Bipolar disorder comorbid with alcohol use disorder: focus on neurocognitive correlates

Bipolar disorder (BD) and alcohol use disorders (AUDs) are usually comorbid, and both have been associated with significant neurocognitive impairment. Patients with the BD-AUD comorbidity (dual diagnosis) may have more severe neurocognitive deficits than those with a single diagnosis, but there is paucity of research in this area. To explore this hypothesis more thoroughly, we carried out a systematic literature review through January 2015. Eight studies have examined the effect of AUDs on the neurocognitive functioning of BD patients. Most studies found that BD patients with current or past history of comorbid AUDs show more severe impairments, especially in verbal memory and executive cognition, than their non-dual counterparts. Greater neurocognitive dysfunction is another facet of this severe comorbid presentation. Implications for clinical practice and research are discussed. Specifically, the application of holistic approaches, such as clinical staging and systems biology, may open new avenues of discoveries related to the BD-AUD comorbidity

Rediscovering the value of families for psychiatric genetics research

As it is likely that both common and rare genetic variation are important for complex disease risk, studies that examine the full range of the allelic frequency distribution should be utilized to dissect the genetic influences on mental illness. The rate limiting factor for inferring an association between a variant and a phenotype is inevitably the total number of copies of the minor allele captured in the studied sample. For rare variation, with minor allele frequencies of 0.5% or less, very large samples of unrelated individuals are necessary to unambiguously associate a locus with an illness. Unfortunately, such large samples are often cost prohibitive. However, by using alternative analytic strategies and studying related individuals, particularly those from large multiplex families, it is possible to reduce the required sample size while maintaining statistical power. We contend that using whole genome sequence (WGS) in extended pedigrees provides a cost-effective strategy for psychiatric gene mapping that complements common variant approaches and WGS in unrelated individuals. This was our impetus for forming the “Pedigree-Based Whole Genome Sequencing of Affective and Psychotic Disorders” consortium. In this review, we provide a rationale for the use of WGS with pedigrees in modern psychiatric genetics research. We begin with a focused review of the current literature, followed by a short history of family-based research in psychiatry. Next, we describe several advantages of pedigrees for WGS research, including power estimates, methods for studying the environment, and endophenotypes. We conclude with a brief description of our consortium and its goals.This research was supported by National Institute of Mental Health grants U01 MH105630 (DCG), U01 MH105634 (REG), U01 MH105632 (JB), R01 MH078143 (DCG), R01 MH083824 (DCG & JB), R01 MH078111 (JB), R01 MH061622 (LA), R01 MH042191 (REG), and R01 MH063480 (VLN).UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí

Shared Genetic Factors Influence Risk for Bipolar Disorder and Alcoholism

Bipolar disorder and alcoholism have high rate comorbidity, with more than 50% of alcoholism occurrence in bipolar disorder. While there is evidence that both disorders are heritable, it is unclear if the same genetic factors predispose them. The aim of this study is to determine if common genetic factors influence risk for bipolar disorder and alcoholism. A total of 733 Costa Rican individuals from 61 extended pedigrees, selected for sibling pairs with a diagnosis of bipolar disorder, participated in the study. All subjects completed a diagnostic interview, the Barratt Impulsiveness Scale (BIS-11) and Fagerström questionnaire for Nicotine Dependence. Heritability and bivariate correlations were estimated using SOLAR. Based on a best-estimate process, twenty-nine percent of the sample met criteria for broad bipolar phenotype, 23% bipolar I disorder, 15% alcoholism, 32% smoking, only 2% drug abuse, and 20% for an anxiety disorder. Thirty-three present did not meet criteria for a lifetime diagnosis. In the broad bipolar phenotype group, 28% had a lifetime diagnosis of alcoholism. The heritability estimated for broad bipolar phenotype was h2=0.559 (p=7.0x10-6) and for alcoholism was h2=0.752 (p=3.0x10-7). Only alcoholism (ρg=0.600, p=0.002) and habitual smoking (ρg=0.717, p=2.1x10-4) were significantly genetically correlated with the broad bipolar phenotype. A similar pattern of results was observed for the bipolar I disorder phenotype. The current findings strongly imply that shared genetic factors increase risk for bipolar disorder and addictive disorders. A better understanding of this comorbidity could improve clinical outcomes and potentially facilitate novel treatments.National Institutes of Health/[MH080912]/NIH/Estados UnidosNational Institutes of Health/[MH059490]/NIH/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí