Gender differences in cognitive function in antipsychotic-treated chronic schizophrenia patients with hyperprolactinemia: a large-scale cross-sectional study.

objectivesPrevious studies have reported gender differences in clinical characteristics and cognitive abilities, as well as the impact of hyperprolactinemia in schizophrenia patients. However, these factors are not fully understood, particularly in the context of chronic schizophrenia. Chronic schizophrenia patients exhibit distinct neurobiological changes and prolonged antipsychotic exposure that may amplify cognitive deficits and alter prolactin-cognition relationships. This study aimed to explore the gender differences in clinical characteristics and cognitive abilities in chronic schizophrenia patients and to examine the influence of hyperprolactinemia on these outcomes.

methodsThis cross‑sectional study included 1271 patients with chronic schizophrenia (DSM‑5). Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS), and cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Serum prolactin was measured by chemiluminescence. Between‑group comparisons, gender‑stratified analyses, two‑way ANOVA, and linear regressions were performed.

resultsHyperprolactinemia was present in 48.4% (615/1271) of patients, with significantly higher prevalence in males (67.7%, 547/808) than in females (21.8%, 101/463) (P < 0.05). Compared to normoprolactinemic patients (*n* = 656), those with hyperprolactinemia (n = 615) had longer untreated illness, lower marriage rates, higher smoking/alcohol use, lower PANSS scores (indicating milder symptoms), and less suicidal ideation (all P < 0.05). Importantly, hyperprolactinemic patients showed better visuospatial, language, and delayed memory performance (P < 0.05). Within the hyperprolactinemic group, males outperformed females in visuospatial and language domains. Regression analyses confirmed that hyperprolactinemia was independently associated with visuospatial (β = 0.104, P < 0.01) and delayed memory (β = 0.070, P < 0.05), while gender was independently associated with visuospatial (positively) and language (negatively) (both P < 0.05). Two‑way ANOVA revealed significant gender × hyperprolactinemia interactions on visuospatial and language (P < 0.05), indicating that the cognitive effects of hyperprolactinemia differ by sex.

conclusionThis study identified significant gender differences in clinical and cognitive profiles among patients with chronic schizophrenia. Notably, despite treatment with various antipsychotics, patients with hyperprolactinemia exhibited better clinical status (lower PANSS scores) and superior visuospatial and delayed memory performance compared to their normoprolactinemic counterparts. Strikingly, these cognitive advantages associated with hyperprolactinemia were most pronounced in male patients, whereas comparable gender differences were not evident among patients with normal prolactin levels.