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Association of thyroid function and clinical severity of first-episode depression in adolescents : a retrospective study

diabetes-and-endocrinology
psychiatry-and-psychology
womens-health
mental-health

Abstract

Background. Adolescent depression prevalence is rising globally, yet biomarkers and mechanisms remain poorly understood. The hypothalamic-pituitary-thyroid axis is implicated in depression, but its specific role and potential sex differences in adolescents are unclear.

Methods. This retrospective study analyzed 861 first-episode adolescent depression outpatients (613 females, 248 males). Patients were stratified by depression severity into non-major depression disorder (MDD) (n=377) and MDD (n=484) groups. Serum levels of thyroid hormones and sex hormones (testosterone, estradiol, progesterone) were measured. Group comparisons, correlation analyses, multivariate logistic regression, and moderation analysis were performed.

Results. MDD patients were younger, predominantly female (79.5% vs 46.0% in non-MDD), and had higher anxiety and depression scores. SDS scores correlated negatively with TSH, T4, and T3. Multivariate regression identified younger age, female sex, lower T3, lower testosterone, and higher estradiol as independent predictors of MDD (AUC=0.74). Moderation analysis demonstrated that testosterone significantly moderates the T3-depression relationship (interaction β = -0.08, p=0.042). Higher T3 was associated with lower depression severity in high-testosterone subgroups (simple slope=-1.41, p=0.004).

Conclusions. Thyroid dysfunctions are associated with adolescent MDD, showing distinct sex-specific patterns. Testosterone moderates the relationship between T3 and depression severity. Assessing thyroid function and testosterone-T3 dynamics may aid in risk stratification for adolescent MDD.

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