Childhood Trauma Clusters, Klotho, Matrix Metalloproteinase-9, and Cognitive Function in Adolescents with Major...

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.

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.

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.

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.