically and clinically compelling topic of creativity in bipolar disorder.
Tas, Cumhur; Brown, Elliot C; Aydemir, Omer; Brüne, Martin; Lysaker, Paul H
While deficits in metacognition have been observed in schizophrenia (SZ), it is less clear whether these are specific to the disorder. Accordingly, this study compared metacognitive abilities of patients with schizophrenia and bipolar disorder (BD) and examined the degree to which neurocognition contributed to metacognitive deficits in both groups. Participants were 30 patients with SZ and 30 with BD. Metacognitive capacity was measured using the Metacognition Assessment Scale Abbreviated (MAS-A). This scale comprises four domains: self-reflectivity, understanding others' minds, decentration and mastery. Verbal memory, executive functioning and symptoms were concurrently assessed. Group comparisons revealed that SZ patients had greater deficits in metacognitive self-reflectivity, which correctly classified 85.2% of patients with SZ in a logistic regression. Self-reflectivity and understanding others'minds were related to verbal memory and executive functioning in the SZ group, but not in the BD group. Furthermore, greater positive and general psychotic symptoms were associated with poorer metacognition in SZ. Results suggest SZ involves unique deficits in the ability to self-reflect and that these deficits may be uniquely linked with neurocognition.
Full Text Available Bipolar disorder is a complex psychiatric disorder with high heritability, but its genetic determinants are still largely unknown. Copy number variation (CNV is one of the sources to explain part of the heritability. However, it is a challenge to estimate discrete values of the copy numbers using continuous signals calling from a set of markers, and to simultaneously perform association testing between CNVs and phenotypic outcomes. The goal of the present study is to perform a series of data filtering and analysis procedures using a DNA pooling strategy to identify potential CNV regions that are related to bipolar disorder. A total of 200 normal controls and 200 clinically diagnosed bipolar patients were recruited in this study, and were randomly divided into eight control and eight case pools. Genome-wide genotyping was employed using Illumina Human Omni1-Quad array with approximately one million markers for CNV calling. We aimed at setting a series of criteria to filter out the signal noise of marker data and to reduce the chance of false-positive findings for CNV regions. We first defined CNV regions for each pool. Potential CNV regions were reported based on the different patterns of CNV status between cases and controls. Genes that were mapped into the potential CNV regions were examined with association testing, Gene Ontology enrichment analysis, and checked with existing literature for their associations with bipolar disorder. We reported several CNV regions that are related to bipolar disorder. Two CNV regions on chromosome 11 and 22 showed significant signal differences between cases and controls (p < 0.05. Another five CNV regions on chromosome 6, 9, and 19 were overlapped with results in previous CNV studies. Experimental validation of two CNV regions lent some support to our reported findings. Further experimental and replication studies could be designed for these selected regions.
Corradini, Andrea; Lyck Festersen, Pia
Several personal healthcare monitoring systems have been proposed to target somatic diseases and specific mental illness. This paper reports on the re:Mind system, which is a helpful tool that supports the treatment of people diagnosed with bipolar disorder. We developed the system as a hybrid...... mobile application to help bipolar patients self-monitor a set of parameters that are known to affect their illness while also allowing them to communicate with their physician. Based on data collected from medical personnel, clinicians, patients, patients’ relatives and persons akin to them, we created...
Grigoroiu-Serbanescu, Maria; Diaconu, Carmen C; Heilmann-Heimbach, Stefanie; Neagu, Ana Iulia; Becker, Tim
We investigated the influence of the age-of-onset (AO) on the association of 45 loci conferring risk for bipolar disorder (BP) and schizophrenia with BP-type-I in a Romanian sample (461 patients, 436 controls). The AO-analysis implicated the EGFR gene, as well as loci in other genes, in the AO variation of BP-type-I and revealed for the first time the link between BP-type-I and risk variants considered specific to schizophrenia (polymorphisms in MMP16/RIPK2 and CNNM2 genes).
Stephen E Nicolson
Full Text Available Stephen E Nicolson1, Charles B Nemeroff21From the Department of Psychiatry, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA; 2From the Department of Psychiatry and Behavioral Sciences, Emory University, School of Medicine, Atlanta, GA, USAAbstract: Ziprasidone is an atypical antipsychotic with a unique receptor-binding profile. Currently, ziprasidone is approved by the US Food and Drug Administration for the acute treatment of psychosis in schizophrenia and mania in bipolar disorder. When compared to certain other atypical antipsychotics, ziprasidone appears to have a relatively benign side effect profile, especially as regards metabolic effects eg, weight gain, serum lipid elevations and glucose dysregulation. Taken together, these data suggest that ziprasidone may be a first line treatment for patients with bipolar mania. However, ziprasidone is a relatively new medication for which adverse events after long-term use and/or in vulnerable patient populations must be studied. Unstudied areas of particular importance include the efficacy and safety of ziprasidone in the treatment of bipolar depression and relapse prevention of mania as, well as in the subpopulations of pregnant women, the elderly and pediatric patients. The emergence of mania in patients taking ziprasidone is another topic for further study.Keywords: antipsychotic, bipolar disorder, mania, mood disorder, neuroleptic, ziprasidone
Clark, Luke; Sahakian, Barbara J
Bipolar disorder is characterized by a combination of state-related changes in psychological function that are restricted to illness episodes, coupled with trait-related changes that persist through periods of remission, irrespective of symptom status. This article reviews studies that have investigated the brain systems involved in these state- and trait-related changes, using two techniques: (i) indirect measures of neurocognitive function, and (ii) direct neuroimaging measures of brain function during performance of a cognitive task. Studies of neurocognitive function in bipolar disorder indicate deficits in three core domains: attention, executive function, and emotional processing. Functional imaging studies implicate pathophysiology in distributed neural circuitry that includes the prefrontal and anterior cingulate cortices, as well as subcortical limbic structures including the amygdala and the ventral striatum. Whilst there have been clear advances in our understanding of brain changes in bipolar disorder, there are limited data in bipolar depression, and there is limited understanding of the influence of clinical variables including medication status, illness severity, and specific symptom dimensions.
Full Text Available Young Sup Woo, Hee Ryung Wang, Won-Myong Bahk Department of Psychiatry, Yeouido St Mary's Hospital, The Catholic University of Korea, Seoul, Korea Abstract: Lurasidone is a benzisothiazol derivative and an atypical antipsychotic approved by the US Food and Drug Administration for the acute treatment of adults with schizophrenia (October 2010 and bipolar 1 depression (June 2013. Lurasidone has a strong antagonistic property at the D2, serotonin (5-HT2A, and 5-HT7 receptors, and partial agonistic property at the 5-HT1A receptor. Lurasidone also has lower binding affinity for the α2C and 5-HT2C receptor. Lurasidone is rapidly absorbed (time to maximum plasma concentration: 1–3 hours, metabolized mainly by CYP3A4 and eliminated by hepatic metabolism. In two large, well-designed, 6-week trials in adult patients with bipolar 1 depression, lurasidone monotherapy and adjunctive therapy with mood stabilizers were significantly more effective than placebo at improving depressive symptoms assessed using the Montgomery–Åsberg Depression Rating Scale total score. In both trials, lurasidone also reduced the Clinical Global Impression–Bipolar Severity depression score to a greater extent than placebo. In these two trials, discontinuation rates due to adverse events in the lurasidone group were small (<7% and were not different from those of the placebo group. The most common adverse events in the lurasidone group were headache, nausea, somnolence, and akathisia. The changes in lipid profiles, weight, and parameters of glycemic control were minimal, and these findings were in line with those observed in schizophrenia trials. Further active comparator trials and long-term tolerability and safety data in bipolar patients are required. Lurasidone may be an option for the management of depressive symptoms in patients with bipolar 1 disorder, and it may be considered as a treatment alternative for patients who are at high risk for metabolic abnormalities
Kivilcim, Yigit; Altintas, Merih; Domac, Fusun Mayda; Erzincan, Erkal; Gülec, Huseyin
Purpose The aim of this study was to evaluate the prevalence of comorbid bipolar disorder (BD) among migraineurs and the impact of migraine–BD comorbidity on disease characteristics. Patients and methods A total of 120 adult patients diagnosed with migraine at a single tertiary care center were included in this cross-sectional study. Data on sociodemographic and migraine-related characteristics, family history of psychiatric diseases, comorbid psychiatric diseases, and first-episode characteristics were recorded. Mood Disorders Diagnosis and Patient Registration Form (SCIP-TURK), Mood Disorder Questionnaire (MDQ), and Hypomania Checklist-32-Revised (HCL-32-R) were applied to all patients by experienced clinicians, and clinical diagnoses were confirmed using Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Migraine Disability Assessment Scale (MIDAS) was used to evaluate the headache-related disability. Study parameters were compared between migraineurs with and without comorbid BD. Results The diagnosis of comorbid BD was confirmed in 19.2% of migraineurs. A significantly higher percentage of patients with comorbid BD than those without comorbid BD had family history of BD (39.1% vs 6.2%, P30 (OR, 3.69; 95% CI, 1.12–12.19; P=0.032) were associated with 14.42 times and 3.69 times increased likelihood of BD, respectively. Conclusion Our findings revealed comorbid BD in a remarkable percentage of migraineurs and a higher likelihood of having BD in case of a positive family history of type I BD and MIDAS scores >30. Comorbid BD was associated with a higher rate for a family history of BD, suicide attempt, and childhood physical abuse as well as aggravated migraine-related disability among migraineurs. Migraineurs with and without comorbid BD showed similar sociodemographic and migraine disease characteristics as well as similar high rates for comorbid anxiety and first-episode depression. PMID:28280345
Montgomery, S A; Schatzberg, A F; Guelfi, J D; Kasper, S; Nemeroff, C; Swann, A; Zajecka, J
The treatment of bipolar depression requires the resolution of depression and the establishment of mood stability. A basic problem is that the treatments used in treating bipolar depression were developed and proven effective for other disease states: antidepressants for unipolar depression, and mood stabilizers for mania. The panel addressed four unresolved questions regarding depression in relation to bipolar disorder: (1) the relative effectiveness of different antidepressant treatments; (2) the relative likelihood of mood destabilization with different antidepressant treatments; (3) the effectiveness and role of mood-stabilizing medicines as antidepressants; and (4) the optimal approach to mixed states. The selection of an antidepressant depends both on its relative lack of mania- or hypomania-provoking potential and on its effectiveness against bipolar depression. There is little definitive evidence distinguishing effectiveness of the major groups of antidepressive agents, so side-effect profiles and pharmacokinetics are major considerations. The underlying bipolar disorder should be treated with mood stabilizers started simultaneously with any antidepressive treatments. Lithium, divalproex sodium and carbamazepine have all been found to be helpful, to some extent, in treating bipolar depressive episodes as well as for long-term mood stabilization. There is little evidence for long-term benefits of antidepressive agents in bipolar disorder, and some evidence that they may destabilize the disorder. Therefore, in contrast to the long-term use of mood-stabilizers, antidepressant use is recommended on a temporary basis. The duration of antidepressant treatment is determined by past history in terms of liability for mood destabilization, and by the ability of the patient to tolerate gradual antidepressant discontinuation without return of depression. Mixed states, where symptoms of depression and mania coexist, are regarded as a predictor of relatively poor
Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression.
Behan, A T
The dorsolateral prefrontal cortex (dlpfc) is strongly implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BPD) and, within this region, abnormalities in glutamatergic neurotransmission and synaptic function have been described. Proteins associated with these functions are enriched in membrane microdomains (MM). In the current study, we used two complementary proteomic methods, two-dimensional difference gel electrophoresis and one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis followed by reverse phase-liquid chromatography-tandem mass spectrometry (RP-LC-MS\\/MS) (gel separation liquid chromatography-tandem mass spectrometry (GeLC-MS\\/MS)) to assess protein expression in MM in pooled samples of dlpfc from SCZ, BPD and control cases (n=10 per group) from the Stanley Foundation Brain series. We identified 16 proteins altered in one\\/both disorders using proteomic methods. We selected three proteins with roles in synaptic function (syntaxin-binding protein 1 (STXBP1), brain abundant membrane-attached signal protein 1 (BASP1) and limbic system-associated membrane protein (LAMP)) for validation by western blotting. This revealed significantly increased expression of these proteins in SCZ (STXBP1 (24% difference; P<0.001), BASP1 (40% difference; P<0.05) and LAMP (22% difference; P<0.01)) and BPD (STXBP1 (31% difference; P<0.001), BASP1 (23% difference; P<0.01) and LAMP (20% difference; P<0.01)) in the Stanley brain series (n=20 per group). Further validation in dlpfc from the Harvard brain subseries (n=10 per group) confirmed increased protein expression in SCZ of STXBP1 (18% difference; P<0.0001), BASP1 (14% difference; P<0.0001) but not LAMP (20% difference; P=0.14). No significant differences in STXBP1, BASP1 or LAMP protein expression in BPD dlpfc were observed. This study, through proteomic assessments of MM in dlpfc and validation in two brain series, strongly implicates LAMP, STXBP1 and BASP1 in SCZ and supports
Full Text Available Objective:To identify, by means of a systematic review, the frequency with which comorbid personality disorders (PDs have been assessed in studies of euthymic bipolar patients.Methods:PubMed, ciELO and PsychINFO databases were searched for eligible articles published between 1997 and 2013. After screening 1,249 empirical papers, two independent reviewers identified three articles evaluating the frequency of PDs in patients with bipolar disorders assessed in a state of euthymia.Results:The total sample comprised 376 euthymic bipolar patients, of whom 155 (41.2% had at least one comorbid PD. Among them, we found 87 (23.1% in cluster B, 55 (14.6% in cluster C, and 25 (6.6% in cluster A. The frequencies of PD subtypes were: borderline, 38 (10.1%; histrionic, 29 (7.7%; obsessive-compulsive, 28 (7.4%; dependent, 19 (5%; narcissistic, 17 (4.5%; schizoid, schizotypal, and avoidant, 11 patients each (2.95%; paranoid, five (1.3%; and antisocial, three (0.79%.Conclusion:The frequency of comorbid PD was high across the spectrum of euthymic bipolar patients. In this population, the most common PDs were those in cluster B, and the most frequent PD subtype was borderline, followed by histrionic and obsessive-compulsive.
Rybakowski, Janusz K
About one-third of lithium-treated, bipolar patients are excellent lithium responders; that is, lithium monotherapy totally prevents further episodes of bipolar disorder for ten years and more. These patients are clinically characterized by an episodic clinical course with complete remission, a bipolar family history, low psychiatric comorbidity, mania-depression episode sequences, a moderate number of episodes, and a low number of hospitalizations in the pre-lithium period. Recently, it has been found that temperamental features of hypomania (a hyperthymic temperament) and a lack of cognitive disorganization predict the best results of lithium prophylaxis. Lithium exerts a neuroprotective effect, in which increased expression of brain-derived neurotrophic factor (BDNF) and inhibition of the glycogen synthase kinase-3 (GSK-3) play an important role. The response to lithium has been connected with the genotype of the BDNF gene and serum BDNF levels. A better response to lithium is connected with the Met allele of the BDNF Val/Met polymorphism, as is a hyperthymic temperament. Excellent lithium responders have normal cognitive functions and serum BDNF levels, even after long-term duration of the illness. The preservation of cognitive functions in long-term lithium-treated patients may be connected with the stimulation of the BDNF system, with the resulting prevention of affective episodes exerting deleterious cognitive effects, and possibly also with lithium's antiviral effects. A number of candidate genes that are related to neurotransmitters, intracellular signaling, neuroprotection, circadian rhythms, and other pathogenic mechanisms of bipolar disorder were found to be associated with the lithium prophylactic response. The Consortium on Lithium Genetics (ConLiGen) has recently performed the first genome-wide association study on the lithium response in bipolar disorder.
Full Text Available Depression, Major Depression or mental disorder creates severe diseases. Mental illness such as Unipolar Major Depression, Bipolar Disorder, Dysthymia, Schizophrenia, Cardiovascular Diseases (Hypertension, Coronary Heart Disease, Stroke etc., are known as Major Depression. Several studies have revealed the possibilities about the association among Bipolar Disorder, Schizophrenia, Coronary Heart Diseases and Stroke with each other. The current study aimed to investigate the relationships between genetic variants in the above four diseases and to create a common pathway or PPI network. The associated genes of each disease are collected from different gene database with verification using R. After performing some preprocessing, mining and operations using R on collected genes, seven (7 common associated genes are discovered on selected four diseases (SZ, BD, CHD and Stroke. In each of the iteration, the numbers of collected genes are reduced up to 51%, 36%, 10%, 2% and finally less than 1% respectively. Moreover, common pathway on selected diseases has been investigated in this research.
Vicente-Herrero, María Teófila; Ruiz-Flores, Miguel; Torres, J Ignacio; Capdevila, Luisa; Ramírez, María Victoria; Terradillos, María Jesús; López-González, Ángel Arturo
We describe the case of a worker with bipolar disorder who was terminated for incompetence, following a determination of being unfit for duty based on a periodic medical examination. The judge reversed the dismissal on the basis of failing to comply with the provisions of Article 52 a) of the Spanish Workers' Law. Social and labor integration of people with bipolar disorder presents challenges due both to the clinical characteristics of the disease and its chronic course, and the limitations associated with continued treatment. These situations can benefit from an evaluation of fitness for duty by an occupational physician and the implementation of preventive measures by the company, as it is necessary to exhaust all options before considering an extreme decision such as work unfitness and subsequent termination. The initial objective should be the social and labor integration of the affected worker, while minimizing risk to self and others.
Miklowitz, David J
The longitudinal course of bipolar disorder (BD) is highly impairing. This article reviews recent research on functional impairment in the course of BD, the roles of social and intrafamilial stress in relapse and recovery, and the role of adjunctive psychosocial interventions in reducing risk and enhancing functioning. Comparative findings in adult and childhood BD are highlighted. Life events and family-expressed emotion have emerged as significant predictors of the course of BD. Studies of social information processing suggest that impairments in the recognition of facial emotions may characterize both adult- and early-onset bipolar patients. Newly developed psychosocial interventions, particularly those that focus on family and social relationships, are associated with more rapid recovery from episodes and better psychosocial functioning. Family-based psychoeducational approaches are promising as early interventions for children with BD or children at risk of developing the disorder. For adults, interpersonal therapy, mindfulness-based strategies, and cognitive remediation may offer promise in enhancing functioning.
Substantial literature has linked bipolar disorder with creative accomplishment. Much of the thinking in this area has been inspired by biographical accounts of poets, musicians, and other highly accomplished groups, which frequently document signs of bipolar disorder in these samples. A smaller literature has examined quantitative measures of creativity among people with bipolar disorder or at risk for the disorder. In this paper, we provide a critical review of such evidence. We then consid...
Luis Pereira Justo
Full Text Available Neste trabalho, os autores, através de revisão bibliográfica narrativa, situam as intervenções psicossociais dentro do panorama terapêutico para o transtorno bipolar e constatam que ainda são insuficientes os estudos primários feitos com metodologia adequada para a obtenção de informações científicas de boa qualidade. São sucintamente descritos os trabalhos mais relevantes.In this paper, the authors review the status of psychosocial interventions within the general treatment for bipolar disorder. They have verified the scantiness of studies performed with adequate methodology to obtain scientific information of good quality. The more relevant studies are briefly described.
Kelly A Sagar
Full Text Available Marijuana is the most widely used illicit substance in those diagnosed with bipolar I disorder. However, there is conflicting evidence as to whether marijuana may alleviate or exacerbate mood symptomatology. As bipolar disorder and marijuana use are individually associated with cognitive impairment, it also remains unclear whether there is an additive effect on cognition when bipolar patients use marijuana. The current study aimed to determine the impact of marijuana on mood in bipolar patients and to examine whether marijuana confers an additional negative impact on cognitive function. Twelve patients with bipolar disorder who smoke marijuana (MJBP, 18 bipolar patients who do not smoke (BP, 23 marijuana smokers without other Axis 1 pathology (MJ, and 21 healthy controls (HC completed a neuropsychological battery. Further, using ecological momentary assessment, participants rated their mood three times daily as well as after each instance of marijuana use over a four-week period. Results revealed that although the MJ, BP, and MJBP groups each exhibited some degree of cognitive impairment relative to HCs, no significant differences between the BP and MJBP groups were apparent, providing no evidence of an additive negative impact of BPD and MJ use on cognition. Additionally, ecological momentary assessment analyses indicated alleviation of mood symptoms in the MJBP group after marijuana use; MJBP participants experienced a substantial decrease in a composite measure of mood symptoms. Findings suggest that for some bipolar patients, marijuana may result in partial alleviation of clinical symptoms. Moreover, this improvement is not at the expense of additional cognitive impairment.
Faurholt-Jepsen, Maria; Frost, Mads; Vinberg, Maj
The daily electronic self-monitoring Smartphone software "MONARCA" was used by 17 patients with bipolar disorder for 3 consecutive months. Patients were rated fortnightly using Hamilton Depression rating Scale 17 items (HDRS-17) and Young Mania rating Scale (YMRS) (102 ratings) with blinding...... for Smartphone data. Objective Smartphone measures such as physical and social activity correlated with clinically rated depressive symptoms. Self-monitored depressive symptoms correlated significantly with HDRS-17 items score....
Kluwe-Schiavon,Bruno; Viola,Thiago Wendt; Levandowski, Mateus Luz; Bortolotto,Vanessa Rezende; Leo Schuch Azevedo e Souza; Tractenberg,Saulo Gantes; Soares, Tárcio
Introduction: It has been shown that bipolar disorder (BD) has a direct impact on neurocognitive functioning and behavior. This finding has prompted studies to investigate cognitive enhancement programs as potential treatments for BD, primarily focusing on cognitive reinforcement and daily functioning and not restricted to psychoeducation and coping strategies, unlike traditional psychosocial treatments. Objective: This study presents a systematic review of controlled trials of cognitive r...
Faurholt-Jepsen, M; Busk, J; Frost, M; Vinberg, M; Christensen, E M; Winther, O; Bardram, J E; Kessing, L V
Changes in speech have been suggested as sensitive and valid measures of depression and mania in bipolar disorder. The present study aimed at investigating (1) voice features collected during phone calls as objective markers of affective states in bipolar disorder and (2) if combining voice features with automatically generated objective smartphone data on behavioral activities (for example, number of text messages and phone calls per day) and electronic self-monitored data (mood) on illness activity would increase the accuracy as a marker of affective states. Using smartphones, voice features, automatically generated objective smartphone data on behavioral activities and electronic self-monitored data were collected from 28 outpatients with bipolar disorder in naturalistic settings on a daily basis during a period of 12 weeks. Depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale 17-item and the Young Mania Rating Scale, respectively, by a researcher blinded to smartphone data. Data were analyzed using random forest algorithms. Affective states were classified using voice features extracted during everyday life phone calls. Voice features were found to be more accurate, sensitive and specific in the classification of manic or mixed states with an area under the curve (AUC)=0.89 compared with an AUC=0.78 for the classification of depressive states. Combining voice features with automatically generated objective smartphone data on behavioral activities and electronic self-monitored data increased the accuracy, sensitivity and specificity of classification of affective states slightly. Voice features collected in naturalistic settings using smartphones may be used as objective state markers in patients with bipolar disorder.
Medici, Clara Reece; Videbech, Poul; Gustafsson, Lea Nørgreen
-ever diagnoses of bipolar disorder (International Classification of Diseases-10: F31) were identified in the nationwide Danish Psychiatric Central Research Register between 1995 and 2012. Causes of death were obtained from The Danish Register of Causes of Death. Age- and gender standardized incidence rates...... significantly from 54.5 years in 1995 to 42.4 years in 2012 (pCauses of death were mainly natural; 9% died from suicide. LIMITATIONS: Only patients in psychiatric care...
Clinical implications of the high rates of creativity within bipolar disorder (BD) have not been explored. The aim of this review is to outline these implications by (i) reviewing evidence for the link between creativity and BD, (ii) developing a provisional model of mechanisms underpinning the creativity–BD link, (iii) describing unique challenges faced by creative-BD populations, and (iv) systematically considering evidence-based psychosocial treatments in the light of this review. While mo...
Full Text Available Adults with mental illness are at a higher risk of aspiration pneumonia than the general population. We describe the case of a patient with bipolar affective disorder and two separate episodes of aspiration pneumonia associated with acute mania. We propose that he had multiple predisposing factors, including hyperverbosity, sedative medications, polydipsia (psychogenic and secondary to a comorbidity of diabetes insipidus, and neuroleptic side effects.
Full Text Available BACKGROUND: The ability to integrate contextual information with social cues to generate social meaning is a key aspect of social cognition. It is widely accepted that patients with schizophrenia and bipolar disorders have deficits in social cognition; however, previous studies on these disorders did not use tasks that replicate everyday situations. METHODOLOGY/PRINCIPAL FINDINGS: This study evaluates the performance of patients with schizophrenia and bipolar disorders on social cognition tasks (emotional processing, empathy, and social norms knowledge that incorporate different levels of contextual dependence and involvement of real-life scenarios. Furthermore, we explored the association between social cognition measures, clinical symptoms and executive functions. Using a logistic regression analysis, we explored whether the involvement of more basic skills in emotional processing predicted performance on empathy tasks. The results showed that both patient groups exhibited deficits in social cognition tasks with greater context sensitivity and involvement of real-life scenarios. These deficits were more severe in schizophrenic than in bipolar patients. Patients did not differ from controls in tasks involving explicit knowledge. Moreover, schizophrenic patients' depression levels were negatively correlated with performance on empathy tasks. CONCLUSIONS/SIGNIFICANCE: Overall performance on emotion recognition predicted performance on intentionality attribution during the more ambiguous situations of the empathy task. These results suggest that social cognition deficits could be related to a general impairment in the capacity to implicitly integrate contextual cues. Important implications for the assessment and treatment of individuals with schizophrenia and bipolar disorders, as well as for neurocognitive models of these pathologies are discussed.
Boudebesse, Carole; Leboyer, Marion; Begley, Amy; Wood, Annette; Miewald, Jean; Hall, Martica; Frank, Ellen; Kupfer, David; Germain, Anne
The goal of this study was to compare five actigraphy scoring methods in a sample of 18 remitted patients with bipolar disorder. Actigraphy records were processed using five different scoring methods relying on the sleep diary; the event-marker; the software-provided automatic algorithm; the automatic algorithm supplemented by the event-marker; visual inspection (VI) only. The Algorithm and the VI methods differed from the other methods for many actigraphy parameters of interest. Particularly...
Di Giorgio Silva, Luiza Wanick; Cartier, Consuelo; Cheniaux, Elie; Novis, Fernanda; Silveira, Luciana Angélica; Cavaco, Paola Anaquim; de Assis da Silva, Rafael; Batista, Washington Adolfo; Tanaka, Guaraci Ken; Gongora, Mariana; Bittencourt, Juliana; Teixeira, Silmar; Basile, Luis Fernando; Budde, Henning; Cagy, Mauricio; Ribeiro, Pedro; Velasques, Bruna
Bipolar disorder (BD) is characterized by an alternated occurrence between acute mania episodes and depression or remission moments. The objective of this study is to analyze the information processing changes in BP (Bipolar Patients) (euthymia, depression and mania) during the oddball paradigm, focusing on the P300 component, an electric potential of the cerebral cortex generated in response to external sensorial stimuli, which involves more complex neurophysiological processes related to stimulus interpretation. Twenty-eight bipolar disorder patients (BP) (17 women and 11 men with average age of 32.5, SD: 9.5) and eleven healthy controls (HC) (7 women and 4 men with average age of 29.78, SD: 6.89) were enrolled in this study. The bipolar patients were divided into 3 major groups (i.e., euthymic, depressive and maniac) according to the score on the Clinical Global Impression--Bipolar Version (CGI-BP). The subjects performed the oddball paradigm simultaneously to the EEG record. EEG data were also recorded before and after the execution of the task. A one-way ANOVA was applied to compare the P300 component among the groups. After observing P300 and the subcomponents P3a and P3b, a similarity of amplitude and latency between euthymic and depressive patients was observed, as well as small amplitude in the pre-frontal cortex and reduced P3a response. This can be evidence of impaired information processing, cognitive flexibility, working memory, executive functions and ability to shift the attention and processing to the target and away from distracting stimuli in BD. Such neuropsychological impairments are related to different BD symptoms, which should be known and considered, in order to develop effective clinical treatment strategies.
Full Text Available Abstract Background: Recently, a growing number of publications have suggested that the immune-inflammatory system may be involved in the etiology of bipolar disorder (BD. Objective: The aim of this study was to investigate neutrophil-lymphocyte ratio (NLR, platelet-lymphocyte ratio (PLR, and red cell distribution width (RDW in the three different phases of BD patients compared to each other and controls. Methods: One hundred eighty-seven bipolar patients (78 euthymic, 53 manic/hypomanic and 56 depressed, and 62 age and sex matched controls were enrolled. Sociodemographic variables and complete blood count parameters of the patients and the control group were recorded. Results: The groups did not differ from each other on the hematological parameters, except for NLR and RDW. Post-hoc analyses revealed that NLR values were significantly higher in the euthymic and manic/hypomanic bipolar groups compared to control group. In addition, post-hoc analyses revealed that RDW values were significantly higher in the manic/hypomanic bipolar group relative to the control group. Discussion: Longitudinal studies evaluating the levels of inflammatory markers in the early phases of the disorder, and their relationship with the development of different episodes and medical comorbidities may be useful to understand the role of inflammation in BD.
Savino, M; Perugi, G; Simonini, E; Soriani, A; Cassano, G B; Akiskal, H S
Although theoretical explanations for comorbidity in panic disorder (PD) abound in the literature, the complex clinical challenges of these patients have been neglected, especially where panic, obsessive-compulsive and 'soft' bipolar (e.g., hypomanic, cyclothymic and hyperthymic) conditions might co-exist. The aim of the present study has been to systematically explore the spectrum of intra-episodic and longitudinal comorbidity of 140 DSM-III-R PD patients--67.1% of whom concomitantly met the criteria for Agoraphobia--and who were consecutively admitted to the ambulatory service of the Psychiatric Clinic of the University of Pisa over a 2-year period. Comorbidity with strictly defined anxiety disorders--i.e., not explained as mere symptomatic extensions of PD--was relatively uncommon, and included Simple Phobia (10.7%), Social Phobia (6.4%), Generalized Anxiety Disorder (3.6%), and Obsessive-Compulsive Disorder (4.2%). Comorbidity with Major Depression--strictly limited to the melancholic subtype--occurred in 22.9%. Comorbidity with Bipolar Disorders included 2.1% with mania, 5% with hypomania, as well as 6.4% with cyclothymia, for a total of 13.5%; an additional 34.3% of PD patients met the criteria for hyperthymic temperament. We submit that such comorbid patterns are at the root of unwieldy clinical constructs like 'atypical depression' and 'borderline personality'. The relationship of panic disorder to other anxious-phobic and depressive states has been known for some time. Our data extend this relationship to soft bipolar disorders. Studies from other centers are needed to verify that the proposed new link is not merely due to referral bias to a tertiary university setting.
Both bipolar disorder and borderline personality disorder (BPD) are serious mental health disorders resulting in significant psychosocial morbidity, reduced health-related quality of life, and excess mortality. Yet research on BPD has received much less funding from the National Institute of Health (NIH) than has bipolar disorder during the past 25 years. Why hasn't the level of NIH research funding for BPD been commensurate with the level of psychosocial morbidity, mortality, and health expenditures associated with the disorder? In the present article, the author illustrates how the bipolar disorder research community has done a superior job of "marketing" their disorder. Studies of underdiagnosis, screening, diagnostic spectra, and economics are reviewed for both bipolar disorder and BPD. Researchers of bipolar disorder have conducted multiple studies highlighting the problem with underdiagnosis, developed and promoted several screening scales, published numerous studies of the operating characteristics of these screening measures, attempted to broaden the definition of bipolar disorder by advancing the concept of the bipolar spectrum, and repeatedly demonstrated the economic costs and public health significance of bipolar disorder. In contrast, researchers of BPD have almost completely ignored each of these four issues and research efforts. Although BPD is as frequent as (if not more frequent than) bipolar disorder, as impairing as (if not more impairing than) bipolar disorder, and as lethal as (if not more lethal than) bipolar disorder, it has received less than one-tenth the level of funding from the NIH and has been the focus of many fewer publications in the most prestigious psychiatric journals. The researchers of BPD should consider adopting the strategy taken by researchers of bipolar disorder before the diagnosis is eliminated in a future iteration of the DSM or the ICD.
Davari-Tanha, Fatemeh; Hosseini Rashidi, Batool; Ghajarzadeh, Mahsa; Noorbala, Ahmad Ali
This study was designed to determine the prevalence of bipolar disorder in women with polycystic ovarian syndrome (PCO). One hundred and ten women with definite diagnosis of PCO and one hundred and ten age-matched infertile women due to other reasons except for PCO were enrolled in this case-control study. Ten ml fasting venous blood sample obtained to measure fasting glucose, LH and FSH. Height, weight and waist-to-hip ratio (WHR) were also recorded by an expert technician. A psychiatrist examined all 220 cases in order to determine the prevalence of depression and bipolarity. Mean age of each group participants were not significantly different while FBS, LH and LH/FSH levels were significantly higher in PCO patients. Eighty eight case were depressed in PCO group while 96 were depressed in control group (P=0.03). Bipolar disorder were higher in PCO group in comparison with controls (8 vs. 0, P=0.004). Psychiatric disorders should be considered in PCO women.
Full Text Available OBJECTIVE: Summarize data on metabolic syndrome (MS in bipolar disorder (BD. METHODS: A systematic review of the literature was conducted using the Medline, Embase and PsycInfo databases, using the keywords "metabolic syndrome", "insulin resistance" and "metabolic X syndrome" and cross-referencing them with "bipolar disorder" or "mania". The following types of publications were candidates for review: (i clinical trials, (ii studies involving patients diagnosed with bipolar disorder or (iii data about metabolic syndrome. A 5-point quality scale was used to assess the methodological weight of the studies. RESULTS: Thirty-nine articles were selected. None of studies reached the maximum quality score of 5 points. The prevalence of MS was significantly higher in BD individuals when compared to a control group. The analysis of MS subcomponents showed that abdominal obesity was heterogeneous. Individuals with BD had significantly higher rates of hypertriglyceridemia than healthy controls. When compared to the general population, there were no significant differences in the prevalence of low HDL-c in individuals with BD. Data on hypertension were also inconclusive. Rates of hyperglycemia were significantly greater in patients with BD compared to the general population. CONCLUSIONS: The overall results point to the presence of an association between BD and MS, as well as between their subcomponents.
Full Text Available This study was designed to determine the prevalence of bipolar disorder in women with polycystic ovarian syndrome (PCO. One hundred and ten women with definite diagnosis of PCO and one hundred and ten age-matched infertile women due to other reasons except for PCO were enrolled in this case-control study. Ten ml fasting venous blood sample obtained to measure fasting glucose, LH and FSH. Height, weight and waist-to-hip ratio (WHR were also recorded by an expert technician. A psychiatrist examined all 220 cases in order to determine the prevalence of depression and bipolarity. Mean age of each group participants were not significantly different while FBS, LH and LH/FSH levels were significantly higher in PCO patients. Eighty eight case were depressed in PCO group while 96 were depressed in control group (P=0.03. Bipolar disorder were higher in PCO group in comparison with controls (8 vs. 0, P=0.004. Psychiatric disorders should be considered in PCO women.
Paris, Joel; Black, Donald W
Borderline personality disorder (BPD) and bipolar disorder (types I and II) are frequently confused because of their symptomatic overlap. Although affective instability is a prominent feature of each, the pattern is entirely different. BPD is characterized by transient mood shifts that occur in response to interpersonal stressors, whereas bipolar disorder is associated with sustained mood changes. These disorders can be further distinguished by comparing their phenomenology, etiology, family history, biological studies, outcome, and response to medication. Their distinction is of great clinical importance because misdiagnosis can deprive the patient of potentially effective treatment, whether it is psychotherapy for BPD or medication for bipolar disorder. On the basis of a comprehensive literature review, guidelines for differential diagnosis are suggested, and priorities for further research are recommended.
Wen, Zujia; Chen, Jianhua; Khan, Raja Amjad Waheed; Song, Zhijian; Wang, Meng; Li, Zhiqiang; Shen, Jiawei; Li, Wenjin; Shi, Yongyong
Schizophrenia, major depressive disorder, and bipolar disorder are three major psychiatric disorders affecting around 0.66%, 3.3%, and 1.5% of the Han Chinese population respectively. Several genetic linkage analyses and genome wide association studies identified NRG1 as a susceptibility gene of schizophrenia, which was validated by its role in neurodevelopment, glutamate, and other neurotransmitter receptor expression regulation. To further investigate whether NRG1 is a shared risk gene for major depressive disorder, bipolar disorder as well as schizophrenia, we performed an association study among 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls. Totally 15 tag SNPs were genotyped and analyzed, and no population stratification was found in our sample set. Among the sites, rs4236710 (corrected Pgenotye = 0.015) and rs4512342 (Pallele = 0.03, Pgenotye = 0.045 after correction) were associated with schizophrenia, and rs2919375 (corrected Pgenotye = 0.004) was associated with major depressive disorder. The haplotype rs4512342-rs6982890 showed association with schizophrenia (P = 0.03 for haplotype "TC" after correction), and haplotype rs4531002-rs11989919 proved to be a shared risk factor for both major depressive disorder ("CC": corrected P = 0.009) and bipolar disorder ("CT": corrected P = 0.003). Our results confirmed that NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population.
Vince D Calhoun
Full Text Available Intrinsic functional brain networks (INs are regions showing temporal coherence with one another. These INs are present in the context of a task (as opposed to an undirected task such as rest, albeit modulated to a degree both spatially and temporally. Prominent networks include the default mode, attentional fronto-parietal, executive control, bilateral temporal lobe and motor networks. The characterization of INs has recently gained considerable momentum, however; most previous studies evaluate only a small subset of the intrinsic networks (e.g. default mode. In this paper we use independent component analysis to study INs decomposed from fMRI data collected in a large group of schizophrenia patients, healthy controls, and individuals with bipolar disorder, while performing an auditory oddball task. Schizophrenia and bipolar disorder share significant overlap in clinical symptoms, brain characteristics, and risk genes which motivates our goal of identifying whether functional imaging data can differentiate the two disorders. We tested for group differences in properties of all identified intrinsic networks including spatial maps, spectra, and functional network connectivity. A small set of default mode, temporal lobe, and frontal networks with default mode regions appearing to play a key role in all comparisons. Bipolar subjects showed more prominent changes in ventromedial and prefrontal default mode regions whereas schizophrenia patients showed changes in posterior default mode regions. Anti-correlations between left parietal areas and dorsolateral prefrontal cortical areas were different in bipolar and schizophrenia patients and amplitude was significantly different from healthy controls in both patient groups. Patients exhibited similar frequency behavior across multiple networks with decreased low frequency power. In summary, a comprehensive analysis of intrinsic networks reveals a key role for the default mode in both schizophrenia and
Nusslock, Robin; Almeida, Jorge RC; Forbes, Erika E; Versace, Amelia; Frank, Ellen; LaBarbara, Edmund J; Klein, Crystal R; Phillips, Mary L
Objective Bipolar disorder may be characterized by a hypersensitivity to reward-relevant stimuli, potentially underlying the emotional lability and dysregulation that characterizes the illness. In parallel, research highlights the predominant role of striatal and orbitofrontal cortical (OFC) regions in reward-processing and approach-related affect. We aimed to examine whether bipolar disorder, relative to healthy, participants displayed elevated activity in these regions during reward processing. Methods Twenty-one euthymic bipolar I disorder and 20 healthy control participants with no lifetime history of psychiatric disorder underwent functional magnetic resonance imaging (fMRI) scanning during a card-guessing paradigm designed to examine reward-related brain function to anticipation and receipt of monetary reward and loss. Data were collected using a 3T Siemens Trio scanner. Results Region-of-interest analyses revealed that bipolar disorder participants displayed greater ventral striatal and right-sided orbitofrontal [Brodmann area (BA) 11] activity during anticipation, but not outcome, of monetary reward, relative to healthy controls (p < 0.05, corrected). Wholebrain analyses indicated that bipolar disorder, relative to healthy, participants also displayed elevated left-lateral OFC activity (BA 47) activity during reward anticipation (p < 0.05, corrected). Conclusions Elevated ventral striatal and OFC activity during reward anticipation may represent a neural mechanism for predisposition to expansive mood and hypo/mania in response to reward-relevant cues that characterizes bipolar disorder. Our findings contrast with research reporting blunted activity in the ventral striatum during reward processing in unipolar depressed individuals, relative to healthy controls. Examination of reward-related neural activity in bipolar disorder is a promising research focus to facilitate identification of biological markers of the illness. PMID:22548898
Sutton, Kimberly Kode
Identifying children with emotional or behavior disorders has long been problematic. In a general sense, those children who are most likely to be noticed by teachers and, therefore, referred for possible special education placement are those who exhibit externalizing behaviors, including physical aggression, noncompliance, and rule-breaking. It is…
Perlman, Greg; Kotov, Roman; Fu, Jinmiao; Bromet, Evelyn J; Fochtmann, Laura J; Medeiros, Helena; Pato, Michele T; Pato, Carlos N
Several studies have reported differences between African Americans and Caucasians in relative proportion of psychotic symptoms and disorders, but whether this reflects racial bias in the assessment of psychosis is unclear. The purpose of this study was to examine the distribution of psychotic symptoms and potential bias in symptoms assessed via semi-structured interview using a cohort of 3,389 African American and 5,692 Caucasian participants who were diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. In this cohort, the diagnosis of schizophrenia was relatively more common, and the diagnosis of bipolar disorder and schizoaffective disorder-bipolar type was less relatively common, among African Americans than Caucasians. With regard to symptoms, relatively more African Americans than Caucasians endorsed hallucinations and delusions symptoms, and this pattern was striking among cases diagnosed with bipolar disorder and schizoaffective-bipolar disorder. In contrast, the relative endorsement of psychotic symptoms was more similar among cases diagnosed with schizophrenia and schizoaffective disorder-depressed type. Differential item function analysis revealed that African Americans with mild psychosis over-endorsed "hallucinations in any modality" and under-endorsed "widespread delusions" relative to Caucasians. Other symptoms did not show evidence of racial bias. Thus, racial bias in assessment of psychotic symptoms does not appear to explain differences in the proportion of symptoms between Caucasians and African Americans. Rather, this may reflect ascertainment bias, perhaps indicative of a disparity in access to services, or differential exposure to risk factors for psychosis by race. © 2015 Wiley Periodicals, Inc.
Miskowiak, Kamilla Woznica; Ehrenreich, Hannelore; Christensen, Ellen M
disorder. METHOD: Patients with an ICD-10 diagnosis of bipolar disorder in remission were randomized, with stratification by age and gender, to receive 8 weekly erythropoietin (40,000 IU) or saline (sodium chloride [NaCl], 0.9%) infusions in a double-blind, parallel-group design. The first patient....... The statistical threshold for which results were considered significant was P ≤ .05 (2-tailed). RESULTS: 44 patients were randomized; given 1 dropout after baseline, results were analyzed for 43 patients (erythropoietin: n = 23; saline: n = 20). There was no significant improvement of verbal memory...
Berecz, Hajnalka; Csábi, Györgyi; Jeges, Sára; Herold, Róbert; Simon, Maria; Halmai, Tamás; Trixler, Dániel; Hajnal, András; Tóth, Ákos Levente; Tényi, Tamás
Minor physical anomalies (MPAs) are external markers of abnormal brain development, so the more common appearence of these signs among bipolar I and bipolar II patients can confirm the possibility of a neurodevelopmental deficit in these illnesses. The aim of the present study was to investigate the rate and topological profile of minor physical anomalies in patients with bipolar I and - first in literature - with bipolar II disorders compared to matched healthy control subjects. Using a list of 57 minor physical anomalies (the Méhes Scale), 30 bipolar I and 30 bipolar II patients, while as a comparison 30 matched healthy control subjects were examined. Significant differences were detected between the three groups comparing the total number of minor physical anomalies, minor malformations and phenogenetic variants and in the cases of the ear and the mouth regions. The individual analyses of the 57 minor physical anomalies by simultaneous comparison of the three groups showed, that in the cases of furrowed tongue and high arched palate were significant differences between the three groups. The results can promote the concept, that a neurodevelopmental deficit may play a role in the etiology of both bipolar I and bipolar II disorders.
Rodrigo da Silva Dias
Full Text Available Embora o transtorno bipolar (TB ocorra quase igualmente em ambos os sexos, a fenomenologia e o curso da doença diferem no homem e na mulher. No entanto, há evidências de que mulheres bipolares, mais que os homens, apresentariam início mais tardio (em especial na quinta década de vida, ciclagem rápida, mais episódios depressivos, mais mania disfórica que eufórica, estados mistos e evolução do tipo bipolar II, ainda que os achados nem sempre sejam consistentes. Embora o risco de comorbidades no TB inclua, para ambos os gêneros, abuso de álcool e drogas, homens bipolares teriam maior probabilidade de ser alcoolistas, não procurar tratamento e de se suicidar. Hipóteses sugeridas para explicar tais diferenças variam daquelas centradas em aspectos culturais ou psicológicos para as que focalizam os sistemas hormonais, como os esteróides gonadais ou o eixo tireoidiano, e até mesmo a anatomia cerebral. A influência do ciclo reprodutivo (ciclo menstrual, gravidez e menopausa sobre as opções terapêuticas no tratamento do TB é apresentada na última parte desta revisão.Although the bipolar disorder (BD occurs almost with the same frequency in both genders, the phenomenology and the outcome of the illness differ between them. Nevertheless, there is evidence that women with BD show, more than men, delayed beginning, especially in their fifth decade, more rapid cycling outcome, more depressive episodes, more dysphoric mania, more mixed states and more BD type II. Even so, the findings are not always consistent. Although the risk of comorbidities in BD includes, for both the sorts, excessive alcoholic consumption and drugs, bipolar men would have greater probability of being alcohol dependent, of not seeking treatment and of committing suicide. Suggested hypotheses to explain such differences vary from those centered in cultural or psychological aspects to those that focus on the steroids hormones, and other hormones such as cortisol
Schaffer, Ayal; Isometsä, Erkki T; Tondo, Leonardo
OBJECTIVES: Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts...... and deaths in bipolar disorder. METHODS: Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies...... to women. People with bipolar disorder account for 3.4-14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23-26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic...
Full Text Available Neste artigo, os autores revisam importantes aspectos associados às bases biológicas do transtorno de humor bipolar (THB. O THB está relacionado com o surgimento de diversas alterações bioquímicas e moleculares em sistemas de neurotransmissão e vias de segundos-mensageiros geradores de sinais intracelulares. Essas modificações em neurônios e glia parecem estar associadas com o surgimento de sintomas maníacos e depressivos. Ainda neste contexto, disfunções na homeostasia e no metabolismo energético cerebral tem sido associado com alterações comportamentais, na modulação do humor e ritmo circadiano em humanos e em modelos animais da doença. Assim, alterações metabólicas em neurônios e células gliais têm sido associadas com quadros depressivos e maníacos. Nos últimos anos, avanços nas técnicas de neuroimagem, genéticos e de biologia moleculares têm gerado novos conhecimentos acerca das bases biológicas da bipolaridade. Os autores destacam que a doença parece estar relacionada diretamente com disfunções em diferentes mecanismos adaptativos a estresse em células neurais, gerando perda na capacidade celular de induzir neuroplasticidade e neurotrofismo, facilitando assim o surgimento da doença.In this article, the authors review relevant aspects related to the neurobiological basis of bipolar disorder. This illness has been associated with complex biochemical and molecular changes in brain circuits linked to neurotransmission and intracellular signal transduction pathways, and changes on neurons and glia have been proposed to be directly associated with clinical presentation of mania and depression. In the same context, dysfunctions on brain homeostasis and energy metabolism have been associated with alterations on circadian rythms, behavior and mood in human and animal models of bipolarity. In the recent years, advances on techniques of neuroimaging, molecular biology and genetics has provided new insights about
Kilbourne, Amy M.; Farmer Teh, Carrie; Welsh, Deborah; Pincus, Harold Alan; Lasky, Elaine; Perron, Brian; Bauer, Mark S
Objective We implemented a set of processes of care measures for bipolar disorder that reflect psychosocial, patient preference, and continuum of care approaches to mental health, and examined whether veterans with bipolar disorder receive care concordant with these practices. Method Data from medical record reviews were used to assess key processes of care for 433 VA mental health outpatients with bipolar disorder. Both composite and individual processes of care measures were ope...
Background: Despite significant advances in pharmacological and psychological therapies for bipolar disorder, many people continue to have less than optimal outcomes, which are associated with significant disability and poor quality of life (QOL). This study aimed to assess the disability and QOL and factors associated with such suboptimal outcomes in subjects with bipolar disorder in remission. Methods: Consecutive patients diagnosed to have bipolar disorder in remission attending the Depart...
Raquel Calvão de Melo
Full Text Available The onset of bipolar disorder (BD secondary to a stroke event is a rare clinical entity. Although it may be related to specific regions of the brain, several other factors have been linked to its expression such as subcortical atrophy or chronic vascular burden. While precise locations and cerebral circuits involved in the bipolarity expression after stroke still need to be determined, their investigation represents an opportunity to study brain function and BD etiopathogenesis. We present a BD secondary to multiple subcortical biparietal lacunar infarctions, a lacunar infarction in left putamen and an ischemic lesion at the cerebral trunk evolving the right median portion, in a 65-year-old male patient who experienced manic, hypomanic, and depressive episodes, after 6, 10, and 16 months, respectively, of the cerebrovascular events.
Seymour, Karen E.; Pescosolido, Matthew F.; Reidy, Brooke L.; Galvan, Thania; Kim, Kerri L.; Young, Matthew; Dickstein, Daniel P.
Objective: Bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) are often comorbid or confounded; therefore, we evaluated emotional face identification to better understand brain/behavior interactions in children and adolescents with either primary BD, primary ADHD, or typically developing controls (TDC). Method: Participants…
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),…
Ellard, Kristen K.; Deckersbach, Thilo; Sylvia, Louisa G.; Nierenberg, Andrew A.; Barlow, David H.
Bipolar disorder (BD) is a chronic, debilitating disorder with recurrent manic and depressive episodes. More than 75% of bipolar patients have a current or lifetime diagnosis of a comorbid anxiety disorder. Comorbid anxiety in BD is associated with greater illness severity, greater functional impairment, and poorer illness-related outcomes.…
Kafantaris, Vivian; Kingsley, Peter; Ardekani, Babak; Saito, Ema; Lencz, Todd; Lim, Kelvin; Szeszko, Philip
Patients with bipolar I disorder demonstrated white matter abnormalities in white matter regions as seen through the use of diffusion tensor imaging. The findings suggest that white matter abnormalities in pediatric bipolar disorder may be useful in constructing neurobiological models of the disorder.
Towbin, Kenneth; Axelson, David; Leibenluft, Ellen; Birmaher, Boris
Objective: Bipolar disorder--not otherwise specified (BP-NOS) and severe mood dysregulation (SMD) are severe mood disorders that were defined to address questions about the diagnosis of bipolar disorder (BD) in youth. SMD and BP-NOS are distinct phenotypes that differ in clinical presentation and longitudinal course. The purpose of this review is…
Zhang, Haowei; Gao, Yanni; Yuan, Chengmei; Liu, Ying; Ding, Yuqing
Multi-layer perceptron (MLP) neural network belongs to multi-layer feedforward neural network, and has the ability and characteristics of high intelligence. It can realize the complex nonlinear mapping by its own learning through the network. Bipolar disorder is a serious mental illness with high recurrence rate, high self-harm rate and high suicide rate. Most of the onset of the bipolar disorder starts with depressive episode, which can be easily misdiagnosed as unipolar depression and lead to a delayed treatment so as to influence the prognosis. The early identifica- tion of bipolar disorder is of great importance for patients with bipolar disorder. Due to the fact that the process of early identification of bipolar disorder is nonlinear, we in this paper discuss the MLP neural network application in early identification of bipolar disorder. This study covered 250 cases, including 143 cases with recurrent depression and 107 cases with bipolar disorder, and clinical features were statistically analyzed between the two groups. A total of 42 variables with significant differences were screened as the input variables of the neural network. Part of the samples were randomly selected as the learning sample, and the other as the test sample. By choosing different neu- ral network structures, all results of the identification of bipolar disorder were relatively good, which showed that MLP neural network could be used in the early identification of bipolar disorder.
Kalmar, Jessica H.; Wang, Fei; Chepenik, Lara G.; Womer, Fay Y.; Jones, Monique M.; Pittman, Brian; Shah, Maulik P.; Martin, Andres; Constable, R. Todd; Blumberg, Hilary P.
Adolescents with bipolar disorder showed decreased amygdala volume and increased amygdala response to emotional faces. Amygdala volume is inversely related to activation during emotional face processing.
Antipsychotic Drugs for Schizophrenia and Bipolar Disorder: What You Should Know What are antipsychotic drugs? Antipsychotics are prescription drugs used to treat schizophrenia. They can also be used— ...
Alloy, Lauren B; Abramson, Lyn Y; Urosevic, Snezana; Walshaw, Patricia D; Nusslock, Robin; Neeren, Amy M
In this article, we review empirical research on the role of individuals' current environmental contexts, cognitive styles, and developmental histories as risk factors for the onset, course, and expression of bipolar spectrum disorders. Our review is focused on the following over arching question: Do psychosocial factors truly contribute risk to the onset, course, or expression of bipolar disorders? As a secondary issue, we also address whether the psychosocial risks for bipolar disorders are similar to those for unipolar depression. We begin by discussing the methodological requirements for demonstrating a psychosocial risk factor and the challenges posed by bipolar spectrum disorders for psychosocial risk research. Next, we review the extant studies on the role of recent life events and supportive and non-supportive social interactions (current environment) in bipolar disorders, as well as psychosocial treatments designed to remediate these current environmental factors. We then review the role of cognitive styles featured as vulnerabilities in theories of unipolar depression as risk factors for bipolar disorder alone and in combination with life events, including studies of cognitive-behavioral therapies for bipolar disorder. Finally, we review studies of parenting and maltreatment histories in bipolar disorders. We conclude with an assessment of the state of the psychosocial risk factors literature in bipolar disorder with regard to our guiding questions.
Strakowski Stephen M
Full Text Available Abstract The aim of this paper is to provide a systematic review of the literature examining the epidemiology, outcome, and treatment of patients with bipolar disorder and co-occurring substance use disorders (SUDs. Articles for this review were initially selected via a comprehensive Medline search and further studies were obtained from the references in these articles. Given the lack of research in this field, all relevant studies except case reports were included. Prior epidemiological research has consistently shown that substance use disorders (SUDs are extremely common in bipolar I and II disorders. The lifetime prevalence of SUDs is at least 40% in bipolar I patients. Alcohol and cannabis are the substances most often abused, followed by cocaine and then opioids. Research has consistently shown that co-occurring SUDs are correlated with negative effects on illness outcome including more frequent and prolonged affective episodes, decreased compliance with treatment, a lower quality of life, and increased suicidal behavior. Recent research on the causal relationship between the two disorders suggests that a subgroup of bipolar patients may develop a relatively milder form of affective illness that is expressed only after extended exposure to alcohol abuse. There has been very little treatment research specifically targeting this population. Three open label medication trials provide limited evidence that quetiapine, aripiprazole, and lamotrigine may be effective in treating affective and substance use symptoms in bipolar patients with cocaine dependence and that aripiprazole may also be helpful in patients with alcohol use disorders. The two placebo controlled trials to date suggest that valproate given as an adjunct to lithium in bipolar patients with co-occurring alcohol dependence improves both mood and alcohol use symptoms and that lithium treatment in bipolar adolescents improves mood and SUD symptoms. Given the high rate of SUD co
Carla P D Fernandes
Full Text Available BACKGROUND: Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders. METHODS: Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar disorder were generated from a genome-wide association study (GWAS on a sample comprising 670 healthy Norwegian adults who were phenotyped for a broad battery of cognitive tests. These gene sets were then tested for enrichment of association in GWASs of schizophrenia and bipolar disorder. The GWAS data was derived from three independent single-centre schizophrenia samples, three independent single-centre bipolar disorder samples, and the multi-centre schizophrenia and bipolar disorder samples from the Psychiatric Genomics Consortium. RESULTS: The strongest enrichments were observed for visuospatial attention and verbal abilities sets in bipolar disorder. Delayed verbal memory was also enriched in one sample of bipolar disorder. For schizophrenia, the strongest evidence of enrichment was observed for the sets of genes associated with performance in a colour-word interference test and for sets associated with memory learning slope. CONCLUSIONS: Our results are consistent with the increasing evidence that cognitive functions share genetic factors with schizophrenia and bipolar disorder. Our data provides evidence that genetic studies using polygenic and pleiotropic models can be used to link specific cognitive functions with psychiatric disorders.
@@ The diagnosis of bipolar rather than unipolar depression is currently a clinicaI diagnosis which cannot be validated by specific biological measures,such as laboratory tests.Certainly the characteristics of bipolar depression frequently differ from unipolar major depression in that patients with bipolar depression generally have an earlier age of onset and more frequent episodes than individuals with unipolar major depressionSome,but not all,studies support an increase in suicidal behaviors among bipolar as compared with unipolar major depression,and"atypical features"such as hypersomnia and hyperphagia also may be found more frequently among individuals with bipolar depression.Furthermore family histories of subjects with bipolar disorders more frequently reveal relatives with bipolar disorder.In contrast,relatives of patients with unipolar depression's family history generally reflects major depression but not bipolar disorder.
Oruc, L.; Verheyen, G.R.; Raeymaekers, P.; Van Broeckhoven, C. [Univ. of Antwerp (Belgium)] [and others
Family, twin, and adoption studies consistently have indicated that the familial aggregation of bipolar (BP) disorder and unipolar recurrent major depression (UPR) is accounted for largely by genetic factors. However, the mode of inheritance is complex. One of the possible explanations could be that a gene with variable penetrance and variable expression is involved. Recently there have been reports on a new class of genetic diseases caused by an abnormal trinucleotide-repeat expansion (TRE). In a number of genetic disorders, these dynamic mutations were proved to be the biological basis for the clinically observed phenomenon of anticipation. DNA consisting of repeated triplets of nucleotides becomes unstable and increases in size over generations within families, giving rise to an increased severity and/or an earlier onset of the disorder. It has been recognized for a long time that anticipation occurs in multiplex families transmitting mental illness. More recent studies also suggest that both BP disorder and UPR show features that are compatible with anticipation. Although the findings of anticipation in BP disorders and in UPR must be interpreted with caution because of the possible presence of numerous ascertainment biases, they support the hypothesis that pathological TREs are implicated in the transmission of these disorders. TRE combined with variable penetrance of expression could explain the complex transmission pattern observed in BP disorder. In view of this, the recent reports of an association between CAG-repeat length and BP disorder in a Belgian, Swedish, and British population are promising. 14 refs., 1 fig., 1 tab.
Vreeker, Annabel; van Bergen, Annet H; Kahn, René S
Cognitive dysfunction is a core feature of schizophrenia and is also present in bipolar disorder (BD). Whereas decreased intelligence precedes the onset of psychosis in schizophrenia and remains relatively stable thereafter; high intelligence is a risk factor for bipolar illness but cognitive function decreases after onset of symptoms. While in schizophrenia, many studies have been conducted on the development of cognitive enhancing agents; in BD such studies are almost non-existent. This review focuses on the pharmacological agents with putative effects on cognition in both schizophrenia and bipolar illness; specifically agents targeting the dopaminergic, cholinergic and glutamatergic neurotransmitter pathways in schizophrenia and the cognitive effects of lithium, anticonvulsants and antipsychotics in BD. In the final analysis we conclude that cognitive enhancing agents have not yet been produced convincingly for schizophrenia and have hardly been studied in BD. Importantly, studies should focus on other phases of the illness. To be able to treat cognitive deficits effectively in schizophrenia, patients in the very early stages of the illness, or even before - in the ultra-high risk stages - should be targeted. In contrast, cognitive deficits occur later in BD, and therefore drugs should be tested in BD after the onset of illness. Hopefully, we will then find effective drugs for the incapacitating effects of cognitive deficits in these patients.
Alexandre Martins Valença
Full Text Available CONTEXTO: Matricídio é o assassinato de uma mãe pelo filho ou filha, uma forma de homicídio raramente vista na prática psiquiátrica. Estudos de casos de matricídio têm revelado a presença de transtornos mentais, tais como esquizofrenia, transtorno bipolar, transtornos de personalidade e alcoolismo, assim como casos em que não há evidência de transtorno mental. OBJETIVO: Tem-se como objetivo relatar o caso de uma mulher com transtorno bipolar que assassinou a sua genitora e que foi avaliada em perícia psiquiátrica para avaliação da responsabilidade penal. MÉTODOS: Foi realizada entrevista psiquiátrica, sendo o diagnóstico psiquiátrico estabelecido com base na entrevista e observação dos registros periciais e hospitalares, utilizando-se os critérios diagnósticos DSM-IV-TR. RESULTADOS: A examinanda foi considerada inimputável, em virtude da presença de doença mental que afetou inteiramente o seu entendimento e determinação em relação ao delito praticado. Ela cumpre medida de segurança em Hospital de Custódia e Tratamento Psiquiátrico há dois anos. CONCLUSÃO: É importante que psiquiatras e outros profissionais da saúde mental estejam atentos para risco de comportamento violento em pacientes que apresentam história de doença mental de longa duração, com episódios de violência durante a fase aguda, ameaças contra familiares ou amigos e falta de tratamento psiquiátrico regular.BACKGROUND: Matricide is the killing of one's own mother, and a type of homicide rarely seen on psychiatric practice. Matricide cases studies have shown the presence of mental disorders, such as schizophrenia, bipolar disorder, personality disorders and alcoholism, and have also found cases where there is no evidence of mental disorders. OBJECTIVE: We aim to report a case of a woman with bipolar disorder that murdered her own mother and had a psychiatric forensic evaluation to ascertain her penal imputability. METHODS: Psychiatric
Murray, Greg; Johnson, Sheri L.
Clinical implications of the high rates of creativity within bipolar disorder (BD) have not been explored. The aim of this review is to outline these implications by (i) reviewing evidence for the link between creativity and BD, (ii) developing a provisional model of mechanisms underpinning the creativity–BD link, (iii) describing unique challenges faced by creative-BD populations, and (iv) systematically considering evidence-based psychosocial treatments in the light of this review. While more research into the creativity–BD nexus is urgently required, treatment outcomes will benefit from consideration of this commonly occurring phenotype. PMID:20579791
Murray, Greg; Johnson, Sheri L
Clinical implications of the high rates of creativity within bipolar disorder (BD) have not been explored. The aim of this review is to outline these implications by (i) reviewing evidence for the link between creativity and BD, (ii) developing a provisional model of mechanisms underpinning the creativity-BD link, (iii) describing unique challenges faced by creative-BD populations, and (iv) systematically considering evidence-based psychosocial treatments in the light of this review. While more research into the creativity-BD nexus is urgently required, treatment outcomes will benefit from consideration of this commonly occurring phenotype.
Calkin, Cynthia V; Gardner, David M; Ransom, Thomas; Alda, Martin
Type 2 diabetes mellitus (T2DM) rates are three times higher in patients with bipolar disorder (BD), compared to the general population. This is a major contributing factor to the elevated risk of cardiovascular mortality, the leading cause of death in bipolar patients. There may be shared pathophysiology linking the two disorders, including hypothalamic-pituitary-adrenal and mitochondrial dysfunction, common genetic links, and epigenetic interactions. Life-style, phenomenology of bipolar symptoms, and adverse effects of pharmacotherapy may be contributing factors. Patients with BD and T2DM have a more severe course of illness and are more refractory to treatment. Control of their diabetes is poorer when compared to diabetics without BD, and an existing disparity in medical care may be partly responsible. Glucose abnormalities in bipolar patients need to be screened for and treated. Metformin appears to have the best benefit/risk ratio, and the dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists and analogues also appear promising, although these agents have not been specifically studied in populations with mood disorders. Physicians need to be aware of the increased risk for T2DM and cardiovascular disease in bipolar patients, and appropriate prevention, screening, case finding, and treatment is recommended.
Lackner, N; Birner, A; Bengesser, S A; Reininghaus, B; Kapfhammer, H P; Reininghaus, E
In recent years, intense controversies have evolved about the existence and exact diagnostic criteria of pediatric bipolar affective disorder. The present study aims to discuss pediatric bipolar affective disorder based on the current literature focussing on the diagnostic prospects. Based on a case study, a process of bipolar disorder developed in childhood is depicted exemplarily. Because of the high comorbidity and overlapping symptoms of paediatric bipolar affective disorder and other psychiatric disorders, the major impact of the differential diagnosis has to be stressed. An early diagnosis and the treatment possibilities are discussed.
Jensen, H.M.; Christensen, E.M.; Kessing, Lars Vedel
Background: The aim of the study was to investigate whether patients with bipolar depression and patients with recurrent depressive disorder present with different subtypes of depressive episode as according to ICD-10. Sampling and Methods: All patients who got a diagnosis of bipolar affective......: Totally, 389 patients got a diagnosis of bipolar disorder, current episode of depression, and 5.391 patients got a diagnosis of recurrent depressive disorder, current episode of depression, at first contact. Compared with patients with a diagnosis of recurrent depressive disorder, patients with bipolar...... for patients with bipolar disorder, current episode of depression, compared with patients with a current depression as part of a recurrent depressive disorder (HR = 1.50, 95% CI = 1.20-1.86). Conclusions: The results consistently indicate that a depressive episode is severer and/or more often associated...
Rasgon, NL; Altshuler, LL; Fairbanks, L; Elman, S; Bitran, J; Labarca, R; Saad, M; Kupka, R; Nolen, WA; Frye, MA; Suppes, T; McElroy, SL; Keck, PE; Leverich, G; Grunze, H; Walden, J; Post, R; Mintz, J
Introduction: This study examined the reproductive function and prevalence of polycystic ovary syndrome (PCOS) in women with bipolar disorder taking antimanic medications. Method: Women aged 18-45 treated for bipolar disorder and not taking steroid contraceptives were recruited to complete questionn
Demant, Kirsa M; Almer, Glennie Marie; Vinberg, Maj
A large proportion of patients with bipolar disorder experience persistent cognitive dysfunction, such as memory, attention and planning difficulties, even during periods of full remission. The aim of this trial is to investigate whether cognitive remediation, a new psychological treatment......, improves cognitive function and, in turn, psychosocial function in patients with bipolar disorder in partial or full remission....
Nilsson, Kristine Kahr; Kugathasan, Pirathiv; Nielsen Straarup, Krista
The aim of this study was to elucidate the characteristics, correlates and outcomes of perceived stigmatization in patients with Bipolar Disorder (BD).......The aim of this study was to elucidate the characteristics, correlates and outcomes of perceived stigmatization in patients with Bipolar Disorder (BD)....
Oostervink, Frits; Boomsma, Maarten M; Nolen, Willem A
Information about differences between younger and elderly patients with bipolar disorder and between elderly patients with early and late age of onset of illness is limited.......Information about differences between younger and elderly patients with bipolar disorder and between elderly patients with early and late age of onset of illness is limited....
Kessing, Lars Vedel
Objective: To investigate the prevalence of mixed episodes during the course of illness in bipolar disorder. Method: A total of 1620 patients with an ICD-10 diagnosis of bipolar affective disorder at the first psychiatric contact were identified in a period from 1994 to 2003 in Denmark...
Faurholt-Jepsen, Maria; Brage, Søren; Kessing, Lars Vedel
Heart rate variability (HRV) is a validated measure of sympato-vagal balance in the autonomic nervous system. HRV appears decreased in patients with bipolar disorder (BD) compared with healthy individuals, but the extent of state-related alterations has been sparingly investigated. The present...... bipolar disorder and could...
Bearden, Carrie E.; Soares, Jair C.; Klunder, Andrea D.; Nicoletti, Mark; Dierschki, Nicole; Hayashi, Kiralee M.; Narr, Katherine L.; Bhrambilla, Paolo; Sassi, Roberto B.; Axelson, David; Ryan, Neal; Birmaher, Boris; Thompson, Paul M.
The article discusses the use of three-dimensional mapping methods in children and adolescents with bipolar disorder to find out if localized alterations in hippocampal structure are exhibited. It also explores the developmental differences where the patient with bipolar disorder showed increasing hippocampal size with increasing age.
Abstract Background Cognitive processing in Bipolar Disorder is characterized by a number of attentional abnormalities. Mindfulness Based Cognitive Therapy combines mindfulness meditation, a form of attentional training, along with aspects of cognitive therapy, and may improve attentional dysfunction in bipolar disorder patients. Methods 12 euthymic BD patients and 9 control participants underwent record of electroencephalography (EEG, band frequency analysis) during resting states (eyes open...
Hawke, Lisa D; Provencher, Martin D; Parikh, Sagar V
Schema therapy (ST) is an integrative form of psychotherapy developed for complex, chronic psychological disorders with a characterlogical underpinning. Bipolar disorder is just such a disorder--complex and often comorbid, with demonstrated stable cognitive and personality features that complicate the course of illness. This article presents the reasons justifying the application of ST to bipolar disorder and proposes a treatment rationale and future directions for treatment and research. If well adapted to the characteristics of bipolar disorder, ST might prove to be an effective adjunctive psychotherapy option that attenuates emotional reactivity, reduces symptoms and improves quality of life.
van Enkhuizen, Jordy; Janowsky, David S; Olivier, Berend; Minassian, Arpi; Perry, William; Young, Jared W; Geyer, Mark A
Bipolar disorder is a unique illness characterized by fluctuations between mood states of depression and mania. Originally, an adrenergic-cholinergic balance hypothesis was postulated to underlie these different affective states. In this review, we update this hypothesis with recent findings from human and animal studies, suggesting that a catecholaminergic-cholinergic hypothesis may be more relevant. Evidence from neuroimaging studies, neuropharmacological interventions, and genetic associations support the notion that increased cholinergic functioning underlies depression, whereas increased activations of the catecholamines (dopamine and norepinephrine) underlie mania. Elevated functional acetylcholine during depression may affect both muscarinic and nicotinic acetylcholine receptors in a compensatory fashion. Increased functional dopamine and norepinephrine during mania on the other hand may affect receptor expression and functioning of dopamine reuptake transporters. Despite increasing evidence supporting this hypothesis, a relationship between these two neurotransmitter systems that could explain cycling between states of depression and mania is missing. Future studies should focus on the influence of environmental stimuli and genetic susceptibilities that may affect the catecholaminergic-cholinergic balance underlying cycling between the affective states. Overall, observations from recent studies add important data to this revised balance theory of bipolar disorder, renewing interest in this field of research.
Sylvia, Louisa G.; Reilly-Harrington, Noreen A.; Leon, Andrew C.; Kansky, Christine I.; Calabrese, Joseph R.; Bowden, Charles L.; Ketter, Terence A.; Friedman, Edward S.; Iosifescu, Dan V.; Thase, Michael E.; Ostacher, Michael J.; Keyes, Michelle; Rabideau, Dustin; Nierenberg, Andrew A.
Objective Psychopharmacology remains the foundation of treatment for bipolar disorder, but medication adherence in this population is low (Range = 20% to 64%). We examined medication adherence in a multi-site, comparative effectiveness study of lithium. Method The Lithium Moderate Dose Use Study (LiTMUS) was a six-month, six-site, randomized effectiveness trial of adjunctive moderate dose lithium therapy compared to optimized treatment in adult outpatients with bipolar I or II disorder (N=283). Medication adherence was measured at each study visit with the Tablet Routine Questionnaire. Results We found that 4.50% of participants reported missing at least 30% of their medications in the past week at baseline and non-adherence remained low throughout the trial (< 7%). Poor medication adherence was associated with more manic symptoms and side effects as well as lower lithium serum levels at mid- and post-treatment, but not with poor quality of life, overall severity of illness, or depressive symptoms. Conclusion Participants in LiTMUS were highly adherent with taking their medications. The lack of association with possible predictors of adherence, such as depression and quality of life, could be explained by the limited variance or other factors as well as by not using an objective measure of adherence. PMID:24117232
Łojko, Dorota; Suwalska, Aleksandra; Rybakowski, Janusz
In 2013, a version of the Diagnostic and Statistical Manual of Mental Disorders (DSM), having number 5, was published. The DSM is a textbook which aims to present diagnostic criteria for each psychiatric disorder recognized by the U.S. healthcare system. The DSM-5 comprises the most updated diagnostic criteria of psychiatric disorders as well as their description, and provides a common language for clinicians to communicate about the patients. Diagnostic criteria of the DSM-5 have been popula...
Kim, Sung Hwa; Ryu, Vin; Ha, Ra Yeon; Lee, Su Jin; Cho, Hyun-Sang
The ability to accurately perceive dominance in the social hierarchy is important for successful social interactions. However, little is known about dominance perception of emotional stimuli in bipolar disorder. The aim of this study was to investigate the perception of social dominance in patients with bipolar I disorder in response to six facial emotional expressions. Participants included 35 euthymic patients and 45 healthy controls. Bipolar patients showed a lower perception of social dominance based on anger, disgust, fear, and neutral facial emotional expressions compared to healthy controls. A negative correlation was observed between motivation to pursue goals or residual manic symptoms and perceived dominance of negative facial emotions such as anger, disgust, and fear in bipolar patients. These results suggest that bipolar patients have an altered perception of social dominance that might result in poor interpersonal functioning. Training of appropriate dominance perception using various emotional stimuli may be helpful in improving social relationships for individuals with bipolar disorder.
C.P.D. Fernandes (Carla P.); A. Christoforou (Andrea); S. Giddaluru (Sudheer); K.M. Ersland (Kari); S. Djurovic (Srdjan); M. Mattheisen (Manuel); A.J. Lundervold (Astri); I. Reinvang (Ivar); M.M. Nöthen (Markus); M. Rietschel (Marcella); R.A. Ophoff (Roel); A. Hofman (Albert); A.G. Uitterlinden (André); T.M. Werge (Thomas); S. Cichon (Sven); T. Espeseth (Thomas); O.A. Andreassen (Ole); V.M. Steen (Vidar); S. Le Hellard (Stephanie)
textabstractBackground: Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function i
Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel
Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case......-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3...... were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF and NT-3 were evaluated in various affective states in bipolar disorder...
Sacchet, Matthew D; Livermore, Emily E; Iglesias, Juan Eugenio; Glover, Gary H; Gotlib, Ian H
Subcortical gray matter regions have been implicated in mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It is unclear, however, whether or how these regions differ among mood disorders and whether such abnormalities are state- or trait-like. In this study, we examined differences in subcortical gray matter volumes among euthymic BD, MDD, remitted MDD (RMD), and healthy (CTL) individuals. Using automated gray matter segmentation of T1-weighted MRI images, we estimated volumes of 16 major subcortical gray matter structures in 40 BD, 57 MDD, 35 RMD, and 61 CTL individuals. We used multivariate analysis of variance to examine group differences in these structures, and support vector machines (SVMs) to assess individual-by-individual classification. Analyses yielded significant group differences for caudate (p = 0.029) and ventral diencephalon (VD) volumes (p = 0.003). For the caudate, both the BD (p = 0.004) and the MDD (p = 0.037) participants had smaller volumes than did the CTL participants. For the VD, the MDD participants had larger volumes than did the BD and CTL participants (ps disorders are characterized by anomalies in subcortical gray matter volumes and that the caudate and VD contribute uniquely to differential affective pathology. Identifying abnormalities in subcortical gray matter may prove useful for the prevention, diagnosis, and treatment of mood disorders.
Bergink, V; Larsen, J T; Hillegers, M H J; Dahl, S K; Stevens, H; Mortensen, P B; Petersen, L; Munk-Olsen, T
Childhood adverse events are risk factors for later bipolar disorder. We quantified the risks for a later diagnosis of bipolar disorder after exposure to adverse life events in children with and without parental psychopathology. This register-based population cohort study included all persons born in Denmark from 1980 to 1998 (980 554 persons). Adversities before age 15 years were: familial disruption; parental somatic illness; any parental psychopathology; parental labour market exclusion; parental imprisonment; placement in out-of-home care; and parental natural and unnatural death. We calculated risk estimates of each of these eight life events as single exposure and risk estimates for exposure to multiple life events. Main outcome variable was a diagnosis of bipolar disorder after the age of 15 years, analysed with Cox proportional hazard regression. Single exposure to most of the investigated adversities were associated with increased risk for bipolar disorder, exceptions were parental somatic illness and parental natural death. By far the strongest risk factor for bipolar disorder in our study was any mental disorder in the parent (hazard ratio 3.53; 95% confidence interval 2.73-4.53) and the additional effects of life events on bipolar risk were limited. An effect of early adverse life events on bipolar risk later in life was mainly observed in children without parental psychopathology. Our findings do not exclude early-life events as possible risk factors, but challenge the concept of adversities as important independent determinants of bipolar disorder in genetically vulnerable individuals.
Full Text Available ABSTRACT. New evidence suggests that the cerebellum has structural and functional abnormalities in psychiatric disorders. Objective: In this research, the goal was to measure the volume of the cerebellum and its subregions in individuals with psychiatric disorders and to relate these findings to their symptoms. Methods: Patients with different degrees of cognitive impairment (Epidemiology of the Elderly - UNIFESP and patients with post-traumatic stress disorder (PTSD from population studies were analyzed. Also, patients with bipolar disorder from an outpatient clinic (Center for the Study of Mood and Anxiety Disorders, Universidade Federal da Bahia were recruited for this study. All subjects underwent a 1.5T structural magnetic resonance scan. Volumetric measures and symptom measurements, by psychometric scales, were performed and compared between patients and controls. Results: The cerebellum volume was reduced in patients with cognitive impairment without dementia and with dementia, in patients with PTSD, and in patients with bipolar disorder compared to controls. In dementia and PTSD, the left cerebellar hemisphere and vermis volume were reduced. In bipolar disorder, volumes of both hemispheres and the vermis were reduced. In the first two studies, these cerebellar volumetric reductions correlated with symptoms of the disease. Conclusion: The exact nature of cerebellar involvement in mental processes is still not fully understood. However, abnormalities in cerebellar structure and its functions have been reported in some of these diseases. Future studies with larger samples are needed to clarify these findings and investigate whether they are important for treatment and prognosis.
Kupka, RW; Luckenbaugh, DA; Post, RM; Suppes, T; Altshuler, LL; Keck, PE; Frye, MA; Denicoff, KD; Grunze, H; Leverich, GS; McElroy, SL; Walden, J; Nolen, WA
Objective: To detect risk factors for rapid cycling in bipolar disorder, the authors compared characteristics of rapid-cycling and non-rapid-cycling patients both from a categorical and a dimensional perspective. Method: Outpatients with bipolar I disorder (N = 419), bipolar II disorder (N = 104), a
Biederman, Joseph; Wozniak, Janet; Martelon, Mary Kate; Spencer, Thomas J; Woodworth, Yvonne; Joshi, Gagan; Spencer, Andrea; Uchida, Mai; Kotte, Amelia; Faraone, Stephen V
Despite ongoing concerns that traumatized children with severe symptoms of emotional dysregulation may be inappropriately receiving a diagnosis of pediatric bipolar-I (BP-I) disorder, this issue has not been adequately examined in the literature. Because both pediatric BP-I disorder and posttraumatic stress disorder (PTSD) are familial disorders, if children with both BP-I and PTSD were to be truly affected with BP-I disorder, their relatives would be at high risk for BP-I disorder. To this end, we compared patterns of familial aggregation of BP-I disorder in BP-I children with and without PTSD with age and sex matched controls. Participants were 236 youths with BP-I disorder and 136 controls of both sexes along with their siblings. Participants completed a large battery of measures designed to assess psychiatric disorders, psychosocial, educational, and cognitive parameters. Familial risk analysis revealed that relatives of BP-I probands with and without PTSD had similar elevated rates of BP-I disorder that significantly differed from those of relatives of controls. Pediatric BP-I disorder is similarly highly familial in probands with and without PTSD indicating that their co-occurrence is not due to diagnostic error.
Liu, Yu-Ming; Tsai, Shang-Ying; Fleck, David E; Strakowski, Stephen M
We compared executive dysfunction with the Wisconsin Card Sorting Test (WCST) among distinct national and ethnic patients with bipolar disorder in euthymia. Bipolar patients, aged 16-45years, from the United States (n=25) and Taiwan (n=30) did not differ significantly on any measure. The WCST score for number Failure to Maintain Set was significantly positively correlated with residual affective symptoms in Taiwanese and US patients. Selective executive dysfunction in euthymia is inherent to bipolar disorder. Euthymic bipolar patients of various ethnic groups may exhibit similar executive dysfunction.
Increased mortality among patients admitted with major psychiatric disorders: a register-based study comparing mortality in unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia
Laursen, Thomas Munk; Munk-Olsen, Trine; Nordentoft, Merete
: Unipolar depressive disorder, bipolar affective disorder, and schizoaffective disorder were associated with the same pattern of excess mortality. Schizophrenia had a lower mortality from unnatural causes of death and a higher mortality from natural causes compared to the 3 other disorders. Family history...... disorder has never been examined in a population-based study. OBJECTIVE: Our objective was to examine and compare mortality rates after admission with schizophrenia, schizoaffective disorder, unipolar depressive disorder, or bipolar affective disorder and to examine the impact of family history...
Background Bipolar disorder (BD) is a severe, familial psychiatric condition. Progress in understanding the aetiology of BD has been hampered by substantial phenotypic and genetic heterogeneity. We sought to mitigate these confounders by studying a multi-generational family multiply affected by BD and major depressive disorder (MDD), who carry an illness-linked haplotype on chromosome 4p. Within a family, aetiological heterogeneity is likely to be reduced, thus conferring greater power to det...
Rayan K Al Jurdi
Full Text Available Rayan K Al Jurdi1,2, Lena A Dixit1, Martha Sajatovic3 1Baylor College of Medicine, Department of Psychiatry, Houston, Texas, USA; 2South Central Mental Illness Research and Clinical Core, Department of Veterans Affairs, Houston, Texas; 3Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USAAbstract: Atypical antipsychotics have become a widely utilized component of the bipolar disorder treatment armamentarium, with approximately 45% of bipolar patients prescribed atypicals. Over the last decade all atypical drugs except for clozapine have received a Food and Drug Administration (FDA bipolar indication. In October 2008, the FDA approved quetiapine XR monotherapy for the treatment of acute depressive episodes of bipolar disorder and acute manic or mixed episodes in bipolar I disorder based on two placebo-control trials. Quetiapine was also approved as adjunct therapy with lithium and divalproex for the treatment of acute manic or mixed episodes as well as maintenance of bipolar I disorder. In contrast to immediate release quetiapine which may require a twice-daily regimen, the XR formulation is intended for once-daily administration. This drug profile of quetiapine XR will address chemistry, pharmacodynamics, pharmacokinetics, metabolism, safety and tolerability and clinical trials in bipolar disorder.Keywords: quetiapine XR, bipolar disorder
Joanna H. Cox
Full Text Available Bipolar disorder is a severe affective disorder which can present in adolescence, or sometimes earlier, and often requires a pharmacotherapeutic approach. The phenomenology of bipolar disorder in children and adolescents appears to differ from that of adult patients, prompting the need for specific pharmacotherapy guidelines for long-term management in this patient population. Current treatment guidelines were mainly developed based on evidence from studies in adult patients, highlighting the requirement for further research into the pharmacotherapy of children and adolescents with bipolar disorder. This review compares and critically analyzes the available guidelines, discussing the recommended medication classes, their mechanisms of action, side effect profiles and evidence base.
Full Text Available Abstract Background & aim: Attention deficit has significant effect on the life of patients suffering from schizophrenia and bipolar disorder. The aim of this study was to assess the attention deficit in patients with schizophrenia. Methods: In the present post-hoc study, 132 patients with schizophrenia and bipolar disorder were selected via non-randomized sampling at Shafa Hospital (Rasht, Iran and then divided into four equal groups: chronic schizophrenia patients, first-episode patients, chronic bipolar patients, and first-episode bipolar patients. Thirty-three healthy individuals were selected as the control group. Subjects were evaluated by Stroop color-word test. The gathered Data were analyzed by one-way ANOVA. Results: Attention deficit among chronic schizophrenics and patients suffering from bipolar disease was higher than the control group (p <1. Chronic schizophrenic patients compared with schizophrenia bipolar disease and first round schizophrenia showed more attention deficit. There was no significant difference among the first bipolar disease and schizophrenia, bipolar disorder, as well as the first round schizophrenia (p<0.05. Conclusion: Attention deficit is more severe in schizophrenic patients than bipolar disorder, and chronicity is more effective in schizophrenic patients. Key words: Attention, Schizophrenia, Chronicity
Full Text Available BACKGROUND: Some preliminary findings have suggested that patients with bipolar disorder show a disparate pattern of obsessive-compulsive (OC symptoms. This study aimed to reevaluate this subject on a different sample within a different cultural background.METHODS: The present cross-sectional study was carried out in a clinical non-experimental setting on 78 obsessivecompulsive disorder (OCD patients; 39 with and 39 without bipolar disorder (BD. Subjects underwent a Structured Clinical Diagnostic Interview for DSM-IV (SCID-I as well as the Yale-Brown Obsessive-Compulsive Rating Scale (YBOCS.RESULTS: The diagnoses in the non-bipolar group were mostly major depressive disorder (38% and dysthymic disorder (38%. The mean age of the bipolar group was significantly lower than that of the non-bipolars (P CONCLUSIONS: The content of OC symptoms which is not traditionally considered a helpful factor for diagnosing a psychiatric disorder might be able to lead the clinician to the diagnosis of bipolarity in a depressed patient with OCD.KEY WORDS: Bipolar disorder, obsessive-compulsive disorder, obsessive-compulsive symptoms.
Moore R Andrew
Full Text Available Abstract Background Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics. Methods We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library, and data combined for analysis where there was clinical homogeneity, with especial reference to trial duration. Results In five trials (2,206 patients participants presented with a depressive episode, and in 25 trials (6,174 patients the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5–6, but more adverse event withdrawals (NNH 12. With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6–12 weeks, but more adverse event withdrawals (NNH of about 22 in studies of 6–12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10. In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of ≥7% (mainly olanzapine trials, somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics
Niitsu, Tomihisa; Fabbri, Chiara; Serretti, Alessandro
Manic switch is a relevant issue when treating bipolar depression. Some risk factors have been suggested, but unequivocal findings are lacking. We therefore investigated predictors of switch from depression to mania in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample. Manic switch was defined as a depressive episode followed by a (hypo)manic or mixed episode within the following 12 weeks. We assessed possible predictors of switch using generalized linear mixed models (GLMM). 8403 episodes without switch and 512 episodes with switch (1720 subjects) were included in the analysis. Several baseline variables were associated with a higher risk of switch. They were younger age, previous history of: rapid cycling, severe manic symptoms, suicide attempts, amphetamine use and some pharmacological and psychotherapeutic treatments. During the current depressive episode, the identified risk factors were: any possible mood elevation, multiple mania-associated symptoms with at least moderate severity, and comorbid panic attacks. In conclusion, our study suggests that both characteristics of the disease history and clinical features of the current depressive episode may be risk factors for manic switch.
Carter, Julia M; Arentsen, Timothy J; Cordova, Matthew J; Ruzek, Josef; Reiser, Robert; Suppes, Trisha; Ostacher, Michael J
Suicide risk increases for those with Bipolar Disorder or PTSD, however little research has focused on risk for co-occurring Bipolar Disorder and PTSD. The aim of this article was to evaluate increased suicide risk in co-occurring disorders, and differences in suicide risk for patients with Bipolar I versus Bipolar II. This study evaluated suicide risk in patients with co-occurring PTSD and Bipolar Disorder (n = 3,158), using the MADRS and Suicide Questionnaire. Those with history of PTSD had significantly higher suicidal ideation than those without (U = 1063375.00, p suicidal ideation, implying the importance of diagnosis and risk assessment.
Dando, Toni M; Keating, Gillian M
Quetiapine (Seroquel), an atypical antipsychotic with established efficacy in the treatment of schizophrenia, shows efficacy in the treatment of acute mania and depression associated with bipolar disorder.Quetiapine, either as monotherapy or in combination with lithium or divalproex sodium (valproate semisodium), is generally well tolerated and effective in reducing manic symptoms in adult and adolescent patients with acute bipolar mania, and is approved for use in adults for this indication. As monotherapy, the drug is also effective in reducing depressive symptoms in patients with bipolar depression. It is associated with a low incidence of extrapyramidal symptom (EPS)-related adverse events and low EPS ratings in bipolar disorder. Quetiapine thus shows potential in the treatment of bipolar depression, and represents a useful agent for the treatment of acute bipolar mania.
Nusslock, Robin; Harmon-Jones, Eddie; Alloy, Lauren B; Urosevic, Snezana; Goldstein, Kim; Abramson, Lyn Y
Bipolar disorder is characterized by a hypersensitivity to reward-relevant cues and a propensity to experience an excessive increase in approach-related affect, which may be reflected in hypo/manic symptoms. The present study examined the relationship between relative left-frontal electroencephalographic (EEG) activity, a proposed neurophysiological index of approach-system sensitivity and approach/reward-related affect, and bipolar course and state-related variables. Fifty-eight individuals with cyclothymia or bipolar II disorder and 59 healthy control participants with no affective psychopathology completed resting EEG recordings. Alpha power was obtained and asymmetry indices computed for homologous electrodes. Bipolar spectrum participants were classified as being in a major/minor depressive episode, a hypomanic episode, or a euthymic/remitted state at EEG recording. Participants were then followed prospectively for an average 4.7-year follow-up period with diagnostic interview assessments every 4 months. Sixteen bipolar spectrum participants converted to bipolar I disorder during follow-up. Consistent with hypotheses, elevated relative left-frontal EEG activity at baseline (a) prospectively predicted a greater likelihood of converting from cyclothymia or bipolar II disorder to bipolar I disorder over the 4.7-year follow-up period, (b) was associated with an earlier age-of-onset of first bipolar spectrum episode, and (c) was significantly elevated in bipolar spectrum individuals in a hypomanic episode at EEG recording. This is the first study to our knowledge to identify a neurophysiological marker that prospectively predicts conversion to bipolar I disorder. The fact that unipolar depression is characterized by decreased relative left-frontal EEG activity suggests that unipolar depression and vulnerability to hypo/mania may be characterized by different profiles of frontal EEG asymmetry.
James A. Harley
With correction for mood state, total harm avoidance (HA was higher than unaffected in both MDD and BP groups, but the mood disorder groups did not differ from each other. However, BP1 individuals had higher self-transcendence (ST than those with MDD and unaffected relatives. HA may reflect a trait marker of mood disorders whereas high ST may be specific to BP. As ST is heritable, genes that affect ST may be of relevance for vulnerability to BP.
Full Text Available Abstract Background Bipolar disorder is recognized as a major mental health issue, and its economic impact has been examined in the United States. However, there exists a general scarcity of published studies and lack of standardized data on the burden of the illness across European countries. In this systematic literature review, we highlight the epidemiological, clinical, and economic outcomes of bipolar disorder in Europe. Methods A systematic review of publications from the last 10 years relating to the burden of bipolar disorder was conducted, including studies on epidemiology, patient-related issues, and costs. Results Data from the UK, Germany, and Italy indicated a prevalence of bipolar disorder of ~1%, and a misdiagnosis rate of 70% from Spain. In one study, up to 75% of patients had at least one DSM-IV comorbidity, commonly anxiety disorders and substance/alcohol abuse. Attempted suicide rates varied between 21%–54%. In the UK, the estimated rate of premature mortality of patients with bipolar I disorder was 18%. The chronicity of bipolar disorder exerted a profound and debilitating effect on the patient. In Germany, 70% of patients were underemployed, and 72% received disability payments. In Italy, 63%–67% of patients were unemployed. In the UK, the annual costs of unemployment and suicide were £1510 million and £179 million, respectively, at 1999/2000 prices. The estimated UK national cost of bipolar disorder was £4.59 billion, with hospitalization during acute episodes representing the largest component. Conclusion Bipolar disorder is a major and underestimated health problem in Europe. A number of issues impact on the economic burden of the disease, such as comorbidities, suicide, early death, unemployment or underemployment. Direct costs of bipolar disorder are mainly associated with hospitalization during acute episodes. Indirect costs are a major contributor to the overall economic burden but are not always recognized in
Etain, Bruno; Mathieu, Flavie; Liquet, Stéphanie; Raust, Aurélie; Cochet, Barbara; Richard, J. R.; Gard, Sébastien; Zanouy, L.; Kahn, Jean-Pierre; Cohen, Renaud,; Bougerol, Thierry; Henry, Chantal; Leboyer, Marion; Bellivier, Frank
International audience; BACKGROUND: A strong association has been reported between trait-impulsiveness and bipolar disorder (BD). Much attention has been focused on this association, but subgroup analysis has generated conflicting results, raising questions about the role of trait-impulsiveness in suicidal behavior and substance misuse in bipolar patients. METHOD: We compared Barratt Impulsiveness Scale-10 scores between 385 euthymic bipolar patients and 185 healthy controls. We then investig...
Full Text Available The Dandy-Walker malformation is a congenital brain malformation, typically involving the fourth ventricle and the cerebellum. To date, the Dandy-Walker syndrome has not been described in association with bipolar disorder type I mania, and therefore we briefly report the case of a Dandy-Walker variant associated with acute mania. A 10-year-old boy was brought by his mother to the outpatient clinic of the Department of Psychiatry of a tertiary care hospital, with symptoms of mania. The MRI brain of the patient showed a posterior fossa cystic lesion, a giant cisterna magna communicating with the fourth ventricle and mild hypoplasia of the cerebellar vermis, with the rest of the structures being normal and no signs of hydrocephalus. These findings showed that the patient had a Dandy-Walker variant. He responded partially to valproate and olanzepine, which controlled the acute manic symptoms in the ward.
Full Text Available Normothymic, antidepressant and antipsychotic pharmaceutics are, in accordance with international guidelines, employed both in the therapy and the prevention of bipolar disorder (BD. Long-term studies on the mechanisms of action of such medications, as well as on the pathogenetic background of BD, have led to the discovery of effective, albeit unconventional pharmacotherapeutic approaches. These methods have the potential to successfully treat mania and depression, as well as to counter affective episode relapse. Allopurinol - commonly used to treat gout, secondary hyperuricemia and Lesch-Nyhan syndrome, acts by inhibiting the synthesis of uric acid, levels of which are often increased in manic patients. Due to this, an evaluation of the potential effect of allopurinol on the reduction of mania symptoms seems to be reasonable. Additionally, the numerable research papers coming out of research regarding the role of purine neurotransmitters in mood alterations, indicate that adenosine agonists act analogously to dopamine antagonists.
Boudebesse, Carole; Leboyer, Marion; Begley, Amy; Wood, Annette; Miewald, Jean; Hall, Martica; Frank, Ellen; Kupfer, David; Germain, Anne
The goal of this study was to compare 5 actigraphy scoring methods in a sample of 18 remitted patients with bipolar disorder. Actigraphy records were processed using five different scoring methods relying on the sleep diary; the event-marker; the software-provided automatic algorithm; the automatic algorithm supplemented by the event-marker; visual inspection (VI) only. The algorithm and the VI methods differed from the other methods for many actigraphy parameters of interest. Particularly, the algorithm method yielded longer sleep duration, and the VI method yielded shorter sleep latency compared to the other methods. The present findings provide guidance for the selection of signal processing method based on sleep parameters of interest, time-cue sources and availability, and related scoring time costs for the study.
Leverich, GS; Altshuler, LL; Frye, MA; Suppes, T; Keck, PE; McElroy, SL; Denicoff, KD; Obrocea, G; Nolen, WA; Kupka, R; Walden, J; Grunze, H; Perez, S; Luckenbaugh, DA; Post, RM
Background: Clinical factors related to suicide and suicide attempts have been studied much more extensively in unipolar depression compared with bipolar disorder. We investigated demographic and course-of-illness variables to better understand the incidence and potential clinical correlates of seri
Bauer, Rita; Conell, Jörn; Glenn, Tasha; Alda, Martin; Ardau, Raffaella; Baune, Bernhard T; Berk, Michael; Bersudsky, Yuly; Bilderbeck, Amy; Bocchetta, Alberto; Bossini, Letizia; Castro, Angela M Paredes; Cheung, Eric Yw; Chillotti, Caterina; Choppin, Sabine; Del Zompo, Maria; Dias, Rodrigo; Dodd, Seetal; Duffy, Anne; Etain, Bruno; Fagiolini, Andrea; Hernandez, Miryam Fernández; Garnham, Julie; Geddes, John; Gildebro, Jonas; Gonzalez-Pinto, Ana; Goodwin, Guy M; Grof, Paul; Harima, Hirohiko; Hassel, Stefanie; Henry, Chantal; Hidalgo-Mazzei, Diego; Kapur, Vaisnvy; Kunigiri, Girish; Lafer, Beny; Larsen, Erik R; Lewitzka, Ute; Licht, Rasmus W; Lund, Anne Hvenegaard; Misiak, Blazej; Monteith, Scott; Munoz, Rodrigo; Nakanotani, Takako; Nielsen, René E; O'Donovan, Claire; Okamura, Yasushi; Osher, Yamima; Piotrowski, Patryk; Reif, Andreas; Ritter, Philipp; Rybakowski, Janusz K; Sagduyu, Kemal; Sawchuk, Brett; Schwartz, Elon; Scippa, Ângela M; Slaney, Claire; Sulaiman, Ahmad H; Suominen, Kirsi; Suwalska, Aleksandra; Tam, Peter; Tatebayashi, Yoshitaka; Tondo, Leonardo; Vieta, Eduard; Vinberg, Maj; Viswanath, Biju; Volkert, Julia; Zetin, Mark; Whybrow, Peter C; Bauer, Michael
There is considerable international interest in online education of patients with bipolar disorder, yet little understanding of how patients use the Internet and other sources to seek information. 1171 patients with a diagnosis of bipolar disorder in 17 countries completed a paper-based, anonymous survey. 81% of the patients used the Internet, a percentage similar to the general public. Older age, less education, and challenges in country telecommunications infrastructure and demographics decreased the odds of using the Internet. About 78% of the Internet users looked online for information on bipolar disorder or 63% of the total sample. More years of education in relation to the country mean, and feeling very confident about managing life decreased the odds of seeking information on bipolar disorder online, while having attended support groups increased the odds. Patients who looked online for information on bipolar disorder consulted medical professionals plus a mean of 2.3 other information sources such as books, physician handouts, and others with bipolar disorder. Patients not using the Internet consulted medical professionals plus a mean of 1.6 other information sources. The percentage of patients with bipolar disorder who use the Internet is about the same as the general public. Other information sources remain important.
Full Text Available Background: Resilient adaptation can be construed in different ways, but as used here it refers to the adaptive brain changes associated with avoidance of psychopathology despite familiar risk for Bipolar Disorder (BD. Although family history of BD is associated with elevated risk of affective morbidity a significant proportion of first-degree relatives of BD patients remains free of psychopathology. Examination of brain structure and function in these individuals may inform on adaptive changes that may pre-empt disease expression. Methods: Data presented here are derived from the Vulnerability to Bipolar Disorders (VIBES study which includes patients with BD, asymptomatic relatives and healthy controls. Participants underwent extensive investigations including brain structural (sMRI and functional magnetic resonance imaging (fMRI. The data presented here focus on sMRI voxel-based-morphometry and on conventional and connectivity analyses of fMRI data obtained during the Stroop Colour Word Test (SCWT, a task of cognitive control during conflict resolution. All analyses were implemented in SPM (www.fil.ion.ucl.ac.uk/spm. Resilience in relatives was operationalized as the absence of clinical-range symptoms.Results: Resilient relatives of BD patients expressed structural, functional and connectivity changes reflecting the effect of genetic risk on the brain. These included increased insular volume, decreased activation within the posterior and inferior parietal regions involved in selective attention during the SCWT, and reduced fronto-insular and fronto-cingulate connectivity.Resilience was associated with increased cerebellar vermal volume and enhanced functional coupling between the dorsal and the ventral prefrontal cortex. Conclusions: Our findings suggests the presence of biological mechanisms associated with resilient adaptation of brain networks and pave the way for the identification of outcome-specific trajectories given a particular
Carla P D Fernandes; Andrea Christoforou; Sudheer Giddaluru; Kari M Ersland; Srdjan Djurovic; Manuel Mattheisen; Lundervold, Astri J; Ivar Reinvang; Nöthen, Markus M.; Marcella Rietschel; Ophoff, Roel A; Albert Hofman; Uitterlinden, André G.; Thomas Werge; Sven Cichon
textabstractBackground: Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders. Methods: Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar dis...
Background: Bipolar disorder is a common, chronic and severe mental illness, causing suffering and large costs. Lithium treatment is the golden standard and works in 2/3 of patients, of which 50% are called lithium responders. There is strong evidence that both bipolar disorder and the degree of lithium response are highly heritable, although many mechanisms are unknown. Short telomere length has been found in both somatic and psychiatric disorders, but little is known about te...
Full Text Available BACKGROUND: We have previously reported linkage of markers on chromosome 1q22 to schizophrenia, a finding supported by several independent studies. Within this linkage region, we have identified significant linkage disequilibrium between schizophrenia and markers within the gene for carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON. Prior sequencing of the ten exons of CAPON failed to reveal a coding mutation associated with illness. METHODS AND FINDINGS: We screened a human fetal brain cDNA library and identified a new isoform of CAPON that consists of the terminal two exons of the gene, and verified the expression of the predicted corresponding protein in human dorsolateral prefrontal cortex (DLPFC. We examined the expression levels of both the ten-exon CAPON transcript and this new isoform in postmortem brain samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA from the DLPFC in 105 individuals (35 with schizophrenia, 35 with bipolar disorder, and 35 psychiatrically normal controls revealed significantly (p < 0.005 increased expression of the new isoform in both schizophrenia and bipolar disorder. Furthermore, this increased expression was significantly associated (p < 0.05 with genotype at three single-nucleotide polymorphisms previously identified as being in linkage disequilibrium with schizophrenia. CONCLUSION: Based on the known interactions between CAPON, neuronal nitric oxide synthase (nNOS, and proteins associated with the N-methyl-D-aspartate receptor (NMDAR complex, overexpression of either CAPON isoform would be expected to disrupt the association between nNOS and the NMDAR, leading to changes consistent with the NMDAR hypofunctioning hypothesis of schizophrenia. This study adds support to a role of CAPON in schizophrenia, produces new evidence implicating this gene in the etiology of bipolar disorder, and suggests a possible mechanism of action of CAPON in psychiatric illness.
Kim, Yeni; Santos, Renata; Gage, Fred H.; Marchetto, Maria C.
Bipolar disorder (BD) is a chronic and progressive psychiatric illness characterized by mood oscillations, with episodes of mania and depression. The impact of BD on patients can be devastating, with up to 15% of patients committing suicide. This disorder is associated with psychiatric and medical comorbidities and patients with a high risk of drug abuse, metabolic and endocrine disorders and vascular disease. Current knowledge of the pathophysiology and molecular mechanisms causing BD is still modest. With no clear biological markers available, early diagnosis is a great challenge to clinicians without previous knowledge of the longitudinal progress of illness. Moreover, despite recommendations from evidence-based guidelines, polypharmacy is still common in clinical treatment of BD, reflecting the gap between research and clinical practice. A major challenge in BD is the development of effective drugs with low toxicity for the patients. In this review article, we focus on the progress made and future challenges we face in determining the pathophysiology and molecular pathways involved in BD, such as circadian and metabolic perturbations, mitochondrial and endoplasmic reticulum (ER) dysfunction, autophagy and glutamatergic neurotransmission; which may lead to the development of new drugs. PMID:28261061
Claudia Del Grande
Full Text Available Toxoplasma gondii, a ubiquitous intracellular parasite, has a strong tropism for the brain tissue, where it forms intracellular cysts within the neurons and glial cells, establishing a chronic infection. Although latent toxoplasmosis is generally assumed to be asymptomatic in immunocompetent individuals, it is now clear that it can induce behavioral manipulations in mice and infected humans. Moreover, a strong relation has emerged in recent years between toxoplasmosis and psychiatric disorders. The link between T. gondii and schizophrenia has been the most widely documented; however, a significant association with bipolar disorder (BD and suicidal/aggressive behaviors has also been detected. T. gondii may play a role in the etiopathogenesis of psychiatric disorders affecting neurotransmitters, especially dopamine, that are implicated in the emergence of psychosis and behavioral Toxoplasma-induced abnormalities, and inducing brain inflammation by the direct stimulation of inflammatory cytokines in the central nervous system. Besides this, there is increasing evidence for a prominent role of immune dysregulation in psychosis and BD. The aim of this review is to describe recent evidence suggesting a link between Toxoplasma gondii and BD, focusing on the interaction between immune responses and this infectious agent in the etiopathogenesis of psychiatric symptoms.
Bellivier, Frank; Geoffroy, Pierre Alexis; Scott, Jan; Schurhoff, Franck; Leboyer, Marion; Etain, Bruno
Kraepelin's observations of the differences in the course and outcome of dementia praecox and manic depression fundamentally influenced thinking about bipolar disorder (BP) and schizophrenia (SZ) for over a century. In modern times, there is increasing awareness that a greater understanding of the similarities between these two highly prevalent and disabling conditions can teach us as many lessons about the pathophysiology of severe mental disorders as does the pursuit of differentiating factors. We review publications on developmental, genetic, epidemiological, and outcome research that challenges the Kraepelian dichotomy. We highlight the increasing evidence of the overlap in genetic susceptibility. Neuro-developmental studies provide evidence of shared early pathological processes, whilst neurophysiological investigations also suggest that different genes may have a role in the development of both phenotypes. There is also evidence of overlapping neurocognitive phenotypes. It has become increasingly clear that a simple binary classification of these disorders represents an oversimplification. It may be more apposite to think in terms of genetic inﬂuences on six continuous symptom dimensions: neurobiological, cognitive, positive, negative, depressive and manic symptoms.
Haustgen, Thierry; Akiskal, Hagop
Although first detailed descriptions of what we today term "bipolar disorders" are generally attributed to E. Kraepelin [Kraepelin, E., 1899 (1976 tr). Manic depressive insanity and paranoia. (reprint of English translation). Arno, New York], a review of French psychiatric literature from Esquirol to the middle of 20th century reveals major clinical contributions to the development of the concept of cyclic mood disorders, their phenomenology and classification as embodied in DSM-IV. The main treatise was published by the Paris psychiatric schools of Salpêtrière, Bicêtre, Charenton, Sainte-Anne and Vanves. Already much before Kraepelin, French authors had described most symptoms and the course of future DSM-IV bipolar, manic, major depressive [Falret, J.-P., 1854. De la folie circulaire ou forme de maladie mentale caracterisée par l'alternative régulière de la manie et de la mélancolie, Bull. Acad. Méd. XIX, 382-400.; Baillarger, J., 1854. Note sur un genre de folie dont les accès sont caractérisés par deux périodes régulières, l'une de dépression, l'autre d'excitation, Bull. Acad. Méd. XIX, 340 et Ann. Méd. Psychol. XII, 369], hypomanic and mixed episodes [Falret, J., 1861. Principes à suivre dans la classification des maladies mentales, Ann. Méd. Psychol. XIX, 145.; Falret, J., 1866, 1867. La folie raisonnante ou folie morale, Ann. Méd. Psychol. XXIV, 382, XXV, 68], as well as - under other names - the characteristics of bipolar II disorder, various specifiers describing mood episode and course of recurrent episodes [Ritti, A., 1883. Traité clinique de la folie à double forme (folie, circulaire, délire à formes alternes). Doin, Paris]. The synthesis of these clinical observations led to Magnan's "intermittent madness" (1893), a precursor of Kraepelin's "manic-depressive psychosis". After 1899, French authors generally adhered to their classification of autonomous depressive disorder (melancholia), as distinct from manic-depressive insanity
Full Text Available Young Sup Woo,1 Jung Goo Lee,2,3 Jong-Hyun Jeong,1 Moon-Doo Kim,4 Inki Sohn,5 Se-Hoon Shim,6 Duk-In Jon,7 Jeong Seok Seo,8 Young-Chul Shin,9 Kyung Joon Min,10 Bo-Hyun Yoon,11 Won-Myong Bahk1 1Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Department of Psychiatry, Inje University Haeundae Paik Hospital, Busan, South Korea;3Paik Institute for Clinical Research, Inje Univeristy, Busan, South Korea; 4Department of Psychiatry, Jeju National University Hospital, Jeju, South Korea; 5Department of Psychiatry, Keyo Hospital, Keyo Medical Foundation, Uiwang, South Korea; 6Department of Psychiatry, Soonchunhyang University Cheonan Hospital, Soonchunhyang University, Cheonan, South Korea; 7Department of Psychiatry, Sacred Heart Hospital, Hallym University, Anyang, South Korea; 8Department of Psychiatry, School of Medicine, Konkuk University, Chungju, South Korea; 9Department of Psychiatry, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, South Korea; 10Department of Psychiatry, College of Medicine, Chung-Ang University, Seoul, South Korea; 11Department of Psychiatry, Naju National Hospital, Naju, South Korea Objective: To constitute the third revision of the guidelines for the treatment of bipolar disorder issued by the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP 2014. Methods: A 56-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for the various phases of bipolar disorder and for special populations. The review committee included 110 Korean psychiatrists and 38 experts for child and adolescent psychiatry. Of the committee members, 64 general psychiatrists and 23 child and adolescent psychiatrists responded to the survey. Results: The treatment of choice (TOC for euphoric, mixed, and psychotic mania was the combination of a mood stabilizer (MS and an atypical antipsychotic (AAP; the TOC for
Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E
Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family
Sharma, V; Ainsworth, P J; McCabe, S B; Persad, E; Kueneman, K M
The authors describe a pair of monozygotic twins with bipolar disorder but with a different course of the illness including age of onset, sequence of episodes, and cycle length. Based on these findings, the clinical course of bipolar illness does not appear to be genetically determined. PMID:9074308
Lam, Dominic; Mansell, Warren
A case study of a bipolar patient whose mood changes every 24 hours is described to illustrate the changes in cognitive processing and content during different phases of bipolar disorder. The participant completed a battery of questionnaires and tasks on 4 separate occasions: twice when depressed and twice when manic. Depression tended to be…
Stringaris, Argyris; Baroni, Argelinda; Haimm, Caroline; Brotman, Melissa; Lowe, Catherine H.; Myers, Frances; Rustgi, Eileen; Wheeler, Wanda; Kayser, Reilly; Towbin, Kenneth; Leibenluft, Ellen
Objective: An important question in pediatric bipolar research is whether marked nonepisodic irritability is a manifestation of bipolar disorder in youth. This study tests the hypothesis that youth with severe mood dysregulation (SMD), a category created for the purpose of studying children presenting with severe nonepisodic irritability, will be…
Vonk, Ronald; van der Schot, Astrid C.; Kahn, Rene S.; Nolen, Willem A.; Drexhage, Hemmo A.
Background: Both genetic and environmental factors are involved in the etiology of bipolar disorder; however, biological markers for the transmission of the bipolar genotype ("endophenotypes") have not been found. Autoimmune thyroiditis with raised levels of thyroperoxidase antibodies (TPO-Abs) is r
Frye, MA; Altshuler, LL; McElroy, SL; Suppes, T; Keck, PE; Denicoff, K; Nolen, WA; Kupka, R; Leverich, GS; Pollio, C; Grunze, H; Walden, J; Post, RM
Objective: The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have pre
Geoffroy, Pierre Alexis; Etain, Bruno; Franchi, Jean-Arthur Micoulaud; Bellivier, Frank; Ritter, Philipp
Bipolar disorders (BD) present with abnormalities of circadian rhythmicity and sleep homeostasis, even during phases of remission. These abnormalities are linked to the underlying neurobiology of genetic susceptibility to BD. Melatonin is a pineal gland secreted neurohormone that induces circadian-related and sleep-related responses. Exogenous melatonin has demonstrated efficacy in treating primary insomnia, delayed sleep phase disorder, improving sleep parameters and overall sleep quality, and some psychiatric disorders like autistic spectrum disorders. In order to evaluate the efficacy of melatonin among patients with BD, this comprehensive review emphasizes the abnormal melatonin function in BD, the rationale of melatonin action in BD, the available data about the exogenous administration of melatonin, and melatonin agonists (ramelteon and tasimelteon), and recommendations of use in patients with BD. There is a scientific rationale to propose melatonin-agonists as an adjunctive treatment of mood stabilizers in treating sleep disorders in BD and thus to possibly prevent relapses when administered during remission phases. We emphasized the need to treat insomnia, sleep delayed latencies and sleep abnormalities in BD that are prodromal markers of an emerging mood episode and possible targets to prevent future relapses. An additional interesting adjunctive therapeutic effect might be on preventing metabolic syndrome, particularly in patients treated with antipsychotics. Finally, melatonin is well tolerated and has little dependence potential in contrast to most available sleep medications. Further studies are expected to be able to produce stronger evidence-based therapeutic guidelines to confirm and delineate the routine use of melatonin-agonists in the treatment of BD.
Goghari, Vina M.; Sponheim, Scott R.
Schizophrenia and bipolar disorder, although diagnostically separate, likely share elements of their genetic etiology. This study assessed whether COMT Val158Met polymorphism has shared or specific associations with clinical phenotypes evident in schizophrenia and bipolar disorder. Schizophrenia and bipolar patients completed a clinical assessment encompassing premorbid functioning and current and lifetime symptomatology. Multivariate analyses yielded a three-way interaction of diagnosis, COM...
Louise K Sjöholm
Full Text Available BACKGROUND: Bipolar disorder patients often display abnormalities in circadian rhythm, and they are sensitive to irregular diurnal rhythms. CRY2 participates in the core clock that generates circadian rhythms. CRY2 mRNA expression in blood mononuclear cells was recently shown to display a marked diurnal variation and to respond to total sleep deprivation in healthy human volunteers. It was also shown that bipolar patients in a depressive state had lower CRY2 mRNA levels, nonresponsive to total sleep deprivation, compared to healthy controls, and that CRY2 gene variation was associated with winter depression in both Swedish and Finnish cohorts. PRINCIPAL FINDINGS: Four CRY2 SNPs spanning from intron 2 to downstream 3'UTR were analyzed for association to bipolar disorder type 1 (n = 497, bipolar disorder type 2 (n = 60 and bipolar disorder with the feature rapid cycling (n = 155 versus blood donors (n = 1044 in Sweden. Also, the rapid cycling cases were compared with bipolar disorder cases without rapid cycling (n = 422. The haplotype GGAC was underrepresented among rapid cycling cases versus controls and versus bipolar disorder cases without rapid cycling (OR = 0.7, P = 0.006-0.02, whereas overrepresentation among rapid cycling cases was seen for AAAC (OR = 1.3-1.4, P = 0.03-0.04 and AGGA (OR = 1.5, P = 0.05. The risk and protective CRY2 haplotypes and their effect sizes were similar to those recently suggested to be associated with winter depression in Swedes. CONCLUSIONS: We propose that the circadian gene CRY2 is associated with rapid cycling in bipolar disorder. This is the first time a clock gene is implicated in rapid cycling, and one of few findings showing a molecular discrimination between rapid cycling and other forms of bipolar disorder.
Reichart, CG; van der Ende, J; Wals, M; Hillegers, MHJ; Nolen, WA; Ormel, J; Verhulst, FC
Objective: To assess the usefulness of the General Behavior Inventory (GBI) to predict the development of mood disorders in the offspring of parents with bipolar disorder. Method: The GBI and the K-SADS (first measurement) and the SCID (last measurement) were used to assess psychopathology among 129
Maier, Robert; Moser, Gerhard; Chen, Guo-Bo;
approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy...... could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any......Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk...
Adelson, Stewart; Bell, Robinette; Graff, Adam; Goldenberg, David; Haase, Elizabeth; Downey, Jennifer I; Friedman, Richard C
While there is consensus that bipolar disorder exists in children and adolescents, its diagnostic criteria are debated. Excessive sexual behavior has been reported in youth who may have juvenile bipolar disorder (JBD), and has been termed "hypersexuality." Although there is no universal definition of this term, this observation has led to a hypothesis that increased sexual behavior characterizes the bipolar syndrome in children and adolescents, and differentiates it from attention deficit hyperactivity disorder. Although this hypothesis is plausible, evidence for it is incomplete, because testing it definitively would require both establishing a standard definition of hypersexuality in children and adolescents, and also reaching consensus about the other nonsexual criteria for pediatric bipolar disorder. In addition, studies to test it would need to control factors other than JBD that are known to increase sexual behavior in children and adolescents. These include sexual abuse and related posttraumatic stress disorder, excessive exposure to sexual stimuli, psychiatric illness in general, and social variables such as family chaos and social stress. Some of these factors might increase sexual behavior in youth with bipolar disorder through psychodynamic mechanisms rather than as a result of the illness itself. Therefore, further research is needed to determine whether increased sexual behavior can serve as a diagnostically valuable criterion for bipolar disorder in children and adolescents, and whether it differentiates the disorder from other conditions known to be associated with increased sexual behavior in youth.
Quintana, Humberto; Butterbaugh, Grant J.; Purnell, William; Layman, Ann K.
Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing comorbid non-bipolar mood disorders. Fluoxetine monotherapy is an established treatment for pediatric mood disorders; however its efficacy in ADHD and comorbid mood disorder is unknown. Therefore, we evaluated 30 children who met DSM-IV criteria for…
Santelmann, Hanno; Franklin, Jeremy; Bußhoff, Jana; Baethge, Christopher
Schizoaffective disorder is a common diagnosis in clinical practice but its nosological status has been subject to debate ever since it was conceptualized. Although it is key that diagnostic reliability is sufficient, schizoaffective disorder has been reported to have low interrater reliability. Evidence based on systematic review and meta-analysis methods, however, is lacking. Using a highly sensitive literature search in Medline, Embase, and PsycInfo we identified studies measuring the interrater reliability of schizoaffective disorder in comparison to schizophrenia, bipolar disorder, and unipolar disorder. Out of 4126 records screened we included 25 studies reporting on 7912 patients diagnosed by different raters. The interrater reliability of schizoaffective disorder was moderate (meta-analytic estimate of Cohen's kappa 0.57 [95% CI: 0.41-0.73]), and substantially lower than that of its main differential diagnoses (difference in kappa between 0.22 and 0.19). Although there was considerable heterogeneity, analyses revealed that the interrater reliability of schizoaffective disorder was consistently lower in the overwhelming majority of studies. The results remained robust in subgroup and sensitivity analyses (e.g., diagnostic manual used) as well as in meta-regressions (e.g., publication year) and analyses of publication bias. Clinically, the results highlight the particular importance of diagnostic re-evaluation in patients diagnosed with schizoaffective disorder. They also quantify a widely held clinical impression of lower interrater reliability and agree with earlier meta-analysis reporting low test-retest reliability.
Lakshmanan, Manu N; Meier, Stacey L Colton; Meier, Robert S; Lakshmanan, Ramaswamy
We present a case where dissociative identity disorder was effectively treated with memory retrieval psychotherapy. However, the patient's comorbid bipolar disorder contributed to the patient's instability and fortified the amnesiac barriers that exist between alter personality states in dissociative identity disorder, which made memory retrieval difficult to achieve. Implications from this case indicate that a close collaboration between psychologist and psychiatrist focused on carefully diagnosing and treating existing comorbid conditions may be the most important aspect in treating dissociative identity disorder. We present our experience of successfully treating a patient with dissociative identity disorder and bipolar disorder using this collaborative method.
Bernardo Carramão Gomes
treatment of bipolar patients. However, little is known about the effects of these approaches. OBJECTIVE: Evaluate the effectiveness of Group Therapy in the treatment of bipolar affective disorder. METHOD: Review of the literature using Medline, Lilacs, PubMed e ISI, selecting English language articles published between the years of 1975 and 2005. The reference sections of the selected articles, review articles and specialized books were also consulted. Only randomized controlled trails, with more than twenty subjects, were selected. RESULTS: Five published studies were identified; three of them have been published in the last five years. In three of the selected studies, models of Psychoeducation were used, showing an increase in the adherence to the pharmacological treatment. One showed reduction in the number of relapses and hospital admissions. The other two studies combined psychoeducation with some other form of psychotherapeutic approach. In one of them, not only an increase in the remission period but also symptom reduction was identified, concerning manic episodes. DISCUSSION: There has been a growing interest in evidence based psychotherapy interventions for the treatment of bipolar affective disorder over the last years. This fact contrasts with the low number of studies dedicated to group therapy, which could be very useful in institutions where a great number of patients are assisted. The clinical complexities of this disease, the presence of several comorbidities and the different levels of adherence to pharmacotherapy demand the development of diverse therapeutic options, in order to meet the needs of each individual. The studies show that group therapy could be an effective treatment option that deserves better investigations so that it can be used in clinical practice.
Ricardo Alberto Moreno
Full Text Available O transtorno bipolar é uma condição médica complexa e até o momento não há um tratamento único comprovadamente eficaz no controle de todos aspectos da doença. Foram revisadas a literatura disponível sobre o uso de anticonvulsivantes (valproato, carbamazepina, oxcarbazepina, lamotrigina, gabapentina, topiramato, clonazepam e antipsicóticos atípicos (clozapina, risperidona, olanzapina, quetiapina, ziprasidona e aripiprazole no tratamento agudo e profilático do transtorno bipolar. Existe um acúmulo de evidências acerca da eficácia do lítio na profilaxia e de ser melhor no tratamento da mania aguda do que nos episódios depressivos. Outros dados indicam que a carbamazepina e o valproato são eficazes na mania aguda. A lamotrigina parece reduzir ciclagem e ser eficaz em episódios depressivos. Baseado nas informações disponíveis, as evidências apontam a olanzapina como o antipsicótico atípico mais apropriado no tratamento de pacientes bipolares em mania, embora existam estudos sugerindo a eficácia da risperidona, aripiprazol e da clozapina. Resultados preliminares avaliando a eficácia de ziprasidona e quetiapina no transtorno bipolar ainda são bastante limitadas. Não há dados consistentes apoiando o uso profilático dos novos antipsicóticos.Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are
Full Text Available Abstract Background We aimed at studying the seasonal changes in mood and behaviour, the distribution of hospital admissions by season, and the persistence of the circadian type in twins with bipolar disorder and their healthy co-twins. Methods All Finnish like-sex twins born from 1940 to 1969 were screened for a diagnosis of bipolar type I disorder. The diagnosis was assessed with a structured research interview, and the study subjects (n = 67 filled in the Seasonal Pattern Assessment Questionnaire (SPAQ and the Morningness-Eveningness Questionnaire (MEQ. For studying the persistence of the habitual sleep length and circadian type, we used data derived from the Finnish Twin Cohort Questionnaire (FTCQ. Bipolar twins were compared with their healthy co-twins. Results Bipolar twins had greater seasonal changes in sleep length (p = 0.01 and mood (p = 0.01, and higher global seasonality scores (p = 0.03 as compared with their co-twins with no mental disorder. Sunny days (p = 0.03 had a greater positive effect on wellbeing in the bipolar than healthy co-twins. Conclusions Our results support the view that bipolar disorder is sensitive to the environmental influence in general and to the seasonal effect in specific. Exposure to natural light appears to have a substantial effect on wellbeing in twins with bipolar disorder.
Teixeira, Ana Maria A; Kleinman, Ana; Zanetti, Marcus; Jackowski, Marcel; Duran, Fábio; Pereira, Fabrício; Lafer, Beny; Busatto, Geraldo F; Caetano, Sheila C
White matter (WM) abnormalities have been reported in bipolar disorder (BD) patients, as well as in their non-BD relatives, both children and adults. Although it is considered an emerging vulnerability marker for BD, there are no studies investigating WM alterations in pediatric unmedicated patients and young healthy offspring. In this study, we evaluated the presence of WM alterations in 18 pediatric, non medicated BD patients, as well as in 18 healthy offspring of BD type I parents and 20 healthy controls. 3T DT-MRI data were acquired and scans were processed with tract-based spatial statistics to provide measures of fractional anisotropy and diffusivity. We found no significant differences in WM microstructure between BD patients, healthy offspring and healthy controls. Previous studies that reported WM alterations investigated older subjects, either on medication (BD patients) or with psychiatric diagnoses other than BD (unaffected offspring). Our findings highlight the importance of the understanding of disease ontogeny and brain development dynamics in the search for early vulnerability markers for psychiatric disorders.
Full Text Available A pathophysiological relationship has been reported between inflammatory processes, decreased levels of neurotrophins, increased oxidative stress and psychiatric disorders in both juvenile and adult ages. Moreover, this relationship remains unclear in juvenile bipolar disorder (BD. We performed a systematic literature review of studies reporting measurements of inflammatory markers, oxidative stress markers or neurotrophins in juvenile and young adult subjects with BD. Concordant findings showed that inflammatory markers are increased since the earlier stages of BD. A positive correlation between decreased levels of a peripheral brain-derived neurotrophic factor and juvenile BD is controversial suggesting that those changes might occur only during the late stage of BD. No changes in central glutathione levels were reported in young adult age BD indicating that oxidative stress may be an outcome of long illness duration and repeated affective episodes. In conclusion, preliminary findings indicate that a certain relationship exists between inflammatory process and juvenile BD but evidence are insufficient to support a causal relationship. Adequately powered and prospective studies are warranted to clarify the role of inflammation, neurotrophins and oxidative stress in juvenile BD.
Wessa, Michèle; Kanske, Philipp; Linke, Julia
Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60-80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.
Full Text Available Joseph Biederman, Paul Hammerness, Robert Doyle, Gagan Joshi, Megan Aleardi, Eric MickPediatric Psychopharmacology Research Department, Massachusetts General Hospital, Boston, MA, USAObjective: Children and adolescents with bipolar disorder are also at high risk of having comorbid attention-deficit hyperactivity disorder (ADHD. The objective of this study was to estimate improvement in ADHD symptoms in children with bipolar disorder.Methods: This was an open-label, study of risperidone monotherapy for the treatment of pediatric bipolar disorder. Thirty-one children and adolescents 4–15 years of age (7.2 ± 2.8 years of both sexes (71%, N = 22 male with pediatric bipolar disorder (YMRS score = 32.9 ± 8.8 and ADHD (ADHD-RS score = 37.9 ± 8.9 were included in these analyses.Results: Improvement in ADHD symptoms was contingent on improvement in manic symptoms. Although both hyperactive/impulsive (−7.5 ± 5.5.6, p < 0.05 and inattentive (−6.8 ± 5.0, p < 0.05 ADHD symptoms were significantly improved with risperidone, improvement was modest, and only 29% of subjects (N = 6 showed a 30% reduction in ADHD rating scale scores and had a CGI-I ≤ 2.Conclusions: These results suggest that that treatment with risperidone is associated with tangible but generally modest improvement of symptoms of ADHD in children with bipolar disorder.Keywords: ADHD, bipolar disorder, children, risperidone
Karege, F; Perroud, N; Schürhoff, F; Méary, A; Marillier, G; Burkhardt, S; Ballmann, E; Fernandez, R; Jamain, S; Leboyer, M; La Harpe, R; Malafosse, A
The AKT1 gene has been associated with the genetic aetiology of schizophrenia. Following the overlap model of bipolar disorder and schizophrenia, we aimed to investigate AKT1 genetic variants and protein expression in both diseases. A total of 679 subjects with European ancestry were included: 384 with schizophrenia, 130 with bipolar disorder and 165 controls. Six single nucleotide polymorphisms (SNPs) were investigated for association with the diseases using single- and multi-locus analyses. AKT1 and AKT2 protein levels were measured in post-mortem brain tissues from ante-mortem diagnosed schizophrenia (n = 30) and bipolar disorder subjects (n = 12) and matched controls. The analysis identified a significant global distortion in schizophrenia (P = 0.0026) and a weak association in bipolar disorder (P = 0.046). A sliding window procedure showed a five-SNP haplotype (TCGAG) to be associated with schizophrenia (P = 1.22 x 10(-4)) and bipolar disorder (P = 0.0041) and a four-SNP haplotype (TCGA) with the combined sample (1.73 x 10(-5)). On the basis of selected genotypes, a significant difference in protein expression emerged between subjects (P gene in both schizophrenia and bipolar disorder, support the role of AKT1 in the genetics of both disorders and add support to the view that there is some genetic overlap between them.
Meier, Sandra; Strohmaier, Jana; Breuer, Rene; Mattheisen, Manuel; Degenhardt, Franziska; Mühleisen, Thomas W; Schulze, Thomas G; Nöthen, Markus M; Cichon, Sven; Rietschel, Marcella; Wüst, Stefan
Linkage and fine mapping studies have established that the neuregulin 3 gene (NRG3) is a susceptibility locus for schizophrenia. Association studies of this disorder have implicated NRG3 variants in both psychotic symptoms and attention performance. Psychotic symptoms and cognitive deficits are also frequent features of bipolar disorder. The aims of the present study were to extend analysis of the association between NRG3 and psychotic symptoms and attention in schizophrenia and to determine whether these associations also apply to bipolar disorder. A total of 358 patients with schizophrenia and 111 patients with bipolar disorder were included. Psychotic symptoms were evaluated using the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and attention performance was assessed using the Trail Making Test (TMT). Symptoms and performance scores were then tested for association with the NRG3 variant rs6584400. A significant association was found between the number of rs6584400 minor alleles and the total OPCRIT score for psychotic symptoms in patients with schizophrenia. Moreover, in both schizophrenia and bipolar disorder patients, minor allele carriers of rs6584400 outperformed homozygous major allele carriers in the TMT. The results suggest that rs6584400 is associated with psychotic symptoms and attention performance in schizophrenia. The finding of a significant association between rs6584400 and attention performance in bipolar disorder supports the hypothesis that this NRG3 variant confers genetic susceptibility to cognitive deficits in both schizophrenia and bipolar disorder.
Jensen, Johan Høy; Støttrup, Mette Marie; Nayberg, Emilie;
Introduction Cognitive impairment is common in bipolar disorder and contributes to socio-occupational difficulties. The objective was to validate and evaluate instruments to screen for and monitor cognitive impairments, and improve the understanding of the association between cognitive measures...
Srivastava, Shefali; Ketter, Terence A
Although extensive literature supports connections between bipolar disorder and creativity, possible mechanisms underlying such relationships are only beginning to emerge. Herein we review evidence supporting one such possible mechanism, namely that personality/temperament contribute to enhanced creativity in individuals with bipolar disorder, a theory supported by studies showing that certain personality/temperamental traits are not only common to bipolar disorder patients and creative individuals but also correlate with measures of creativity. Thus, we suggest based on studies using three important personality/temperament measures-the Neuroticism, Extraversion, and Openness Personality Inventory (NEO); the Myers-Briggs Type Indicator (MBTI); and the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A)-that changeable (increased TEMPS-A-cyclothymia) and at times negative (increased NEO-neuroticism) affect and open-minded (increased NEO-openness) and intuitive (increased MBTI-intuition) cognition may contribute importantly to enhanced creativity in individuals with bipolar disorder.
Nielsen, Ditte Dencker; Bak-Jensen, Henriette Husum
Retigabine is a novel compound with anticonvulsant efficacy. Preclinical studies have indicated that the compound, like other anticonvulsants may also have antimanic efficacy. Bipolar disorder is characterized by episodes of depression and mania, which show a progressively faster recurrence...
Munkholm, Klaus; Peijs, L; Vinberg, M
as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6-12-month period and in 40 age......- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with healthy control...... subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver...
Baandrup, Lone; Jennum, Poul Jørgen
PURPOSE: Sleep disturbances are frequent in patients with schizophrenia or bipolar disorder. Actigraphy has been established as a generally reliable method to examine these disturbances across varying time spans, but the validity against polysomnography (PSG) is not well investigated...... for this population. We validated wrist-worn actigraphy against PSG in a population of chronic, medicated patients with schizophrenia or bipolar disorder. PATIENTS AND METHODS: From a clinical trial, we derived data from 37 patients with schizophrenia and five patients with bipolar disorder who were examined with one...... for the number of awakenings, and low or zero for the other examined sleep variables. These findings were reproduced in the subgroup analyses that compared men and women, as well as patients with bipolar versus schizophrenia spectrum disorders. When excluding patients with extensive periods of wakefulness after...
Full Text Available Jean-Michel Azorin1, Charles L Bowden2, Ricardo P Garay3, Giulio Perugi4, Eduard Vieta5, Allan H Young61Department of Psychiatry, CHU Sainte Marguerite, Marseilles, France; 2Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA; 3CNRS-UMR 8162, Université Paris-Sud, and Hôpital Marie Lannelongue, Le Plessis-Robinson, France; 4Vincent P Dole Dual Diagnosis Team, Santa Chiara and University Hospital, Department of Psychiatry, University of Pisa, Italy; 5Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBER -SAM, Barcelona, Spain; 6Institute of Mental Health, University of British Columbia, Vancouver, CanadaAbstract: About half of all bipolar patients have an alcohol abuse problem at some point of their lifetime. However, only one randomized, controlled trial of pharmacotherapy (valproate in this patient population was published as of 2006. Therefore, we reviewed clinical trials in this indication of the last four years (using mood stabilizers, atypical antipsychotics, and other drugs. Priority was given to randomized trials, comparing drugs with placebo or active comparator. Published studies were found through systematic database search (PubMed, Scirus, EMBASE, Cochrane Library, Science Direct. In these last four years, the only randomized, clinically relevant study in bipolar patients with comorbid alcoholism is that of Brown and colleagues (2008 showing that quetiapine therapy decreased depressive symptoms in the early weeks of use, without modifying alcohol use. Several other open-label trials have been generally positive and support the efficacy and tolerability of agents from different classes in this patient population. Valproate efficacy to reduce excessive alcohol consumption in bipolar patients was confirmed and new controlled studies revealed its therapeutic benefit to prevent relapse in newly abstinent alcoholics and to improve alcohol hallucinosis. Topiramate
Wang, Ke-Sheng; Liu, Xue-Feng; Aragam, Nagesh
Schizophrenia and bipolar disorder both have strong inherited components. Recent studies have indicated that schizophrenia and bipolar disorder may share more than half of their genetic determinants. In this study, we performed a meta-analysis (combined analysis) for genome-wide association data of the Affymetrix Genome-Wide Human SNP array 6.0 to detect genetic variants influencing both schizophrenia and bipolar disorder using European-American samples (653 bipolar cases and 1034 controls, 1172 schizophrenia cases and 1379 controls). The best associated SNP rs11789399 was located at 9q33.1 (p=2.38 × 10(-6), 5.74 × 10(-4), and 5.56 × 10(-9), for schizophrenia, bipolar disorder and meta-analysis of schizophrenia and bipolar disorder, respectively), where one flanking gene, ASTN2 (220kb away) has been associated with attention deficit/hyperactivity disorder and schizophrenia. The next best SNP was rs12201676 located at 6q15 (p=2.67 × 10(-4), 2.12 × 10(-5), 3.88 × 10(-8) for schizophrenia, bipolar disorder and meta-analysis, respectively), near two flanking genes, GABRR1 and GABRR2 (15 and 17kb away, respectively). The third interesting SNP rs802568 was at 7q35 within CNTNAP2 (p=8.92 × 10(-4), 1.38 × 10(-5), and 1.62 × 10(-7) for schizophrenia, bipolar disorder and meta-analysis, respectively). Through meta-analysis, we found two additional associated genes NALCN (the top SNP is rs2044117, p=4.57 × 10(-7)) and NAP5 (the top SNP is rs10496702, p=7.15 × 10(-7)). Haplotype analyses of above five loci further supported the associations with schizophrenia and bipolar disorder. These results provide evidence of common genetic variants influencing schizophrenia and bipolar disorder. These findings will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in schizophrenia and bipolar disorder.
Munafò, M R; Kempton, M J
There has been extensive discussion of problems of reproducibility of research. Analytical flexibility may contribute to this, by increasing the likelihood that a reported finding represents a chance result. We explored whether analytical flexibility has increased over time, using human imaging studies of bipolar disorder and major depression. Our results indicate that the number of measures collected per study has increased over time for studies of bipolar disorder, but not for studies of major depression.
Shital S Muke
Full Text Available Background: Marital adjustment is considered as a part of social well-being. Disturbed marital relationship can directly affect the disease adjustment and the way they face disease outcomes and complications. It may adversely affect physical health, mental health, the quality-of-life and even economic status of individuals. Aim: The aim of this study was to compare the marital adjustment among patients with substance dependence, schizophrenia and bipolar affective disorder. Materials and Methods: The sample consisted of each 30 patients with substance dependence, bipolar affective disorder and schizophrenia, diagnosed as per international classification of diseases-10 diagnostic criteria for research with a minimum duration of illness of 1 year were evaluated using marital adjustment questionnaire. The data was analyzed using parametric and non-parametric statistics. Results: Prevalence of poor marital adjustment in patients with schizophrenia, bipolar affective disorder and substance dependence was 60%, 70% and 50% respectively. There was a significant difference on overall marital adjustment among substance dependence and bipolar affective disorder patients. There was no significant difference on overall marital adjustment among patients with substance dependence and schizophrenia as well as among patients with schizophrenia and bipolar affective disorder. On marital adjustment domains, schizophrenia patients had significantly poor sexual adjustment than substance dependence patients while bipolar affective disorder patients had significantly poor sexual and social adjustment compared with substance dependence patients. Conclusion: Patients with substance dependence have significant better overall marital adjustment compared with bipolar affective disorder patients. Patients with substance dependence have significantly better social and sexual adjustment than patients with bipolar affective disorder as well as significantly better sexual
Background Intellectual ability may be an endophenotypic marker for bipolar disorder. Aims Within a large birth cohort, we aimed to assess whether childhood IQ (including both verbal IQ (VIQ) and performance IQ (PIQ) subscales) was predictive of lifetime features of bipolar disorder assessed in young adulthood. Method We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large UK birth cohort, to test for an association between measures of childhood IQ at age 8 yea...
Mannu, Piero; Rinaldi, Salvatore; Fontani, Vania; Castagna, Alessandro
Background: The bipolar spectrum disorders are considered an important and frequent psychiatric problem. The clinical complexity of these illnesses due to the coexistence of depressive and excitative phases is correlated with the global difficulty of adequate treatment; consequently, the prognosis is not optimal. For this reason, in recent years, novel nonpharmacologic physical approaches have been tested for bipolar disorders, with encouraging results. The aim of this study was to evaluate t...
Drancourt, Noëmie; Etain, Bruno; Lajnef, Mohamed; Henry, Chantal; Raust, Aurélie; Cochet, Barbara; Mathieu, Flavie; Gard, Sébastien; M'Bailara, Katia; Zanouy, L.; Kahn, Jean-Pierre; Cohen, Renaud,; Wajsbrot-Elgrabli, O.; Leboyer, Marion; SCOTT, J.
International audience; OBJECTIVE: Duration of untreated illness represents a potentially modifiable component of any diagnosis-treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically defined or not been applied to large clinically representative samples. METHOD: In a well-characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood ...
Leila Ahmadi; Seyyed Reza Kazeminezhad; Niloufar Khajehdin; Mehdi Pourmehdi-Boroujeni; Parisima Behbahani
Background: Schizophrenia and bipolar disorder are common and often destructive brain disorders. It has generally been assumed that dozens of genes, along with environmental factors, contribute to the development of these diseases. Schizophrenia and bipolar mood disorder affect many families simultaneously. This theme suggests that these disorders have a shared genetic etiology at least to some extent. The DAOA/G72 gene is one of the common loci shared both by schizophrenia and bipolar disord...
Full Text Available Prashant Gajwani1, David J Muzina2, David E Kemp3, Keming Gao1, Joseph R Calabrese11Case Western Reserve University (CWRU School of Medicine, 2Cleveland Clinic Lerner College of Medicine of CWRU, 3Case Western Reserve University, Cleveland OH, USAAbstract: The essential features of bipolar affective disorder involve the cyclical occurrence of high (manic or hypomanic episodes and low mood states. Depressive episodes in both bipolar I and II disorder are more numerous and last for longer duration than either manic or hypomanic episodes. In addition depressive episodes are associated with higher morbidity and mortality. While multiple agents, including all 5 atypical antipsychotics, have demonstrated efficacy and earned US FDA indication for manic phase of bipolar illness, the acute treatment of bipolar depression is less well-studied. The first treatment approved by the US FDA for acute bipolar depression was the combination of the atypical antipsychotic olanzapine and the antidepressant fluoxetine. Recently, quetiapine monotherapy has demonstrated efficacy in the treatment of depressive episodes associated with both bipolar I and II disorder and has earned US FDA indication for the same.Keywords: bipolar disorder, quetiapine, BOLDER studies
Rapinesi, Chiara; Del Casale, Antonio; Serata, Daniele; Caccia, Federica; Di Pietro, Simone; Scatena, Paola; Carbonetti, Paolo; Fensore, Claudio; Angeletti, Gloria; Tatarelli, Roberto; Kotzalidis, Georgios D; Girardi, Paolo
A 41-year-old man with comorbid binge-eating disorder, severe obesity, and bipolar disorder since the age of 20 years, resistant to drug and psychotherapy combinations, worsened progressively. Relentless weight gain forced him to immobility and dependence on others. He was hospitalized for a mixed-mood episode with anxiety, mystical delusions, and auditory hallucinations. To overcome treatment resistance, we suggested electroconvulsive therapy. After 1 electroconvulsive therapy cycle, psychological symptoms promptly improved. He received clozapine and lithium. After 2 years, he reached normal weight and fair psychopathological compensation.
Bobo, William V; Reilly-Harrington, Noreen A; Ketter, Terence A; Brody, Benjamin D; Kinrys, Gustavo; Kemp, David E; Shelton, Richard C; McElroy, Susan L; Sylvia, Louisa G; Kocsis, James H; McInnis, Melvin G; Friedman, Edward S; Singh, Vivek; Tohen, Mauricio; Bowden, Charles L; Deckersbach, Thilo; Calabrese, Joseph R; Thase, Michael E; Nierenberg, Andrew A; Rabideau, Dustin J; Schoenfeld, David A; Faraone, Stephen V; Kamali, Masoud
Benzodiazepines are widely prescribed for patients with bipolar disorders in clinical practice, but very little is known about the subtypes of patients with bipolar disorder or aspects of bipolar illness that contribute most to benzodiazepine use. We examined the prevalence of and factors associated with benzodiazepine use among 482 patients with bipolar I or II disorder enrolled in the Bipolar CHOICE study. Eighty-one subjects were prescribed benzodiazepines at study entry and were considered benzodiazepine users. Stepwise logistic regression was used to model baseline benzodiazepine use versus nonuse, using entry and exit criteria of P benzodiazepine users were prescribed a significantly higher number of other psychotropic medications and were more likely to be prescribed lamotrigine or antidepressants as compared with benzodiazepine nonusers. Benzodiazepine users were more likely to have a diagnosis of bipolar I disorder and comorbid anxiety disorder, but not comorbid alcohol or substance use disorders. Benzodiazepine users also had experienced more anxiety and depressive symptoms and suicidality, but not irritability or manic symptoms, than did benzodiazepine nonusers. In the multivariate model, anxiety symptom level (regardless of diagnosis), lamotrigine use, number of concomitant psychotropic medications, college education, and high household income predicted benzodiazepine use. Benzodiazepine use in patients with bipolar disorders is associated with greater illness complexity as indicated by a higher number of concomitant psychotropic medications and higher anxiety symptom burden, regardless of a comorbid anxiety disorder diagnosis. Demographic factors were also important determinants of benzodiazepine use, which may be related to access to care and insurance coverage for benzodiazepines.
双相情感障碍（bipolar disorder，BD）又称心境障碍，目前其发病机制尚不明确。BD 具有遗传性，目前发现一些染色体区域和特定基因与 BD 相关，但尚不能明确这些特定基因的参与或序列变异的发生与 BD 的关系。因此，仍需进行大量研究来进一步探究 BD 遗传方式。%Bipolar disorder is also known as mood disorders and the pathogenesis is unclear until now. Family and twin studies have confirmed the genetics of bipolar disorder. Although the researchers have dis-covered some related chromosomal regions and specific genes,they have not confirmed the relationship be-tween the involvement of any specific gene or sequence variant and the bipolar disorder. The scholars both at home and abroad still needs a lot of studies to explore the genetics of bipolar disorder. We review the re-search status of the genetic of bipolar disorder in this paper.
Johnson, Sheri L; Carver, Charles S
Recent evidence suggests that anger and aggression are of concern even during remission for persons with bipolar I disorder, although there is substantial variability in the degree of anger and aggression across individuals. Little research is available to examine psychological models of anger and aggression for those with remitted bipolar disorder, and that was the goal of this study. Participants were 58 persons diagnosed with bipolar I disorder using the Structured Clinical Interview for DSM-IV, who were followed with monthly symptom severity interviews until they achieved remission, and then assessed using the Aggression-Short Form. We examined traditional predictors of clinical parameters and trauma exposure, and then considered three trait domains that have been shown to be elevated in bipolar disorder and have also been linked to aggression outside of bipolar disorder: emotion-relevant impulsivity, approach motivation, and dominance-related constructs. Emotion-relevant impulsivity was related to anger, hostility, verbal aggression, and physical aggression, even after controlling for clinical variables. Findings extend the importance of emotion-relevant impulsivity to another important clinical outcome and suggest the promise of using psychological models to understand the factors driving aggression and anger problems that persist into remission among persons with bipolar disorder.
Bipolar disorder (or manic-depressive disorder) is a severe mood disorder in which episodes of (hypo) mania (e.g. elevated mood en hyperactivity) and depression (e.g. decreased mood and reduced activity) alternate with periods of normal mood and functioning. Genetic factors as well as environmental
Fernandes, Carla P D; Christoforou, Andrea; Giddaluru, Sudheer
Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals...... and in the dysfunction observed in psychiatric disorders....
Full Text Available Challenges encountered in the diagnosis and treatment of frontotemporal dementia (FTD are further confounded when presented with comorbid psychiatric disorder. Here we report a case of progressive FTD in a patient with a long history of bipolar affective disorder (BAD 1, depressed type. We also report beneficial effects of electroconvulsive therapy and its potential application in similar comorbid disorders.
Liu, Jie; Li, Junyan; Li, Tao; Wang, Ti; Li, You; Zeng, Zhen; Li, Zhiqiang; Chen, Peng; Hu, Zhiwei; Zheng, Lingqing; Ji, Jue; Lin, He; Feng, Guoyin; Shi, Yongyong
Previous studies have reported that the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene, which is related to immunological function such as T-cell regulation, is associated with psychiatric disorders. In this study, we studied the relationship between CTLA-4 and three major psychiatric disorders, schizophrenia, major depressive disorder and bipolar disorder in the Chinese Han population. We recruited 1140 schizophrenia patients, 1140 major depressive disorder patients, 1140 bipolar disorder patients, and 1140 normal controls to examine the risk conferred by 6 tag SNPs (rs231777, rs231775, rs231779, rs3087243, rs5742909, rs16840252) in the CTLA-4 gene. We found that rs231779 conferred a risk for schizophrenia (P(allele)=0.0003, P(genotype)=0.0016), major depressive disorder (P(allele)=0.0006, P(genotype)=0.0026) and bipolar disorder (P(allele)=0.0004, P(genotype)=0.0018). In addition, rs231777 and rs16840252 had a significant association with schizophrenia (rs231777: P(allele)=0.0201, rs16840252: P(allele)=0.0081, P(genotype)=0.0117), and rs231777 had significant association with bipolar disorder (rs231777: P(allele)=0.0199). However, after 10,000 permutations, only rs231779 remained significant (schizophrenia: P(allele)=0.0010, P(genotype)=0.0145, major depressive disorder: P(allele)=0.0010, P(genotype)=0.0201, bipolar disorder: P(allele)=0.0008, P(genotype)=0.0125). Our results suggest that shared common risk factors for schizophrenia, major depressive disorder and bipolar disorder exist in the CTLA-4 gene in the Chinese Han population.
Full Text Available Young-Min Park,1 Bun-Hee Lee2 1Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, 2Department of Psychiatry, Seoul Eunpyeong Hospital, Seoul, Republic of Korea Background: The aim of this observational study was to determine whether subthreshold bipolarity affects treatment response and remission in patients with major depressive disorder receiving antidepressant (AD monotherapy over a 6-month follow-up period. Methods: Seventy-eight patients with major depressive disorder were stratified into two subgroups according to the presence of subthreshold bipolarity, identified using the Korean version of the Mood Disorder Questionnaire (K-MDQ, which classifies patients as positive for a screening of bipolarity based on the cutoff for the total K-MDQ score (ie, 7 points. They received AD monotherapy such as escitalopram, sertraline, paroxetine, or tianeptine for 6 months. The Beck Depression Inventory (BDI, Hamilton Depression Rating Scale (HAMD, Hamilton Anxiety Scale, and Beck Scale for Suicide Ideation were applied at baseline, 1 week, 3 weeks, 2 months, 3 months, and 6 months. Results: The mean HAMD, BDI, and Beck Scale for Suicide Ideation scores were higher in the bipolarity group than in the nonbipolarity group at 3 weeks. The mean BDI score was also higher in the bipolarity group than in the nonbipolarity group at 6 months. Evaluation of the ratio of improvement for each scale revealed different patterns of percentage changes between the two groups over the 6-month follow-up period. Furthermore, the response and remission rates (as assessed using BDI and HAMD scores were higher in the nonbipolarity group than in the bipolarity group, with the exception of HAMD scores at the 3-week follow-up time point. Conclusion: The findings of this study showed that depressed patients with bipolarity had a worse response to AD monotherapy than did those without bipolarity. Keywords: subthreshold bipolarity
Maciukiewicz, Malgorzata; Pawlak, Joanna; Kapelski, Pawel; Łabędzka, Magdalena; Skibinska, Maria; Zaremba, Dorota; Leszczynska-Rodziewicz, Anna; Dmitrzak-Weglarz, Monika; Hauser, Joanna
Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5-1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder.
Elhaik, Eran; Zandi, Peter
A century of investigations enhanced our understanding of bipolar disorder although it remains a complex multifactorial disorder with a mostly unknown pathophysiology and etiology. The role of the immune system in this disorder is one of the most controversial topics in genetic psychiatry. Though inflammation has been consistently reported in bipolar patients, it remains unclear how the immunologic process influences the disorder. One of the core components of the immune system is the NF-κB pathway, which plays an essential role in the development of innate and adaptive immunity. Remarkably, the NF-κB pathway received only little attention in bipolar studies, as opposed to studies of related psychiatric disorders where immune dysregulation has been proposed to explain the neurodegeneration in patient conditions. If immune dysregulation can also explains the neurodegeneration in bipolar disorder, it will underscore the role of the immune system in the chronicity and pathophysiology of the disorder and may promote personalized therapeutic strategies. This is the first review to summarize the current knowledge of the pathophysiological functions of NF-κB in bipolar disorder.
Chen, H; Huo, Y; Patel, S; Zhu, X; Swift-Scanlan, T; Reeves, R H; DePaulo, R; Ross, C A; McInnis, M G
We previously reported linkage between bipolar disorder and a region on human chromosome (HC) 18q21. To identify genes in this region, exon trapping was performed on cosmids isolated from an HC18-specific cosmid library (LL18NC02) using 47 sequence tagged site (STS) markers from 18q21 as hybridization probes. A total of 285 unique sequences (exons) were obtained from 850 sequenced clones. Homology searching of the databases using NCBI's BLAST algorithms revealed that 31 exons have identity to known genes and/or ESTs, seven are identical to regions of finished genomic sequences in the 18q21 region, 20 have significant similarity (>30% sequence identity) to genes from human and/or other species, 19 were repetitive sequences, and 208 sequences (72%) are novel. Seventy per cent of the trapped sequences were predicted to be derived from genes using library screening and RT-PCR analyses. This represents an initial stage in characterizing genes in a susceptibility region for further study in bipolar disorder or other diseases that map to this region.
Sauer, Cathrin; Pfeiffer, Steffi; Bauer, Michael; Pfennig, Andrea
Background. Several studies have described but not formally tested discrepancies between subjective and objective measures of sleep. Study Objectives. To test the hypothesis that patients with bipolar disorder display a systematic bias to underestimate sleep duration and overestimate sleep latency. Methods. Actimetry was used to assess sleep latency and duration in 49 euthymic participants (bipolar = 21; healthy controls = 28) for 5–7 days. Participants simultaneously recorded estimated sleep duration and sleep latency on a daily basis via an online sleep diary. Group differences in the discrepancy between subjective and objective parameters were calculated using t-tests and corrected for multiple comparisons. Results. Patients with bipolar disorder significantly underestimated their sleep duration but did not overestimate their sleep latency compared to healthy controls. Conclusions. Studies utilizing diaries or questionnaires alone in patients with bipolar disorders may systematically underestimate sleep duration compared to healthy controls. The additional use of objective assessment methods such as actimetry is advisable. PMID:27891255
Full Text Available Introduction: It has been shown that bipolar disorder (BD has a direct impact on neurocognitive functioning and behavior. This finding has prompted studies to investigate cognitive enhancement programs as potential treatments for BD, primarily focusing on cognitive reinforcement and daily functioning and not restricted to psychoeducation and coping strategies, unlike traditional psychosocial treatments. Objective: This study presents a systematic review of controlled trials of cognitive rehabilitation (CR for BD. Our main objective is to describe the results of studies of rehabilitation programs for BD and related methodological issues. Method: Electronic database searches (MEDLINE, Web of Science, and Embase were conducted to identify articles using terms related to BD and CR. The methodological quality of each article was measured using the 5-item Jadad scale. Results: A total of 239 articles were initially identified, but after application of exclusion criteria, only four were retained for this review. An average of 17 hours of intervention sessions were conducted, distributed as 0.95 hours per week and three of the four studies reported better executive function performance after CR interventions. Conclusions: We did not find robust evidence to support cognitive rehabilitation as an effective treatment for BD, because of: 1 the variety of intervention designs; 2 the methodological limitations of the studies; and 3 the lack of studies in the field.
Outhred, Tim; Kemp, Andrew H; Malhi, Gin S
Bipolar spectrum disorders (BSDs) are associated with great personal and socioeconomic burden, with patients often facing a delay in detection, misdiagnosis when detected, and a trial-and-error approach to finding the most appropriate treatment. Therefore, improvement in the assessment and management of patients with BSDs is critical. Should valid physiological measures for BSDs be identified and implemented, significant clinical improvements are likely to be realized. This chapter reviews the physiological correlates of BSDs and treatment, and in doing so, examines the neuroimaging, electroencephalogram, and event-related potential, and peripheral physiological correlates that both characterize and differentiate BSDs and their response to treatment. Key correlates of BSDs involve underlying disturbances in prefrontal and limbic network neural activity, early neural processing, and within the autonomic nervous system. These changes appear to be mood-related and can be normalized with treatment. We adopt an "embodied" perspective and propose a novel, working framework that takes into account embodied psychophysiological mechanisms in which the physiological correlates of BSD are integrated. This approach may in time provide the objective physiological measures needed to improve assessment and decision making when treating patients with BSDs. Future research with integrative, multimodal measures is likely to yield potential applications for physiological measures of BSD that correlate closely with diagnosis and treatment.
de Almeida, Karla M; Moreira, Camila L R L; Lafer, Beny
This paper reviews the association between bipolar disorder (BD) and metabolic syndrome (MetS), focusing on the etiopathogenetic and pathophysiological aspects of this association and on the recommendations for preventing and managing MetS in patients with BD. We conducted a nonsystematic literature review by means of a MEDLINE search. The exact causal relationship between MetS and BD is still uncertain. The side effects of psychotropic medications may be a major contributor to the increased rates of MetS in patients with BD. Other factors such as unhealthy lifestyles, common neuroendocrine and immuno-inflammatory abnormalities, and genetic vulnerability may also play a role in explaining the high rates of MetS in BD. Strategies to prevent and treat the MetS and its cardiovascular consequences in patients with BD include accurate screening and monitoring of the patient and appropriate psychoeducation on weight control, healthy nutrition, and increased physical activity. When deciding on pharmacological therapy for the treatment of the components of the MetS, drug interactions and the effects of the medications on mood must be taken into account.
Full Text Available Background. The prevalence of psychiatric disturbance for patients with multiple sclerosis (MS is higher than that observed in other chronic health conditions. We report three cases of MS and bipolar disorder and we discuss the possible etiological hypothesis and treatment options. Observations. All patients fulfilled the McDonald criteria for MS. Two patients were followed up in psychiatry for manic or depressive symptoms before developing MS. A third patient was diagnosed with MS and developed deferred psychotic symptoms. Some clinical and radiological features are highlighted in our patients: one manic episode induced by high dose corticosteroids and one case of a new orbitofrontal MRI lesion concomitant with the emergence of psychiatric symptoms. All patients needed antipsychotic treatment with almost good tolerance for high dose corticosteroids and interferon beta treatment. Conclusions. MRI lesions suggest the possible implication of local MS-related brain damage in development of pure “psychiatric fits” in MS. Genetic susceptibility is another hypothesis for this association. We have noticed that interferon beta treatments were well tolerated while high dose corticosteroids may induce manic fits.
Izabela Guimarães Barbosa
Full Text Available INTRODUCTION: Bipolar disorder (BD is a prevalent, chronic and progressive illness. There is a growing body of evidence indicating that brain-derived neurotrophic factor (BDNF plays an important role in the pathophysiology of BD. OBJECTIVE: The aim of this study was to evaluate BDNF plasma levels in BD patients with long term illness in comparison with controls. METHODS: 87 BD type I patients and 58 controls matched by age, gender and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of BDNF were measured by ELISA. RESULTS: On average, patients had suffered from BD for 23.4 years. In comparison with controls, BD patients with mania presented a 1.90-fold increase in BDNF plasma levels (p = .001, while BD patients in remission presented a 1.64-fold increase in BDNF plasma levels (p = .03. BDNF plasma levels were not influenced by age, length of illness or current medications. CONCLUSIONS: The present study suggests that long-term BD patients exhibit increased circulating levels of BDNF.
Alsuwaidan, Mohammad T; Kucyi, Aaron; Law, Candy W Y; McIntyre, Roger S
Extant evidence indicates that individuals with bipolar disorder (BD) are differentially affected by overweight/obesity and abdominal obesity. Excess weight is associated with a more complex illness presentation, non-recovery, and recurrence. Herein, we sought to review literature describing the effects of structured individualized physical exercise on disparate neurobiological substrates implicated in the pathophysiology of BD. We conducted a PubMed search of all English-language articles published between 1966 and July 2008 with BD cross-referenced with the following search terms: exercise, neurobiology, pathophysiology, pathoetiology, brain, cognition, neuroplasticity, and neurodegeneration. Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality. Contemporary models of disease pathophysiology in BD implicate disturbances in cellular resilience, plasticity, and survival in the central nervous system. Individualized exercise interventions are capable of alleviating the severity of affective and cognitive difficulties in heterogeneous samples. It is posited that exercise is a pleiotropic intervention that engages aberrant neurobiological systems implicated in metabolism, immuno-inflammatory function, and cellular respiration. Structured exercise regimens exert a salutary effect on interacting networks mediating metabolism, immuno-inflammatory function, and cellular respiration. In keeping this view, buttressed by controlled evidence describing robust anti-depressant effects with exercise (e.g., public health dose), a testable hypothesis is that structured exercise is capable of improving psychiatric and somatic health in BD.
Pettorruso, Mauro; De Risio, Luisa; Di Nicola, Marco; Martinotti, Giovanni; Conte, Gianluigi; Janiri, Luigi
Bipolar disorders (BDs) and addictions constitute reciprocal risk factors and are best considered under a unitary perspective. The concepts of allostasis and allostatic load (AL) may contribute to the understanding of the complex relationships between BD and addictive behaviors. Allostasis entails the safeguarding of reward function stability by recruitment of changes in the reward and stress system neurocircuitry and it may help to elucidate neurobiological underpinnings of vulnerability to addiction in BD patients. Conceptualizing BD as an illness involving the cumulative build-up of allostatic states, we hypothesize a progressive dysregulation of reward circuits clinically expressed as negative affective states (i.e., anhedonia). Such negative affective states may render BD patients more vulnerable to drug addiction, fostering a very rapid transition from occasional drug use to addiction, through mechanisms of negative reinforcement. The resulting addictive behavior-related ALs, in turn, may contribute to illness progression. This framework could have a heuristic value to enhance research on pathophysiology and treatment of BD and addiction comorbidity. PMID:25520673
Goghari, Vina M; Sponheim, Scott R
Schizophrenia has been reliably associated with impairments in backward masking performance, while bipolar disorder has less consistently been tied to such a deficit. To examine the genetic determinants of visual perception abnormalities in schizophrenia and bipolar disorder, this study evaluated the diagnostic specificity of backward masking performance deficits and whether masking deficits were associated with catechol-O-methyl transferase (COMT) genotype. A location-based backward masking task, which equated participants on the perceptual intensity of stimuli, was completed by 41 schizophrenia outpatients, 28 bipolar outpatients, and 43 nonpsychiatric controls. COMT genotype data were available for 39 schizophrenia outpatients, 28 bipolar outpatients, and 20 nonpsychiatric controls. Schizophrenia patients demonstrated impaired backward masking performance compared to controls and bipolar patients. A group by COMT genotype interaction was detected with schizophrenia Met homozygotes performing more poorly than control and bipolar Met homozygotes, and worse than Val homozygote and heterozygote schizophrenia patients. This study provides novel evidence for differential effects of the COMT gene on neural systems underlying visual perception in schizophrenia and bipolar disorder. The COMT Met allele may be associated with deficits in schizophrenia that are unrelated to neural systems supporting sustained attention or working memory.
Yingli Zhang; Huan Yang; Shichang Yang; Wei Liang; Ping Dai; Changhong Wang; Yalin Zhang
OBJECTIVE: To examine the efficacy and safety of short-term and long-term use of antidepres-sants in the treatment of bipolar disorder. DATA SOURCES:A literature search of randomized, double-blind, control ed trials published until December 2012 was performed using the PubMed, ISI Web of Science, Medline and Cochrane Central Register of Control ed Trials databases. The keywords“bipolar disorder, bipolar I disorder, bipolar II disorder, bipolar mania, bipolar depression, cyclothymia, mixed mania and depression, rapid cycling and bipolar disorder”, AND “antidepressant agent, antidepressive agents second-generation, antidepressive agents tricyclic, monoamine oxidase inhibitor, noradrenaline uptake in-hibitor, serotonin uptake inhibitor, and tricyclic antidepressant agent” were used. The studies that were listed in the reference list of the published papers but were not retrieved in the above-mentioned databases were supplemented. STUDY SELECTION: Studies selected were double-blind randomized control ed trials assessing the efficacy and safety of antidepressants in patients with bipolar disorder. Al participants were aged 18 years or older, and were diagnosed as having primary bipolar disorder. Antidepressants or antidepressants combined with mood stabilizers were used in experimental interventions. Placebos, mood stabilizers, antipsychotics and other antide pressants were used in the control interventions. Studies that were quasi-randomized studies, or used antidepressants in combination with antipsy-chotics in the experimental group were excluded. Al analyses were conducted using Review Man-ager 5.1 provided by the Cochrane Col aboration. MAIN OUTCOME MEASURES:The primary outcome was the response and switching to mania. The secondary outcomes included remission, discontinuation rate, and suicidality. RESULTS: Among 5 001 treatment studies published, 14 double-blind randomized control ed trials involving 1 244 patients were included in the meta
Ruderfer, D M; Fanous, A H; Ripke, S
Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study...... (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L...
Seyed Ali Ahmadi Abhari
Full Text Available Objective: Bipolar spectrum disorders may often go undiagnosed or unrecognized. The aim of this study was to determine the proportion of bipolar disorder symptoms in Iranian patients with a major depressive episode.Methods: 313 patients with a current DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders 4th ed. Text rev. diagnosed with a major depressive episode entered this cross-sectional study. Thirty two items revised Hypomania/ mania Symptoms Checklist (HCL-32 was used to determine the frequency of bipolar episodes.Results: Considerable proportion of patients (53.9% previously diagnosed as major depressive disorder fulfilled the criteria for bipolar disorder by Bipolarity Specifier. The Bipolarity Specifier additionally identified significant association for manic / hypomanic states during antidepressants therapy (p<0.0003 and current mixed mood symptoms (p<0.0001Conclusion: Bipolar symptoms meeting the criteria for bipolar disorders in depressed patients who have not been previously diagnosed with bipolar disorder are frequent. Current DSM criteria may not be sufficient to diagnose more subtle or atypical forms of bipolar disorders.
Bipolar disorder continues to be underrecognized, despite being known for 2000 years. Mania, the fullest expression of the disease affects approximately 1% of the population; the less-than-manic forms of the disease dominated by depressive episodes have recently been found to be more common, affecting 4-5% of the population. In reviewing the international literature on this broadened bipolar spectrum, this paper pays particular tribute to the French EPIDEP and EPIMAN studies and Italo-American collaboration which have generated the largest set of systematic data on the new clinical portrait of bipolar disorders. Early detection is crucial, because untreated bipolar disorder has a high mortality rate. A review of the diagnostic criteria for the various subtypes of bipolar disorder has identified several factors that interfere with making an accurate diagnosis. These include age at onset, ethnic differences, co-morbidity (particularly substance abuse and alcoholism), and the broad range of clinical presentations. Moreover, symptoms frequently overlap with those of other psychiatric disorders including schizophrenia, attention-deficit disorder and personality disorders. Misdiagnosis is a major factor leading to a poor outcome for patients. Accurate identification and diagnosis of the different forms of mania can lead to specific treatment choices that may improve prognosis. Particularly important are recent data indicating reduced mortality with a variety of psychopharmacologic agents including, but not limited to, lithium and valproate.
Full Text Available Background. Evaluation of family system is an important area in the context of child and adolescent mental health. This study aimed to estimate psychiatric disorders in parents of children and adolescents with bipolar I disorder (BID. Methods and Materials. In this cross-sectional study, during 2012-2013, all of the children and adolescents diagnosed with BID based on Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version were included. All of the parents (both mother and father were evaluated by Structured Clinical Interview for DSM-IV-TR. Statistical Analysis. Prevalence rates are reported and independent-sample t-test and chi-square test were used when appropriate. Results. A total of 108 families were interviewed. 25% of mothers and 33% of fathers met the criteria for at least one psychiatric disorder, with major depressive disorder, BMD, and cluster B personality disorder being more prevalent. Fathers were more likely to receive a dual psychiatric diagnosis. Cluster B personality disorder and substance dependence were more prevalent among fathers while major depressive disorder was more prevalent among mothers. Conclusion. This study confirmed a higher prevalence of psychiatric disorders in parents of children with BID and emphasizes parental evolution.
Miskowiak, Kamilla W; Vinberg, Maj; Harmer, Catherine J
depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission. METHODS/DESIGN: The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission......BACKGROUND: Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus...... a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive...
Gaudiano, Brandon A.; Weinstock, Lauren M.; Miller, Ivan W.
Treatment adherence is a frequent problem in bipolar disorder, with research showing that more than 60% of bipolar patients are at least partially nonadherent to medications. Treatment nonadherence is consistently predictive of a number of negative outcomes in bipolar samples, and the discontinuation of mood stabilizers places these patients at…
Vreeker, A.; Boks, M. P M; Abramovic, L.; Verkooijen, S.; Van Bergen, A. H.; Hillegers, M. H J; Spijker, A. T.; Hoencamp, E.; Regeer, E. J.; Riemersma-Van Der Lek, R. F.; Stevens, A. W M M; Schulte, P. F J; Vonk, R.; Hoekstra, R.; Van Beveren, N. J M; Kupka, R. W.; Brouwer, R. M.; Bearden, C. E.; MacCabe, J. H.; Ophoff, R. A.
Background Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relative
Full Text Available Background Drug addiction, obsessive compulsive disorders (OCD, and other anxiety disorders are the disorders most commonly found in patients with bipolar disorder. Objectives The purpose of this study was to identify the factors affecting the risk of drug addiction, obsessive compulsive disorders, and other anxiety disorders in patients with bipolar disorder. Patients and Methods In this retrospective cohort study, the medical records of 400 patients with bipolar disorder hospitalized in Hamadan, Iran, between 2008 and 2014 were examined. Patient information, including demographic characteristics and comorbidity, was collected. A data analysis was performed using a separate logistic regression for each disorder. The statistical package used was STATA software version 11. A P-value of less than 0.05 was considered statistically significant. Results The mean (SD age of the patients with bipolar disorder was 34.62 (1.68 years. Of the 400 patients with bipolar disorder, 135 (33.75% patients had anxiety disorders, 67 (16.8% patients suffered from drug addiction, and 45 (11% patients had OCD. An association was established between drug addiction and OCD, and gender (P ≤ 0.05. The ORs of anxiety disorders, drug addiction, and OCD were 1.05 (95% CI = 0.65 - 1.68, 0.26 (95% CI = 0.10 - 0.63, and 2.33 (95% CI = 1.21 - 4.48 for women, and 0.92 (95% CI = 0.52 - 2.13, 3.01 (95% CI = 1.64 - 5.55, and 0.64 (95% CI = 0.25 - 1.62 for the patients who smoked, respectively. In addition, there was no significant association between the different disorders and age, marital status, history of relapse, and history of suicide. Conclusions The results showed that there was a greater risk of anxiety disorders with bipolar disorder than other disorders. While women with bipolar disorder were at higher risk of anxiety disorders and OCD, men were at greater risk of drug addiction.
Todd, R.D.; Chakraverty, S.; Parsian, A. [Washington Univ. School of Medicine, St. Louis, MO (United States)
A variety of studies have reported possible genetic associations between bipolar affective disorder and different loci using relative risk approaches. An alternative approach is to determine untransmitted genotypes from families selected through a single affected individual. We have used both approaches to test for possible associations between alleles of the dopamine D3 receptor gene and bipolar affective disorder. For relative risk studies, the probands of multiple incidence bipolar affective disorder (n=66) and alcoholism (n=132) families and psychiatric normal controls (n=91) have been compared. Non-transmitted allele approaches have used bipolar affective disorder (n=28) and alcoholic (n=25) probands in which both parents were available for genotyping. Using the Bal I restriction enzyme site polymorphism of Lannfelt, we have found no differences in the allele or genotype frequencies for bipolar or alcoholic probands versus psychiatrically normal controls. In contrast, we have found evidence for an increased frequency of allele 1 and allele 1 containing genotypes in transmitted alleles from bipolar families.
Corrado, Alisa C; Walsh, John P
Close to 3% of the world's population suffers from bipolar disease (I and II). Of this 3%, bipolar disease affects largely women (∼ 3 : 2 compared with men). The median age of diagnosis is 25 in women and even lower in men. A diagnosis of bipolar disease is an expensive psychiatric diagnosis, costing patients more than twice as much money as a diagnosis of unipolar depression. Bipolar I is characterized by one or more manic or mixed episodes, with both mania and depression occurring each day for at least 1 week, whereas bipolar II is characterized by one or more major depressive episode and at least one episode of hypomania. Bipolar I is the more severe diagnosis. A wide range of medications are available to help patients maintain a healthy lifestyle, including lithium, antidepressants, and anticonvulsants. Improved methods for identifying bipolar disease, including a more structured approach and a more complete use of medical records, have increased the rate of diagnosis, especially in children, which underscores the need for innovation in development and in practice of new treatment options for treating bipolar disease. Although lithium has been the 'gold standard' for treating bipolar disorder for decades, new research into other forms of treatment has shown anticonvulsants to be a particularly useful therapy for treating bipolar disease. Anticonvulsants have remarkable mood-stabilization abilities and they do not lead to serious side effects, which increases the tolerability, and consequently, patient adherence to this form of treatment. Recent studies have shown that anticonvulsants improve behavior in bipolar disease by modulating the balance of excitatory and inhibitory synapses through a number of complementary molecular cascades that affect gene expression and cell survival.
Severance, Emily G.; Gressitt, Kristin L.; Yang, Shuojia; Stallings, Cassie R.; Origoni, Andrea E.; Vaughan, Crystal; Khushalani, Sunil; Alaedini, Armin; Dickerson, Faith B.; Yolken, Robert H.
Objectives Immune sensitivity to wheat glutens and bovine milk caseins may affect a subset of individuals with bipolar disorder. Digested byproducts of these foods are exorphins that have the potential to impact brain physiology through action at opioid receptors. Inflammation in the gastrointestinal (GI) tract might accelerate exposure of food antigens to systemic circulation and help explain elevated gluten and casein antibody levels in individuals with bipolar disorder. Methods We measured a marker of GI inflammation, anti-Saccharomyces cerevisiae antibodies (ASCA), in non-psychiatric controls (n=207), bipolar disorder without a recent onset of psychosis (n=226), and bipolar disorder with a recent onset of psychosis (n=38). We compared ASCA levels to antibodies against gluten, casein, EBV, HSV-1, Influenza A, Influenza B, measles, and Toxoplasma gondii. Results Elevated ASCA conferred a 3.5 to 4.4-fold increased odds ratio of disease association (age-, race- and gender-corrected multinomial logistic regressions, p≤0.00001) that was independent of type of medication received. ASCA correlated with food antibodies in both bipolar groups (R2=0.29–0.59, p≤0.0005), and with measles and T. gondii IgG in the recent onset psychosis bipolar disorder group (R2=0.31–0.36, p≤0.004–0.01). Conclusions Elevated seropositivity of a GI-related marker and its association with antibodies to food-derived proteins and self-reported GI symptoms suggests a GI comorbidity in at least a subgroup of individuals with bipolar disorder. Marker seroreactivity may also represent part of an overall heightened activated immune state inherent to this mood disorder. PMID:24313887
Rachel L. C. Mitchell
Full Text Available Our ability to make sense of information on the potential intentions and dispositions of others is of paramount importance for understanding their communicative intent, and for judging what an appropriate reaction might be. Thus anything that impinges on this ability has the potential to cause significant social impairment, and compromise an individual’s level of functioning. Both bipolar disorder and schizophrenia are known to feature theory of mind impairment. We conducted a theoretical review to determine the extent and types of theory of mind impairment in bipolar disorder, and evaluate their relationship to medication and symptoms. We also considered possible mediatory mechanisms, and set out to discover what else could be learnt about the impairment in bipolar disorder by comparison to the profile of impairment in schizophrenia. The literature established that in bipolar disorder (i some form of theory of mind impairment has been observed in all mood states, including euthymia, (ii the form of theory of mind assessed and task used to make the assessment influence the impairment observed, and (iii there might be some relationship to cognitive impairment, although a relationship to standard clinical variables was harder to establish. What also became clear in the literature on bipolar disorder itself was the possible relationship of theory of mind impairment to history of psychotic symptoms. Direct comparative studies including patients with schizophrenia were thus examined, and provided several important directions for future research on the bases of impairment in bipolar disorder. Particularly prominent was the issue of whether theory of mind impairment could be considered a candidate endophenotype for the psychoses, although current evidence suggests this may be premature. The differences in impairment across schizophrenia and bipolar disorder may, however, have genuine differential effects on social functioning and the likely success
Mitchell, Rachel L C; Young, Allan H
Our ability to make sense of information on the potential intentions and dispositions of others is of paramount importance for understanding their communicative intent, and for judging what an appropriate reaction might be. Thus, anything that impinges on this ability has the potential to cause significant social impairment, and compromise an individual's level of functioning. Both bipolar disorder and schizophrenia are known to feature theory of mind impairment. We conducted a theoretical review to determine the extent and types of theory of mind impairment in bipolar disorder, and evaluate their relationship to medication and symptoms. We also considered possible mediatory mechanisms, and set out to discover what else could be learnt about the impairment in bipolar disorder by comparison to the profile of impairment in schizophrenia. The literature established that in bipolar disorder (i) some form of theory of mind impairment has been observed in all mood states, including euthymia, (ii) the form of theory of mind assessed and task used to make the assessment influence the impairment observed, and (iii) there might be some relationship to cognitive impairment, although a relationship to standard clinical variables was harder to establish. What also became clear in the literature on bipolar disorder itself was the possible relationship of theory of mind impairment to history of psychotic symptoms. Direct comparative studies, including patients with schizophrenia, were thus examined, and provided several important directions for future research on the bases of impairment in bipolar disorder. Particularly prominent was the issue of whether theory of mind impairment could be considered a candidate endophenotype for the psychoses, although current evidence suggests that this may be premature. The differences in impairment across schizophrenia and bipolar disorder may, however, have genuine differential effects on social functioning and the likely success of
Pastorello, Bruno F.; Leite, Cláudia da Costa; Henning, Anke; Moreno, Ricardo A.; Garcia Otaduy, Maria Concepción
Objective: Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. Methods: Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm3) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. Results: Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. Conclusion: This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis. PMID:27207914
Full Text Available Abstract Background Manic-depression or bipolar disorder (BD is a multi-faceted illness with an inevitably complex treatment. Methods This article summarizes the current status of our knowledge and practice of its treatment. Results It is widely accepted that lithium is moderately useful during all phases of bipolar illness and it might possess a specific effectiveness on suicidal prevention. Both first and second generation antipsychotics are widely used and the FDA has approved olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole for the treatment of acute mania. These could also be useful in the treatment of bipolar depression, but only limited data exists so far to support the use of quetiapine monotherapy or the olanzapine-fluoxetine combination. Some, but not all, anticonvulsants possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be effective in the treatment of depression but not mania. Antidepressant use is controversial. Guidelines suggest their cautious use in combination with an antimanic agent, because they are supposed to induce switching to mania or hypomania, mixed episodes and rapid cycling. Conclusion The first-line psychosocial intervention in BD is psychoeducation, followed by cognitive-behavioral therapy. Other treatment options include Electroconvulsive therapy and transcranial magnetic stimulation. There is a gap between the evidence base, which comes mostly from monotherapy trials, and clinical practice, where complex treatment regimens are the rule.
Jeffrey R Bishop
Full Text Available Jeffrey R Bishop1,2, Mani N Pavuluri21Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA; 2Department of Psychiatry, Pediatric Mood Disorders Program and Center for Cognitive Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, USAAbstract: Risperidone is a commonly used medication for the treatment of bipolar disorder and schizophrenia in children and adolescents. It has been studied as a monotherapy treatment in early onset schizophrenia and as both monotherapy and combination therapy for pediatric bipolar disorder. Studies to date indicate that risperidone is an effective treatment for positive and negative symptoms of schizophrenia and mania symptoms of bipolar disorder. In young patient populations, side effects such as weight gain, extrapyramidal side effects, and prolactin elevation require consideration when evaluating the risk benefit ratio for individual patients. Here we review published studies of risperidone for the treatment of bipolar disorder and schizophrenia in children and adolescents to provide practitioners with an overview of published data on the efficacy and safety of risperidone in these patient populations.Keywords: risperidone, bipolar disorder, schizophrenia, children, adolescents
Demjaha, Arsime; MacCabe, James H; Murray, Robin M
The debate endures as to whether schizophrenia and bipolar disorder are separate entities or different manifestations of a single underlying pathological process. Here, we argue that this sterile argument obscures the fact that the truth lies somewhere in between. Thus, recent studies support a model whereby, on a background of some shared genetic liability for both disorders, patients with schizophrenia have been subject to additional genetic and/or environmental factors that impair neurodevelopment; for example, copy number variants and obstetric complications are associated with schizophrenia but not with bipolar disorder. As a result, children destined to develop schizophrenia show an excess of neuromotor delays and cognitive difficulties while those who later develop bipolar disorder perform at least as well as the general population. In keeping with this model, cognitive impairments and brain structural abnormalities are present at first onset of schizophrenia but not in the early stages of bipolar disorder. However, with repeated episodes of illness, cognitive and brain structural abnormalities accumulate in both schizophrenia and bipolar disorder, thus clouding the picture.
Takaesu, Yoshikazu; Inoue, Yuichi; Murakoshi, Akiko; Komada, Yoko; Otsuka, Ayano; Futenma, Kunihiro; Inoue, Takeshi
Recent studies have suggested that there are certain pathophysiological relationships between bipolar disorder (BD) and circadian rhythm dysfunction. However, apparently no studies have clarified the prevalence of circadian rhythm sleep-wake disorders (CRSWD) in patients with BD. This study was set out to investigate the prevalence of CRSWD and associated factors in patients with BD. One hundred four euthymic BD outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of BD, and family history of psychiatric disorders and suicide. Severity of BD was assessed by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview, together with sleep logs, according to the International Classification of Sleep Disorders, third edition (ICSD-3). Thirty-five subjects (32.4%) met the criteria for CRSWD. The age at the time of investigation and that at the onset of BD were both lower in the CRSWD group than in the non-CRSWD group. The rates of family history of psychiatric disorders and suicide in the CRSWD group were higher than those in the non-CRSWD group. Multiple logistic regression analysis revealed that the presence of CRSWD was significantly associated with younger onset age of BD and family history of suicide. The prevalence of CRSWD could be quite high in BD patients. Younger onset age of BD and family history of suicide were associated with presence of CRSWD in BD patients. PMID:27442503
Castilla-Puentes, Ruby; Sala, Regina; Ng, Bernardo; Galvez, Juan; Camacho, Alvaro
Anxiety disorders (ADs) are common in youths with bipolar disorder (BD). We examine psychiatric comorbidity, hospitalization, and treatment in youths with versus without AD and rapid cycling (four or more cycles per year). Data from the Integrated Healthcare Information Services cohort were used and included 8129 youths (ages ≤18 years). Prevalence of AD, demographic, type of AD, hospitalization, and use of psychotropics were compared between rapid and nonrapid cycling. Overall, 51% of the youths met criteria for at least one comorbid AD; they were predominantly female and were between 12 and 17 years of age. The most common comorbid ADs were generalized ADs and separation ADs. In the patients with rapid cycling, 65.5%met criteria for comorbid AD. The BD youths with AD were more likely to have major depressive disorders and other comorbid ADs, to be given more psychotropics, and to be hospitalized for depression and medical conditions more often than were those without AD. PMID:24284641
Full Text Available OBJECTIVES: The objective of this article is to discuss the rationale/background for early intervention in bipolar disorder. METHOD: Narrative review. RESULTS: There are often significant delays before the diagnosis of bipolar disorder is made and effective management initiated. Growing evidence from both preclinical and clinical literature points to a clear need for improved early identification and early intervention in bipolar disorder. Increasing efforts are being applied to the identification of those at high risk of onset of bipolar disorder. It is hoped that identification of an early prodrome of illness will allow preventative measures to be taken. CONCLUSIONS: There is a clear rationale for improved early identification and early intervention in bipolar disorder.OBJETIVOS: O objetivo do artigo é discutir os fundamentos para a intervenção precoce no transtorno bipolar. MÉTODO: Revisão narrativa. RESULTADOS: Frequentemente existe um atraso significativo com relação ao momento em que o transtorno bipolar é detectado e o início do tratamento. Evidências crescentes oriundas de estudos pré-clínicos e clínicos apontam para a clara necessidade de melhorar a detecção e o tratamento precoces no transtorno bipolar. Esforços também tem sido direcionados para a identificação de indivíduos em alto risco. Espera-se que a identificação do pródromo do transtorno bipolar permita a instauração de medidas preventivas. CONCLUSÕES: Existem bases claras para o investimento na melhora da detecção e tratamento precoces do transtorno bipolar.
Full Text Available Introduction. Major depressive disorder (MDD and bipolar affective disorder (BAD are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group were included in the study. Patients were recruited in depressive phase (moderate to severe depression. Patients having age outside 18–45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT. Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P=0.031 with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression.
Martini, Thaís; Czepielewski, Letícia Sanguinetti; Fijtman, Adam; Sodré, Leonardo; Wollenhaupt-Aguiar, Bianca; Pereira, Caroline Silveira; Vianna-Sulzbach, Mireia; Goi, Pedro D.; Rosa, Adriane Ribeiro; Kapczinski, Flavio; Kunz, Maurício; Kauer-Sant'Anna, Marcia
Background Bipolar disorder (BD) is a significant cause of functional, cognitive, and social impairment. However, classic studies of functioning and social skills have not investigated how BD may impact behavior on the Internet. Given that the digital age has been changing the way people communicate, this study aims to investigate the pattern of Internet use in patients with BD. Methods This cross-sectional study assessed 30 patients with BD I or II and 30 matched controls. Patients were not in an acute mood episode, according to DSM-IV. A standard protocol examined sociodemographic variables and social behavior on the Internet, assessed by Facebook number of friends (FBN) and lifetime estimated number of offline contacts (social network number, SNN). Results SNN (p<0.001) and FBN (p = 0.036) of patients with BD were significantly lower than those of controls. Also, variables related with Internet use were significantly lower in patients, e.g., close contacts on Facebook (p = 0.021), Internet experience (p = 0.020), and knowledge of terms associated with social networking sites (p = 0.042). Also, patients showed lower rates of the expected pattern of Internet use (based on their age generation), including a poorer knowledge of SNS (p = 0.018) and a lower frequency of Internet use (p = 0.010). Discussion This study suggests that patients with BD show smaller social networks both in real-world settings and on the Internet. Also, patients tend to use the Internet and social networking sites less frequently and show a poorer knowledge of Internet and social media than healthy controls, below the expected for their generation. These significant differences between patients and controls suggest that the effects of BD on social relationships and functioning extend to electronic media. PMID:24244541
Hajek, Tomas; Calkin, Cynthia; Blagdon, Ryan; Slaney, Claire; Uher, Rudolf; Alda, Martin
Type 2 diabetes mellitus (T2DM) damages the brain, especially the hippocampus, and frequently co-occurs with bipolar disorders (BD). Reduced hippocampal volumes are found only in some studies of BD subjects and may thus be secondary to the presence of certain clinical variables. Studying BD patients with abnormal glucose metabolism could help identify preventable risk factors for hippocampal atrophy in BD. We compared brain structure using optimized voxel-based morphometry of 1.5T MRI scans in 33 BD subjects with impaired glucose metabolism (19 with insulin resistance/glucose intolerance (IR/GI), 14 with T2DM), 15 euglycemic BD participants and 11 euglycemic, nonpsychiatric controls. The group of BD patients with IR, GI or T2DM had significantly smaller hippocampal volumes than the euglycemic BD participants (corrected p=0.02) or euglycemic, nonpsychiatric controls (corrected p=0.004). Already the BD subjects with IR/GI had smaller hippocampal volumes than euglycemic BD participants (t(32)=−3.15, p=0.004). Age was significantly more negatively associated with hippocampal volumes in BD subjects with IR/GI/T2DM than in the euglycemic BD participants (F(2, 44)=9.96, p=0.0003). The gray matter reductions in dysglycemic subjects extended to the cerebral cortex, including the insula. In conclusion, this is the first study demonstrating that T2DM or even prediabetes may be risk factors for smaller hippocampal and cortical volumes in BD. Abnormal glucose metabolism may accelerate the age-related decline in hippocampal volumes in BD. These findings raise the possibility that improving diabetes care among BD subjects and intervening already at the level of prediabetes could slow brain aging in BD. PMID:25074491
Maier, Robert; Moser, Gerhard; Chen, Guo-Bo; Ripke, Stephan; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H.R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breen, Gerome; Breuer, René; Bruggeman, Richard; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Cormican, Paul; Corvin, Aiden; Coryell, William H.; Craddock, Nicholas; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Daly, Mark J.; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Devlin, Bernie; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Faraone, Stephen V.; Farmer, Anne E.; Ferrier, I. Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Geschwind, Daniel H.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A.; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Ian; Jones, Lisa; Kähler, Anna K.; Kahn, René S.; Kandaswamy, Radhika; Keller, Matthew C.; Kelsoe, John R.; Kendler, Kenneth S.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Långström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lee, Phil H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A.F.; Maestrini, Elena; Magnusson, Patrik K.E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Mowry, Bryan J.; Muglia, Pierandrea; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Benjamin M.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Nöthen, Markus M.; Nurnberger, John I.; Nwulia, Evaristus A.; Nyholt, Dale R.; O’Donovan, Michael C.; O’Dushlaine, Colm; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Perlis, Roy H.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Posthuma, Danielle; Potash, James B.; Poustka, Fritz; Propping, Peter; Purcell, Shaun M.; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P.; Rietschel, Marcella; Ripke, Stephan; Roeder, Kathryn; Roeyers, Herbert; Rossin, Lizzy; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Sergeant, Joseph A.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Sklar, Pamela; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Smoller, Jordan W.; Sonuga-Barke, Edmund J.S.; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sullivan, Patrick F.; Sutcliffe, James; Szatmari, Peter; Szelinger, Szabocls; Thapar, Anita; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Tzeng, Jung-Ying; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weiss, Lauren A.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wiersma, Durk; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Wray, Naomi R.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zöllner, Sebastian; Coryell, William; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Hultman, Christina M.; Landén, Mikael; Levinson, Douglas F.; Kendler, Kenneth S.; Smoller, Jordan W.; Wray, Naomi R.; Lee, S. Hong
Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk. PMID:25640677
Schultz Jennifer F
Full Text Available Abstract Background Previous research has documented that the symptoms of bipolar disorder are often mistaken for unipolar depression prior to a patient's first bipolar diagnosis. The assumption has been that once a patient receives a bipolar diagnosis they will no longer be given a misdiagnosis of depression. The objectives of this study were 1 to assess the rate of subsequent unipolar depression diagnosis in individuals with a history of bipolar disorder and 2 to assess the increased cost associated with this potential misdiagnosis. Methods This study utilized a retrospective cohort design using administrative claims data from 2002 and 2003. Patient inclusion criteria for the study were 1 at least 2 bipolar diagnoses in 2002, 2 continuous enrollment during 2002 and 2003, 3 a pharmacy benefit, and 4 age 18 to 64. Patients with at least 2 unipolar depression diagnoses in 2003 were categorized as having an incongruent diagnosis of unipolar depression. We used propensity scoring to control for selection bias. Utilization was evaluated using negative binomial models. We evaluated cost differences between patient cohorts using generalized linear models. Results Of the 7981 patients who met all inclusion criteria for the analysis, 17.5% (1400 had an incongruent depression diagnosis (IDD. After controlling for background differences, individuals who received an IDD had higher rates of inpatient and outpatient psychiatric utilization and cost, on average, an additional $1641 per year compared to individuals without an IDD. Conclusions A strikingly high proportion of bipolar patients are given the differential diagnosis of unipolar depression after being identified as having bipolar disorder. Individuals with an IDD had increased acute psychiatric care services, suggesting higher levels of relapses, and were at risk for inappropriate treatment, as antidepressant therapy without a concomitant mood-stabilizing medication is contraindicated in bipolar
Breakspear, Michael; Roberts, Gloria; Green, Melissa J; Nguyen, Vinh T; Frankland, Andrew; Levy, Florence; Lenroot, Rhoshel; Mitchell, Philip B
The emotional and cognitive vulnerabilities that precede the development of bipolar disorder are poorly understood. The inferior frontal gyrus-a key cortical hub for the integration of cognitive and emotional processes-exhibits both structural and functional changes in bipolar disorder, and is also functionally impaired in unaffected first-degree relatives, showing diminished engagement during inhibition of threat-related emotional stimuli. We hypothesized that this functional impairment of the inferior frontal gyrus in those at genetic risk of bipolar disorder reflects the dysfunction of broader network dynamics underlying the coordination of emotion perception and cognitive control. To test this, we studied effective connectivity in functional magnetic resonance imaging data acquired from 41 first-degree relatives of patients with bipolar disorder, 45 matched healthy controls and 55 participants with established bipolar disorder. Dynamic causal modelling was used to model the neuronal interaction between key regions associated with fear perception (the anterior cingulate), inhibition (the left dorsolateral prefrontal cortex) and the region upon which these influences converge, namely the inferior frontal gyrus. Network models that embodied non-linear, hierarchical relationships were the most strongly supported by data from our healthy control and bipolar participants. We observed a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral prefrontal cortex to the inferior frontal gyrus that is unique to the at-risk cohort. Non-specific, non-hierarchical mechanisms appear to compensate for this network disturbance. We thus establish a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control in those at high genetic risk for bipolar disorder.
Jones, Ian R.; Howard, Louise M.
Background Women with bipolar disorder are at increased risk of having a severe episode of illness associated with childbirth. Aims To explore the factors that influence the decision-making of women with bipolar disorder regarding pregnancy and childbirth. Method Qualitative study with a purposive sample of women with bipolar disorder considering pregnancy, or currently or previously pregnant, supplemented by data from an online forum. Data were analysed using thematic analysis. Results Twenty-one women with bipolar disorder from an NHS organisation were interviewed, and data were used from 50 women’s comments via the online forum of the UK’s national bipolar charity. The centrality of motherhood, social and economic contextual factors, stigma and fear were major themes. Within these themes, new findings included women considering an elective Caesarian section in an attempt to avoid the deleterious effects of a long labour and loss of sleep, or trying to avoid the risks of pregnancy altogether by means of adoption or surrogacy. Conclusions This study highlights the information needs of women with bipolar disorder, both pre-conception and when childbearing, and the need for improved training for all health professionals working with women with bipolar disorder of childbearing age to reduce stigmatising attitudes and increase knowledge of the evidence base on treatment in the perinatal period. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:27703792
García de la Orden, Lucía; García Carretero, Rafael
Bipolar disorder is one of the most common, severe and persistent mental disorders. The evaluation of all data and variables related to bipolar disorder is a difficult task, because there is no clear agreement on what should be included in this category. One of the traditional treatments for this disease is the lithium metal that is administered in the form of lithium salt. Lithium has a narrow therapeutic window and there is a significant risk of complications arising from its use, mainly neurological and renal. In the case presented, the preparation of a care plan is described for a patient diagnosed with bipolar disorder who suffered a complication with lithium treatment. To do this, it was decided to use a standardized care plan and later completed it with diagnostic, objectives and interventions to the specific needs of the patient, aimed at achieving optimal levels of independence.
Oedegaard, K. J.; Greenwood, T. A.; Lunde, Asger
Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genomewide linkage studies in BPAD...... that using migraine comorbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with comorbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar...... osome 4 (not co-segregating with BPAD) in a sample of BPAD families with comorbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a gene for the migraine/BPAD phenotype. Together these data suggest that some genes may predispose to both bipolar disorder and migraine....
Tsuchiya, Kenji; Agerbo, Esben; Mortensen, Preben Bo
aimed to explore whether suicide as well as the non-suicidal death of father, mother, or siblings are associated with an increased risk for bipolar disorder, and whether the possible association is modified by the age at which the subject experiences such a death in the family. METHODS: The subjects...... followed until, but not exceeding, the age of 38. CONCLUSION: Early parental, particularly maternal, suicide increases the risk for bipolar disorder in the offspring. Possible explanations include a family history of mental disorders as well as psychosocial factors.......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...
Schoeneman, Thomas J; Putnam, Janel; Rasmussen, Ian; Sparr, Nina; Beechem, Stephanie
Content analysis of three chapters of Jamison's memoir, An Unquiet Mind, shows that depression, mania, and Bipolar Disorder have a common metaphoric core as a sequential process of suffering and adversity that is a form of malevolence and destruction. Depression was down and in, while mania was up, in and distant, circular and zigzag, a powerful force of quickness and motion, fieriness, strangeness, seduction, expansive extravagance, and acuity. Bipolar Disorder is down and away and a sequential and cyclical process that partakes of the metaphors of its component moods. We conclude that metaphors of mood disorders share a number of structural features and are consistent across different authors.
Full Text Available Koichiro Watanabe,1 Eiji Harada,2 Takeshi Inoue,3 Yuka Tanji,2 Toshiaki Kikuchi1 1Department of Neuropsychiatry, Kyorin University, School of Medicine, Tokyo, 2Medical Science, Medicines Development Unit-Japan, Eli Lilly Japan KK, Hyogo, 3Department of Psychiatry, Tokyo Medical University, Tokyo, Japan Abstract: Bipolar disorder is a recurrent and episodic illness. This survey study assessed experiences and identified clinical insights of individuals with bipolar disorder. An Internet-based monitor system database was screened for patients with bipolar disorder in Japan (February and March 2013. Of 1,050 patients, 457 completed surveys, and results were analyzed with descriptive statistics. Approximately one-fourth of respondents were diagnosed with bipolar disorder on their first visit to medical institutions, although the most common initial diagnosis was depression/depressive state (65%. Mean time lag between first-time visit to a medical institution and receipt of correct diagnosis of bipolar disorder was 4 years; one-third of patients experienced more than 5 years of lag time. Three perceived reasons for lapsed time before correct diagnosis were “(patients Did not consider manic symptoms as illness, and did not tell the doctor about them,” “I (patient did not know of bipolar disorder,” and “Lack of communication between my doctor and myself (patient.” Among participants who believed that they were initially incorrectly diagnosed and improperly treated, most experienced socioeconomic problems, such as having long-term inability to work or to study (65%. Sources of encouragement for participants included “To have someone to consult with” (41% followed by having “People around me treat me the same as before” (40%. Individuals with bipolar disorder reported a time lag of many years before accurate diagnosis, and substantial burden imposed by the illness. Encouragement should be provided for individuals to live positively
Lee, Nam Young; Kim, Se Hyun; Cho, Belong; Lee, Yeon Ji; Chang, Jae Seung; Kang, Ung Gu; Kim, Yong Sik; Ahn, Yong Min
Despite growing concerns about the co-morbidity of metabolic syndrome (MetS) and bipolar disorder, few studies have been conducted on this topic in Asian populations. This study examined Korean patients with bipolar disorder to assess its co-morbidity with MetS and to compare the prevalence of MetS in patients with medication for bipolar disorder with that of healthy patients. We used cross-sectional data from the medical records of patients with bipolar disorder who presented to the psychiatric clinic in Seoul National University Hospital between June 2007 and June 2008. The control group, matched for age and gender, was randomly drawn from visitors to the Health Promotion Center at the same hospital during the same period. We compared the prevalence of MetS between these two groups with independent sample t-tests and chi-squared tests. We also calculated the indirectly standardized prevalence ratio (ISPR) with a standardization that used the Fourth Korean National Health and Nutrition Examination Survey (KNHNES, 2007). The prevalence of MetS in patients who took medication for bipolar disorder (N=152) was 27.0%, 25.0% and 25.7%, based on the definitions of the American Heart Association and the National Heart, Lung and Blood Institute's adaptation of the Adult Treatment Panel III (AHA), the National Cholesterol Education Program for Adult Treatment Panel III (ATPIII) and the International Diabetes Federation (IDF), respectively. The present study determined that the prevalence of MetS was significantly higher in patients with bipolar disorder than in the control group; the odds ratios (OR) (95% CI) were 2.44 (1.35-4.40), 2.48 (1.34-4.59) and 2.57 (1.40-4.74), based on the definition of the AHA, ATPIII and IDF, respectively. The ISPR (95% CI) was 1.48 (1.02-1.93), 1.54 (1.05-2.03) and 1.98 (1.36-2.60), respectively. Patients with medications for bipolar disorder showed a significantly higher prevalence of increased waist circumference, elevated triglycerides, and
Gupta, Pavan Kumar; T., Sivakumar; Agarwal, Vivek; Sitholey, Prabhat
Background: Considerable controversy exists regarding clinical presentation, diagnosis, and comorbidities especially with Attention Deficit Hyperactivity Disorder (ADHD), in paediatric Bipolar Disorder (BPD). Aims and objectives: To describe phenomenology and comorbidities of paediatric BPD. Method: 78 Subjects (6-16 years) attending child and…
Lejeune, Simon M. W.
Bipolar disorder is a relatively common mental disorder that often has its onset during the college years. This means that students simultaneously face both the challenge of late adolescent development and the challenge of adapting to a major mental illness. As a further complication, the college environment is not well suited to the kinds of…
Schenkel, Lindsay S.; West, Amy E.; Jacobs, Rachel; Sweeney, John A.; Pavuluri, Mani N.
Background: Impaired profiles of neurocognitive function have been consistently demonstrated among pediatric patients with bipolar disorder (BD), and may aid in the identification of endophenotypes across subtypes of the disorder. This study aims to determine phenotypic cognitive profiles of patients with BD Type I and II. Methods: Subjects (N =…
Haarman, Bartholomeus C.M.; Riemersma -van der Lek, Rixt; de Groot, Jan Cees; Ruhe, Eric; Klein, Hans C; Zandstra, Tjitske E; Burger, Huibert; Schoevers, Robert A.; de Vries, Erik F.J.; Drexhage, Hemmo A; Nolen, Willem A.; Doorduin, Janine
Background: The "monocyte-T-cell theory of mood disorders" regards neuroinflammation, i.e. marked activation of microglia, as a driving force in bipolar disorder. Microglia activation can be visualized in vivo using [C-11]-(R)-PK11195 PET. Indirect evidence suggests the hippocampus as a potential fo
van Enkhuizen, J.
Bipolar disorder (BD) is a severe neuropsychiatric disorder, affecting approximately 2% of the worldwide population. It is characterized by euphoric states of mania and opposite mood states of depression, which are devastating to the patients’ quality of life. Current treatment options are poor and
Jenkins, Melissa M.; Youngstrom, Eric A.; Youngstrom, Jennifer Kogos; Feeny, Norah C.; Findling, Robert L.
Bipolar disorder is frequently clinically diagnosed in youths who do not actually satisfy Diagnostic and Statistical Manual of Mental Disorders (4th ed., text revision; DSM-IV-TR; American Psychiatric Association, 1994) criteria, yet cases that would satisfy full DSM-IV-TR criteria are often undetected clinically. Evidence-based assessment methods…
Liu, Xinmin; Akula, Nirmala; Skup, Martha; Brotman, Melissa A.; Leibenluft, Ellen; McMahon, Francis J.
Objective: Functional magnetic resonance imaging is commonly used to characterize brain activity underlying a variety of psychiatric disorders. A previous functional magnetic resonance imaging study found that amygdala activation during a face-processing task differed between pediatric patients with bipolar disorder (BD) and healthy controls. We…
Kilbourne, Amy M.; Farmer, Carrie; Welsh, Deborah; Pincus, Harold Alan; Lasky, Elaine; Perron, Brian; Bauer, Mark S.
Objective We implemented a set of processes of care measures for bipolar disorder that reflect psychosocial, patient preference, and continuum of care approaches to mental health, and examined whether veterans with bipolar disorder receive care concordant with these practices. Method Data from medical record reviews were used to assess key processes of care for 433 VA mental health outpatients with bipolar disorder. Both composite and individual processes of care measures were operationalized. Results Based on composite measures, 17% had documented assessment of psychiatric symptoms (e.g., psychotic, hallucinatory), 28% had documented patient treatment preferences (e.g., reasons for treatment discontinuation), 56% had documented substance abuse and psychiatric comorbidity assessment, and 62% had documentation of adequate cardiometabolic assessment. No-show visits were followed up 20% of the time and monitoring of weight gain was noted in only 54% of the patient charts. In multivariate analyses, history of homelessness (OR=1.61; 95% CI=1.05-2.46) and nonwhite race (OR=1.74; 95%CI=1.02-2.98) were associated with documentation of psychiatric symptoms and comorbidities, respectively. Conclusions Only half of patients diagnosed with bipolar disorder received care in accordance with clinical practice guidelines. High quality treatment of bipolar disorder includes not only adherence to treatment guidelines but also patient-centered care processes. PMID:21112457
Full Text Available Itaru Miura,1,2 Soichi Kono,1 Sachie Oshima,1 Keiko Kanno-Nozaki,1 Hirobumi Mashiko,1 Shin-Ichi Niwa,1 Hirooki Yabe11Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, Japan; 2Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USAAbstract: Misdiagnosis of bipolar disorder is a serious, but not unusual problem for patients. Nevertheless, there are few biomarkers for distinguishing unipolar and bipolar disorder. Near-infrared spectroscopy (NIRS is a noninvasive and useful method for the measurement of hemoglobin concentration changes in the cortical surface area, which enables the assessment of brain function. We measured NIRS and plasma monoamine metabolite levels in a patient with bipolar disorder. A 22-year-old man was admitted due to major depression. At admission, NIRS findings showed oxygenated hemoglobin reincrease in the posttask period, which is characteristic of schizophrenia. After treatment with paroxetine, he became manic with psychotic symptoms. His plasma level of homovanillic acid just before the manic switch was ten times higher than that just after paroxetine initiation. Treatment with lithium and antipsychotics was successful, and plasma homovanillic acid decreased after treatment. In this case, the NIRS findings may predict a possible risk of a manic switch, which is likely induced by paroxetine. NIRS may be able to help distinguish unipolar and bipolar disorder in clinical settings.Keywords: near-infrared spectroscopy, bipolar disorder, homovanillic acid, diagnosis, biomarker
Aldinger, Fanny; Schulze, Thomas G
The etiology and clinical course of bipolar disorder are considered to be determined by genetic and environmental factors. Although the kindling hypothesis emphasizes the impact of environmental factors on initial onset, their connection to the outcome and clinical course have been poorly established. Hence, there have been numerous research efforts to investigate the impact of environmental factors on the clinical course of illness. Our aim is to outline recent research on the impact of environmental determinants on the clinical course of bipolar disorder. We carried out a computer-aided search to find publications on an association between environmental factors, life events, and the clinical course of bipolar disorder. Publications in the reference lists of suitable papers have also been taken into consideration. We performed a narrative overview on all eligible publications. The available body of data supports an association between environmental factors and the clinical course of bipolar disorder. These factors comprise prenatal, early-life, and entire lifespan aspects. Given varying sample sizes and several methodological limitations, the reported quality and extent of the association between environmental factors and the clinical course of bipolar disorder should be interpreted with utmost caution. Systematic longitudinal long-term follow-up trials are needed to obtain a clearer and more robust picture.
Bartoli, Francesco; Crocamo, Cristina; Mazza, Mario Gennaro; Clerici, Massimo; Carrà, Giuseppe
Previous research has hypothesised increased uric acid levels, possibly because of an amplified purinergic metabolism and a reduced adenosine activity, in subjects with bipolar disorder. This systematic review and meta-analysis aimed at estimating if individuals with bipolar disorder had uric acid levels higher than both healthy controls and subjects with major depression (trait marker hypothesis). It also tested if uric acid levels could differ in different phases of bipolar disorder (state marker hypothesis). Meta-analyses were carried out generating pooled standardized mean differences (SMDs), using random-effects models. Heterogeneity between studies was estimated using the I(2) index. Relevant sensitivity and meta-regression analyses were conducted. We searched main Electronic Databases, identifying twelve studies that met our inclusion criteria. Meta-analyses showed increased uric acid levels in individuals with bipolar disorder as compared with both healthy controls (SMD = 0.65, p meta-regression analyses confirmed this association only as compared with healthy controls. Finally, though uric acid levels were higher in manic/mixed phases as compared with depressive ones (SMD = 0.34; p = 0.04, I(2) = 58.8%), a sensitivity analysis did not confirm the association. In sum, our meta-analysis shows that subjects with bipolar disorder have uric acid levels higher than healthy controls. The potential role of factors that might clarify the nature of this association deserves additional research.
Nierenberg, Andrew A.; Sylvia, Louisa G.; Leon, Andrew C.; Reilly-Harrington, Noreen; Shesler, Leah W.; McElroy, Susan L.; Friedman, Edward S.; Thase, Michael E.; Shelton, Richard C.; Bowden, Charles; Tohen, Mauricio; Singh, Vivek; Deckersbach, Thilo; Ketter, Terence; Kocsis, James; McInnis, Melvin G.; Schoenfeld, David; Bobo, William V.; Calabrese, Joseph R.
Background Classic and second generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the “real-world” advantages and disadvantages of these medications Purpose We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This paper outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder. Methods Bipolar CHOICE was a 6-month, multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. This study compares the effectiveness of quetiapine versus lithium, each with adjunctive personalized treatments. The co-primary outcomes selected are the overall benefits and harms of the study medications (as measured by the Clinical Global Impression-Efficacy Index) and the Necessary Clinical Adjustments (a measure of the number of medication changes). Secondary outcomes are continuous measures of mood, the Framingham General Cardiovascular Risk Score and the Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool. Results The final study design consisted of a single-blind, randomized comparative effectiveness trial of quetiapine versus lithium, plus adjunctive personalized treatment (APT), across ten sites. Other important study considerations included limited exclusion criteria to maximize generalizability, flexible dosing of APT medications to mimic real-world treatment, and an intent-to-treat analysis plan. 482 participants were randomized to the study and 364 completed. Limitations The potential limitations of the study include the heterogeneity of APT, selection of study medications, lack of a placebo-control group, and participants’ ability to pay for study medications
Cederlöf, Martin; Lichtenstein, Paul; Larsson, Henrik; Boman, Marcus; Rück, Christian; Landén, Mikael; Mataix-Cols, David
Obsessive-compulsive disorder (OCD) often co-occurs with psychotic and bipolar disorders; this comorbidity complicates the clinical management of these conditions. In this population-based longitudinal and multigenerational family study, we examined the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders. Participants were individuals with a diagnosis of OCD (n = 19,814), schizophrenia (n = 58,336), bipolar disorder (n = 48,180), and schizoaffective disorder (n = 14,904) included in the Swedish Patient Register between January 1969 and December 2009; their first-, second-, and third-degree relatives; and population-matched (1:10 ratio) unaffected comparison individuals and their relatives. The Swedish Prescribed Drug Register was used to control for the potential effect of medication in the longitudinal analyses. Individuals with OCD had a 12-fold increased risk of having a comorbid diagnosis of schizophrenia and a 13-fold increased risk of bipolar disorder and schizoaffective disorder. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for later diagnosis of all other disorders, and vice versa. The risk of bipolar disorder was reduced, but not eliminated, when the use of selective serotonin reuptake inhibitors was adjusted for. OCD-unaffected first-, second-, and third-degree relatives of probands with OCD had a significantly increased risk for all 3 disorders; the magnitude of this risk decreased as the genetic distance increased. We conclude that OCD is etiologically related to both schizophrenia spectrum and bipolar disorders. The results have implications for current gene-searching efforts and for clinical practice.
Kerner, Berit; Jasinska, Anna J; DeYoung, Joseph; Almonte, Maricel; Choi, Oi-Wa; Freimer, Nelson B
We reported previously a significant linkage signal between psychotic bipolar disorder (BP) and microsatellite markers on chromosome 5q31-34 in the National Institute of Mental Health Bipolar Genetics Initiative (NIMH-BPGI) data set, Wave 1. In an attempt to fine-map this linkage signal we genotyped 1,134 single nucleotide polymorphisms (SNPs) under the linkage peak in 23 informative families (131 individuals) with evidence of linkage. We tested family based association in the presence of linkage with the computer software package FBAT. The most significant association in these families was with a SNP in the second intron of GRIA1 (alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) subunit 1 receptor gene) (rs490922, Z-score = 3.3, P = 0.001). The analysis of 37 additional families with psychotic BP from NIMH-BPGI data sets, Waves 2, 3, and 4 revealed a signal at a SNP in intron 5 of the GRIA1 gene (rs4385264, Z-score = 3.2, P-value = 0.002). A combined analysis of all 60 families continued to support evidence for association of GRIA1 with psychotic BP; however, individual SNPs could not be replicated across datasets. The AMPA1 receptor has been shown to influence cognitive function, such as working memory and reward learning. Our findings suggest that variations in this receptor may contribute to the pathophysiology of BP with psychotic features in some families.
Full Text Available Background Children of parents with bipolar disorder appear to have an increased risk of early-onset Bipolar Disorder (BP, mood disorders and other psychiatric disorders. Objectives The aim of this study was to compare the mental health of school-age children of parents, with/without bipolar disorder. Materials and Methods This case-control study included one hundred children aged six to twelve years, who had parents with bipolar disorder and 200 children of 163 demographically-matched control parents. Parents with bipolar disorder were recruited from Farshchian Psychiatric Hospital of Hamadan, Iran, during year 2014. The parent version of the Child Symptom Inventory-4 questionnaire was used to measure mental health. Mean comparisons were performed using Student’s t test while effect sizes were estimated by Cohen’s d coefficient. The Chi-square test was used to assess significant differences between frequency distribution of demographic variables in both groups. The significance level was considered less than 0.05. Results There were statistically significant differences between children of parents with and those without bipolar disorder regarding attention deficit hyperactivity disorder, oppositional defiant disorder, conduct, generalized anxiety disorder, schizophrenia, major depression, separation anxiety (P< 0.001 and social phobia (P < 0.05. Children of parents with BP are at high risk for psychiatric disorders. Conclusions These findings support that the careful evaluation and prospective following of the psychopathology of children of parents with bipolar disorder are critical for early identification and treatment.
Thomsen, Morten Skøtt; Weyn, Annelies; Mikkelsen, Jens D
The α7 nicotinic acetylcholine receptor (nAChR) is involved in cognitive function and synaptic plasticity. Consequently, changes in α7 nAChR function have been implicated in a variety of mental disorders, especially schizophrenia. However, there is little knowledge regarding the levels of the α7 n......AChR in patients with bipolar disorder....
Perugi, Giulio; Fornaro, Michele; Akiskal, Hagop S
The constructs of atypical depression, bipolar II disorder and borderline personality disorder (BPD) overlap. We explored the relationships between these constructs and their temperamental underpinnings. We examined 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features. Those who also met the DSM-IV criteria for BPD (BPD+), compared with those who did not (BPD-), had a significantly higher lifetime comorbidity for body dysmorphic disorder, bulimia nervosa, narcissistic, dependent and avoidant personality disorders, and cyclothymia. BPD+ also scored higher on the Atypical Depression Diagnostic Scale items of mood reactivity, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the Hopkins Symptoms Check List obsessive-compulsive, interpersonal sensitivity, anxiety, anger-hostility, paranoid ideation and psychoticism factors. Logistic regression revealed that cyclothymic temperament accounted for much of the relationship between atypical depression and BPD, predicting 6 of 9 of the defining DSM-IV attributes of the latter. Trait mood lability (among BPD patients) and interpersonal sensitivity (among atypical depressive patients) appear to be related as part of an underlying cyclothymic temperamental matrix.
Full Text Available The Sp4 transcription factor plays a critical role for both development and function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results in a variety of behavioral abnormalities relevant to human psychiatric disorders. The human SP4 gene is therefore examined for its association with both bipolar disorder and schizophrenia in European Caucasian and Chinese populations respectively. Out of ten SNPs selected from human SP4 genomic locus, four displayed significant association with bipolar disorder in European Caucasian families (rs12668354, p = 0.022; rs12673091, p = 0.0005; rs3735440, p = 0.019; rs11974306, p = 0.018. To replicate the genetic association, the same set of SNPs was examined in a Chinese bipolar case control sample. Four SNPs displayed significant association (rs40245, p = 0.009; rs12673091, p = 0.002; rs1018954, p = 0.001; rs3735440, p = 0.029, and two of them (rs12673091, rs3735440 were shared with positive SNPs from European Caucasian families. Considering the genetic overlap between bipolar disorder and schizophrenia, we extended our studies in Chinese trios families for schizophrenia. The SNP7 (rs12673091, p = 0.012 also displayed a significant association. The SNP7 (rs12673091 was therefore significantly associated in all three samples, and shared the same susceptibility allele (A across all three samples. On the other hand, we found a gene dosage effect for mouse Sp4 gene in the modulation of sensorimotor gating, a putative endophenotype for both schizophrenia and bipolar disorder. The deficient sensorimotor gating in Sp4 hypomorphic mice was partially reversed by the administration of dopamine D2 antagonist or mood stabilizers. Both human genetic and mouse pharmacogenetic studies support Sp4 gene as a susceptibility gene for bipolar disorder or schizophrenia. The studies on the role of Sp4 gene in hippocampal development may provide novel insights for the contribution of hippocampal abnormalities in these
Full Text Available Comorbidity of bipolar disorder (BD with attention deficit hyperactivity disorder (ADHD is frequent. The management of comorbid ADHD and BD is complicated by the risk of induction of (hypo mania by the medications used for ADHD treatment. Earlier reports in children and adolescents with ADHD-BD suggest that the possibility of (hypo mania induction is low when atomoxetine is used along mood stabilizers or antipsychotics. Here, we report induction of hypomania by atomoxetine when used for the treatment of comorbid ADHD in a BD patient while on prophylactic treatment with mood stabilizers. This report indicates that atomoxetine carries the risk of induction of (hypo mania even in stabilized BD patients. Clinicians should closely monitor such patients for (hypo mania symptoms.
Castagnini, Augusto; Foldager, Leslie; Bertelsen, Aksel
cardiovascular, digestive, neoplastic and respiratory diseases. Suicide was the major cause of premature death in patients with ATPDs. Conclusion: These findings suggest that ATPDs are associated with an increased mortality from both natural causes and suicide.......Objective: To investigate mortality and causes of death of short-lived psychotic disorders, by carrying out a comparison with bipolar disorder and schizophrenia. Method: Record linkage study to the official register of causes of death of all cases aged 15–64 years who were listed for the first time.......1%) with schizophrenia had died over a mean follow-up period of 6.6 years. The standardized mortality ratio for all causes, natural causes and unnatural causes was significantly high for the three conditions. Mortality of ATPDs was greater in men, with about two-thirds of all deaths resulting from natural causes mainly...
Kumar, Vijaya; Varambally, Shivarama
Comorbidity of bipolar disorder (BD) with attention deficit hyperactivity disorder (ADHD) is frequent. The management of comorbid ADHD and BD is complicated by the risk of induction of (hypo) mania by the medications used for ADHD treatment. Earlier reports in children and adolescents with ADHD-BD suggest that the possibility of (hypo) mania induction is low when atomoxetine is used along mood stabilizers or antipsychotics. Here, we report induction of hypomania by atomoxetine when used for the treatment of comorbid ADHD in a BD patient while on prophylactic treatment with mood stabilizers. This report indicates that atomoxetine carries the risk of induction of (hypo) mania even in stabilized BD patients. Clinicians should closely monitor such patients for (hypo) mania symptoms.
The role of stimulants for treating severe depression remains controversial, especially when it comes to bipolar depression. Potential benefits have to be weighed against risks, including addictive potential and treatment-emergent mania. But not all stimulants are the same. Modafinil and its R-enantiomer armodafinil seem to have positive augmentation effects when coupled with standard treatment of bipolar depression, while also having a relative low risk of addiction and manic switches. A recent hypothesis derived from the observation of hypovigilance in manic patients postulates that modafinil may also have a beneficial effect in reducing manic behaviors. Further controlled studies are needed to clarify the benefits and risks of stimulants, both in bipolar depression and mania.
Vonk, R; van der Schot, A C; van Baal, G C M; van Oel, C J; Nolen, W A; Kahn, R S
Palmar and finger dermatoglyphics are formed between the 10th and the 17th weeks of gestation and their morphology can be influenced by genetic or environmental factors, interfering with normal intrauterine development. As both the skin and the brain develop from the same embryonal ectoderm, dermatoglyphic alterations may be informative for early abnormal neurodevelopmental processes in the brain. We investigated whether dermatoglyphic alterations are related to structural brain abnormalities in bipolar disorder and to what extent they are of a genetic and of an environmental origin. Dermatoglyphics and volumetric data from structural MRI were obtained in 53 twin pairs concordant or discordant for bipolar disorder and 51 healthy matched control twin pairs. Structural equation modeling was used. Bipolar disorder was significantly positively associated with palmar a-b ridge count (ABRC), indicating higher ABRC in bipolar patients (rph=.17 (CI .04-.30)). Common genes appear to be involved because the genetic correlation with ABRC was significant (rph-A=.21 (CI .05-.36). Irrespective of disease, ABRC showed a genetically mediated association with brain volume, indicated by a significant genetic correlation rph-A of respectively -.36 (CI -.52 to -.22) for total brain, -.34 (CI -.51 to -.16) total cortical volume, -.27 (CI -.43 to -.08) cortical gray matter and -.23 (CI -.41 to -.04) cortical white matter. In conclusion, a genetically determined abnormal development of the foetal ectoderm between the 10th and 15th week of gestation appears related to smaller brain volumes in (subjects at risk for) bipolar disorder.
Rafael de Assis da Silva
Full Text Available Objective: To evaluate whether having general insight into bipolar disorder and its symptoms is affected by the mood state of the patient, using the Insight Scale for Affective Disorders, a hetero-application scale for people with mood disorders.Methods: Ninety-five patients with bipolar disorder were evaluated and divided into different groups according to the mood state presented during assessment (i.e., euthymia, mania and depression. Sociodemographic and clinical data (Hamilton Depression Scale, Young Mania Rating Scale, and Clinical Global Impressions Scale were recorded. Insight was evaluated using the Insight Scale for Affective Disorders.Results: Patients with bipolar disorder in mania show less insight about their condition than patients in depression or euthymia, and less insight about their symptoms than patients with depression, with the exception of awareness of weight change.Conclusions: Loss of insight during mania may have important implications for treatment compliance and adherence and needs to be taken into account in the clinical management of people with bipolar disorder.
Full Text Available The production of free radicals in an organism is under the control of various antioxidant mechanisms. If their production overcomes the capacity of antioxidant protection, oxidative stress occurs which is capable of damaging different cellular structures and biomolecules, leading to various diseases. The importance of oxidative stress was proven in many psychiatric diseases among which are depression and bipolar disorder. Different studies show the significant improvement of clinical presentation when antioxidant substances are administered, suggesting that redox imbalance can influence their symptoms appearance and severity. In addition, oxidative stress is intercrossed with the different comorbidities that appear among depressive and bipolar patients. Beside the clinical presentation, oxidative stress influences the chronicity of depression, which was demonstrated in patients with recurrent depressive disorder. Better understanding of oxidant/antioxidant imbalance and its role in the pathophysiology of depression and bipolar disorder could be useful for the development of a novel therapeutic approach to the management of these diseases.
Kessing, Lars Vedel; Vradi, Eleni; McIntyre, Roger S
BACKGROUND: Accelerated aging has been proposed as a mechanism explaining the increased prevalence of comorbid general medical illnesses in bipolar disorder. AIMS: To test the hypothesis that lost life years due to natural causes starts in early and mid-adulthood, supporting the hypothesis...... of accelerated aging. METHODS: Using individual data from nationwide registers of patient with a diagnosis of bipolar disorder we calculated remaining life expectancies before age 90 years for values of age 15, 25, 35…75 years among all individuals alive in year 2000. Further, we estimated the reduction in life...... expectancy due to natural causes (physical illnesses) and unnatural causes (suicide and accidents) in relation to age. RESULTS: A total of 22,635 patients with bipolar disorder were included in the study in addition to data from the entire Danish general population of 5.4 million people. At age 15 years...
Osman (O)zdel; Demet Kalayci; Gülfizar S(o)zeri-Varma; Yilmaz Kiro(g)lu; Selim Tümkaya; Tu(g)(c)e Toker-U(g)urlu
The aim of this study was to investigate proton magnetic resonance spectroscopy metabolite values in the medial prefrontal cortex of individuals with euthymic bipolar disorder. The subjects consisted of 15 patients with euthymic bipolar disorder type I and 15 healthy controls. We performed proton magnetic resonance spectroscopy of the bilateral medial prefrontal cortex and measured levels of N-acetyl aspartate, choline and creatine. Levels of these three metabolites in the medial prefrontal cortex were found to be lower in patients with bipolar disorder compared with healthy controls. A positive correlation was found between illness duration and choline levels in the right medial prefrontal cortex. Our study suggests that during the euthymic period, there are abnormalities in cellular energy and membrane phospholipid metabolism in the medial prefrontal cortex, and that this may impair neuronal activity and integrity.
Gregory, Virgil L
Given the prevalence of null hypothesis significance testing, cognitive-behavioral therapy's effect on depressive symptoms of bipolar disorder is not fully understood in the absence of effect size statistics. The present study discusses the disadvantages associated with null hypothesis significance testing and seeks to overcome these shortcomings via conducting a meta-analysis which examines cognitive-behavioral therapy for depressive symptoms in persons with bipolar disorder. A systematic literature search was conducted and included articles were subject to meta-analytic procedures. With a mean weighted Cohen's d of -0.29, relative to treatment as usual, cognitive-behavioral therapy has a small effect on depressive symptoms in persons with bipolar disorder. The strengths, limitations, and need for future research are discussed.
Bergink, Veerle; Tidselbak Larsen, Janne; Hillegers, M H J
Childhood adverse events are risk factors for later bipolar disorder. We quantified the risks for a later diagnosis of bipolar disorder after exposure to adverse life events in children with and without parental psychopathology. This register-based population cohort study included all persons born...... in Denmark from 1980 to 1998 (980 554 persons). Adversities before age 15 years were: familial disruption; parental somatic illness; any parental psychopathology; parental labour market exclusion; parental imprisonment; placement in out-of-home care; and parental natural and unnatural death. We calculated...... risk estimates of each of these eight life events as single exposure and risk estimates for exposure to multiple life events. Main outcome variable was a diagnosis of bipolar disorder after the age of 15 years, analysed with Cox proportional hazard regression. Single exposure to most...
Munkholm, Klaus; Poulsen, Henrik Enghusen; Kessing, Lars Vedel;
investigated oxidatively generated damage to DNA and RNA in patients with bipolar disorder and its relationship with the affective phase compared with healthy control subjects. METHODS: Urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), markers...... of oxidatively generated DNA and RNA damage, respectively, was measured in 37 rapid cycling patients with bipolar disorder and in 40 age- and gender-matched healthy control subjects. Employing a longitudinal design, repeated measurements of both markers were evaluated in various affective phases in patients...... with bipolar disorder during a six- to 12-month period and compared with repeated measurements in healthy control subjects. RESULTS: In linear mixed models, adjusting for demographical, metabolic, and lifestyle factors, the excretion of 8-oxodG and 8-oxoGuo was significantly elevated in euthymic patients...
李春阳; 陈超; 许志平
An old people was diagnosed as depression by attending doctor after admission because of repeated depressive episode and lack of past typical mania and hypomania manifestations ,but he was considered as depressive episode of soft bipolar disorder (SBD) higher-level doctor according to his positive family history of affective disorder and hyperthymia type temperament. He showed hy-pomania manifestations soon after admission ,was diagnosed as bipolar Ⅱ disorder ,and correctness of SBD consideration at that time confirmed. Clinical underdiagnosis of bipolar Ⅱ disorder is easily misdiagnosed as unipolar depression. SBD depressive episode should be treated in terms of bipolar disorder treatment , mood-stabiliziers are used as basic treatment ,and applications of antidepressant drugs should be careful.%老年反复抑郁发作1例，因既往无典型躁狂或轻躁狂表现，入院后经治医生诊断为抑郁症，但结合其有情感性精神障碍阳性家族史，且具有情感旺盛型气质，上级医生考虑为软双相障碍抑郁发作。患者住院不久即出现轻躁狂表现，确诊为双相Ⅱ型障碍，证实了当时考虑软双相抑郁的正确性。临床上双相Ⅱ型障碍的诊断不足，容易误诊为单相抑郁。对于软双相障碍的抑郁发作，需要按照双相抑郁障碍进行治疗，以心境稳定剂作为基础治疗，慎用抗抑郁药物。
Wang, Jinglu; Qu, Susu; Wang, Weixiao; Guo, Liyuan; Zhang, Kunlin; Chang, Suhua; Wang, Jing
Numbers of gene expression profiling studies of bipolar disorder have been published. Besides different array chips and tissues, variety of the data processes in different cohorts aggravated the inconsistency of results of these genome-wide gene expression profiling studies. By searching the gene expression databases, we obtained six data sets for prefrontal cortex (PFC) of bipolar disorder with raw data and combinable platforms. We used standardized pre-processing and quality control procedures to analyze each data set separately and then combined them into a large gene expression matrix with 101 bipolar disorder subjects and 106 controls. A standard linear mixed-effects model was used to calculate the differentially expressed genes (DEGs). Multiple levels of sensitivity analyses and cross validation with genetic data were conducted. Functional and network analyses were carried out on basis of the DEGs. In the result, we identified 198 unique differentially expressed genes in the PFC of bipolar disorder and control. Among them, 115 DEGs were robust to at least three leave-one-out tests or different pre-processing methods; 51 DEGs were validated with genetic association signals. Pathway enrichment analysis showed these DEGs were related with regulation of neurological system, cell death and apoptosis, and several basic binding processes. Protein-protein interaction network further identified one key hub gene. We have contributed the most comprehensive integrated analysis of bipolar disorder expression profiling studies in PFC to date. The DEGs, especially those with multiple validations, may denote a common signature of bipolar disorder and contribute to the pathogenesis of disease.
While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.
Beyer, John L; Weisler, Richard H
Suicide behaviors (ideation, attempts, and completions) are unfortunately common in patients with bipolar disorder. It is estimated that 25 to 50% attempt suicide at least once during their lifetime, and 6% to 19% complete suicide. Risk factors include a family history of suicide, previous suicide attempts, younger age of onset, comorbid psychiatric illnesses, and psychological constructs like hopelessness. Pharmacologic treatment may impact suicidal behaviors, either increasing vulnerability or resilience. Clinicians need to be particularly sensitive to their patient's thoughts and beliefs about death, particularly during stressful times of life or when in a depressive/mixed episode of bipolar disorder.
Naraiana de Oliveira Tavares
Full Text Available The aim of this study is to present an updated view of the writings on the endophenotype model for bipolar disorder using analytical methodologies. A review and analysis of networks was performed through descriptors and keywords that characterize the composition of the endophenotype model as a model of health. Information was collected from between 1992 and 2014, and the main thematic areas covered in the articles were identified. We discuss the results and question their cohesion, emphasizing the need to strengthen and identify the points of connection between etiological factors and characteristics that make up the model of endophenotypes for bipolar disorder.
Kessing, Lars Vedel; Hellmund, Gunnar; Andersen, Per Kragh
It is not clear whether the effectiveness of lamotrigine versus lithium differs for patients with bipolar disorder treated in clinical practice. We compared rates of switch to, or add on of, another psychotropic, and rates of psychiatric hospitalization for patients treated with lamotrigine...... or lithium in clinical practice. Using linkage of nationwide Danish registers we identified 730 patients who received lamotrigine and 3518 patients received lithium subsequent to a diagnosis of bipolar disorder in psychiatric hospital settings during a period from 1995 to 2006. The overall rate of switch...
Kamath, Jayesh; Zhang, Wanli; Kesten, Karen; Wakai, Sara; Shelton, Deborah; Trestman, Robert
The objective of this study was to assess adaptation of the Texas Implementation of Medication Algorithm (TIMA) for bipolar disorder (BD) in the Connecticut Department of Correction. A nonrandomized sample of 20 males and 20 females, with diagnoses of BD Type I or II, was enrolled in the study. Two TIMA-trained psychiatrists treated the participants over a 12-week period following the TIMA protocol. The primary outcome measure was the Bipolar Disorder Symptom Scale. Secondary outcome measures evaluated global clinical status, comorbid symptomatology, and quality of life. Significant improvement was seen with the primary and secondary outcome measures (p effectiveness and benefits of TIMA for BD adaptation in the correctional setting.
Full Text Available Abstract Background There is little published guideline or evidence on treating bipolar affective disorder in patients with renal failure having haemodialysis. Case We present two patients with bipolar affective disorder with renal failure having haemodialysis. We used lorazepam in one patient to manage the immediate risk of non-engagement with dialysis. Risperidone was added in the second patient for managing psychotic symptoms. Valproate was started as a mood stabiliser and titrated upwards for long-term management of the illness. Conclusion We discuss the similarities in the two cases and the care plan we used to manage them.
Kumar, S; Jacobson, R R; Sathananthan, K
The appearance of bipolar affective disorder after stroke depends on the presence of two factors: a predisposing factor of either genetic loading or subcortical atrophy, and a lesion of specific corticolimbic pathways involving the right hemisphere. Whether cyclothymia and seasonal affective disorder further predispose to poststroke affective disorder is not clear. A case is described which highlights these issues. The aetiological factors, pathophysiology, and diagnosis are discussed.
Forstner, Andreas J; Hecker, Julian; Hofmann, Andrea
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap...... insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders....
S. Kumar; Jacobson, R; Sathananthan, K
The appearance of bipolar affective disorder after stroke depends on the presence of two factors: a predisposing factor of either genetic loading or subcortical atrophy, and a lesion of specific corticolimbic pathways involving the right hemisphere. Whether cyclothymia and seasonal affective disorder further predispose to poststroke affective disorder is not clear. A case is described which highlights these issues. The aetiological factors, pathophysiology, and diagnosis ...
Full Text Available The objective of the present study was to assess the performance of lithium treated euthymic bipolar patients in tests measuring spatial working memory (SWM, planning, and verbal fluency and to delineate the influence of gender on cognitive functioning. Fifty-nine euthymic bipolar patients, treated with lithium carbonate for at least 5 yr, were studied. Patients and controls underwent a neuropsychological assessment. Bipolar patients had significantly worse results than the healthy controls in the spatial memory and planning as well as verbal fluency tests. We detected a gender-related imbalance in the SWM results. Deficits in SWM were observed in male-only comparisons but not in female-only comparisons. The SWM scores were significantly poorer in male patients than in male controls. In female-only comparisons, female patients did not have significantly poorer SWM results in any category than their controls. Bipolar women scored worse in some other tests. The present study points to the different patterns of neuropsychological disturbances in female and male patients and suggests that sex-dependent differences should be taken into account in order to tailor the therapeutic intervention aimed at the improvement of cognitive functions.
University counseling centers are faced with the challenge of effectively treating bipolar students while also utilizing brief treatment frameworks and managing high patient volumes. Potential destabilization, particularly within the elevated mood phase, poses significant behavioral management issues for university clinicians and administrators,…
Objective Misdiagnoses of bipolar disorder(BD)as unipolar disorder(UPD)may lead to inappropriate treatment and poor outcomes.This study aimed to compare demographic and clinical features of patients with BD and MDD in China.Methods A total of 1 487 patients treated for MDD were consecutively evaluated in 13 psychiatric hospitals or units in China.The Mood Disorder Questionnaire(MDQ)and the Hypomania Checklist(HCL-
Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nordestgaard, Børge Grønne
BACKGROUND: No prospective studies have examined the role of C-reactive protein (CRP) in late-onset bipolar disorder. AIMS: We tested the hypothesis that elevated levels of CRP are associated cross-sectionally and prospectively with late-onset bipolar disorder, and that such an association possibly...... levels of CRP were associated both cross-sectionally and prospectively with late-onset bipolar disorder. When CRP was on a continuous scale, a doubling in CRP yielded an observational odds ratio for late-onset bipolar disorder of 1.28 (1.08-1.52) with a corresponding causal odds ratio of 4.66 (0.......89-24.3). CONCLUSION: Elevated CRP is associated with increased risk of late-onset bipolar disorder in the general population which was supported by the genetic analysis....
Goghari, Vina M; Sponheim, Scott R
Schizophrenia and bipolar disorder, although diagnostically separate, likely share elements of their genetic etiology. This study assessed whether the COMT Val158Met polymorphism has shared or specific associations with clinical phenotypes evident in schizophrenia and bipolar disorder. Schizophrenia and bipolar patients completed a clinical assessment encompassing premorbid functioning and current and lifetime symptomatology. Multivariate analyses yielded a three-way interaction of diagnosis, COMT genotype for lifetime symptomatology. The COMT Val allele was associated with greater positive symptomatology in schizophrenia, whereas Met homozygosity was associated with greater positive symptomatology in bipolar disorder. Findings support the COMT Val158Met polymorphism conferring vulnerability for different clinical phenotypes in schizophrenia and bipolar disorder. Lifetime symptomatology may be particularly useful in determining the relationship between genes and clinical phenotypes across mental disorders.
Full Text Available Abstract Background Beck Cognitive Insight Scale (BCIS has been designed for assessment of self-reflection on patients' anomalous experiences and interpretations of own beliefs. The scale has been developed and validated for patients with schizophrenia. We wanted to study the utility of the scale for patients with bipolar disorder. The relationship between the BCIS as a measure of cognitive insight and established methods for assessment of insight of illness was explored in both diagnostic groups. Methods The BCIS self-report inventory was administered to patients with schizophrenia (n = 143, bipolar disorder (n = 92 and controls (n = 64. The 15 items of the inventory form two subscales, self-reflectiveness and self-certainty. Results The internal consistency of the subscales was good for the patient groups and the controls. The mean subscale scores were not significantly different for the three groups. Four items in subscale self-reflectiveness referring to psychotic experiences gave, however, different results in the control subjects. Self-certainty and scores on insight item PANSS correlated significantly in the schizophrenia, but not in the bipolar group. Conclusion BCIS with its two subscales seems applicable for patients with bipolar disorder as well as for patients with schizophrenia. The self-report inventory can also be applied to control subjects if the items referring to psychotic experiences are omitted. In schizophrenia high scores on self-certainty is possibly associated with poor insight of illness. For the bipolar group the subscales are largely independent of traditional insight measures.
Johnson, C P; Follmer, R L; Oguz, I; Warren, L A; Christensen, G E; Fiedorowicz, J G; Magnotta, V A; Wemmie, J A
Abnormal metabolism has been reported in bipolar disorder, however, these studies have been limited to specific regions of the brain. To investigate whole-brain changes potentially associated with these processes, we applied a magnetic resonance imaging technique novel to psychiatric research, quantitative mapping of T1 relaxation in the rotating frame (T1ρ). This method is sensitive to proton chemical exchange, which is affected by pH, metabolite concentrations and cellular density with high spatial resolution relative to alternative techniques such as magnetic resonance spectroscopy and positron emission tomography. Study participants included 15 patients with bipolar I disorder in the euthymic state and 25 normal controls balanced for age and gender. T1ρ maps were generated and compared between the bipolar and control groups using voxel-wise and regional analyses. T1ρ values were found to be elevated in the cerebral white matter and cerebellum in the bipolar group. However, volumes of these areas were normal as measured by high-resolution T1- and T2-weighted magnetic resonance imaging. Interestingly, the cerebellar T1ρ abnormalities were normalized in participants receiving lithium treatment. These findings are consistent with metabolic or microstructural abnormalities in bipolar disorder and draw attention to roles of the cerebral white matter and cerebellum. This study highlights the potential utility of high-resolution T1ρ mapping in psychiatric research.
Cruz, Mario; Pincus, Harold Alan; Welsh, Deborah E; Greenwald, Devra; Lasky, Elaine; Kilbourne, Amy M
Objective Religion and spirituality are important coping strategies in depression but have been rarely studied within the context of bipolar disorder. The present study assessed the association between different forms of religious involvement and the clinical status of individuals treated for bipolar disorder. Methods A cross-sectional observation study of follow-up data from a large cohort study of patients receiving care for bipolar disorder (n = 334) at an urban Veterans Affairs mental health clinic was conducted. Bivariate and multivariate analyses were performed to assess the association between public (frequency of church attendance), private (frequency of prayer/meditation), as well as subjective forms (influence of beliefs on life) of religious involvement and mixed, manic, depressed, and euthymic states when demographic, anxiety, alcohol abuse, and health indicators were controlled. Results Multivariate analyses found significant associations between higher rates of prayer/meditation and participants in a mixed state [odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.10-1.52, chi square = 9.42, df = 14, p < 0.05], as well as lower rates of prayer/meditation and participants who were euthymic (OR = 0.84; 95% CI = 0.72-0.99, chi square = 4.60, df = 14, p < 0.05). Depression and mania were not associated with religious involvement. Conclusions Compared to patients with bipolar disorder in depressed, manic, or euthymic states, patients in mixed states have more active private religious lives. Providers should assess the religious activities of individuals with bipolar disorder in mixed states and how they may complement/deter ongoing treatment. Future longitudinal studies linking bipolar states, religious activities, and treatment-seeking behaviors are needed. PMID:20148868
Aydin, Adem; Selvi, Yavuz; Besiroglu, Lutfullah; Boysan, Murat; Atli, Abdullah; Ozdemir, Osman; Kilic, Sultan; Balaharoglu, Ragıp
It has been commonly recognized that circadian rhythm and sleep/wake cycle are causally involved in bipolar disorder. There has been a paucity of systematic research considering the relations between sleep and mood states in bipolar disorder. The current study examines the possible influences of sleep deprivation on mood states and endocrine functions among first-degree relatives of patients with bipolar disorder and healthy controls. Blood samples were taken at two time points in the consecutive mornings at predeprivation and postdeprivation periods. Participants simultaneously completed the Profiles of Mood States at two time points after giving blood samples. Plasma T3 and TSH levels increased after total sleep deprivation in both groups. Sleep deprivation induced TSH levels were reversely associated with depression-dejection among healthy controls. A paradoxical effect was detected for only the first-degree relatives of the patients that changes in plasma cortisol levels negatively linked to depression-dejection and anger-hostility scores after total sleep deprivation. Plasma DHEA levels became correlated with vigor-activity scores after sleep deprivation among first-degree relatives of bipolar patients. On the contrary, significant associations of depression-dejection, anger-hostility, and confusion-bewilderment with the baseline plasma DHEA levels became statistically trivial in the postdeprivation period. Findings suggested that first-degree relatives of patients with bipolar disorder had completely distinct characteristics with respect to sleep deprivation induced responses in terms of associations between endocrine functions and mood states as compared to individuals whose relatives had no psychiatric problems. Considering the relationships between endocrine functions and mood states among relatives of the patients, it appears like sleep deprivation changes the receptor sensitivity which probably plays a pivotal role on mood outcomes among the first
Anticevic, Alan; Brumbaugh, Margaret S.; Winkler, Anderson M.; Lombardo, Lauren E.; Barrett, Jennifer; Corlett, Phillip R.; Kober, Hedy; Gruber, June; Repovs, Grega; Cole, Michael W.; Krystal, John H.; Pearlson, Godfrey D.; Glahn, David C.
Background Pathophysiological models of bipolar disorder postulate that mood dysregulation arises from fronto-limbic dysfunction, marked by reduced prefrontal cortex (PFC) inhibitory control. This may occur both due to disruptions within PFC networks and abnormal inhibition over subcortical structures involved in emotional processing. However, no study has examined global PFC dysconnectivity in bipolar disorder and tested if regions with within-PFC dysconnectivity also exhibit fronto-limbic connectivity deficits. Further, no study has investigated whether such connectivity disruptions differ for bipolar patients with psychosis history, who may exhibit a more severe clinical course. Methods We collected resting-state fMRI at 3T in 68 remitted bipolar I patients (34 with psychosis history) and 51 demographically-matched healthy participants. We employed a recently developed Global Brain Connectivity method, restricted to PFC (rGBC). We also independently tested connectivity between anatomically-defined amygdala and PFC. Results Bipolar patients exhibited reduced medial PFC (mPFC) rGBC, increased amygdala-MPFC connectivity, and reduced connectivity between amygdala and dorso-lateral PFC. All effects were driven by psychosis history. Moreover, the magnitude of observed effects was significantly associated with lifetime psychotic symptom severity. Conclusions This convergence between rGBC, seed-based amygdala findings and symptom severity analyses highlights that mPFC, a core emotion regulation region, exhibits both within-PFC dysconnectivity and connectivity abnormalities with limbic structures in bipolar illness. Furthermore, lateral PFC dysconnectivity in patients with psychosis history converges with published work in schizophrenia, indicating possible shared risk factors. Observed dysconnectivity in remitted patients suggests a bipolar trait characteristic and may constitute a risk factor for phasic features of the disorder. PMID:22980587
Marshall, David F; Walker, Sara J; Ryan, Kelly A; Kamali, Masoud; Saunders, Erika F H; Weldon, Anne L; Adams, Kenneth M; McInnis, Melvin G; Langenecker, Scott A
Measures of cognitive dysfunction in Bipolar Disorder (BD) have identified state and trait dependent metrics. An influence of substance abuse (SUD) on BD has been suggested. This study investigates potential differential, additive, or interactive cognitive dysfunction in bipolar patients with or without a history of SUD. Two hundred fifty-six individuals with BD, 98 without SUD and 158 with SUD, and 97 Healthy Controls (HC) completed diagnostic interviews, neuropsychological testing, and symptom severity scales. The BD groups exhibited poorer performance than the HC group on most cognitive factors. The BD with SUD exhibited significantly poorer performance than BD without SUD in visual memory and conceptual reasoning/set-shifting. In addition, a significant interaction effect between substance use and depressive symptoms was found for auditory memory and emotion processing. BD patients with a history of SUD demonstrated worse visual memory and conceptual reasoning skills above and beyond the dysfunction observed in these domains among individuals with BD without SUD, suggesting greater impact on integrative, gestalt-driven processing domains. Future research might address longitudinal outcome as a function of BD, SUD, and combined BD/SUD to evaluate neural systems involved in risk for, and effects of, these illnesses.
Hawken, Emily R; Harkness, Kate L; Lazowski, Lauren K; Summers, David; Khoja, Nida; Gregory, James Gardner; Milev, Roumen
Bipolar disorder is associated with significant deficits in the decoding of others' mental states in comparison to healthy participants. However, differences in theory of mind decoding ability among patients in manic, depressed, and euthymic phases of bipolar disorder is currently unknown. Fifty-nine patients with bipolar I or II disorder (13 manic, 25 depressed, 20 euthymic) completed the "Reading the Mind in the Eyes" Task (Eyes task) and the Animals Task developed to control for non-mentalistic response demands of the Eyes Task. Patients also completed self-report and clinician-rated measures of depression, mania, and anxiety symptoms. Patients in the manic phase were significantly less accurate than those in the depressed and euthymic phases at decoding mental states in the Eyes task, and this effect was strongest for eyes of a positive or neutral valence. Further Eyes task performance was negatively correlated with the symptoms of language/thought disorder, pressured speech, and disorganized thoughts and appearance. These effects held when controlling for accuracy on the Animals task, response times, and relevant demographic and clinical covariates. Results suggest that the state of mania, and particularly psychotic symptoms that may overlap with the schizophrenia spectrum, are most strongly related to social cognitive deficits in bipolar disorder.
Stratford, Hannah J; Cooper, Myra J; Di Simplicio, Martina; Blackwell, Simon E; Holmes, Emily A
Comorbid anxiety is common in bipolar spectrum disorders [BPSD], and is associated with poor outcomes. Its clinical relevance is highlighted by the "anxious distress specifier" in the revised criteria for Bipolar Disorders in the Diagnostic and Statistical Manual 5th Edition [DSM-5]. This article reviews evidence for the effectiveness of psychological therapy for anxiety in adults with BPSD (bipolar I, II, not otherwise specified, cyclothymia, and rapid cycling disorders). A systematic search yielded 22 treatment studies that included an anxiety-related outcome measure. Cognitive behavioural therapy [CBT] for BPSD incorporating an anxiety component reduces anxiety symptoms in cyclothymia, "refractory" and rapid cycling BPSD, whereas standard bipolar treatments have only a modest effect on anxiety. Preliminary evidence is promising for CBT for post-traumatic stress disorder and generalised anxiety disorder in BPSD. Psychoeducation alone does not appear to reduce anxiety, and data for mindfulness-based cognitive therapy [MBCT] appear equivocal. CBT during euthymic phases has the greatest weight of evidence. Where reported, psychological therapy appears acceptable and safe, but more systematic collection and reporting of safety and acceptability information is needed. Development of psychological models and treatment protocols for anxiety in BPSD may help improve outcomes.
Murray, Robin M; Sham, Pak; Van Os, Jim; Zanelli, Jolanta; Cannon, Mary; McDonald, Colm
Schizophrenia and mania have a number of symptoms and epidemiological characteristics in common, and both respond to dopamine blockade. Family, twin and molecular genetic studies suggest that the reason for these similarities may be that the two conditions share certain susceptibility genes. On the other hand, individuals with schizophrenia have more obvious brain structural and neuropsychological abnormalities than those with bipolar disorder; and pre-schizophrenic children are characterised by cognitive and neuromotor impairments, which are not shared by children who later develop bipolar disorder. Furthermore, the risk-increasing effect of obstetric complications has been demonstrated for schizophrenia but not for bipolar disorder. Perinatal complications such as hypoxia are known to result in smaller volume of the amygdala and hippocampus, which have been frequently reported to be reduced in schizophrenia; familial predisposition to schizophrenia is also associated with decreased volume of these structures. We suggest a model to explain the similarities and differences between the disorders and propose that, on a background of shared genetic predisposition to psychosis, schizophrenia, but not bipolar disorder, is subject to additional genes or early insults, which impair neurodevelopment, especially of the medial temporal lobe.
Warren, Barbara Jones
Bipolar disorder is a complicated mental illness to diagnose and treat. The symptoms of the disorder cause a multitude of fluctuations in mood and behavior, affecting the way individuals function and interact with others on a daily basis. Individuals diagnosed with bipolar disorder experience symptoms within a framework that is grounded in their cultural beliefs, values, and norms. Culture is a complex and personal biopsychosocial phenomenon that provides meaning within life for an individual, a group, or a community. It is essential that psychiatric-mental health (PMH) nurses understand the role of culture and integrate this knowledge into the biopsychosocial care of clients. The development and maintenance of the interpersonal therapeutic relationship between PMH nurses and their clients requires the use of a cultural framework, which refers to the connection of culture and cultural competence. The purposes of this article are to define culture and the process of cultural competence, provide a brief overview of bipolar disorder, propose the use of a cultural framework for bipolar disorder, and discuss the implications for PMH nurses who care for culturally and ethnically diverse clients.
Araujo, Jaciana Marlova Gonçalves; dos Passos, Miguel Bezerra; Molina, Mariane Lopez; da Silva, Ricardo Azevedo; Souza, Luciano Dias de Mattos
The aim of this study was to determine the differences in personality traits between individuals with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) during a depressive episode, when it can be hard to differentiate them. Data on personality traits (NEO-FFI), mental disorders (Mini International Neuropsychiatric Interview Plus) and socioeconomic variables were collected from 245 respondents who were in a depressive episode. Individuals with MDD (183) and BD (62) diagnosis were compared concerning personality traits, clinical aspects and socioeconomic variables through bivariate analyses (chi-square and ANOVA) and multivariate analysis (logistic regression). There were no differences in the prevalence of the disorders between socioeconomic and clinical variables. As for the personality traits, only the difference in Agreeableness was statistically significant. Considering the control of suicide risk, gender and anxiety comorbidity in the multivariate analysis, the only variable that remained associated was Agreeableness, with an increase in MDD cases. The brief version of the NEO inventories (NEO-FFI) does not allow for the analysis of personality facets. During a depressive episode, high levels of Agreeableness can indicate that MDD is a more likely diagnosis than BD.
Full Text Available Bipolar disorder types I (BD I and II (BD II behave differently in clinical manifestations, normal personality traits, responses to pharmacotherapies, biochemical backgrounds and neuroimaging activations. How the varied emotional states of BD I and II are related to the comorbid personality disorders remains to be settled.We therefore administered the Plutchick - van Praag Depression Inventory (PVP, the Mood Disorder Questionnaire (MDQ, the Hypomanic Checklist-32 (HCL-32, and the Parker Personality Measure (PERM in 37 patients with BD I, 34 BD II, and in 76 healthy volunteers.Compared to the healthy volunteers, patients with BD I and II scored higher on some PERM styles, PVP, MDQ and HCL-32 scales. In BD I, the PERM Borderline style predicted the PVP scale; and Antisocial predicted HCL-32. In BD II, Borderline, Dependent, Paranoid (- and Schizoid (- predicted PVP; Borderline predicted MDQ; Passive-Aggressive and Schizoid (- predicted HCL-32. In controls, Borderline and Narcissistic (- predicted PVP; Borderline and Dependent (- predicted MDQ.Besides confirming the different predictability of the 11 functioning styles of personality disorder to BD I and II, we found that the prediction was more common in BD II, which might underlie its higher risk of suicide and poorer treatment outcome.
Mansour, Hader A; Talkowski, Michael E; Wood, Joel; Chowdari, Kodavali V; McClain, Lora; Prasad, Konasale; Montrose, Debra; Fagiolini, Andrea; Friedman, Edward S; Allen, Michael H; Bowden, Charles L; Calabrese, Joseph; El-Mallakh, Rif S; Escamilla, Michael; Faraone, Stephen V; Fossey, Mark D; Gyulai, Laszlo; Loftis, Jennifer M; Hauser, Peter; Ketter, Terence A; Marangell, Lauren B; Miklowitz, David J; Nierenberg, Andrew A; Patel, Jayendra; Sachs, Gary S; Sklar, Pamela; Smoller, Jordan W; Laird, Nan; Keshavan, Matcheri; Thase, Michael E; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J; Devlin, Bernie; Nimgaonkar, Vishwajit L
Objective Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods We assayed 276 publicly available ‘tag’ single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results. PMID:19839995
Jian, J; Li, C; Xu, J; Qiao, D; Mi, G; Chen, X; Tang, M
Single nucleotide polymorphisms (SNPs) in HTR3A and HTR3B have been reported to be associated with bipolar disorder in European and Japanese populations. We explored the roles of 21 tag SNPs in HTR3A and HTR3B in susceptibility to bipolar disorder in a Chinese cohort. Twenty-one Tag SNPs were genotyped in a study consisting of 130 patients with bipolar disorder, who visited Shandong Mental Health Center between June 2013 and May 2014, and 109 healthy individuals as controls. All of the tag SNPs were genotyped using Sequenom MassArray matrix-assisted laser desorption/ionization time of flight spectrometry. Plink 1.07, Haploview 4.2, and SPSS 20.0 were used for the analysis of the genotypes and the associations of the haplotypes with bipolar disorder. Association analyses of tag SNPs detected significant associations with the A allele in HTR3A rs1176719 (P = 0.030) and the C allele in HTR3A rs1176713 (P = 0.048). Haplotype-based association analyses indicated a statistically significant (P = 0.035) five-SNP haplotype (rs1062613:C, rs11604247:C, rs1176722:G, rs2276302:A, rs1176719:G) of linkage disequilibrium in block 3. Analysis of our small Chinese sample revealed a significant association of HTR3A with bipolar disorder, but yielded no evidence of an association between HTR3B and bipolar disorder. Furthermore, evidence for an association was found for a haplotype of HTR3A. Studies with larger Chinese samples are needed to verify our findings.
Alloy, Lauren B; Abramson, Lyn Y; Flynn, Megan; Liu, Richard T; Grant, David A; Jager-Hyman, Shari; Whitehouse, Wayne G
We examined concurrent and prospective associations of self-focused cognitive styles with bipolar spectrum disorders. Controlling for depressive and hypomanic/manic symptoms, 125 individuals with bipolar spectrum disorders scored higher than 149 demographically similar normal controls on the rumination scale of the Response Styles Questionnaire (RSQ) and the private self-consciousness subscale of the Self-Consciousness Scale (SCS). The two groups did not differ on the distraction scale of the RSQ or the public self-consciousness and social anxiety subscales of the SCS. In addition, among the bipolar individuals, controlling for initial depressive and hypomanic/manic symptoms, rumination predicted the number, but not the likelihood of onset, of depressive episodes, whereas private self-consciousness predicted the likelihood of onset, but not the number, of hypomanic/manic episodes over a 3.5-year follow-up.
Aashal B. Shah
Full Text Available Bipolar disorder (BD is a chronic disorder which usually has its onset in early adulthood. At one end of the spectrum is depression and at other is mania. Like many psychiatric illnesses, it is not treatable but its symptoms are completely manageable with medications. Commonly used drugs are mood stabilizers and atypical antipsychotics along with adjunctive medications such as anxiolytics and antidepressants. In general, a combination of these drugs is used for treatment. These drugs have significant adverse effects which add to the burden of the disease. Presently, there are 11 US Food and Drug Administration - approved drugs for management of acute mania, 3 for bipolar depression and 7 for bipolar maintenance. This review article details the use of these drugs in BD. [Int J Basic Clin Pharmacol 2015; 4(4.000: 623-631
Carta, MG; Mura, G; Sorbello, O; Farina, G; Demelia, L
Introduction: Wilson’s disease is an inherited disorder caused by a gene located on chromosome 13, which involved copper transportation across cell membranes. The disease can cause a reduced incorporation of copper into ceruloplasmin resulting in accumulation of this metal in the liver, central nervous system, kidneys and other organs. The objective is to define the frequencies of psychiatric disorders in WD, the amount of impairment of Quality of Life [QoL] in patients with WD and the relevance of the psychiatric disorders in the QoL of people suffering by WD. Methods: This is a systematic review. The search of the significant articles was carried out in PubMed using specific key words. Results: Such other neurological diseases, WD is characterized by chronic course and need of treatments, impairment of functional outcomes and high frequency of psychiatric symptoms, although a specific association between Bipolar Disorders and WD was recently found. Despite this, since today few studies are carried on WD patients’ quality of life related to psychiatric symptoms. Some new reports showed a link between presence of Bipolar Disorders diagnosis, cerebral damage and low Qol. Conclusion: Prospective studies on large cohorts are required to establish the effective impact of psychiatric disorders comorbidity, particularly Bipolar Disorders, on quality of life in WD and to clarify the causal link between brain damage, psychiatric disorders and worsening of QoL. PMID:23049615
Andreasen, N C; Glick, I D
Research on the relationship between creativity and mental illness is summarized, and studies documenting a relationship in writers between creativity and affective illness (particularly bipolar illness) are described. Writers have a high prevalence of affective illness, and both affective illness and creativity have increased frequency in their first-degree relatives. The clinical management of the creative individual is challenging. In general, creative individuals are most productive when their affective symptoms are under good control.
Huang, Joanne H; Berkovitch, Shaunna S; Iaconelli, Jonathan; Watmuff, Bradley; Park, Hyoungjun; Chattopadhyay, Shrikanta; McPhie, Donna; Öngür, Dost; Cohen, Bruce M; Clish, Clary B; Karmacharya, Rakesh
Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects showed distinct separation by principal components analysis methods. The most statistically significant findings were observed in the perturbation experiments. The metabolite with the lowest p value in both the low-glucose and dexamethasone experiments was α-aminoadipate, whose intracellular level was consistently lower in bipolar subjects. Our study implicates α-aminoadipate as a possible biomarker in bipolar disorder that manifests under cellular stress. This is an intriguing finding given the known role of α-aminoadipate in the modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid levels have been implicated in bipolar disorder.
Timothy R Powell
Full Text Available Mood disorders consist of two etiologically related, but distinctly treated illnesses, major depressive disorder (MDD and bipolar disorder (BPD. These disorders share similarities in their clinical presentation, and thus show high rates of misdiagnosis. Recent research has revealed significant transcriptional differences within the inflammatory cytokine pathway between MDD patients and controls, and between BPD patients and controls, suggesting this pathway may possess important biomarker properties. This exploratory study attempts to identify disorder-specific transcriptional biomarkers within the inflammatory cytokine pathway, which can distinguish between control subjects, MDD patients and BPD patients. This is achieved using RNA extracted from subject blood and applying synthesized complementary DNA to quantitative PCR arrays containing primers for 87 inflammation-related genes. Initially, we use ANOVA to test for transcriptional differences in a 'discovery cohort' (total n = 90 and then we use t-tests to assess the reliability of any identified transcriptional differences in a 'validation cohort' (total n = 35. The two most robust and reliable biomarkers identified across both the discovery and validation cohort were Chemokine (C-C motif ligand 24 (CCL24 which was consistently transcribed higher amongst MDD patients relative to controls and BPD patients, and C-C chemokine receptor type 6 (CCR6 which was consistently more lowly transcribed amongst MDD patients relative to controls. Results detailed here provide preliminary evidence that transcriptional measures within inflammation-related genes might be useful in aiding clinical diagnostic decision-making processes. Future research should aim to replicate findings detailed in this exploratory study in a larger medication-free sample and examine whether identified biomarkers could be used prospectively to aid clinical diagnosis.