Gender-Based Differences in Heritability of Hypomanic Symptoms in Bipolar Disorder

A multi-exposure of an emotional woman.
In a sample of young people, the genetic and environmental architecture of hypomanic symptoms were compared with the levels of severity and if they had any association with bipolar disorder.

A cohort study found that hypomanic symptoms were more heritable among men than women, indicating a possible dimensional model for bipolar disorder (BD). These findings were published in JAMA Psychiatry.

Since 2004, every year families of twins aged 9 or 12 years living in Sweden have been invited to participate in the Child and Adolescent Twin Study in Sweden (CATSS). At baseline, study participants provided saliva samples for genetic assessment.

Between inclusion and age 18 years, 8,568 twin pairs have been evaluated for hypomanic symptoms by the parent-rated Mood Disorder Questionnaire (MDQ). Instances of BD at 24 years of age were identified using the Swedish National Patient Register or by prescription for lithium since 2005 through the Prescribed Drug Register.

The twins were monozygotic (30.1%), dizygotic same gender (34.5%), or dizygotic opposite gender (35.3%). Nearly half of mothers attended college or university (49.0%) and nearly half of fathers attended upper secondary education (49.7%).

A total of 0.8% were at high risk for BD according to the MDQ and 0.3% had been diagnosed with BD or given a prescription for lithium. Having a high-risk MDQ score increased risk for a BD diagnosis (odds ratio [OR], 1.32; 95% CI, 1.13-1.55; P <.001) and the BD cohort had higher hypomania scores (β, 3.01; standard error [SE], 0.73; P <.001).

More women had hypomanic symptoms than men (β, 0.11; SE, 0.04; P =.01).

Among men, the variance in hypomania was explained by genetic influences (59%; 95% CI, 52%-64%) and nonshared environmental factors (42%; 95% CI, 36%-47%). Among women, the variance in hypomania was explained by nonshared environmental factors (45%; 95% CI, 40%-50%), genetic factors (29%; 95% CI, 16%-44%), and shared environmental factors (26%; 95% CI, 13%-38%).

Hypomania and BD were correlated (r, 0.38). This correlation was explained primarily by genetic factors (72%; 95% CI, 41%-98%) followed by nonshared environmental factors (28%; 95% CI, 2%-59%).

Hypomania had a small correlation with major depressive disorder (r, 0.12). There was insufficient data to assess the relationship between hypomanic symptoms and schizophrenia.

Symptoms of hypomania were associated with polygenic risk scores for major depressive disorder (β, 0.09; SE, 0.027; P =.001) and schizophrenia (β, 0.08; SE, 0.026; P =.002) but not for BP, BP I, or BP II.

This study was limited by the low number of individuals with a mental health disorder diagnosis.

This study identified differential heritabilities of hypomanic symptoms on the basis of gender and that common BD genetic factors did not account for these hypomanic symptoms. Additional study is needed to assess gender differences in hypomanic symptoms in the setting of BD.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Hosang GM, Martin J, Karlsson R, et al. Association of etiological factors for hypomanic symptoms, bipolar disorder, and other severe mental illnesses. JAMA Psychiatry. Published online December 15, 2021. doi:10.1001/jamapsychiatry.2021.3654