{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:03:40Z","timestamp":1793747020378,"version":"4.6.1"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":65,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK2CX002627"],"award-info":[{"award-number":["IK2CX002627"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR003142"],"award-info":[{"award-number":["UL1TR003142"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA124435"],"award-info":[{"award-number":["P30CA124435"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"U.S. Department of Health & Human Services | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH135076"],"award-info":[{"award-number":["R01MH135076"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Converging evidence implicates elevated inflammation in the pathophysiology of depression and its medical comorbidities. Despite known sex differences in both inflammatory activity and depression, a dedicated large-scale review of these differences is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a sex-stratified systematic review and meta-analysis of studies examining associations between depression and blood-based inflammatory markers in adult humans. Searches of PubMed, PsycINFO, and Scopus, and reference treeing, yielded 124 eligible papers including data from 423,421 participants (53% female). Analyses focused on depression and inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-\u03b1, IL-1\u03b2, and fibrinogen. Sex-stratified meta-analyses and meta regressions for the effects of sex were conducted, separately for cross-sectional and longitudinal designs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cross-sectionally, depression was modestly associated with higher levels of all markers combined in both females (Cohen\u2019s\n                      <jats:italic>d<\/jats:italic>\n                      \u2009=\u20090.06, 95% CI [0.03\u20130.10]) and males (Cohen\u2019s\n                      <jats:italic>d<\/jats:italic>\n                      \u2009=\u20090.14, 95% CI [0.09\u20130.19]). Depression was associated with elevated IL-6 in females, and elevated CRP and IL-6 in males. Longitudinally, elevated IL-6 was associated with subsequent depression among females and elevated CRP was associated with depression in males, whereas depression was not associated with subsequent inflammation in either sex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, results indicated modest associations between depression and elevated inflammation in both sexes, with slightly stronger associations in males. Associations between specific inflammatory markers (i.e., IL-6 in females and CRP in males) and subsequent depression differed by sex. These findings highlight the cross-sex relevance of inflammation in depression, and subtle sex differences in directionality and specific markers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41398-026-04139-7","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:20:54Z","timestamp":1780410054000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sex-specific associations of depression with inflammatory markers: a systematic review and meta-analysis"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5436-7081","authenticated-orcid":false,"given":"Yvette Z.","family":"Szabo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6189-830X","authenticated-orcid":false,"given":"Kristen","family":"Nishimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Smirnova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Niles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Skovgaard","family":"Lerche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-An","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Afroz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Huey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Mathur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife","family":"O\u2019Donovan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"4139_CR1","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.jpsychires.2019.08.002","volume":"126","author":"Q Liu","year":"2020","unstructured":"Liu Q, He H, Yang J, Feng X, Zhao F, Lyu J. Changes in the global burden of depression from 1990 to 2017: findings from the Global Burden of Disease study. J Psychiatr Res. 2020;126:134\u201340. https:\/\/doi.org\/10.1016\/j.jpsychires.2019.08.002.","journal-title":"J Psychiatr Res"},{"key":"4139_CR2","doi-asserted-by":"publisher","first-page":"e69637.","DOI":"10.1371\/journal.pone.0069637","volume":"8","author":"AJ Ferrari","year":"2013","unstructured":"Ferrari AJ, Charlson FJ, Norman RE, Flaxman AD, Patten SB, Vos T, et al. The epidemiological modelling of major depressive disorder: application for the Global Burden of Disease Study 2010. PloS One. 2013;8:e69637. https:\/\/doi.org\/10.1371\/journal.pone.0069637.","journal-title":"PloS One"},{"key":"4139_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/s12991-023-00486-7","volume":"22","author":"S Li","year":"2023","unstructured":"Li S, Zhang X, Cai Y, Zheng L, Pang H, Lou L. Sex difference in incidence of major depressive disorder: an analysis from the Global Burden of Disease Study 2019. Ann Gen Psychiatry. 2023;22:53. https:\/\/doi.org\/10.1186\/s12991-023-00486-7.","journal-title":"Ann Gen Psychiatry"},{"key":"4139_CR4","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1037\/bul0000102","volume":"143","author":"RH Salk","year":"2017","unstructured":"Salk RH, Hyde JS, Abramson LY. Gender differences in depression in representative national samples: meta-analyses of diagnoses and symptoms. Psychol Bull. 2017;143:783\u2013822. https:\/\/doi.org\/10.1037\/bul0000102.","journal-title":"Psychol Bull"},{"key":"4139_CR5","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.pneurobio.2019.01.006","volume":"176","author":"RS Eid","year":"2019","unstructured":"Eid RS, Gobinath AR, Galea LAM. Sex differences in depression: Insights from clinical and preclinical studies. Prog Neurobiol. 2019;176:86\u2013102. https:\/\/doi.org\/10.1016\/j.pneurobio.2019.01.006.","journal-title":"Prog Neurobiol"},{"key":"4139_CR6","first-page":"1","volume":"377","author":"DJ Brody","year":"2020","unstructured":"Brody DJ, Gu Q. Antidepressant use among adults: United States, 2015\u20132018. NCHS Data Brief. 2020;377:1\u20138.","journal-title":"NCHS Data Brief"},{"key":"4139_CR7","doi-asserted-by":"publisher","first-page":"100368.","DOI":"10.1016\/j.lanepe.2022.100368","volume":"17","author":"S Chen","year":"2022","unstructured":"Chen S, Ford TJ, Jones PB, Cardinal RN. Prevalence, progress, and subgroup disparities in pharmacological antidepressant treatment of those who screen positive for depressive symptoms: a repetitive cross-sectional study in 19 European countries. Lancet Reg Health Eur. 2022;17:100368. https:\/\/doi.org\/10.1016\/j.lanepe.2022.100368.","journal-title":"Lancet Reg Health Eur."},{"key":"4139_CR8","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.amepre.2022.05.014","volume":"63","author":"RD Goodwin","year":"2022","unstructured":"Goodwin RD, Dierker LC, Wu M, Galea S, Hoven CW, Weinberger AH. Trends in U.S. depression prevalence from 2015 to 2020: the widening treatment gap. Am J Prev Med. 2022;63:726\u201333. https:\/\/doi.org\/10.1016\/j.amepre.2022.05.014.","journal-title":"Am J Prev Med."},{"key":"4139_CR9","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1001\/jamapsychiatry.2025.0206","volume":"82","author":"MK Jha","year":"2025","unstructured":"Jha MK, Leboyer M, Pariante CM, Miller AH. Should inflammation be a specifier for major depression in the DSM-6?. JAMA Psychiatry. 2025;82:549\u201350. https:\/\/doi.org\/10.1001\/jamapsychiatry.2025.0206.","journal-title":"JAMA Psychiatry"},{"key":"4139_CR10","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1002\/wps.20723","volume":"19","author":"AH Miller","year":"2020","unstructured":"Miller AH. Beyond depression: the expanding role of inflammation in psychiatric disorders. World Psychiatry. 2020;19:108\u20139. https:\/\/doi.org\/10.1002\/wps.20723.","journal-title":"World Psychiatry"},{"key":"4139_CR11","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/s41573-021-00368-1","volume":"21","author":"WC Drevets","year":"2022","unstructured":"Drevets WC, Wittenberg GM, Bullmore ET, Manji HK. Immune targets for therapeutic development in depression: towards precision medicine. Nat Rev Drug Discov. 2022;21:224\u201344. https:\/\/doi.org\/10.1038\/s41573-021-00368-1.","journal-title":"Nat Rev Drug Discov"},{"key":"4139_CR12","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1016\/s0006-3223(03)00173-2","volume":"54","author":"L Capuron","year":"2003","unstructured":"Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, et al. Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment. Biol Psychiatry. 2003;54:906\u201314. https:\/\/doi.org\/10.1016\/s0006-3223(03)00173-2.","journal-title":"Biol Psychiatry"},{"key":"4139_CR13","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/s0306-4530(01)00030-0","volume":"26","author":"L Capuron","year":"2001","unstructured":"Capuron L, Ravaud A, Gualde N, Bosmans E, Dantzer R, Maes M, et al. Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. Psychoneuroendocrinology. 2001;26:797\u2013808. https:\/\/doi.org\/10.1016\/s0306-4530(01)00030-0.","journal-title":"Psychoneuroendocrinology"},{"key":"4139_CR14","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1038\/s41380-019-0395-3","volume":"25","author":"GM Khandaker","year":"2020","unstructured":"Khandaker GM, Zuber V, Rees JMB, Carvalho L, Mason AM, Foley CN, et al. Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort. Mol Psychiatry. 2020;25:1477\u201386. https:\/\/doi.org\/10.1038\/s41380-019-0395-3.","journal-title":"Mol Psychiatry"},{"key":"4139_CR15","doi-asserted-by":"publisher","first-page":"169.","DOI":"10.3389\/fncel.2020.00169","volume":"14","author":"A Bruno","year":"2020","unstructured":"Bruno A, Dolcetti E, Rizzo FR, Fresegna D, Musella A, Gentile A, et al. Inflammation-associated synaptic alterations as shared threads in depression and multiple sclerosis. Front Cell Neurosci. 2020;14:169. https:\/\/doi.org\/10.3389\/fncel.2020.00169.","journal-title":"Front Cell Neurosci"},{"key":"4139_CR16","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.biopsych.2014.06.015","volume":"77","author":"A O\u2019Donovan","year":"2015","unstructured":"O\u2019Donovan A, Cohen BE, Seal KH, Bertenthal D, Margaretten M, Nishimi K, et al. Elevated risk for autoimmune disorders in iraq and afghanistan veterans with posttraumatic stress disorder. Biol Psychiatry. 2015;77:365\u201374. https:\/\/doi.org\/10.1016\/j.biopsych.2014.06.015.","journal-title":"Biol Psychiatry"},{"key":"4139_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-02156-w","volume":"12","author":"K Nishimi","year":"2022","unstructured":"Nishimi K, Neylan TC, Bertenthal D, Dolsen EA, Seal KH, O\u2019Donovan A. Posttraumatic stress disorder and risk for hospitalization and death following COVID-19 infection. Transl Psychiatry. 2022;12:482.","journal-title":"Transl Psychiatry"},{"key":"4139_CR18","doi-asserted-by":"publisher","first-page":"10.","DOI":"10.1038\/nri.2016.90","volume":"16","author":"SL Klein","year":"2016","unstructured":"Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16:10. https:\/\/doi.org\/10.1038\/nri.2016.90.","journal-title":"Nat Rev Immunol"},{"key":"4139_CR19","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1038\/npp.2015.17","volume":"40","author":"M Moieni","year":"2015","unstructured":"Moieni M, Irwin MR, Jevtic I, Olmstead R, Breen EC, Eisenberger NI. Sex differences in depressive and socioemotional responses to an inflammatory challenge: implications for sex differences in depression. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2015;40:1709\u201316. https:\/\/doi.org\/10.1038\/npp.2015.17.","journal-title":"Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol"},{"key":"4139_CR20","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1002\/cpt.618","volume":"102","author":"S Benson","year":"2017","unstructured":"Benson S, Engler H, Wegner A, Rebernik L, Spreitzer I, Schedlowski M, et al. What makes you feel sick after inflammation? Predictors of acute and persisting physical sickness symptoms induced by experimental endotoxemia. Clin Pharmacol Ther. 2017;102:141\u201351. https:\/\/doi.org\/10.1002\/cpt.618.","journal-title":"Clin Pharmacol Ther"},{"key":"4139_CR21","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1097\/HRP.0000000000000230","volume":"28","author":"JS Hyde","year":"2020","unstructured":"Hyde JS, Mezulis AH. Gender differences in depression: biological, affective, cognitive, and sociocultural factors. Harv Rev Psychiatry. 2020;28:4\u201313. https:\/\/doi.org\/10.1097\/HRP.0000000000000230.","journal-title":"Harv Rev Psychiatry"},{"key":"4139_CR22","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.jad.2021.07.018","volume":"294","author":"J Lin","year":"2021","unstructured":"Lin J, Zou L, Lin W, Becker B, Yeung A, Cuijpers P, et al. Does gender role explain a high risk of depression? A meta-analytic review of 40 years of evidence. J Affect Disord. 2021;294:261\u201378. https:\/\/doi.org\/10.1016\/j.jad.2021.07.018.","journal-title":"J Affect Disord"},{"key":"4139_CR23","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1017\/S0033291719001454","volume":"49","author":"EF Osimo","year":"2019","unstructured":"Osimo EF, Baxter LJ, Lewis G, Jones PB, Khandaker GM. Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels. Psychol Med. 2019;49:1958\u201370. https:\/\/doi.org\/10.1017\/S0033291719001454.","journal-title":"Psychol Med"},{"key":"4139_CR24","doi-asserted-by":"publisher","first-page":"7.","DOI":"10.1038\/s41380-020-00867-4","volume":"26","author":"N Mac Giollabhui","year":"2021","unstructured":"Mac Giollabhui N, Ng TH, Ellman LM, Alloy LB. The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression. Mol Psychiatry. 2021;26:7. https:\/\/doi.org\/10.1038\/s41380-020-00867-4.","journal-title":"Mol Psychiatry"},{"key":"4139_CR25","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1097\/PSY.0b013e3181907c1b","volume":"71","author":"MB Howren","year":"2009","unstructured":"Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009;71:171\u201386. https:\/\/doi.org\/10.1097\/PSY.0b013e3181907c1b.","journal-title":"Psychosom Med"},{"key":"4139_CR26","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/j.bbi.2020.02.010","volume":"87","author":"EF Osimo","year":"2020","unstructured":"Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, Pariante CM, Howes OD. Inflammatory markers in depression: a meta-analysis of mean differences and variability in 5166 patients and 5083 controls. Brain Behav Immun. 2020;87:901\u20139. https:\/\/doi.org\/10.1016\/j.bbi.2020.02.010.","journal-title":"Brain Behav Immun"},{"key":"4139_CR27","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.bbi.2015.06.001","volume":"49","author":"R Haapakoski","year":"2015","unstructured":"Haapakoski R, Mathieu J, Ebmeier KP, Alenius H, Kivim\u00e4ki M. Cumulative meta-analysis of interleukins 6 and 1\u03b2, tumour necrosis factor \u03b1 and C-reactive protein in patients with major depressive disorder. Brain Behav Immun. 2015;49:206\u201315. https:\/\/doi.org\/10.1016\/j.bbi.2015.06.001.","journal-title":"Brain Behav Immun"},{"key":"4139_CR28","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.bbi.2024.07.037","volume":"121","author":"DA Jarkas","year":"2024","unstructured":"Jarkas DA, Villeneuve AH, Daneshmend AZB, Villeneuve PJ, McQuaid RJ. Sex differences in the inflammation-depression link: a systematic review and meta-analysis. Brain Behav Immun. 2024;121:257\u201368. https:\/\/doi.org\/10.1016\/j.bbi.2024.07.037.","journal-title":"Brain Behav Immun"},{"key":"4139_CR29","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.psyneuen.2018.05.035","volume":"95","author":"AN Niles","year":"2018","unstructured":"Niles AN, Smirnova M, Lin J, O\u2019Donovan A. Gender differences in longitudinal relationships between depression and anxiety symptoms and inflammation in the health and retirement study. Psychoneuroendocrinology. 2018;95:149\u201357. https:\/\/doi.org\/10.1016\/j.psyneuen.2018.05.035.","journal-title":"Psychoneuroendocrinology"},{"key":"4139_CR30","doi-asserted-by":"publisher","first-page":"n71.","DOI":"10.1136\/bmj.n71","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https:\/\/doi.org\/10.1136\/bmj.n71.","journal-title":"BMJ"},{"key":"4139_CR31","unstructured":"Deeks J, Higgins J, Altman D, McKenzie J, Veroniki A. Chapter 10: analysing data and undertaking meta-analyses. In: Cochrane Handbook for Systematic Reviews of Interventions Version 6.5. London, United Kingdom: Cochrane; 2024."},{"key":"4139_CR32","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1046\/j.1445-2197.2003.02748.x","volume":"73","author":"K Slim","year":"2003","unstructured":"Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg. 2003;73:712\u20136. https:\/\/doi.org\/10.1046\/j.1445-2197.2003.02748.x.","journal-title":"ANZ J Surg"},{"key":"4139_CR33","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.bbi.2020.04.078","volume":"88","author":"YZ Szabo","year":"2020","unstructured":"Szabo YZ, Slavish DC, Graham-Engeland JE. The effect of acute stress on salivary markers of inflammation: a systematic review and meta-analysis. Brain Behav Immun. 2020;88:887\u2013900. https:\/\/doi.org\/10.1016\/j.bbi.2020.04.078.","journal-title":"Brain Behav Immun"},{"key":"4139_CR34","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/jrsm.5","volume":"1","author":"LV Hedges","year":"2010","unstructured":"Hedges LV, Tipton E, Johnson MC. Robust variance estimation in meta-regression with dependent effect size estimates. Res Synth Methods. 2010;1:39\u201365. https:\/\/doi.org\/10.1002\/jrsm.5.","journal-title":"Res Synth Methods"},{"key":"4139_CR35","doi-asserted-by":"publisher","unstructured":"Fisher Z, Tipton E robumeta: an R-package for robust variance estimation in meta-analysis. arXiv. Preprint posted online March 7. arXiv:1503.02220 [Preprint]. 2015. Available from: https:\/\/doi.org\/10.48550\/arXiv.1503.02220.","DOI":"10.48550\/arXiv.1503.02220"},{"key":"4139_CR36","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1146\/annurev-publhealth-051920-114020","volume":"43","author":"MB Mathur","year":"2022","unstructured":"Mathur MB, VanderWeele TJ. Methods to address confounding and other biases in meta-analyses: review and recommendations. Annu Rev Public Health. 2022;43:19\u201335. https:\/\/doi.org\/10.1146\/annurev-publhealth-051920-114020.","journal-title":"Annu Rev Public Health"},{"key":"4139_CR37","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.bbi.2014.06.003","volume":"42","author":"D Lindqvist","year":"2014","unstructured":"Lindqvist D, Wolkowitz OM, Mellon S, Yehuda R, Flory JD, Henn-Haase C, et al. Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress. Brain Behav Immun. 2014;42:81\u201388. https:\/\/doi.org\/10.1016\/j.bbi.2014.06.003.","journal-title":"Brain Behav Immun"},{"key":"4139_CR38","first-page":"65","volume":"6","author":"S Holm","year":"1979","unstructured":"Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat. 1979;6:65\u201370.","journal-title":"Scand J Stat"},{"key":"4139_CR39","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1002\/sim.8057","volume":"38","author":"MB Mathur","year":"2019","unstructured":"Mathur MB, VanderWeele TJ. New metrics for meta-analyses of heterogeneous effects. Stat Med. 2019;38:1336\u201342. https:\/\/doi.org\/10.1002\/sim.8057.","journal-title":"Stat Med"},{"key":"4139_CR40","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1097\/EDE.0000000000001180","volume":"31","author":"MB Mathur","year":"2020","unstructured":"Mathur MB, VanderWeele TJ. Robust metrics and sensitivity analyses for meta-analyses of heterogeneous effects. Epidemiol Camb Mass. 2020;31:356\u20138. https:\/\/doi.org\/10.1097\/EDE.0000000000001180.","journal-title":"Epidemiol Camb Mass"},{"key":"4139_CR41","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1080\/01621459.2018.1529598","volume":"115","author":"MB Mathur","year":"2020","unstructured":"Mathur MB, VanderWeele TJ. Sensitivity analysis for unmeasured confounding in meta-analyses. J Am Stat Assoc. 2020;115:163\u201372. https:\/\/doi.org\/10.1080\/01621459.2018.1529598.","journal-title":"J Am Stat Assoc"},{"key":"4139_CR42","doi-asserted-by":"publisher","first-page":"268","DOI":"10.7326\/M16-2607","volume":"167","author":"TJ VanderWeele","year":"2017","unstructured":"VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med. 2017;167:268\u201374. https:\/\/doi.org\/10.7326\/M16-2607.","journal-title":"Ann Intern Med"},{"key":"4139_CR43","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1172\/JCI18921","volume":"111","author":"MB Pepys","year":"2003","unstructured":"Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111:1805\u201312. https:\/\/doi.org\/10.1172\/JCI18921.","journal-title":"J Clin Invest"},{"key":"4139_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jad.2021.04.035","volume":"290","author":"G Lombardo","year":"2021","unstructured":"Lombardo G, Mondelli V, Dazzan P, Pariante CM. Sex hormones and immune system: a possible interplay in affective disorders? A systematic review. J Affect Disord. 2021;290:1\u201314. https:\/\/doi.org\/10.1016\/j.jad.2021.04.035.","journal-title":"J Affect Disord"},{"key":"4139_CR45","doi-asserted-by":"publisher","first-page":"7393","DOI":"10.1038\/s41380-021-01188-w","volume":"26","author":"Y Milaneschi","year":"2021","unstructured":"Milaneschi Y, Kappelmann N, Ye Z, Lamers F, Moser S, Jones PB, et al. Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts. Mol Psychiatry. 2021;26:7393\u2013402. https:\/\/doi.org\/10.1038\/s41380-021-01188-w.","journal-title":"Mol Psychiatry"},{"key":"4139_CR46","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1176\/appi.ajp.20250289","volume":"182","author":"AH Miller","year":"2025","unstructured":"Miller AH. Advancing an inflammatory subtype of major depression. Am J Psychiatry. 2025;182:516\u201324. https:\/\/doi.org\/10.1176\/appi.ajp.20250289.","journal-title":"Am J Psychiatry"},{"key":"4139_CR47","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1111\/jcpp.13817","volume":"64","author":"EG Carey","year":"2023","unstructured":"Carey EG, Ridler I, Ford TJ, Stringaris A. Editorial perspective: when is a \u201csmall effect\u201d actually large and impactful?. J Child Psychol Psychiatry. 2023;64:1643\u20137. https:\/\/doi.org\/10.1111\/jcpp.13817.","journal-title":"J Child Psychol Psychiatry"},{"key":"4139_CR48","doi-asserted-by":"publisher","first-page":"e06445.","DOI":"10.1016\/j.heliyon.2021.e06445","volume":"7","author":"AL Numis","year":"2021","unstructured":"Numis AL, Fox CH, Lowenstein DJ, Norris PJ, Di Germanio C. Comparison of multiplex cytokine assays in a pediatric cohort with epilepsy. Heliyon. 2021;7:e06445. https:\/\/doi.org\/10.1016\/j.heliyon.2021.e06445.","journal-title":"Heliyon"},{"key":"4139_CR49","doi-asserted-by":"publisher","first-page":"11.","DOI":"10.1186\/s12979-019-0151-1","volume":"16","author":"L Koelman","year":"2019","unstructured":"Koelman L, Pivovarova-Ramich O, Pfeiffer AFH, Grune T, Aleksandrova K. Cytokines for evaluation of chronic inflammatory status in ageing research: reliability and phenotypic characterisation. Immun Ageing. 2019;16:11. https:\/\/doi.org\/10.1186\/s12979-019-0151-1.","journal-title":"Immun Ageing"},{"key":"4139_CR50","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1158\/1055-9965.EPI-11-0221","volume":"20","author":"AK Chaturvedi","year":"2011","unstructured":"Chaturvedi AK, Kemp TJ, Pfeiffer RM, Biancotto A, Williams M, Munuo S, et al. Evaluation of multiplexed cytokine and inflammation marker measurements: a methodologic study. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2011;20:1902\u201311. https:\/\/doi.org\/10.1158\/1055-9965.EPI-11-0221.","journal-title":"Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol"},{"key":"4139_CR51","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1093\/eurpub\/ckv134","volume":"25","author":"M Osler","year":"2015","unstructured":"Osler M, Bruunsgaard H, Lykke Mortensen E. Lifetime socio-economic position and depression: an analysis of the influence of cognitive function, behaviour and inflammatory markers. Eur J Public Health. 2015;25:1065\u20139. https:\/\/doi.org\/10.1093\/eurpub\/ckv134.","journal-title":"Eur J Public Health"},{"key":"4139_CR52","doi-asserted-by":"publisher","first-page":"387.","DOI":"10.3390\/brainsci12030387","volume":"12","author":"E Og\u0142odek","year":"2022","unstructured":"Og\u0142odek E. Changes in the serum levels of cytokines: IL-1\u03b2, IL-4, IL-8 and IL-10 in depression with and without posttraumatic stress disorder. Brain Sci. 2022;12:387. https:\/\/doi.org\/10.3390\/brainsci12030387.","journal-title":"Brain Sci"},{"key":"4139_CR53","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2015.137","volume":"5","author":"J Verduijn","year":"2015","unstructured":"Verduijn J, Milaneschi Y, Schoevers RA, van Hemert AM, Beekman ATF, Penninx BWJH. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression. Transl Psychiatry. 2015;5:e649. https:\/\/doi.org\/10.1038\/tp.2015.137.","journal-title":"Transl Psychiatry"},{"key":"4139_CR54","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1017\/S0033291708003723","volume":"39","author":"D Gimeno","year":"2009","unstructured":"Gimeno D, Kivim\u00e4ki M, Brunner EJ, Elovainio M, De Vogli R, Steptoe A, et al. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med. 2009;39:413\u201323. https:\/\/doi.org\/10.1017\/S0033291708003723.","journal-title":"Psychol Med"},{"key":"4139_CR55","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1016\/j.psyneuen.2013.01.002","volume":"38","author":"HE Duivis","year":"2013","unstructured":"Duivis HE, Vogelzangs N, Kupper N, de Jonge P, Penninx BWJH. Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the Netherlands Study of Depression and Anxiety (NESDA). Psychoneuroendocrinology. 2013;38:1573\u201385. https:\/\/doi.org\/10.1016\/j.psyneuen.2013.01.002.","journal-title":"Psychoneuroendocrinology"},{"key":"4139_CR56","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1016\/j.euroneuro.2015.06.007","volume":"25","author":"R Strawbridge","year":"2015","unstructured":"Strawbridge R, Arnone D, Danese A, Papadopoulos A, Herane Vives A, Cleare AJ. Inflammation and clinical response to treatment in depression: a meta-analysis. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2015;25:1532\u201343. https:\/\/doi.org\/10.1016\/j.euroneuro.2015.06.007.","journal-title":"Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol"},{"key":"4139_CR57","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.euroneuro.2017.04.001","volume":"27","author":"CM Pariante","year":"2017","unstructured":"Pariante CM. Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2017;27:554\u20139. https:\/\/doi.org\/10.1016\/j.euroneuro.2017.04.001.","journal-title":"Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol"},{"key":"4139_CR58","doi-asserted-by":"publisher","unstructured":"Lamers F, Milaneschi Y, Penninx BWJH. Chapter 26 - depression subtypes and inflammation: atypical rather than melancholic depression is linked with immunometabolic dysregulations. In: Baune BT, ed. Inflammation and Immunity in Depression. London, United Kingdom: Academic Press; 2018. pp. 455-71. https:\/\/doi.org\/10.1016\/B978-0-12-811073-7.00026-X","DOI":"10.1016\/B978-0-12-811073-7.00026-X"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04139-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04139-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04139-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T23:48:37Z","timestamp":1785973717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04139-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4139"],"URL":"https:\/\/doi.org\/10.1038\/s41398-026-04139-7","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]},"assertion":[{"value":"21 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"394"}}