Sleep disturbances are prevalent in schizophrenia and are associated with symptom severity, yet findings remain inconsistent, reflecting unmeasured biological moderators. Chronotype and the BDNF genetic variant influence sleep regulation and schizophrenia-related phenotypes. However, their combined contribution to the sleep quality-symptom severity association remains unexplored. We aimed to characterise sleep quality and chronotype in schizophrenia, examine their associations with symptom severity, and determine whether BDNF Val66Met moderates these relationships. In this cross-sectional study, 217 individuals with schizophrenia were assessed for sleep quality (Pittsburgh Sleep Quality Index), chronotype (Morningness-Eveningness Questionnaire), and symptom severity (Positive and Negative Syndrome Scale) and genotyped for BDNF Val66Met. Multivariate regression evaluated the contributions of sleep quality, chronotype, and Val66Met genotype to symptom severity scores, adjusting for covariates. Plasma BDNF levels were measured in a subset of patients (n = 91). Poor sleep quality was prevalent in schizophrenia (69.12%) and was significantly associated with PANSS total (β = 0.35, P < 0.001), positive (β = 0.24, P < 0.001), negative (β = 0.27, P < 0.001), and general psychopathology scores (β = 0.31, P < 0.001). Schizophrenia patients with poor sleep quality had later illness onset (P = 0.02). Morning chronotype was associated with longer illness duration (P = 0.03) but lower general psychopathology (P = 0.02). BDNF Val66Met showed no association with sleep, chronotype, or symptom severity and did not moderate sleep-symptom relationships. Plasma BDNF levels were higher in poor sleepers (P < 0.001, r = 0.65), independent of Val66Met genotype. Our results showed poor sleep quality is associated with symptom severity in schizophrenia, including later illness onset, independent of chronotype or BDNF Val66Met variant.
