Depressive and manic symptoms are not opposite poles in bipolar disorder

Johnson SL, Morriss R, Scott J, Paykel E, Kinderman P, Kolamunnage‐Dona R, Bentall RP. Depressive and manic symptoms are not opposite poles in bipolar disorder. Objective: This study of 236 individuals with bipolar disorders employed longitudinal analyses to determine whether the symptoms of mania and depression can be understood as one dimension (with depression and mania as opposites) or two relatively independent dimensions. Method: Weekly severity ratings of manic and depression were assessed using the Longitudinal Interval Follow‐up Evaluation‐II for 72 weeks. The within‐subjects correlation of manic and depressive severity was examined using random effects regression. Results: Contrary to the one‐dimension model, mania and depression symptoms were not negatively related. Indeed, the correlations of mania with depressive symptoms were quite small. Conclusion: The data suggest that depressive and manic symptoms are not opposite poles. Rather depressive and manic symptoms appear to fluctuate relatively independently within bipolar disorder.     

Changes in insight among patients with bipolar I disorder: a 2-year prospective study

OBJECTIVES: The aim of this 2-year prospective study was to examine changes in insight among bipolar patients with different clinical courses. METHODS: A cohort of 65 patients with bipolar I disorder in remission was recruited for this study. They received six follow-up assessments over a 2-year period. The Schedule of Assessment of Insight-Expanded version (SAI-E) was used to determine their levels of insight, while the Young Mania Rating Scale (YMRS) and the Hamilton Rating Scale for Depression (HAM-D) were used to determine affective symptoms. Types of changes in insight among bipolar patients were analyzed according to the different clinical courses during the 2-year follow-up period. RESULTS: Insight in consistently stable patients was steady during the 2-year period. Insight decreased during the manic period in patients with only a single manic episode as well as in those with repeated manic episodes. However, insight returned to the pre-episode level for patients with only a single manic episode, but did not for most of the patients with repeated episodes. No changes in insight were observed during depressive episodes for either patients with a single or those with repeated depressive episodes. CONCLUSIONS: The types of insight changes among bipolar patients during the 2-year period were various and depended on the different clinical courses. Frequent mood disturbance episodes may cause patient insight to deteriorate.     

Juvenile bipolar disorder

OBJECTIVE: Bipolar disorder in children and adolescents is less well studied than bipolar disorder in adults. This review addresses issues related to its underdiagnosis, precursors of bipolarity, comorbidity, natural course and treatment. METHOD: Literature from Medline and other searches, and earlier relevant articles including references from recent review articles on juvenile bipolarity were reviewed. RESULTS: Bipolar disorder in juveniles is underdiagnosed and misdiagnosed on various counts. Few recent studies have reported high rates of comorbid attention deficit and disruptive disorders, prompting some researchers to consider them as probable developmental precursors of juvenile bipolarity. There is also evidence to suggest that some juvenile depression could be pre-bipolar, and that certain temperamental predispositions are probable precursors to bipolarity. Limited data on the natural course and outcome suggest that juvenile bipolar disorder is a highly recurring illness as in adults, and that it is associated with significant functional impairment. The psychopharmacological treatment of juvenile bipolar disorder is remarkably understudied, and treatment is often based on studies of adults. CONCLUSION: There is a need for epidemiological studies of juvenile bipolar disorder. Similarly, there is an urgent need for the methodologically rigorous studies to establish the efficacy of various antimanic drugs. Finally, issues related to comorbidity and temperamental predispositions to juvenile bipolarity need greater clarity, as they may have important treatment and research implications.     

The role of dopamine in bipolar disorder

Objective: Despite effective pharmacological treatments for bipolar disorder, we still lack a comprehensive pathophysiological model of the illness. Recent neurobiological research has implicated a number of key brain regions and neuronal components in the behavioural and cognitive manifestations of bipolar disorder. Dopamine has previously been investigated in some depth in bipolar disorder, but of late has not been a primary focus of attention. This article examines the role of dopamine in bipolar disorder, incorporating recent advances into established models where possible. Methods: A critical evaluation of the literature was undertaken, including a review of behavioural, neurochemical, receptor, and imaging studies, as well as genetic studies focusing on dopamine receptors and related metabolic pathways. In addition, pharmacologic manipulation of the central dopaminergic pathways and comparisons with other disease states such as schizophrenia were considered, principally as a means of exploring the hypothesised models. Results: Multiple lines of evidence, including data from pharmacological interventions and structural and functional magnetic resonance imaging studies, suggest that the dopaminergic system may play a central role in bipolar disorder. Conclusion: Future research into the pathophysiological mechanisms of bipolar disorder and the development of new treatments for bipolar disorder should focus on the dopaminergic system.     

Evidence-based options for treatment-resistant adult bipolar disorder patients

Poon SH, Sim K, Sum MY, Kuswanto CN, Baldessarini RJ. Evidence‐based options for treatment‐resistant adult bipolar disorder patients. Bipolar Disord 2012: 14: 573–584. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Many patients diagnosed with bipolar disorder (BD) respond incompletely or unsatisfactorily to available treatments. Given the potentially devastating nature of this prevalent disorder, there is a pressing need to improve clinical care of such patients. Methods: We performed a literature review of the research findings related to treatment‐resistant BD reported through February 2012. Results: Therapeutic trials for treatment‐resistant bipolar mania are uncommon, and provide few promising leads other than the use of clozapine. Far more pressing challenges are the depressive‐dysthymic‐dysphoric‐mixed phases of BD and long‐term prophylaxis. Therapeutic trials for treatment‐resistant bipolar depression have assessed anticonvulsants, modern antipsychotics, glutamate [N‐methyl‐D‐aspartate (NMDA)] antagonists, dopamine agonists, calcium‐channel blockers, and thyroid hormones, as well as behavioral therapy, sleep deprivation, light therapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation, and deep brain stimulation—all of which are promising but limited in effectiveness. Several innovative pharmacological treatments (an anticholinesterase, a glutamine antagonist, a calcium‐channel blocker, triiodothyronine, olanzapine and topiramate), ECT, and cognitive‐behavior therapy have some support for long‐term treatment of resistant BD patients, but most of trials of these treatments have been methodologically limited. Conclusions: Most studies identified were small, involved supplementation of typically complex ongoing treatments, varied in controls, randomization, and blinding, usually involved brief follow‐up, and lacked replication. Clearer criteria for defining and predicting treatment resistance in BD are needed, as well as improved trial design with better controls, assessment of specific clinical subgroups, and longer follow‐up.     

Treatment of bipolar disorder in older adults

BACKGROUND: It has been reported that 10% of all patients with bipolar disorder develop their illness after the age of 50, with bipolar disorder accounting for 5-19% of mood disorder presentations in the elderly. There has been a growing awareness regarding the manifestation of bipolar disorder among older adults due to both changes in national demographics, and developing sophistication in the treatment of bipolar illness. A persistent problem in our understanding of management of late life bipolar disorder is the paucity of research and rigorous published studies on the psychopharmacology of this condition. OBJECTIVE: This paper reviews medication treatments, non-medication biological therapies, and psychosocial interventions for bipolar disorder in late life with a particular emphasis on age related modifiers of treatment. METHODS: Findings are based upon review of the current literature. RESULTS: There are multiple, significant gaps in our knowledge of bipolar disorder in late life which have important implications in the optimum treatment of elderly individuals with bipolar illness. CONCLUSION: There are a number of areas of needed future research in late life bipolar disorder.     

Polarity at illness onset in bipolar I disorder and clinical course of illness

Objectives:  Studies have suggested that episode polarity at illness onset in bipolar disorder may be predictive of some aspects of lifetime clinical characteristics. We here examine this possibility in a large, well-characterized sample of patients with bipolar I disorder.
Methods:  We assessed polarity at onset in patients with bipolar I disorder (N = 553) recruited as part of our ongoing studies of affective disorders. Lifetime clinical characteristics of illness were compared in patients who had a depressive episode at first illness onset (n = 343) and patients who had a manic episode at first illness onset (n = 210).
Results:  Several lifetime clinical features differed between patients according to the polarity of their onset episode of illness. A logistic regression analysis showed that the lifetime clinical features significantly associated with a depressive episode at illness onset in our sample were: an earlier age at illness onset; a predominantly depressive polarity during the lifetime; more frequent and more severe depressive episodes; and less prominent lifetime psychotic features.
Conclusions:  Knowledge of pole of onset may help the clinician in providing prognostic information and management advice to an individual with bipolar disorder.     

Aggression and substance abuse in bipolar disorder

Objectives:  The goal of this retrospective study was to examine factors differentiating persons with bipolar disorder who did or did not have comorbid lifetime substance use disorders (SUD) at an index assessment. We also explored the chronology of onset of mood and SUD.
Methods:  We studied 146 subjects with DSM-defined bipolar disorder. Subgroups with and without lifetime SUD were compared on demographic and clinical measures.
Results:  Substance abuse disorders in this bipolar sample were associated with male sex, impulsive-aggressive traits, comorbid conduct and Cluster B personality disorders, number of suicide attempts and earlier age at onset of a first mood episode. In a multivariable logistic regression analysis, male sex and aggression and possibly earlier age at mood disorder onset were associated with SUD. In those with or without SUD, the first mood episode tended to be depressive and to precede the onset of SUD.
Conclusions:  In persons with bipolar disorder, an earlier age of onset and aggressive traits appear to be factors associated with later development of comorbid SUD.     

Association of clinical symptoms and neurocognitive performance in bipolar disorder: a longitudinal study

Chaves OC, Lombardo LE, Bearden CE, Woolsey MD, Martinez DM, Barrett JA, Miller AL, Velligan DI, Glahn DC. Association of clinical symptoms and neurocognitive performance in bipolar disorder: a longitudinal study.
Bipolar Disord 2011: 13: 118–123. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objective: Despite evidence that individuals with bipolar disorder have neurocognitive impairment that persists during euthymia, the impact of changes in affective symptoms on cognitive function has not been well established. Here, we sought to determine whether specific neurocognitive functions are sensitive to mood changes in individuals with bipolar disorder assessed three months apart without changes in treatment regimen. Methods: A total of 29 individuals with DSM‐IV bipolar disorder and 30 healthy controls participated in the study. All participants received a comprehensive neuropsychological assessment and ratings of depressive [Hamilton Depression Rating Scale (HAMD)] and manic [Young Mania Rating Scale (YMRS)] symptoms at baseline and follow‐up. Changes in symptoms over time were calculated and were examined in relation to changes in neurocognitive performance. Results: At baseline, clinically stable but symptomatic patients were impaired on measures of speed of processing and attention. Over the three‐month follow‐up period, HAMD scores changed by 6 points on average [range: ?10 to +18] and YMRS scores changed by 5.31 points on average [range ?11 to +15]. Changes in depressive symptoms were correlated with poorer verbal fluency, while no relationship between manic symptoms and neuropsychological performance was detected. Conclusions: Individuals with bipolar disorder showed consistent impairment on speed of processing and attention over time, despite significant changes in mood.     

Late-onset bipolar disorder due to hyperthyroidism.

OBJECTIVE: Bipolar disorder starts typically in early age and late-onset cases are rare. Late-onset cases are more likely to have comorbid medical illnesses responsible for them. This case report highlights late-onset bipolar disorder due to hyperthyroidism. METHOD: A 65-year-old patient of bipolar disorder has been described. RESULT: Physical examination and laboratory investigations detected presence of hyperthyroidism and the patient was treated with antithyroid and anxiolytics. CONCLUSION: A thorough examination and investigation are required in late-onset cases of bipolar disorder to rule out secondary causes. Definitive antimanic agents or mood stabilizers may not be required in such cases.     

Carbamazepine extended-release capsules in bipolar disorder

Carbamazepine (CBZ) has long been a therapeutic option for bipolar disorder. Carbamazepine extended-release capsules (CBZ-ERC) are a recent formulation of CBZ approved by the US Food and Drug Administration in 2004 for the treatment of acute manic and mixed episodes associated with bipolar I disorder. This new formulation was developed to improve dosing convenience and decrease daily fluctuations in serum CBZ concentration, thereby lowering the incidence of adverse events. Two randomized, double-blind, placebo-controlled trials and an open-label extension study have demonstrated that CBZ-ERC monotherapy is efficacious in patients with bipolar I disorder experiencing either manic or mixed episodes. In these trials, CBZ-ERC was shown to be a safe and well-tolerated therapy. Retrospective chart reviews conducted in private practice settings have shown that clinical response to CBZ-ERC is independent of bipolar subtype, as patients with bipolar I depression and bipolar II disorder responded similarly to patients with bipolar I disorder either manic or mixed episodes. CBZ is currently considered a treatment alternative to lithium and valproate according to the American Psychiatric Association’s treatment guidelines for patients with bipolar disorder. Although further study is required, the clinical evidence presented in these studies may change the treatment paradigm.     

Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder

BACKGROUND: As patients with mood disorders manifest heterogeneity in phenomenology, pathophysiology, etiology, and treatment response, a biological classification of mental disease is urgently needed to advance research. Patient and methodological variability complicates the comparison of neuroimaging study results and limits heuristic model development and a biologically-based diagnostic schema. OBJECTIVE: We have critically reviewed and compared the magnetic resonance neuroimaging literature to determine the degree and directionality of volumetric changes in brain regions putatively implicated in the pathophysiology of major depressive disorder (MDD) versus bipolar disorder (BD). METHODS: A total of 140 published magnetic resonance imaging investigations evaluating subjects with BD or MDD were selected to provide a summary and interpretation of volumetric neuroimaging results in MDD and BD. Further commentary on the pathophysiological implications, and putative cellular and pharmacological mechanisms, is also provided. RESULTS: While whole brain volumes of patients with mood disorders do not differ from those of healthy controls, regional deficits in the frontal lobe, particularly in the anterior cingulate and the orbitofrontal cortex, appear to consistently differentiate subjects with mood disorders from the general population. Preliminary findings also suggest that subcortical structures, particularly the striatum, amygdala, and hippocampus, may be differentially affected in MDD and BD. CONCLUSIONS: Structural neuroimaging studies have consistently identified regional abnormalities in subjects with mood disorders. Future studies should strive to definitively establish the influence of age and medication.     

Social competence and observer-rated social functioning in bipolar disorder

Depp CA, Mausbach BT, Harvey PD, Bowie CR, Wolyniec PS, Thornquist MH, Luke JR, McGrath JA, Pulver AE, Patterson TL. Social competence and observer‐rated social functioning in bipolar disorder.
Bipolar Disord 2010: 12: 843–850. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objective: Impairment in social functioning appears to be common in bipolar disorder, although estimates have been derived largely from self‐report measures. We examined performance‐based and observer‐based ratings of social competence and functioning and assessed the contribution of symptoms and neurocognitive ability to social functioning in bipolar disorder. Methods: In this cross‐sectional study, 164 subjects with bipolar disorder were administered the performance‐based Social Skills Performance Assessment (SSPA), rated by an informant on the Specific Level of Functioning (SLOF)–Interpersonal subscale, received clinical ratings of depression and manic symptoms, and performed neurocognitive tests. We assessed the proportion of patients exhibiting social deficits and examined the associations between composite measures of neurocognitive ability, depression and manic symptoms, and SSPA scores with informant‐rated, real‐world social functioning. Results: Mean age of the sample was 47.6 years (SD = 14.1). Subjects were experiencing, on average, mild levels of depression and minimal manic symptoms. A total of 29% exhibited norm‐referenced impairment on the SSPA, and 64% registered at least one impairment on SLOF items; unemployed subjects had lower SSPA and SLOF ratings. Neurocognitive performance correlated with both performance‐based and observer‐rated social functioning, whereas depressive and manic symptoms correlated only with observer‐rated social impairments. In multivariate models, depression was the most potent association with social functioning, and impairment in social competence (i.e., capacity) increased the strength of the relationships between depression and neurocognitive impairment and social functioning (i.e., real‐world functioning). Conclusions: Our study confirmed the negative relationship of bipolar depression with social functioning. A subgroup of outpatients with bipolar disorder has impaired social competence, which, when present, worsened the impact of depression and cognitive impairment on social functioning.