Twins’ inheritance risk for mental illnesses greater in men than women

Likelihood of inheritance for hypomania, which may lead to bipolar disorder or other mental illnesses, is greater in male twins than in female twins, according to a Swedish cohort study published in JAMA Psychiatry.

“Understanding the early manifestations of bipolar disorder are critical for the development of effective prevention and intervention. One approach to tackle this issue is to study subsyndromal hypomania (symptoms that do not meet diagnostic criteria for hypomanic/manic episodes) in community samples during adolescence and early adulthood,” Georgina M. Hosang, MD, of the Wolfson Institute of Population Health at Queen Mary University of London, and colleagues wrote.

“This approach holds great promise because hypomanic and manic episodes are BD’s defining feature. Focusing on this developmental period is particularly informative for understanding BD’s cause because its onset typically occurs between age 15 and 24 years.”

Hosang and colleagues sought to evaluate genetic and environmental foundations of hypomanic symptoms in a nonclinical youth sample, compare estimates at varying severity levels and assess their association with diagnosed bipolar disorder.

The researchers used phenotypic and genetic data from the Child and Adolescent Twin Study in Sweden and included individuals who were diagnosed with various psychiatric disorders whose information was culled from national registries for Swedish residents.

They investigated associations between hypomania and polygenic risk scores for bipolar disorder, major depressive disorder and schizophrenia. Analysis began in November 2018 and ended October 2021.

The researchers evaluated hypomanic symptoms when the 8,568 participating pairs of twins (54.7% female) were at least 18 years old, via a mood disorder questionnaire. Bipolar disorder diagnosis and/or lithium prescription information was obtained from Swedish national registries. Polygenic risk scores for psychiatric disorders were calculated using independent discovery genetic data.

Results showed inheritability estimates for hypomania in men and boys was 59% and in women and girls was 29%. Unique environmental factors accounted for 41% of hypomania variance in male individuals and 45% in female individuals; however, shared environmental factors for hypomania were only detected in females.

Heritability estimates were consistent across different hypomania severity groups, while data also revealed moderate genetic and shared environmental connections between hypomania and diagnosed bipolar disorder. In addition, hypomania was significantly associated with the polygenic risk scores for schizophrenia and major depressive disorder, but not bipolar disorder I/II.

“Moderate genetic and nonshared environmental correlations between hypomania and BD were found. We found this genetic overlap was not explained by common genetic factors using the BD PRS,” Hosang and colleagues wrote.

“Future research should focus on identifying specific shared genetic and environmental factors. These findings support a possible dimensional model of bipolar disorder, with hypomania representing a continuous trait underlying the disorder.”