Independent inheritance of cognition and bipolar disorder in a family sample.

Cognitive deficits in people with bipolar disorder (BD) may be the result of the illness or its treatment, but they could also reflect genetic risk factors shared between BD and cognition. We investigated this question using empirical genetic relationships within a sample of patients with BD and their unaffected relatives. Participants with bipolar I, II, or schizoaffective disorder ("narrow" BD, n = 69), related mood disorders ("broad" BD, n = 135), and their clinically unaffected relatives (n = 227) completed five cognitive tests. General cognitive function (g) was quantified via principal components analysis (PCA). Heritability and genetic correlations were estimated with SOLAR-Eclipse. Participants with "narrow" or "broad" diagnoses showed deficits in g, although affect recognition was unimpaired. Cognitive performance was significantly heritable (h2 = 0.322 for g, p < 0.005). Coheritability between psychopathology and g was small (0.0184 for narrow and 0.0327 for broad) and healthy relatives of those with BD were cognitively unimpaired. In this family sample, cognitive deficits were present in participants with BD but were not explained by substantial overlaps in genetic determinants of mood and cognition. These findings support the view that cognitive deficits in BD are largely the result of the illness or its treatment.

Strong Genetic Overlaps Between Dimensional and Categorical Models of Bipolar Disorders in a Family Sample.

Background: Bipolar disorder (BD) presents with a wide range of symptoms that vary among relatives, casting doubt on categorical illness models. To address this uncertainly, we investigated the heritability and genetic relationships between categorical and dimensional models of BD in a family sample. Methods: Participants in the Amish-Mennonite Bipolar Genetics (AMBiGen) study were assigned categorical mood disorder diagnoses by structured psychiatric interview and completed the Mood Disorder Questionnaire (MDQ), which assesses lifetime history of manic symptoms and associated impairment. Major MDQ dimensions were analyzed by Principal Component Analysis (PCA) in 726 participants. Heritability and genetic overlaps between categorical diagnoses and MDQ-derived dimensions were estimated with SOLAR-ECLIPSE within 432 genotyped participants. Results: MDQ scores were significantly higher among individuals diagnosed with BD and related disorders, as expected, but varied widely among relatives. PCA suggested a three-component model for the MDQ. Heritability of the MDQ score was 30% (p<0.001), evenly distributed across its three principal components. Strong and significant genetic correlations were found between categorical diagnoses and most MDQ measures. Limitations: Recruitment through probands with BD resulted in increased prevalence of BD in this sample, limiting generalizability. Unavailable genetic data reduced sample size for some analyses. Conclusion: heritability and high genetic correlations between categorical diagnoses and MDQ measures support a genetic continuity between dimensional and categorical models of BD.