Nature and nurture play disease specific roles in psychiatric illness across generations

1. Cross-generational transmission between bipolar disorder and schizophrenia was predominantly based on genetics, while transmission between bipolar disorder and major depression was equally influenced by genetics and child-rearing practices.

Evidence Rating Level: 2 (Good)

Cross-generational transmission of bipolar disorder is less well-known, with specific gaps related to whether parental bipolar disorder translates to schizophrenia and major depression in their children. This national, Swedish cohort study sought to determine the degree to which these transmissions were a result of genetics, parental rearing, or a combination thereof. A total of 2,417,105 parents and offspring born between 1960-1990 (median [range] age = 41 [25-60] years, 48.2% female) included four family types: 1) intact (offspring n = 2,175,259), 2) not-lived-with biological father (offspring n = 152,436), 3) lived-with stepfather (offspring n = 73,785), and 4) adoptive (offspring n = 15,624). Schizophrenia was a broad category of unaffected, nonaffective psychosis, and schizophrenia. Resemblance of parent-child dyads were determined primarily by tetrachoric correlation. Tetrachoric correlations were statistically homogeneous across family type for rearing only (0.07, 95% CI -001 to 0.15), genes only (0.22, 95% CI 0.18 to 0.26), and rearing plus genes (0.25, 95% CI 0.24 to 0.26). Parallel ORs were calculated for these groups: 1.63 (95% CI 0.96 to 2.78), 3.66 (95% CI 2.97 to 4.51), and 5.20 (95% CI 4.91 to 5.50), respectively. Importantly, cross-disorder tetrachoric correlations for bipolar disorder and schizophrenia were for rearing only (-0.03, 95% CI 0.11 to 0.04), genes only (0.12, 95% CI 0.09 to 0.14), and rearing plus genes (0.12, 95% CI 0.11 to 0.13), with parallel ORs of 0.76, 2.04, and 1.95, respectively. For bipolar disorder and major depression, tetrachoric correlations were for rearing only (0.05, 95% CI 0.01 to 0.08), genes only (0.04, 95% CI 0.01 to 0.07), and rearing plus genes (0.09, 95% CI 0.07 to 0.10). Parallel ORs were 1.25, 1.23, and 1.53, respectively. Genetics-based correlations between bipolar disorder and broad schizophrenia were estimated to be 0.572 (95% CI 0.560 to 0.589) and 0.302 (95% CI 0.001 to 0.523) between bipolar disorder and major depression, with an overall bipolar disorder heritability estimate of 0.44 (95% CI 0.36 to 0.48). Overall, this study highlights the role of genetics in cross-generational transmission of bipolar disorder. The transmission between bipolar disorder and major depression, however, seems to be equally influenced by child-rearing practices. Further research is warranted on what these child-rearing practices should be to attenuate this genetic predisposition.

Click to read the study in JAMA Psychiatry

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