Polygenic risk for schizophrenia is associated with psychomotor vigilance performance impairment during sleep deprivation in women.

Schizophrenia (SZ) is a highly heritable psychiatric disorder with gender-specific etiology profiles. SZ may involve altered synaptic plasticity, as supported by genetic studies, and individuals with elevated polygenetic risk may show prodromal characteristics such as increased sensitivity to sleep deprivation. We examined whether polygenic risk for SZ is associated with vulnerability to sleep deprivation-induced psychomotor vigilance impairment in healthy young adults. A total of 120 healthy non-Hispanic Caucasian volunteers (62 women, 58 men; aged 20-40 years) participated in one of six in-laboratory total sleep deprivation (TSD) studies. Performance was assessed using the psychomotor vigilance test (PVT) every 2-3 h during 38 h of TSD. Each participant's SZ polygenic risk score (PRS) was computed using the PRS-CS method, utilizing published GWAS statistics. Gender-specific associations between SZ PRS and PVT performance across 6 h time intervals during hours 3-38 of TSD were investigated using mixed-effects statistical methods. SZ PRS was associated with vulnerability to PVT performance impairment during TSD in women, but not in men. The early morning hours (04:00-10:00) emerged as the most sensitive period for the association with SZ PRS, aligning with peak impairment in PVT performance during acute TSD. Our findings suggest that SZ genetic risk may heighten vulnerability to sleep deprivation-induced psychomotor vigilance impairment in young adult women, but no such effect was observed in men. Future research is needed to determine whether vulnerability to sleep deprivation reflects SZ-related genetic or neurobiological liability and whether this extends to men and older individuals.