Genetic linkage in bipolar disorder

Bipolar disorder is an etiologically complex syndrome that is clearly heritable. Multiple genes, working singly or in concert, are likely to cause susceptibility to bipolar disorder. Bipolar disorder genetics has progressed rapidly in the last few decades. However, specific causal genetic mutations for bipolar disorder have not been identified. Both candidate gene studies and complete genome screens have been conducted. They have provided compelling evidence for several potential bipolar disorder susceptibility loci in several regions of the genome. The strongest evidence suggests that bipolar disorder susceptibility loci may lie in one or more genomic regions on chromosomes 18, 4, and 21. Other regions of interest, including those on chromosomes 5 and 8, are also under investigation. New approaches, such as the use of genetically isolated populations and the use of endophenotypes for bipolar disorder, hold promise for continued advancement in the search to identify specific bipolar disorder genes.     

Suicidality in bipolar I disorder

People with bipolar disorder are at high suicide risk. The literature suggests that suicidality is predicted by higher symptom severity and less use of pharmacological agents, but few studies have examined the joint contributions of these variables. The present study examines the conjoint contribution of symptom severity and pharmacological treatment to suicidal ideation and behavior among participants with bipolar disorder. The model was able to account for 53% of the variance in suicidality scores. Depression, mixed state, and hopelessness were significantly associated with suicidality. All other variables were nonsignificant once symptom severity had been controlled. Implications for future research are described.     

Gender differences in major depressive disorder and bipolar disorder

This paper reviews the literature on gender differences in major depressive disorder (MDD) and bipolar disorder (BPD). Beginning in adolescence, women are at a higher risk than men of becoming depressed. Avenues of investigation that might ultimately help to explain this phenomenon include studies of gender differences in the processing of emotional stimuli, the psychotropic effects of gonadal steroids, and environment/gene interactions in men and women. With the exception of the elevated suicide rate among men, consistent gender differences in the course and symptoms of MDD have not been found. In BPD, women are more likely than men to develop a rapid-cycling course. Gender differences in treatment response, particularly in regard to mood stabilizing medications, warrant further study.     

Generalizability of evidence-based assessment recommendations for pediatric bipolar disorder

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 that incorporate Bayesian reasoning have demonstrated improved diagnostic accuracy and consistency; however, their clinical utility is largely unexplored. The present study examines the effectiveness of promising evidence-based decision-making strategies compared with the clinical gold standard. Participants were 562 youths, ages 5 to 17 and predominantly African American, drawn from a community mental health clinic. Research diagnoses combined a semistructured interview with youths' psychiatric, developmental, and family mental health histories. Independent Bayesian estimates that relied on published risk estimates from other samples discriminated bipolar diagnoses (area under curve = .75, p < .00005). The Bayes and confidence ratings correlated at rs = .30. Agreement about an evidence-based assessment intervention threshold model (wait/assess/treat) was κ = .24, p < .05. No potential moderators of agreement between the Bayesian estimates and confidence ratings, including type of bipolar illness, were significant. Bayesian risk estimates were highly correlated with logistic regression estimates using optimal sample weights (r = .81, p < .0005). Clinical and Bayesian approaches agree in terms of overall concordance and deciding next clinical action, even when Bayesian predictions are based on published estimates from clinically and demographically different samples. Evidence-based assessment methods may be useful in settings in which gold standard assessments cannot be routinely used, and they may help decrease rates of overdiagnosis while promoting earlier identification of true cases.     

A psychoanalytic interpretation of bipolar disorder

Abstract

The author proposes viewing mania as a form of defense against the state of depression resulting from “narcissistic overidentification with the depressive object” (i.e., the object in relation to which the depressive state developed), rather than as a periodic rebellion against such an internalized object. An account of the analytic psychotherapy of a clinical case of bipolar depression serves to illustrate this point of view, linked to the author’s specific conception of the dynamics of depression.     

Brain network dysfunction in bipolar disorder

Bipolar disorder is a common psychiatric condition with significant associated morbidity and mortality. Despite its significance, the neurophysiology and neuropathology of this illness is incompletely understood. Recent advances in neuroimaging techniques have helped to begin clarifying these areas. Specifically, bipolar disorder appears to arise from abnormalities within discrete brain networks (eg, the anterior limbic network). The expression of the symptoms of bipolar disorder does not appear to result from single, localized brain lesions, but rather are emergent properties of dysfunction of these brain networks. As neuroimaging techniques continue to improve, the underlying neural basis of bipolar disorder will be clarified.     

Studies of anticipation in bipolar affective disorder

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

New anticonvulsant medication uses in bipolar disorder

Therapy of bipolar disorders is a rapidly evolving field. Lithium has efficacy in classic bipolar disorders whereas divalproex sodium and carbamazepine may have broader spectrum efficacy that includes non-classic bipolar disorder. In the last 10 years, a series of anticonvulsants have been approved for marketing in the United States. Gabapentin has indirect g-aminobuytric acid-ergic actions, is generally well tolerated, and appears to have anxiolytic, analgesic, and hypnotic effects. Lamotrigine has antiglutamatergic actions and is generally well tolerated (aside from rash in 1 in 10, and serious rash in 1 in 1,000 patients). Lamotrigine is indicated for maintenance treatment in bipolar disorder. Emerging evidence suggests lamotrigine may have utility in bipolar disorder patients with depression and treatment-refractory rapid cycling, as well as analgesic effects. Topiramate and zonisamide may allow both weight loss, while topiramate may have specific efficacy in bulimia, binge eating disorder, and alcohol dependence. Two small studies found oxcarbazepine had similar efficacy to lithium and haloperidol in acute mania. Phenytoin, an older anticonvulsant, may have adjunctive acute mania efficacy. Levetiracetam, a newer anticonvulsant, may be worth exploring and has minimal drug-drug interactions. None of these newer agents has been shown effective in a large placebo controlled trial for acute mania. Although the clinical profiles of these newer anticonvulsants do not appear to overlap markedly with divalproex and carbamazepine (except perhaps for oxcarbazepine), these novel agents may still offer important new options in relieving a variety of specific target symptoms in patients with bipolar disorder.     

Family transactions and relapse in bipolar disorder

This study examined whether patient symptoms and relatives' affective behavior, when expressed during directly observed family interactions, are associated with the short-term course of bipolar disorder. Twenty-seven bipolar patients and their relatives participated in two 10-minute family interactions when patients were discharged after a manic episode. Results indicated that patients who showed high levels of odd and grandiose thinking during the interactions were more likely to relapse during a 9-month followup period than patients who did not show these symptoms during the family discussions. Relapse was also associated with high rates of harshly critical and directly supportive statements by relatives. Patients' odd thinking and relatives' harsh criticism were significantly more likely to be correlated when patients relapsed (r = .53) than when they did not relapse (r = .12). Results suggest that bipolar patients who show increased signs of residual symptomatology during family transactions during the post-hospital period are at increased relapse risk. The data also suggest that relatives of relapsing patients cope with these symptoms by increasing both positive and negative affective behaviors. Moreover, a bidirectional, interactional relationship between patients' symptoms and relatives' coping style seems to capture best the role of the family in predicting relapse in bipolar disorder.     

Attentional bias in euthymic bipolar I disorder

Little is known about the nature of the relation between information-processing biases and affective traits in bipolar disorder. The present study was designed to investigate whether attentional biases are evident in persons diagnosed with bipolar disorder when they are in a positive mood state, and whether biases are related to indices of emotion regulation and to prior history of mood episodes. Ninety adults diagnosed with bipolar I disorder and 81 controls with no lifetime mood disorder underwent a positive mood induction and then completed an emotion face dot-probe task; participants in the bipolar disorder group also completed a self-report measure of responses to positive affect. Attentional bias was not related to a diagnosis of bipolar disorder or to symptom severity. Consistent with hypotheses, analyses within the bipolar group indicated that greater dampening of positive affect related to significantly less attention paid to the positively valenced faces. Discussion focuses on the potential role of affective traits in shaping attentional bias in bipolar disorder.     

Adjunctive psychotherapy for bipolar disorder: effects of changing treatment modality

In a randomized, controlled trial, the authors studied an adjunctive, individual psychotherapy, interpersonal and social rhythm therapy (IPSRT) for bipolar disorder. After stabilizing participants with episode appropriate pharmacotherapy and either IPSRT or intensive clinical management (CM), participants were reassigned to IPSRT or CM in conjunction with pharmacotherapy for 2 years of preventative treatment. Early results (n = 82) suggest that altering participants' treatment assignment at entry to the preventative phase is related to risk of recurrence. Participants remaining in the same treatment for both acute and preventative phases had lower rates of recurrence (< 20% vs. > 40%) and levels of symptomatology over the subsequent 52 weeks than those reassigned to the alternate modality. This finding, consistent with the authors' philosophy that bipolar patients benefit from stable routines, suggests that disruptions in the psychosocial treatment plan contribute to worse outcomes.     

Elevated ambitions for fame among persons diagnosed with bipolar I disorder

A growing body of evidence suggests that people with bipolar disorder are highly goal-oriented. Compared to other persons, they expend more effort to attain rewards and view goal pursuit as more important to their self-worth. Persons at risk for mania and those diagnosed with bipolar spectrum disorders have been shown to endorse highly ambitious life goals, such as becoming a multimillionaire or achieving fame. This study is the first examination of whether such elevated goals characterize persons diagnosed with bipolar I disorder. We also examined whether elevated ambitions predicted symptom change over time. Ninety-two persons with bipolar I disorder and 81 age- and sex-matched controls completed the Willingly Approached Set of Statistically Unlikely Pursuits, a measure of extremely high life ambitions. A subset of the bipolar participants completed a 3-month follow-up interview. Participants with bipolar disorder endorsed higher ambitions for popular fame than did controls; moreover, heightened ambitions for popular fame and financial success predicted increases in manic symptoms in those with bipolar disorder over the next three months. Discussion focuses on goal regulation in bipolar disorder.