Exposome and cognition in psychosis: an exploratory study in sex-specific patterns in patients and their unaffected...

The exposome is strongly linked to psychosis risk and may affect cognition in first-episode psychosis (FEP). Studying FEP patients and their unaffected siblings provides a framework to explore this relationship. This study examined whether environmental risk, measured by the Maudsley Environmental Risk Score (ERS), is associated with sex differences in cognitive performance in FEP patients and their unaffected siblings.

72 individuals with FEP (43 males and 29 females) and 98 siblings (33 males and 65 females) from the PAFIP and PAFIP-FAMILIAS cohorts were assessed. Participants completed sociodemographic, clinical, and neuropsychological assessments covering verbal memory, visual memory (VisM), processing speed (PS), executive functions, motor dexterity (MD), attention, theory of mind (ToM) and Global Cognitive Functioning (GCF). ERS was calculated using data on ethnicity, urbanicity, cannabis use, childhood adversity, paternal age, and obstetric complications. Group comparisons were conducted by linear mixed-effects and regression models.

Across both sex groups, individuals with FEP showed poorer cognitive performance than their unaffected siblings. After correction for multiple comparisons, males with FEP showed significantly lower MD than brothers. In females, lower performance in PS, VisM, and GCF was observed in patients compared with sisters. Adjustment for ERS did not substantially change these differences.

These findings suggest that cognitive differences between individuals with FEP and their unaffected siblings may follow sex-specific patterns. These differences persisted after accounting for cumulative environmental exposure as measured by the ERS, indicating that environmental factors captured by this index may not fully explain cognitive disparities within familial-risk contexts.