{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:59:09Z","timestamp":1793383149766,"version":"4.5.0"},"reference-count":46,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"Importance<\/jats:title>Individuals with psychiatric disorders have been reported to have elevated levels of inflammatory biomarkers, and prospective evidence is limited regarding the association between inflammatory biomarkers and subsequent psychiatric disorders risk.<\/jats:p><\/jats:sec>Objective<\/jats:title>To assess the associations between inflammation biomarkers and subsequent psychiatric disorders risk.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This was a prospective cohort study including individuals from the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort, with no prior psychiatric diagnoses and having a measurement of at least 1 inflammatory biomarker. Data from the UK Biobank were used for validation. Longitudinal trajectories of studied biomarkers were visualized before diagnosis of psychiatric disorders in the AMORIS cohort via a nested case-control study. In addition, genetic correlation and mendelian randomization (MR) analyses were conducted to determine the genetic overlap and causality of the studied associations using publicly available GWAS summary statistics.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Inflammatory biomarkers, eg, leukocytes, haptoglobin, immunoglobulin G (IgG), C-reactive protein (CRP), platelets, or albumin.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Any psychiatric disorder or specific psychiatric disorder (ie, depression, anxiety, and stress-related disorders) was identified through the International Statistical Classification of Diseases, Eighth, Ninth, and Tenth Revision <\/jats:italic>codes.<\/jats:p><\/jats:sec>Results<\/jats:title>Among the 585\u202f279 individuals (mean [SD] age, 45.5 [14.9] years; 306\u202f784 male [52.4%]) in the AMORIS cohort, individuals with a higher than median level of leukocytes (hazard ratio [HR], 1.11; 95% CI, 1.09-1.14), haptoglobin (HR, 1.13; 95% CI, 1.12-1.14), or CRP (HR, 1.02; 95% CI, 1.00-1.04) had an elevated associated risk of any psychiatric disorders. In contrast, we found an inverse association for IgG level (HR, 0.92; 95% CI, 0.89-0.94). The estimates were comparable for depression, anxiety, and stress-related disorders, specifically, and these results were largely validated in the UK Biobank (n = 485\u202f620). Analyses of trajectories revealed that individuals with psychiatric disorders had higher levels of leukocytes and haptoglobin and a lower level of IgG than their controls up to 30 years before the diagnosis. The MR analysis suggested a possible causal relationship between leukocytes and depression.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this cohort study, inflammatory biomarkers including leukocytes, haptoglobin, CRP, and IgG were associated with a subsequent risk of psychiatric disorders, and thus might be used for high-risk population identification. The possible causal link between leukocytes and depression supports the crucial role of inflammation in the development of psychiatric disorders.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2024.2185","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T22:41:16Z","timestamp":1724280076000},"page":"1118","source":"Crossref","is-referenced-by-count":123,"title":["Inflammatory Biomarkers and Risk of Psychiatric Disorders"],"prefix":"10.1001","volume":"81","author":[{"given":"Yu","family":"Zeng","sequence":"first","affiliation":[{"name":"Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China"},{"name":"Med-X Center for Informatics, Sichuan University, Chengdu, China"},{"name":"West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charilaos","family":"Chourpiliadis","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Hammar","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Seitz","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unnur A.","family":"Valdimarsd\u00f3ttir","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden"},{"name":"Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjav\u00edk, Iceland"},{"name":"Department of Epidemiology, Harvard T.H. 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