Bipolar Disorder: Alda M

Yatham LN, Kennedy SH, O'Donovan C, Parikh S, MacQueen G, McIntyre R, Sharma V, Silverstone P, Alda M, Baruch P, Beaulieu S, Daigneault A, Milev R, Young LT, Ravindran A, Schaffer A, Connolly M, Gorman CP, Anonymous00076. · Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. · Bipolar Disord. · Pubmed #15952957 No free full text.

Abstract: Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.

Nimgaonkar VL, Alda M. · No affiliation provided · Bipolar Disord. · Pubmed #11843776 No free full text.

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Alda M, Hajek T, Calkin C, O'Donovan C. · Department of Psychiatry, Dalhousie University, 5909 Veterans Memorial Lane, Halifax, Nova Scotia, Canada. · Ann Med. · Pubmed #18821183 No free full text.

Abstract: Treatment of bipolar disorder (BD) has traditionally focused on alleviation of acute symptoms and prevention of future recurrences. Current treatment guide-lines advocate more or less similar treatment algorithms for all patients. Such approach largely ignores the clinical, genetic, and pathophysiological heterogeneity of BD, which makes certain patients more (or less) likely to respond to specific treatments. Variables such as family history, comorbidity, course of illness, quality and duration of previous remissions, physical and medical comorbidity, and side-effects may help in selecting the most effective treatment for an individual patient, yet their value is not recognized by current algorithms. As well, polymorphisms of specific genes may prove useful in predicting treatment outcome and/or understanding the pharmacological mechanisms of mood stabilization. Novel molecular targets have recently emerged from studies of mechanisms of action of available mood stabilizers. They include inhibitors of protein kinase C, inhibitors of glycogen synthase kinase, or medications modulating glutamatergic neurotransmission. As well, treatment targets are moving beyond acute symptoms and prevention of mood episodes. Cognitive deficits, persistence of residual symptoms, and increased mortality of BD are recognized as important for outcome of BD, yet are not always adequately addressed by traditional treatments.

Hajek T, Carrey N, Alda M. · Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. · Bipolar Disord. · Pubmed #16176432 No free full text.

Abstract: OBJECTIVE: Neuroimaging studies show structural brain abnormalities in bipolar patients. Some of the abnormalities may represent biological risk factors conveying vulnerability for the disease. This paper aims to identify neuroanatomical risk factors for bipolar disorder (BD). METHODS: We reviewed magnetic resonance imaging (MRI) findings in populations in which the effects of the disease or treatment are minimal or where the chances of finding genetically coded risk factors shared within the families are increased. Such populations include unaffected relatives of bipolar patients, first-episode patients, children or adolescents with BD and patients with familial BD. RESULTS: MEDLINE search revealed 30 relevant scientific papers. Abnormalities in the volume of the striatum, left hemispheric white matter, thalamus and anterior cingulate as well as quantitative MRI signal hyperintensities were identified already in unaffected relatives of bipolar patients. Subjects in the early stages of the disease showed volume changes of the ventricles, white matter, caudate, putamen, amygdala, hippocampus and the subgenual prefrontal cortex. Reduction in the subgenual prefrontal cortex volume was replicated in three of four studies in patients with familial BD. CONCLUSIONS: Possible candidates for neuroanatomical risk factors for BD are volumetric abnormalities of the subgenual prefrontal cortex, striatum, white matter, and probably also the hippocampus and amygdala. Qualitative finding of white matter hyperintensities was already utilized as an endophenotype.

MacQueen GM, Hajek T, Alda M. · Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada. · Mol Psychiatry. · Pubmed #15970930 No free full text.

Abstract: The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-term course, comorbid conditions, and response to prophylactic treatment may define groups associated with more or less specific loci. One such group is characterized by symptoms of psychosis and linkage to 13q and 22q. A second group includes mainly bipolar II patients with comorbid panic disorder, rapid mood switching, and evidence of chromosome 18 linkage. A third group comprises typical BD with an episodic course and favourable response to lithium prophylaxis. Reproducibility of cognitive deficits across studies raises the possibility of using cognitive profiles as endophenotypes of BD, with deficits in verbal explicit memory and executive function commonly reported. Brain imaging provides a more ambiguous data set consistent with heterogeneity of the illness.

Alda M, Grof P, Rouleau GA, Turecki G, Young LT. · Department of Psychiatry, Dalhousie University, 5909 Jubilee Road, Halifax, Nova Scotia, Canada B3H 2E2. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #15946781 No free full text.

Abstract: Attempts to map susceptibility genes for bipolar disorder have been complicated by genetic complexity of the illness and, above all by heterogeneity. This paper reviews the genetic research of bipolar disorder aiming to reduce the heterogeneity by focusing on definite responders to long-term lithium treatment. The available evidence strongly suggests that lithium-responsive bipolar disorder is the core bipolar phenotype, characterized by a more prominent role of genetic factors. Responders to lithium have typically a family history of bipolar disorder (often responsive to lithium). They differ from responders to other mood stabilizing drugs in their family histories as well as in other clinical characteristics. The molecular genetic investigations of bipolar disorder responsive to lithium indicate possibly several loci linked to and/or associated with the illness. A combination of research strategies employing multiple methods such as linkage, association, and gene-expression studies will be needed to clarify which of these represent true susceptibility loci.

Alda M. · Department of Psychiatry, Dalhousie University, 5909 Jubilee Road, Halifax, Nova Scotia, Canada B3H 2E2. · Eur Neuropsychopharmacol. · Pubmed #15142614 No free full text.

Abstract: Many findings that seem to be inconsistent in bipolar disorder research could be explained by heterogeneity of the illness and by imprecise diagnostic boundaries. This review of published data finds support for the existence of three main subtypes of bipolar disorder: (1) classical, (2) psychosis spectrum and (3) 'characterological'. These differ with respect to clinical presentation and course of illness, family history and possibly long-term treatment response. For instance, in a series of genetic studies, lithium responders showed an episodic course of illness with a family history of mostly bipolar disorder. In contrast, responders to lamotrigine monotherapy had a rapid-cycling clinical course and frequent comorbid conditions, especially in the anxiety-panic disorder spectrum. Their relatives had elevated rates of anxiety and major depression, but not bipolar disorder. In summary, recognising the clinical and familial subtypes of bipolar disorder might lead to more targeted treatment.

Mamdani F, Groisman IJ, Alda M, Turecki G. · Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada. · Pharmacogenomics J. · Pubmed #15079146 No free full text.

Abstract: Bipolar disorder (BD) is a major psychiatric condition that commonly requires prophylactic and episodic treatment. There is important variability in the therapeutic response and side-effect profiles to currently available pharmacological agents. Pharmacogenetics have provided new hopes to develop more efficient treatment strategies tailored to the individual patient's needs. This review assesses nonsystematically studies using pharmacogenetic strategies in BD. Most of these studies have focused on patients selected according to lithium response, and more recently, a growing number of studies have been investigating genetic factors in mixed samples of patients classified according to response to antidepressant treatment. Although previous clinical and family studies support the use of pharmacogenetic strategies both to increase phenotype homogeneity as well as to identify genetic factors that may mediate response to treatment, most molecular studies carried out to date are still preliminary and in need of external validation. A major problem has been comparability between studies, in part, because of differences in the criteria used to define response. More attention should be paid to standardize the criteria for drug response definition.

Bauer M, Alda M, Priller J, Young LT, Anonymous00102. · Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Campus Charité-Mitte (CCM), Berlin, Germany. · Pharmacopsychiatry. · Pubmed #14677087 No free full text.

Abstract: Bipolar disorder is increasingly recognized as an illness that may progress to impairment in neurocognitive functioning and cell loss in cortical and limbic brain regions. Glutamatergic damage and/or damage due to high glucocorticoid levels that inhibit adult neurogenesis are likely contributing mechanisms. Drug treatments with possible neuroprotective effects are becoming increasingly important both clinically and as research tools. Mood stabilizing drugs and lithium in particular may act to prevent neuronal damage and tissue loss that may occur in the brain of patients with bipolar disorders. Lithium has been shown to exert neuroprotective effects in vitro and to stimulate neurogenesis in the hippocampus. Animal studies have demonstrated pharmacological effects of lithium suggestive of its role in neuroprotection, which range from reducing excitotoxicity through increased glutamate uptake, to regulation of a number of signal transduction intermediates such as myo-inositol, protein kinase C, phosphotidylinositol-3 kinase (PI-3K)/protein kinase B (Akt), ras-mitogen-activated protein kinase (MAPK), glycogen synthase kinase (GSK)-3alpha and -3beta and calcium. It remains to be established whether lithium treatment protects against possible cell damage in the same manner as it protects against recurrences of the illness. We propose to examine the effect of long-term lithium treatment on neurocognitive functioning of bipolar patients and the use of lithium in the treatment of chronic neuropsychiatric disorders.

Mamdani F, Jaitovich Groisman I, Alda M, Turecki G. · Douglas Hospital Research Centre, 6875 LaSalle Boulevard, Verdun, Quebec H4H 1R3, Canada. · Curr Psychiatry Rep. · Pubmed #14609504 No free full text.

Abstract: The importance of genes in the etiology of bipolar disorder has been substantiated through family, twin, and adoption studies. Bipolar disorder is treated at the prophylactic and episodic levels; lithium is one of the most common forms of prophylactic treatment. Recently, pharmacogenetics has come to play an active role in the elucidation of genetic factors that may play a role in modulating lithium response. This strategy has provided hope for advancements in understanding the genetics of lithium-responsive bipolar disorder. This review encompasses studies that have used populations of lithium responders and non-responders to carry out family, linkage, or association studies, as well as some insight into possible mechanisms by which lithium produces its prophylactic effect. Although data examining the pharmacogenetics of bipolar disorder remain scarce, this is a promising avenue of investigation to help genetically define more homogeneous populations or to search for genetic predictors of drug response.

Ruzickova M, Turecki G, Alda M. · Department of Psychiatry, Dalhousie University, Halifax, Canada. · Am J Med Genet C Semin Med Genet. · Pubmed #14601033 No free full text.

Abstract: Bipolar disorder is a severe psychiatric disease characterized by varying treatment response among individual patients. Effects of certain treatments, for instance, lithium, can be predicted from clinical characteristics of patients and their family histories. This led to a suggestion that a treatment response could identify subtypes of bipolar disorder particularly suited for gene-mapping studies. In this paper we review family and molecular studies of bipolar disorder responsive to lithium, as well as studies aiming to identify polymorphisms associated with the treatment response itself. While molecular genetic research and gene expression studies promise to bring new insights into the pathophysiology of the illness and the nature of treatment response, and thus provide new information for better treatment of bipolar disorder in the future, results from family studies and studies of clinical correlates of treatment response may already be utilized in the management of bipolar disorder.

Alda M. · Department of Psychiatry, Dalhousie University, Abbie J. Lane Building, Room 4031, 5909 Jubilee Road, Halifax, Nova Scotia, B3H 2E2, Canada. · Pharmacogenomics. · Pubmed #12517284 No free full text.

Abstract: This paper reviews current knowledge of genetic factors in the treatment of bipolar disorder. Most studies to date have investigated genetic differences between responders and non-responders to lithium. The most provocative findings have been obtained in studies of serotonin transporter gene. Another promising application of pharmacogenetic research is the identification of subgroups of bipolar disorder defined by response (or non-response) to pharmacological treatments. Such subgroups could be used to define more homogeneous patient populations for gene-mapping studies.

Mansour HA, Alda M, Nimgaonkar VL. · Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Room 443, Pittsburgh, PA 15213, USA. · Curr Psychiatry Rep. · Pubmed #11914172 No free full text.

Abstract: To review the pharmacogenetics of bipolar disorders, the authors searched databases for genetic association and linkage studies involving response to long-term prophylactic lithium treatment, as well as treatment with antidepressants or clozapine. Significant ethnic variations in the metabolism and efficacy of antidepressants, as well as clozapine, have been reported by several groups. Systematic studies suggest that that genetic factors affect the response to prophylactic lithium treatment. Numerous associations between the three traits of interest and candidate gene polymorphisms have been proposed. Among these, an association between the serotonin transporter gene and response to serotonin reuptake inhibitors appears robust. Considerable interest has also focused on serotonergic gene polymorphisms and response to clozapine. Response to pharmacotherapy in bipolar disorders may be mediated by genetic factors, but the role played by heritability is unknown.

Alda M. · Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. · Bipolar Disord. · Pubmed #11843781 No free full text.

Abstract: OBJECTIVES: This paper reviews the pharmacogenetics of mood disorders. METHODS: We have searched the literature for published studies and abstracts relevant for genetic effects in acute antidepressant treatment and in long-term prophylactic treatment. RESULTS: The most promising findings to date show an association of the serotonin transporter (5-HTT) gene and the response to serotonin reuptake inhibitors. Genetic factors also appear to play a significant role in the outcome of long-term lithium treatment. The phenotype of lithium-responsive bipolar disorder is associated with stronger genetic effects as well as with an increased phenotypic homogeneity. CONCLUSIONS: Genetic factors likely influence treatment response in mood disorders. Clarifying their precise role will have implications for treatment as well as for understanding the pathophysiological mechanisms of these disorders.

Duffy A, Grof P, Robertson C, Alda M. · Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia. · J Clin Psychiatry. · Pubmed #11030482 No free full text.

Abstract: BACKGROUND: This article is a selective review and synthesis of relevant research findings from genetic studies of major mood disorders and the application of these to clinical practice. METHOD: The article discusses the application of genetic research findings in major mood disorders, including epidemiologic and family study risk estimates, risk modifiers, and the concepts of etiologic and phenotypic heterogeneity, to 3 clinical domains: risk counseling, diagnosis, and treatment prediction. RESULTS: Epidemiologic and family studies have provided general risk estimates useful in counseling mood-disordered patients and their relatives. A complete and accurate family pedigree provides more individualized risk estimates for specific cases and is useful in identifying the phenotypic spectrum of the disorder being transmitted in the family. Both proband course parameters and familial loading for psychiatric illnesses may be relevant for the prediction of treatment response. However, the hypothesis of inherited pharmacologic selectivity remains to be proven. CONCLUSION: Genetic studies of mood disorders have not yet provided conclusive evidence of specific susceptibility genes or their pattern of inheritance. However, they have generated information that is useful to clinical practice.

Alda M. · Department of Psychiatry, Dalhousie University, Halifax, N.S. · J Psychiatry Neurosci. · Pubmed #10212559 links to  free full text

Abstract: Lithium is the first-line treatment for bipolar disorder. In the past, genetic studies have attempted to identify factors associated with positive treatment response or side effects. Several research groups have shown that familial factors, family history of primary bipolar disorder, and negative family history of schizophrenia in particular, correlate well with prophylactic lithium response. Conversely, studies of lithium responsive patients and their families can assist genetic research of bipolar disorder. Lithium responders appear to suffer from a form of bipolar disorder that is more genetically based and more homogeneous. In a series of family studies, the author and his colleagues have confirmed the differences in family histories of lithium responders and nonresponders and shown that the mode of inheritance in lithium responders is compatible with a major-gene model. Subsequently, they initiated an international collaborative study to map the gene(s) predisposing to the illness or treatment response, or both, using both linkage and association strategies. To date, a sample of 32 families, 138 unrelated patients and 163 control subjects has been studied. In these studies, they found support for the role of phospholipase C in lithium responsive bipolar disorder.

Yatham LN, Kennedy SH, Schaffer A, Parikh SV, Beaulieu S, O'Donovan C, MacQueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Young AH, Alda M, Milev R, Vieta E, Calabrese JR, Berk M, Ha K, Kapczinski F. · Department of Psychiatry, University of British Columbia,2255 Wesbrook Mall, Vancouver, BC V6T 2A1, , Canada. · Bipolar Disord. · Pubmed #19419382 No free full text.

Abstract: The Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder in 2005, with a 2007 update. This second update, in conjunction with the International Society for Bipolar Disorders (ISBD), reviews new evidence and is designed to be used in conjunction with the previous publications. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate, and several atypical antipsychotics continue to be first-line treatments for acute mania. Tamoxifen is now suggested as a third-line augmentation option. The combination of olanzapine and carbamazepine is not recommended. For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. New data support the use of adjunctive modafinil as a second-line option, but also indicate that aripiprazole should not be used as monotherapy for bipolar depression. Lithium, lamotrigine, valproate, and olanzapine continue to be first-line options for maintenance treatment of bipolar disorder. New data support the use of quetiapine monotherapy and adjunctive therapy for the prevention of manic and depressive events, aripiprazole monotherapy for the prevention of manic events, and risperidone long-acting injection monotherapy and adjunctive therapy, and adjunctive ziprasidone for the prevention of mood events. Bipolar II disorder is frequently overlooked in treatment guidelines, but has an important clinical impact on patients' lives. This update provides an expanded look at bipolar II disorder.

Berghöfer A, Alda M, Adli M, Baethge C, Bauer M, Bschor T, Glenn T, Grof P, Müller-Oerlinghausen B, Rybakowski J, Suwalska A, Pfennig A. · Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, 10098 Berlin, Germany. · J Clin Psychiatry. · Pubmed #19026269 No free full text.

Abstract: OBJECTIVE: Poor response to long-term lithium treatment has been reported to be associated with atypical features of bipolar disorder. The purpose of this study was to investigate the influence of atypical symptoms on the effectiveness and stability of long-term lithium treatment in a prospective, multicenter cohort of bipolar patients in a naturalistic setting. METHOD: Patients were initially selected according to International Classification of Diseases, 8th Revision, criteria for bipolar disorder and required long-term treatment. Their diagnoses were reconfirmed according to DSM-IV upon its publication. They were prospectively followed for an approximately 20-year period ending in 2004 in 5 centers participating in the International Group for the Study of Lithium-Treated Patients. Examinations included a comprehensive psychiatric evaluation, an assessment of typical and atypical features on an 8-item scale, and an evaluation of clinical course using the morbidity index. Unbalanced repeated-measures regression models with structured covariance matrices were used to assess the extent to which the morbidity index was influenced by atypical symptoms, duration of treatment, and pretreatment features. RESULTS: A total of 242 patients were followed for a mean period of 10 years. In 142 patients, the number of typical features was greater than the number of atypical features, whereas in 100 patients the number of atypical features was greater than or equal to the number of typical features. The mean morbidity index remained stable over a period of 20 years in both groups of patients and was not significantly associated with the presence of atypical features, the duration of lithium treatment, the number or frequency of episodes, or latency from the onset of bipolar disorder to the start of lithium treatment. CONCLUSION: Our study suggests that long-term response to lithium maintenance treatment is stable both in patients with typical and in patients with atypical features. The predominance of either typical or atypical features did not result in different responses to long-term lithium treatment in this sample of bipolar patients.

Passmore MJ, Garnham J, Duffy A, MacDougall M, Munro A, Slaney C, Teehan A, Alda M. · Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. · Bipolar Disord. · Pubmed #12680900 No free full text.

Abstract: OBJECTIVE: We conducted a study of clinical presentation and family history in patients responsive to either of two commonly used mood stabilizers, lithium and lamotrigine. METHODS: The sample included 164 subjects from 21 families of bipolar probands, 14 responders to lithium and seven to lamotrigine. Diagnostic information on first-degree relatives was obtained in a blind fashion through a combination of direct interviews (SADS-L) and family history assessments (FH-RDC). RESULTS: The probands differed with respect to clinical course (episodic in the lithium group, rapid cycling in the lamotrigine group), and comorbidity (panic attacks and substance abuse in the lamotrigine group). The relatives of lithium responders had significantly higher risk of bipolar disorder while relatives of lamotrigine responders had higher prevalence of schizoaffective disorder, major depression and panic attacks. CONCLUSIONS: These findings suggest that lithium- and lamotrigine-responsive patients differ with respect to course of illness, comorbidity and family history and may represent distinct subtypes of bipolar disorder.

Deshauer D, Grof E, Alda M, Grof P. · Royal Ottawa Hospital, Canada. · Biol Psychiatry. · Pubmed #10386185 No free full text.

Abstract: BACKGROUND: While the Dexamethasone Suppression Test (DST) has been extensively used in cross-sectional observations of patients with major affective disorders, studies have tended to ignore the longitudinal application of the DST in patients stabilized on long-term prophylactic medication. METHODS: Monthly DST's were performed on 19 patients, 16 with bipolar disorder and 3 with recurrent major depression. All cases had an excellent response to lithium treatment, and family history positive for bipolar disorder. The average duration of observation was 4 years. RESULTS: All patients remained clinically stable throughout the period of observation. Eleven patients showed intermittent DST positivity ranging from 10% to 60% of tests, and 2 patients exhibited no positivity. Six patients had fewer than 10% positive DST's. Females showed significantly higher positivity than males. The frequency of positivity did not correlate with current age, age of illness onset, duration of illness, duration of lithium treatment, or season. The risk of primary affective disorders in first-degree relatives was also unrelated to the frequency of positivity. CONCLUSIONS: While the highly selected and small sample population limits generalizability, our observations suggest that clinically sufficient lithium prophylaxis does not automatically prevent intermittent HPA dysregulation. We hope that a better understanding of this phenomenon will offer new approaches to the long-term management of mood disorders.

Duffy A, Hajek T, Alda M, Grof P, Milin R, MacQueen G. · Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #19390766 No free full text.

Abstract: INTRODUCTION: Cognitive deficits, including deficits in early information processing, are associated with remitted bipolar disorder. The temporal relationship between these deficits and the clinical course is not known. The current study investigated whether or not deficits in early information processing were present before the onset and/or during the early stages of bipolar disorder. METHODS: Unaffected and remitted high risk offspring of well-characterized bipolar parents completed a visual backward masking task. For comparison we included a cohort of unaffected offspring of well parents and a clinically referred group of remitted bipolar patients. RESULTS: There was no evidence of a deficit in early information processing in well high risk subjects. As expected, the referred patient group had the highest error rates. After excluding the patients, interaction effect showed that the affected remitted high risk subjects performed differently in terms of error rates than unaffected high risk and control subjects. There were no significant differences in response times across study groups. Exploratory analyses revealed an association between a lifetime history of psychosis and increased errors on the task. CONCLUSIONS: There was no evidence of a vulnerability in early information processing in offspring at risk for bipolar disorder. However, there were emergent changes in performance in the affected remitted high risk group. Psychosis appears to be an important clinical correlate associated with cognitive deficits. Mapping of the early course of bipolar disorder and associated changes in cognition has important implications for establishing critical periods for intervention.

Etches SM, Schmidt M, Alda M, Hajek T, Kahn DA. · Columbia University Department of Psychiatry, New York, NY, USA. · J Psychiatr Pract. · Pubmed #19339849 No free full text.

Abstract: Cerebral infarction producing psychiatric disorders such as depression and mania is a recognized phenomenon. However, resolution of affective disorders following stroke has not been previously reported. We describe the case of a 53-year-old woman with a 25-year history of treatment-resistant bipolar II and panic disorders. At the age of 46, she experienced a subarachnoid hemorrhage with secondary vasospasm that resulted in a stroke. Shortly following the hemorrhage, the patient experienced a complete remission of both psychiatric illnesses that has been sustained for 7 years. Initial computed tomography (CT) and angiography studies revealed subarachnoid hemorrhage with intraventricular extension, communicating hydrocephalus, and aneurysms of the left posterior communicating artery and the right anterior cerebral artery. Following clipping of the left internal posterior communicating artery aneurysm, the patient developed vasospasm with further stroke symptoms. A subsequent CT scan showed a fully developed ischemic infarct in the left temporoparietal region that was confirmed by follow-up magnetic resonance imaging (MRI). We present a 7-year follow-up with complete psychiatric interview, chart review, and MRI. The present case demonstrates the importance of continued efforts to localize neural circuits involved in the pathogenesis and maintenance of affective disorders.

Bauer M, Glenn T, Grof P, Rasgon N, Alda M, Marsh W, Sagduyu K, Schmid R, Adli M, Whybrow PC. · Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. · J Affect Disord. · Pubmed #19118904 No free full text.

Abstract: BACKGROUND: Psychosocial interventions may teach patients with bipolar disorder to successfully detect warning signs of relapse. These interventions often include ongoing self-monitoring of sleep. We previously reported that a change in sleep duration (sleep plus bedrest) of >3 h may indicate that a mood change is imminent. This analysis further investigated whether sleep duration, sleep onset or sleep offset was the most useful sleep/wake parameter to monitor for an oncoming mood change. METHODS: 101 adult outpatients receiving treatment as usual recorded mood, sleep and medications every day on a home computer for a mean of 265+/-103 days. A daily time series of mood, sleep duration (sleep plus bedrest), sleep onset and sleep offset was constructed for each patient. After applying an ARIMA (0,1,1) filter, a cross correlation function was used to analyze the temporal relationship between the residuals for lags of +/-7 days. RESULTS: Less frequent significant correlations were found between a change in either sleep onset or sleep offset and mood, than between sleep duration and mood. Patients with a significant correlation between sleep duration and mood included 86% of those with a significant correlation between sleep onset or sleep offset and mood. Mean sleep duration when euthymic was long (> or =8 h in 89% of patients, > or =9 h in 51% of patients). LIMITATIONS: Self-reported data, naturalistic study, and computer access required. CONCLUSIONS: Self-monitoring of sleep duration is recommended for patients with bipolar disorder. Better understanding of the long sleep duration of euthymic patients is required.

Bauer M, Glenn T, Grof P, Rasgon NL, Marsh W, Sagduyu K, Alda M, Murray G, Quiroz D, Malliaris Y, Sasse J, Pilhatsch M, Whybrow PC. · Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany Fetscherstr. 74, 01307 Dresden, Germany. · J Affect Disord. · Pubmed #19091424 No free full text.

Abstract: OBJECTIVE: Many researchers have analyzed seasonal variation in hospital admissions for bipolar disorder with inconsistent results. We investigated if a seasonal pattern was present in daily self-reported daily mood ratings from patients living in five climate zones in the northern and southern hemispheres. We also investigated the influence of latitude and seasonal climate variables on mood. METHOD: 360 patients who were receiving treatment as usual recorded mood daily (59,422 total days of data). Both the percentage of days depressed and hypomanic/manic, and the episodes of depression and mania were determined. The observations were provided by patients from different geographic locations in North and South America, Europe and Australia. These data were analyzed for seasonality by climate zone using both a sinusoidal regression and the Gini index. Additionally, the influence of latitude and climate variables on mood was estimated using generalized linear models for each season and month. RESULTS: No seasonality was found in any climate zone by either method. In spite of vastly different weather, neither latitude nor climate variables were associated with mood by season or month. CONCLUSION: Daily self-reported mood ratings of most patients with bipolar disorder did not show a seasonal pattern. Neither climate nor latitude has a primary influence on the daily mood changes of most patients receiving medication for bipolar disorder.

Hajek T, Gunde E, Slaney C, Propper L, MacQueen G, Duffy A, Alda M. · Department of Psychiatry, Dalhousie University, 5909 Veteran's Memorial Lane, Halifax, Canada. · J Psychiatr Res. · Pubmed #19046588 No free full text.

Abstract: BACKGROUND: Striatal volume changes reported in bipolar disorders could represent artifacts of medication or comorbid conditions, or illness related changes, either biological predispositions or consequences of illness burden. We conducted volumetric high-risk study to investigate whether striatal volume changes represent primary biological risk factor for bipolar disorders. METHODS: High-risk (HR) participants (age range 15-30 years) were recruited from families multiply affected with bipolar disorders. They included 20 affected and 26 unaffected offspring of parents with primary mood disorders, matched by age and sex with 31 controls without a personal or family history of psychiatric disorders. Striatal volumes were measured on 1.5T 3D anatomical MRI images using standard methods. RESULTS: There was a significant difference between groups (affected, unaffected HR and control subjects) in caudate volumes (F=3.50, DF=2; 74 and p=0.04) in absence of putamen volume changes. The caudate volumes were largest in unaffected HR subjects without differences between affected and control or affected and unaffected HR subjects. The maximum changes were found in the head of the caudate. Controlling for non-independence of observations in multiple subjects per family yielded non-significant differences. CONCLUSIONS: Despite the biological plausibility, partial agreement with previous studies and nominal statistical significance, controlling for non-independence of observations within families changed the increased caudate volumes among unaffected subjects to non-significant. We thus present these findings as negative, pending further replication. Striatal volume abnormalities did not meet criteria for endophenotype in this study.