{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:35:29Z","timestamp":1790728529302,"version":"4.1.0"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Psychosom Med"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>Functional somatic syndromes (FSS) are highly prevalent across all levels of health care. The fact that they are characterized by medically unexplained symptoms, such as fatigue and pain, raises the important question of their underlying pathophysiology. Psychosocial stress represents a significant factor in the development of FSS and can induce long-term modifications at the epigenetic level. The aim of this review was to systematically review, for the first time, whether individuals with FSS are characterized by specific alterations in DNA methylation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>MEDLINE and PsycINFO were searched from the first available date to September 2022. The inclusion criteria were as follows: a) adults fulfilling the research diagnostic criteria for chronic fatigue syndrome, fibromyalgia syndrome, and\/or irritable bowel syndrome; b) healthy control group; and c) candidate-gene or genome-wide study of DNA methylation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Sixteen studies (<jats:italic toggle=\"yes\">N<\/jats:italic> = 957) were included. In candidate-gene studies, specific sites within <jats:italic toggle=\"yes\">NR3C1<\/jats:italic> were identified, which were hypomethylated in individuals with chronic fatigue syndrome compared with healthy controls. In genome-wide studies in chronic fatigue syndrome, a hypomethylated site located to <jats:italic toggle=\"yes\">LY86<\/jats:italic> and hypermethylated sites within <jats:italic toggle=\"yes\">HLA-DQB1<\/jats:italic> were found. In genome-wide studies in fibromyalgia syndrome, differential methylation in sites related to <jats:italic toggle=\"yes\">HDAC4<\/jats:italic>, <jats:italic toggle=\"yes\">TMEM44<\/jats:italic>, <jats:italic toggle=\"yes\">KCNQ1<\/jats:italic>, <jats:italic toggle=\"yes\">SLC17A9<\/jats:italic>, <jats:italic toggle=\"yes\">PRKG1<\/jats:italic>, <jats:italic toggle=\"yes\">ALPK3<\/jats:italic>, <jats:italic toggle=\"yes\">TFAP2A<\/jats:italic>, and <jats:italic toggle=\"yes\">LY6G5C<\/jats:italic> was found.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Individuals with chronic fatigue syndrome and fibromyalgia syndrome seem to be characterized by altered DNA methylation of genes regulating cellular signaling and immune functioning. In chronic fatigue syndrome, there is preliminary evidence for these to be implicated in key pathophysiological alterations, such as hypocortisolism and low-grade inflammation, and to contribute to the debilitating symptoms these individuals experience.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Preregistration<\/jats:title>\n            <jats:p>PROSPERO identifier: CRD42022364720.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/psy.0000000000001237","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T16:00:46Z","timestamp":1690992046000},"page":"672-681","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":11,"title":["DNA Methylation Signatures of Functional Somatic Syndromes: Systematic Review"],"prefix":"10.1097","volume":"85","author":[{"given":"Susanne","family":"Fischer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kleinst\u00e4uber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Fiori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Turecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"von K\u00e4nel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"bib1-20250815","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/S0140-6736(98)08320-2","article-title":"Functional somatic syndromes: one or many?","volume":"354","year":"1999","journal-title":"Lancet"},{"key":"bib2-20250815","doi-asserted-by":"crossref","first-page":"910","DOI":"10.7326\/0003-4819-130-11-199906010-00016","article-title":"Functional somatic syndromes","volume":"130","year":"1999","journal-title":"Ann Intern Med"},{"key":"bib3-20250815","doi-asserted-by":"crossref","first-page":"953","DOI":"10.7326\/0003-4819-121-12-199412150-00009","article-title":"The chronic fatigue syndrome: a comprehensive approach to its definition and study. 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