Cortisol and cognition in psychotic disorders: A systematic review and multi-level meta-analysis

Emerging evidence suggests that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, particularly cortisol, may contribute to the cognitive deficits commonly observed in psychotic disorders. We conducted the first combined systematic review and quantitative synthesis of associations between cortisol and cognition in psychosis. Twelve studies met inclusion criteria (940 participants; 74.68% cases; 39.57% female; mean age = 31.83 years). Of these, nine studies (822 participants; 71.04% cases; 35.96% female; mean age = 32.72 years) contributed data to three-level meta-analyses examining associations between basal cortisol and composite cognition, attention, working memory and processing speed (AWP), executive functioning (EF), and verbal learning and memory (VM). Cortisol sampling time significantly moderated the relationship between cortisol and EF (F = 10.98, p = .004), with a significant negative association emerging between afternoon/evening cortisol and EF (r = -0.27, 95% CI [-0.42, -0.12], p = .01). No other robust cortisol-cognition associations were observed. However, sensitivity analyses revealed a negative association between morning cortisol and AWP following exclusion of an influential study. These findings do not support a general association between basal cortisol and cognitive functioning in psychosis. Instead, they suggest that cortisol-cognition relationships may be both domain- and sampling-time-specific, with the strongest evidence linking elevated afternoon/evening cortisol to poorer executive functioning. Further research using more precise assessments of cortisol dynamics is needed to clarify the role of HPA-axis dysregulation in cognitive impairment across psychotic disorders.