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Here, we systematically review studies on peripheral organ systems (cardiovascular, metabolic, immune, liver, kidneys, lungs and muskeloskeletal) in schizophrenia, major depressive disorder (MDD), bipolar disorder (BD) and generalized anxiety disorder (GAD), aiming to synthesize findings on the function of multiple body systems in the early stages of mental illness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EMBASE, MEDLINE and PsycINFO were searched from inception until 19 November 2024, identifying case-control studies comparing physiological markers of peripheral organ systems (i.e., cardiovascular, metabolic, immune, liver, kidney, lung and muskeloskeletal) in adults with one of the four mental illnesses at first-episode and drug naive, with healthy controls. We followed the PRISMA 2020 guidelines (PROSPERO: CRD42023408594).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 2637 citations retrieved, 138 studies met inclusion criteria for review with 52 markers of immune (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200932), metabolic (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911), cardiovascular (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096), liver (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092) and musculoskeletal (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091) function identified. 105 studies were eligible for meta-analysis, including 80, 26, 4 and 0 studies on schizophrenia, MDD, BD and GAD respectively. Meta-analysis revealed increased waist-hip-circumference ratio, triglycerides, insulin, insulin resistance, 2-hr glucose, neutrophil, monocyte, white blood cell, IL-4 and systolic blood pressure, and reduced albumin in schizophrenia; increased TNF-\u03b1 and IL-10 in MDD; and increased IL-6 and IFN-\u03b3 in both schizophrenia and MDD. Other results were narratively discussed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Alterations in peripheral organ function across multiple systems characterizes the onset of psychiatric disorders. However, research on peripheral organ function in psychiatry is limited and primarily focusses on the immune and metabolic systems.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41380-026-03891-y","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:39:49Z","timestamp":1789569589000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered function of peripheral organ systems in first-episode drug na\u00efve mental illnesses: a systematic review and meta-analysis"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0216-6744","authenticated-orcid":false,"given":"Jetro E.","family":"Ang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangqi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0029-1525","authenticated-orcid":false,"given":"Vanessa","family":"Cropley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-9908","authenticated-orcid":false,"given":"Andrew","family":"Zalesky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3107-5550","authenticated-orcid":false,"given":"Ye Ella","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"3891_CR1","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/S2215-0366(19)30132-4","volume":"6","author":"J Firth","year":"2019","unstructured":"Firth J, Siddiqi N, Koyanagi A, Siskind D, Rosenbaum S, Galletly C, et al. 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