Appetite Hormone Regulation Biotypes of Major Affective Disorders in Proinflammatory Cytokines and Executive Function

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

J Clin Psychiatry 2025;86(2):24m15561

Abstract

Backgrounds: Evidence indicates that appetite hormones, namely, insulin, leptin, and adiponectin, play crucial roles in the pathophysiology of major affective disorders. However, whether appetite hormone regulation biotypes differ among patients with major affective disorders remains unclear.

Methods: A total of 501 patients with major affective disorders (278 with bipolar disorder and 223 with major depressive disorder) were enrolled between 2018 and 2022 and clustered into biotype groups on the basis of fasting insulin, leptin, and adiponectin levels. Major affective disorder diagnoses were based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. All participants underwent the Wisconsin Card Sorting Test and proinflammatory cytokine assessment.

Results: A k-means cluster analysis identified 3 biotype groups based on appetite hormone levels: a high insulin/ leptin and low adiponectin group, a low insulin/leptin and high adiponectin group, and an intermediate group. The high insulin/leptin and low adiponectin group exhibited poorer performance on the Wisconsin Card Sorting Test and had higher C-reactive protein and tumor necrosis factor-α levels than did the other biotype groups after adjusting for diagnosis, body mass index, clinical symptoms, and psychotropic medication use.

Discussion: This study identified 3 appetite hormone regulation biotypes among patients with major affective disorders. These biotypes were associated with proinflammatory cytokine profiles and executive function.

J Clin Psychiatry 2025;86(2):24m15561

Author affiliations are listed at the end of this article.

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