Neurocognitive endophenotypes for bipolar disorder identified in multiplex multigenerational families.

CONTEXT: Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, a strategy for identifying risk genes is to identify and map quantitative intermediate phenotypes or endophenotypes. OBJECTIVE: To adjudicate neurocognitive endophenotypes for bipolar disorder. DESIGN: All participants underwent diagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which test results are impaired in affected individuals, are sensitive to the genetic liability for the illness, and are genetically correlated with affection status. SETTING: Central valley of Costa Rica; Mexico City, Mexico; and San Antonio, Texas. PARTICIPANTS: Seven hundred nine Latino individuals participated in the study. Of these, 660 were members of extended pedigrees with at least 2 siblings diagnosed as having bipolar disorder (n = 230). The remaining subjects were community control subjects drawn from each site who did not have a personal or family history of bipolar disorder or schizophrenia. MAIN OUTCOME MEASURE: Neurocognitive test performance. RESULTS: Two of the 22 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 cognitive measures compared with nonrelated healthy controls. Nonbipolar first-degree relatives were impaired on 5 of these, and the following 3 tests were genetically correlated with affection status: Digit Symbol Coding Task, Object Delayed Response Task, and immediate facial memory. CONCLUSION: This large-scale extended pedigree study of cognitive functioning in bipolar disorder identifies measures of processing speed, working memory, and declarative (facial) memory as candidate endophenotypes for bipolar disorder.

Social and clinical comparison between schizophrenia and bipolar disorder type I with psychosis in Costa Rica.

INTRODUCTION: Schizophrenia (SC) and bipolar disorder (BP) are two of the most severe and incapacitating mental disorders. It has been questioned whether these two conditions designate distinct illnesses with different etiologies or whether they represent different ends of a clinical spectrum with a common etiology. MATERIALS AND METHODS: This study compares social and clinical characteristics of 84 SC and 84 BP subjects from the Costa Rican Central Valley (CRCV) using information from the DIGS, FIGS and psychiatric records. Each of these subjects had a best estimate lifetime consensus diagnosis of either bipolar type I or SC. RESULTS: Subjects with SC differed from subjects with BP in social adjustment measures like marital and employment status, and number of children. Both groups were very similar in years of education, age of onset of their illness, history of other psychiatric co-morbidities, and treatment received. DISCUSSION: The high percentage of psychosis in the BP group (97.6%) may largely explain the similarities found between groups in their clinical characteristics. CONCLUSION: The differences in social and functional decline support the original dichotomy described by Kraepelin based on chronicity and periodicity between these two psychotic disorders.

Conceptualizing impulsivity and risk taking in bipolar disorder: importance of history of alcohol abuse.

BACKGROUND: Elevated levels of impulsivity and increased risk taking are thought to be core features of both bipolar disorder (BD) and addictive disorders. Given the high rates of comorbid alcohol abuse in BD, alcohol addiction may exacerbate impulsive behavior and risk-taking propensity in BD. Here we examine multiple dimensions of impulsivity and risk taking, using cognitive tasks and self-report measures, in BD patients with and without a history of alcohol abuse. METHODS: Thirty-one BD subjects with a prior history of alcohol abuse or dependence (BD-A), 24 BD subjects with no history of alcohol abuse/dependence (BD-N), and 25 healthy control subjects (HC) were assessed with the Barratt Impulsiveness Scale (BIS) and the computerized Balloon Analogue Risk Task (BART). RESULTS: Both BD groups scored significantly higher than controls on the BIS. In contrast, only the BD-A group showed impaired performance on the BART. BD-A subjects popped significantly more balloons than the BD-N and HC groups. In addition, subjects in the BD-A group failed to adjust their performance after popping balloons. Severity of mood symptomatology was not associated with performance on either task. DISCUSSION: The current study supports a primary role of prior alcohol abuse in risk-taking propensity among patients with bipolar disorder. In addition, findings suggest that impulsivity and risky behavior, as operationalized by self-report and experimental cognitive probes, respectively, are separable constructs that tap distinct aspects of the bipolar phenotype.

The neurocognitive signature of psychotic bipolar disorder.

BACKGROUND: Psychotic bipolar disorder may represent a neurobiologically distinct subgroup of bipolar affective illness. We sought to ascertain the profile of cognitive impairment in patients with bipolar disorder and to determine whether a distinct profile of cognitive deficits characterizes bipolar patients with a history of psychosis. METHODS: Sixty-nine outpatients with bipolar I disorder (34 with a history of psychotic symptoms and 35 with no history of psychosis) and 35 healthy comparison subjects underwent a comprehensive neurocognitive battery. All three groups were demographically matched. RESULTS: Despite preserved general intellectual function, bipolar I patients overall showed moderate impairments on tests of episodic memory and specific executive measures (average effect size = .58), and moderate to severe deficits on attentional and processing speed tasks (average effect size = .82). Bipolar I patients with a history of psychosis were impaired on measures of executive functioning and spatial working memory compared with bipolar patients without history of psychosis. CONCLUSIONS: Psychotic bipolar disorder was associated with differential impairment on tasks requiring frontal/executive processing, suggesting that psychotic symptoms may have neural correlates that are at least partially independent of those associated with bipolar I disorder more generally. However, deficits in attention, psychomotor speed, and memory appear to be part of the broader disease phenotype in patients with bipolar disorder.