Association of Etiological Factors for Hypomanic Symptoms, Bipolar Disorder, and Other Severe Mental Illnesses

Abstract

Subsyndromal hypomanic symptoms are relatively common in the general population and are linked to the onset of bipolar disorder. Little is known about their etiology and whether this is shared with the etiology of bipolar disorder or other mental illnesses. To examine the genetic and environmental architecture of hypomanic symptoms in a nonclinical youth sample and compare estimates at varying severity levels and their association with diagnosed bipolar disorder. This cohort study used phenotypic and genetic data from the Child and Adolescent Twin Study in Sweden and included individuals with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis of psychiatric disorders from national registries for residents of Sweden. Associations between hypomania and polygenic risk scores for bipolar disorder, major depressive disorder and schizophrenia were also investigated. Analysis began November 2018 and ended October 2021. Hypomanic symptoms were assessed using the parent-rated Mood Disorders Questionnaire when the twins were aged 18 years. Bipolar disorder diagnosis and/or lithium prescription were ascertained from national registries for residents of Sweden. Polygenic risk scores for psychiatric disorders were calculated using independent discovery genetic data. A total of 8568 twin pairs aged 18 years (9381 [54.7%] female) were included in the study. The hypomania heritability estimate was 59% (95% CI, 52%-64%) for male individuals and 29% (95% CI, 16%-44%) for female individuals. Unique environmental factors accounted for 41% (95% CI, 36%-47%) of the hypomania variance in male individuals and 45% (95% CI, 40%-50%) in female individuals. Shared environmental factors were only detected for female individuals and explained 26% (95% CI, 13%-38%) of the variance. The heritability estimates were fairly consistent across different hypomania severity groups. Moderate genetic (0.40; 95% CI, 0.21-0.58) and shared environmental (0.41; 95% CI, 0.03-0.75) correlations between hypomania and diagnosed bipolar disorder were found. Hypomania was significantly associated with the polygenic risk scores for schizophrenia (β = 0.08; SE = 0.026; P = .002) and major depressive disorder (β = 0.09; SE = 0.027; P = .001) but not bipolar disorder (β = 0.017; SE = 0.03; P = 0.57) (bipolar disorder I [β = 0.014; SE = 0.029; P = .64] or bipolar disorder II [β = 0.045; SE = 0.027; P = .10]). Higher heritability for hypomania was found for male compared with female individuals. The results highlight the shared etiologies between hypomanic symptoms, bipolar disorder, major depression, and schizophrenia in youths. 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.