Klotho and Matrix Metalloproteinase-9 Levels and Their Association With Inhibitory Dyscontrol in Adolescents With First-Episode Major Affective Disorders

Li-Chi Chen, MD ; Ya-Mei Bai, MD, PhD ; Shih-Jen Tsai, MD ; Ju-Wei Hsu, MD ; Mu-Hong Chen, MD, PhD

J Clin Psychiatry 2025;86(3):24m15696

Abstract

Background: The roles of Klotho and matrix metalloproteinase (MMP)-9 in the pathomechanisms underlying first episode major affective disorders as well as their impact on related inhibitory control function remain unclear.

Methods: This study included 44 adolescents with first-episode bipolar disorder, 60 with first-episode major depressive disorder, and 46 age matched healthy controls between January 1, 2021, and August 31, 2024. DSM-5 criteria were used to make the diagnoses of 2 major affective disorders. All the participants were assessed for levels of Klotho and MMP-9 and completed the go/no-go task. Generalized linear models (GLMs) were employed to compare Klotho and MMP 9 levels, along with inhibitory control function, between groups.

Results: After adjustments for demographic characteristics, clinical symptoms, and psychotropic medication use, the GLMs indicated that adolescents with bipolar disorder and those with major depressive disorder exhibited significantly lower Klotho levels compared with the control group (P = .007). Additionally, adolescents with bipolar disorder had the highest MMP-9 levels (P = .002), followed by those with major depressive disorder (P = .031), compared with healthy controls. Furthermore, lower Klotho levels and higher MMP-9 levels were associated with inhibitory control deficits.

Conclusions: Adolescents experiencing first-episode bipolar disorder and major depressive disorder exhibited decreased Klotho levels and increased MMP-9 levels, both of which were associated with deficits in inhibitory control function. Additional studies are warranted to clarify the specific pathomechanisms underlying the complex associations between major affective disorders, Klotho and MMP-9 dysregulation, and deficits in inhibitory control function.

J Clin Psychiatry 2025;86(3):24m15696

Author affiliations are listed at the end of this article.

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