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Indicators of despair-related maladies across four domains \u2013 suicidality, substance misuse, sleep problems, and pain \u2013 were assessed at age 45 using multi-modal measures including self-report, informant-report, and national register data.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291723001320_sec_a3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>We identified and validated a syndrome of despair-related maladies at midlife involving suicidality, substance misuse, sleep problems, and pain. Adults who exhibited a more severe syndrome of despair-related maladies at midlife tended to have had early-onset emotional and behavioral disorders [<jats:italic>\u03b2<\/jats:italic> = 0.23, 95% CI (0.16\u20130.30), <jats:italic>p<\/jats:italic> &lt; 0.001], even after adjusting for sex, childhood SES, and childhood IQ. A more pronounced midlife despair syndrome was observed among adults who, as adolescents, were diagnosed with a greater number of mental disorders [<jats:italic>\u03b2<\/jats:italic> = 0.26, 95% CI (0.19\u20130.33), <jats:italic>p<\/jats:italic> &lt; 0.001]. Tests of diagnostic specificity revealed that associations generalized across different adolescent mental disorders.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291723001320_sec_a4\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Midlife adults who exhibited a more severe syndrome of despair-related maladies tended to have had psychopathology as adolescents. Prevention and treatment of adolescent psychopathology may mitigate despair-related maladies at midlife and ultimately reduce deaths of despair.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0033291723001320","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T17:38:07Z","timestamp":1683740287000},"page":"7569-7580","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":11,"title":["Tracing the origins of midlife despair: association of psychopathology during adolescence with a syndrome of despair-related maladies at midlife"],"prefix":"10.1017","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0246-0820","authenticated-orcid":false,"given":"Grace M.","family":"Brennan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrie 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