Perinatal stress as a moderator of the effects of hormonal dysregulation on cognition and symptoms in early psychosis.

BACKGROUND

Psychosis results from a complex interaction between genetic vulnerability and environmental risk factors, including perinatal stress, which may influence neurodevelopment and endocrine function. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and prolactin secretion has been linked to cognitive impairment and symptom severity in early psychosis. This study examined whether perinatal stress moderates the associations between hormonal alterations and cognitive performance or clinical symptoms.

METHODS

Fifty-one outpatients with early psychosis (<3 years since onset) and 50 healthy controls were assessed. Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery and additional tasks. Perinatal stress exposure was determined through clinical interviews and medical records. Hormonal measures included fasting plasma prolactin, morning salivary cortisol, and the dexamethasone suppression test ratio (DSTR; 0.25 mg). Multiple linear regression models tested main and interaction effects between perinatal stress and hormonal variables on cognitive domains and symptom severity, adjusting for relevant covariates.

RESULTS

Perinatal stress significantly moderated associations between prolactin levels and several cognitive domains. Higher prolactin was associated with poorer processing speed, verbal memory, visual memory, and social cognition, particularly among individuals without perinatal stress. DSTR also interacted with perinatal stress in predicting executive functioning: higher DSTR was linked to worse Stroop performance mainly in those without perinatal stress. Additionally, elevated morning cortisol was associated with greater negative symptom severity among individuals with perinatal stress.

CONCLUSIONS

Perinatal stress modifies the relationship between hormonal dysregulation and cognitive and clinical outcomes in early psychosis, highlighting the relevance of early-life stress in shaping endocrine and neurocognitive trajectories.