Nature or Nurture: Cross-Generational Transmission of Major Psychiatric Disorders

Genes appear to play an overwhelming role in the transmission of bipolar disorder across generations, as well as cross-generational transmission between bipolar disorder and disorders on the schizophrenia spectrum, according to study data published in JAMA Psychiatry. However, childrearing and genes equally contribute to bipolar disorder and depression transmission.

Researchers analyzed data on parents and offspring born between 1960 and 1990 from population-based registers in Sweden. The outcome of interest was confirmed diagnosis of bipolar disorder, major depression, or schizophrenia, and the exposure comprised 3 forms of parent-offspring resemblance: genetics only, childrearing environment only, and genes plus childrearing.

Tetrachoric correlation and logistic regression analyses were used to capture parent-offspring resemblance in each diagnostic category. Additionally, cross-generation analyses were conducted to identify any genetic association between bipolar disorder, major depression, and schizophrenia.

The study population (N=2,417,104; age range, 25-60 years; 51.8% men) belonged to 4 family types: intact; families where the biological father resided outside the home; families with a stepfather living at home in lieu of biological father; and adoptive families. In general, the prevalence of psychiatric disorders was lowest among intact families. Bipolar disorder and depression were more commonly observed among women, while nonaffective psychosis and schizophrenia appeared to have an impact on men and women equally.

The magnitude of parent-to-offspring bipolar disorder transmission was estimated at 0.25 (95% CI, 0.24-0.26) when parents provided genes plus rearing, 0.22 (95% CI, 0.18-0.26) when parents provided genes only, and 0.07 (95% CI, -0.01 to 0.15) when parents provided rearing only. Per logistic regression, the corresponding ORs for bipolar disorder transmission were 5.20 (95% CI, 4.91-5.50), 3.66 (95% CI, 2.97-4.51), and 1.63 (95% CI, 0.96-2.78).

Cross-disorder tetrachoric correlations for bipolar disorder and broad schizophrenia were 0.12 (95% CI, 0.11-0.13) for genes plus rearing, 0.12 (95% CI, 0.09-0.14) for genes only, and -0.03 (95% CI, -0.11 to 0.04) for rearing only. For bipolar disorder and major depression, the parallel tetrachoric correlations were estimated at 0.09 (95% CI, 0.07-0.10) for genes plus rearing, 0.04 (95% CI, 0.01-0.07) for genes only, and 0.05 (95% CI, 0.01-0.08) for rearing only. Bipolar disorder heritability was estimated at 0.44 (95% CI, 0.36-0.48) using genes-only parent-offspring data. The genetic correlation between bipolar disorder and schizophrenia was 0.572 (95% CI, 0.560-0.589); between bipolar disorder and major depression, the correlation was 0.302 (95% CI, 0.001-0.523).

The findings identify genetics as the primary driver of parent-to-child bipolar disorder transmission, although childrearing elements may also contribute to risk. Cross-generational transmission of bipolar disorder appeared to be more strongly associated with schizophrenia than major depression. Additionally, transmission of bipolar disorder to schizophrenia appeared to result entirely from genetics, whereas transmission from bipolar disorder to major depression displayed equal contributions from genetics and childrearing.

The investigators noted that the use of registries may have limited data granularity; disease severity, specific symptoms, and change in diagnosis over time could not be ascertained. Even so, these large-scale, prospective findings emphasize the role of genetics and childhood environment in later psychiatric illness.

Reference

Kendler KS, Ohlsson H, Sundquist J, Sundquist K. An extended Swedish national adoption study of bipolar disorder illness and cross-generational familial association with schizophrenia and major depression [published online March 18, 2020]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2020.0223.