Prolactin and morning cortisol concentrations in antipsychotic naïve first episode psychosis: A systematic review and meta-analysis

Importance: Alterations in prolactin and cortisol levels have been reported in antipsychotic naïve patients with first episode psychosis (FEP). However, it has been studied in very small samples, and inter-group variability has never been studied before. Objective: To provide estimates of standardized mean differences (SMD) and inter-group variability for prolactin, cortisol awakening response (CAR) and morning cortisol concentrations in antipsychotic naïve FEP (AN-FEP) patients and healthy controls (HC). Data sources: BIOSIS, KCI, MEDLINE, Russian Science Citation Index, SciELO, Cochrane, PsycINFO, Web of Science were searched from inception to February 28, 2022. Study selection: Peer-reviewed cohort studies that reported on prolactin or cortisol blood concentrations in AN- FEP patients and HC were included. Data extraction and synthesis: Study characteristics, means and standard deviations (SD) were extracted from each article. Inter group differences in magnitude of effect were estimated using Hedges g. Inter-group variability was estimated with the coefficient of variation ratio (CVR). In both cases estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using meta-regression. PRISMA guideline was followed (No. CRD42022303555). Main outcomes and measures: Prolactin, CAR and morning cortisol blood concentrations in AN-FEP group in relation to HC group. Results: Fourteen studies for prolactin (N = 761 for AN-FEP group, N = 687 for HC group) and twelve studies for morning cortisol (N = 434 for AN-FEP group, N = 528 for HC group) were included. No studies were found in CAR in AN-FEP patients. Mean SMD for prolactin blood concentration was 0.88 (95% CI 0.57, 1.20) for male and 0.56 (95% CI 0.26, 0.87) for female. As a group, AN-FEP presented greater inter-group variability for prolactin levels than HC (CVR=1.28, 95% CI 1.02, 1.62). SMD for morning cortisol concentrations was non-significant: 0.34 (95% CI -0.01, 0.69) and no inter-group variability significant differences were detected: CVR= 1.05 (95% CI 0.91, 1.20). Meta-regression analyses for age and quality were non-significant. Funnel plots did not suggest a publication bias. Conclusions and relevance: Increased prolactin levels were found in AN-FEP patients. A greater inter-group variability in the AN-FEP group suggests the existence of patient subgroups with different prolactin levels. No significant abnormalities were found in morning cortisol levels. Further research is needed to clarify whether prolactin concentrations could be used as an illness biomarker