{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:07:40Z","timestamp":1791209260310,"version":"4.1.0"},"reference-count":22,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"unspecified","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031728","name":"Walter Sisulu University","doi-asserted-by":"publisher","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100031728","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,9,9]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Psychosis poses a significant global health challenge, with growing evidence linking dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and altered cortisol levels to its onset and progression. This systematic review protocol aims to synthesise case-control and cohort studies to achieve two main objectives: to evaluate the association between cortisol levels and psychosis, and to examine cortisol levels in individuals at risk of developing psychosis. The review will consolidate existing empirical evidence on the relationship between cortisol levels and psychosis in both at-risk populations and diagnosed patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Electronic searches will be conducted in academic databases, including Web of Science, PubMed, Scopus, Embase and PsycINFO, using a PECO (Population, Exposure, Comparator, Outcome) framework. A search strategy will be developed in Web of Science and adapted for other databases. Additionally, a search will be performed on Google Scholar, reviewing the first 1000 publications to crosscheck findings. The initial PECO-derived search will use Medical Subject Headings terms: (\u2018Cortisol\u2019 OR \u2018Hydrocortisone\u2019) AND (\u2018Psychosis\u2019 OR \u2018Psychotic disorders\u2019 OR \u2018Schizophrenia\u2019) AND (\u2018HPA axis\u2019 OR \u2018Stress response\u2019) AND (\u2018Clinical high risk\u2019 OR \u2018Prodromal\u2019 OR \u2018Ultra-high risk\u2019), along with phrases identified from related literature. The review will focus on case-control and cohort studies reporting original research on individuals at risk of psychosis or with confirmed psychotic disorders, with no restrictions on publication year or language. Exclusion criteria will include randomised controlled trials, pilot studies, reviews, meta-analyses, case reports, conference abstracts, animal studies and studies lacking cortisol measurements, as well as editorials and commentaries. The risk of bias will be assessed using the Joanna Briggs Institute methodology, and the Grading of Recommendations Assessment, Development, and Evaluation will be used to assess the certainty of the evidence. The review is ongoing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>No ethical approval is required. Findings will be disseminated via a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study registration<\/jats:title>\n                    <jats:p>PROSPERO, CRD420251136994 (registered 6 October 2025)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-120909","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:35:33Z","timestamp":1791207333000},"page":"e120909","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Association between cortisol levels and psychosis in at-risk and diagnosed individuals: protocol for a systematic review"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7527-3795","authenticated-orcid":false,"given":"Phakama","family":"Mnyaka-Dawethe","sequence":"first","affiliation":[{"name":"Walter Sisulu University - Mthatha Campus, Mthatha, Eastern Cape, South Africa"},{"name":"School of Biomedical Sciences, Walter Sisulu University, Mthatha, Mthatha, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9767-4850","authenticated-orcid":false,"given":"Hannibal Tafadzwa","family":"Musarurwa","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Walter Sisulu University, Mthatha, Mthatha, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9935-1829","authenticated-orcid":false,"given":"Anelisa","family":"Mahamba","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Walter Sisulu University, Mthatha, Mthatha, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8221-1810","authenticated-orcid":false,"given":"Nomagugu","family":"Ndlovu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Walter Sisulu University, Mthatha, Mthatha, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6179-4463","authenticated-orcid":false,"given":"Yandiswa Yolanda","family":"Yako","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Walter Sisulu University, Mthatha, Mthatha, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constance","family":"Sewani-Rusike","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Walter Sisulu University, Mthatha, Mthatha, Eastern Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"2026100506352139000_16.10.e120909.1","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1097\/NMD.0000000000000699","article-title":"Childhood Adversity, Cortisol Levels, and Psychosis: A Retrospective Investigation","volume":"205","author":"Faravelli","year":"2017","journal-title":"J Nerv Ment Dis"},{"key":"2026100506352139000_16.10.e120909.2","unstructured":"American Psychiatric Association . 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