Polygenic Risk for Insomnia in Relation to Sleep Disturbance and Psychiatric Characteristics in Youth with Mood...

Sleep disturbance is common in youth with mood disorders and correlates with mood symptom burden. Insomnia polygenic risk scores (PRS), computed from adult genome-wide association study (GWAS) data, are associated with sleep disturbance among youth within the general population. However, no studies have examined insomnia-PRS in a clinical sample of youth with mood disorders.

Participants included 374 youth aged 13-20 years, 247 with mood disorders (135 bipolar disorder [BD] and 112 major depressive disorder) and 127 controls. Insomnia-PRS was constructed using an adult insomnia GWAS (N = 360,738). Sleep disturbance was computed using the most severe lifetime insomnia and hypersomnia (i.e., excessive sleep) items from the Kiddie Schedule for Affective Disorders and Schizophrenia Depression Rating Scale. General linear models or logistic regressions examined main effects of insomnia-PRS on sleep disturbance and psychiatric characteristics (mood symptom severity, anxiety comorbidity, suicide risk, global functioning), controlling for age, sex, and genetic principal components.

Insomnia-PRS was higher in youth with mood disorders versus controls (p = 0.03, d = 0.24). Insomnia-PRS was associated with insomnia severity in youth with mood disorders (p = 0.03, η_p² = 0.02), and with mania severity in youth with BD (p = 0.03, η_p² = 0.03), although the insomnia severity finding did not survive Bonferroni correction. In sex-stratified analyses, insomnia-PRS was significantly associated with insomnia (p = 0.02, η_p² = 0.03), depression (p = 0.02, η_p² = 0.03), and mania (p = 0.02, η_p² = 0.05) severity in females but not males. There were no significant findings for excessive sleep.

This study extends prior findings linking adult-derived insomnia-PRS with insomnia in youth with mood disorders, with evidence of differences related to sex and BD. These preliminary findings suggest that sleep and mood in youth may be sensitive to adult-derived insomnia-PRS.