The Role of Cortisol in First Episode of Psychosis: A Systematic Review
Abstract
The stress diathesis hypothesis is currently one of the prevailing models of etiology of psychotic disorders. Cortisol is the most researched stress hormone; yet its role in first episode psychosis (FEP) was only recently investigated. The aim of the present study is to systematically review the evidence on the potential role of cortisol in FEP. Higher cortisol levels in blood samples have been consistently replicated, whereas saliva studies measuring baseline cortisol levels have exhibited divergent results. Moreover, longitudinal studies have revealed a cortisol upregulation in FEP with a subsequent decrease induced by antipsychotic treatment. The evidence suggests a role for cortisol in psychosis, although the association of cortisol with psychopathological symptoms is currently non-specific. Future research should focus on more pure diagnostic entities, clearly defined stages of the disorder and refined methods of hormonal measurement.
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Studies examining saliva cortisol concentrations failed to replicate the finding of higher blood cortisol in FEP.
“However, studies examining saliva cortisol concentrations failed to replicate these findings.”
From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [179]
A higher blood cortisol concentration was shown in a meta-analysis of 911 patients with first-episode psychosis (FEP), most consistent in drug-naive patients of an older presentation (i.e., not adolescents).
“Similarly, a higher blood cortisol concentration was shown in a meta-analysis of 911 patients with first-episode psychosis (FEP), most consistent in drug-naive patients of an older presentation (i.e., not adolescents) (179).”
From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [179]
Subgroup analysis of longitudinal studies suggested that cortisol upregulation may be a phenomenon of FEP only with subsequent decrease after antipsychotic treatment.
“Interestingly, subgroup analysis of longitudinal studies suggested that cortisol upregulation may be a phenomenon of FEP only with subsequent decrease after antipsychotic treatment.”
From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [179]
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Hirt, V., Schalinski, I., & Rockstroh, B. S. (2019) · Mental Health & Prevention · doi:10.1016/j.mhp.2019.01.002 · Cited by 11 · see citing works
Yeşilkaya, Ü. H., Gıca, Ş., Taşdemir, B. G., Menekseoglu, P. O., Cirakli, Z., & Karamustafalıoğlu, N. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.07.056 · Cited by 9 · see citing works
Woldesenbet, Y. M., Alenko, A., Tadesse, I., Gedefaw, L., & Fikru, C. (2021) · SAGE Open Medicine · doi:10.1177/20503121211056216 · Cited by 7 · see citing works
Yeşilkaya, Ü. H., Gıca, Ş., Menekseoglu, P. O., Taşdemir, B. G., Cirakli, Z., & Karamustafalıoğlu, N. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03054-4 · Cited by 6 · see citing works
Mansueto, G., Tosato, S., Brondino, N., Bonetto, C., Tomassi, S., Politi, P., Lasalvia, A., Fioravanti, G., Casale, S., Santi, K. D., et al. (2022) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2022.2137846 · Cited by 6 · see citing works
Karanikas, E. (2022) · Neuroscience Letters · doi:10.1016/j.neulet.2022.137011 · Cited by 5 · see citing works
Self-citationRäsänen, S., Niemelä, M., Nordström, T., Hakko, H. H., Haapea, M., Marshall, C., & Miettunen, J. (2017) · Early Intervention in Psychiatry · doi:10.1111/eip.12479 · Cited by 5 · see citing works
Cortisol and cytokines in early psychosis, do they correlate? A scoping review
Karanikas, E. (2019) · Neurology Psychiatry and Brain Research · doi:10.1016/j.npbr.2019.05.002 · Cited by 2 · see citing works
Self-citationCandemir, M., & Cansız, A. (2022) · Genel Tıp Dergisi · doi:10.54005/geneltip.1032165 · Cited by 2 · see citing works
GRIFA, A. P. D. S. (2024) · International Journal of Humanities and Educational Research · doi:10.47832/2757-5403.25.4
Karanikas, E. (2025) · NeuroSci · doi:10.3390/neurosci6040099
Self-citationMnyaka-Dawethe, P., Musarurwa, H. T., Mahamba, A., Ndlovu, N., Yako, Y. Y., & Sewani-Rusike, C. R. (2026) · BMJ Open · doi:10.1136/bmjopen-2026-120909
Cortisol and cognition in psychotic disorders: A systematic review and multi-level meta-analysis
Chen, Z., Yong, J. X. M., Haussler, S. M., Murray, R. M., Pariante, C. M., Ibrahim, F., & Kravariti, E. (2026) · Psychological Medicine · doi:10.1017/s0033291726106266
- Authors
- Karanikas, E., Antoniadis, D., & Garyfallos, G. D.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- Corresponding author
- Antoniadis, Diomidis
- Venue
- Current Psychiatry Reports
- Published
- 2014-09-09
- Volume
- 16
- Issue
- 11
- Pages
- 503-503
- ISSN
- 1523-3812 (ISSN-L)
- 1535-1645
- OpenAlex
- W2021695398
- Cited by
- 31
- References
- 76
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 6 · 2016: 6 · 2015: 1 · 2014: 1
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Psychiatry Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Keywords
- cortisol, first-episode psychosis, stress hormones, antipsychotic drugs, salivary cortisol, etiology of psychosis, psychiatric symptoms
- MeSH terms
- Humans, Hydrocortisone, Psychotic Disorders
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