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

Claudia Aymerich*, Borja Pedruzo, Malein Pacho, Maria Laborda, Jon Herrero, Toby Pillinger, Robert A. McCutcheon, Daniel Alonso-Alconada, Marta Bordenave, Maria Martinez-Querol, Ainara Arnaiz, Javier Labad, Paolo Fusar-Poli, Miguel Angel Gonzalez-Torres, Ana Catalan Alcantara

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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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 ANFEP 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.
Original languageEnglish
Publication statusAccepted/In press - 2 Feb 2023


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