{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:00:24Z","timestamp":1790010024090,"version":"4.0.1"},"reference-count":61,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropsychobiology"],"abstract":"<jats:p>Introduction: Childhood trauma is common among adolescents with major affective disorders (MADs), including bipolar disorder and major depressive disorder. The relationships between childhood trauma subtypes, cognitive function, and the anti-aging protein Klotho and matrix metalloproteinase-9 (MMP-9) in adolescents with MADs remain unknown. Methods: We enrolled 95 adolescents with MADs (48 bipolar disorder, 47 major depressive disorder) and 45 healthy controls. Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form. A k-means cluster analysis identified trauma-based subgroups among patients. Serum Klotho and MMP-9 levels and cognitive functions (working memory, Wisconsin Card Sorting Test, and Go\/No-Go task) were assessed. Group differences were examined using generalized linear models adjusting for demographic variables, clinical symptoms, and medication use. Results: Three trauma clusters were identified: low trauma (n = 40), emotional neglect (EN)-focused (n = 47), and multi-trauma (n = 8) groups. The EN-focused group exhibited significantly lower Klotho levels than healthy controls and higher MMP-9 levels than all other groups. Cognitively, the EN-focused group showed reduced working memory accuracy and more trials to complete the first category on the Wisconsin Card Sorting Test, whereas the multi-trauma group demonstrated increased working memory errors and reduced Go\/No-Go accuracy. Conclusion: Adolescents with EN-focused trauma displayed a distinct biological-cognitive profile characterized by lower serum Klotho, higher MMP-9, and executive dysfunction. These findings suggest that deprivation-related adversity may be associated with convergent Klotho-MMP-9 alterations and neurobiological vulnerability in MADs. Longitudinal studies are warranted to clarify causal mechanisms.<\/jats:p>","DOI":"10.1159\/000553593","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:02:34Z","timestamp":1790006554000},"page":"1-13","source":"Crossref","is-referenced-by-count":0,"title":["Childhood Trauma Clusters, Klotho, Matrix Metalloproteinase-9, and Cognitive Function in Adolescents with Major Affective 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