J Affect Disord. 2025 Dec 29:121068. doi: 10.1016/j.jad.2025.121068. Online ahead of print.
ABSTRACT
BACKGROUND: Sex differences in both major depressive disorder (MDD) and subclinical hypothyroidism (SCH) are established, but their interplay in overweight/obese, first-episode drug-naïve (FEDN) MDD patients with study-defined higher-TSH subgroup (TSH > 8 mIU/L with normal FT4) is unclear. We investigated sex-specific prevalence and clinical correlates of this elevated TSH phenotype in patients with FEDN-MDD.
METHODS: Among 1026 FEDN-MDD outpatients with BMI ≥ 24 kg/m2 (348 males; 678 females), depression, anxiety, and psychotic symptoms were assessed using the HAMD-17, HAMA, PANSS-Positive subscale. The CGI-S scale was used to measure overall severity. Morning fasting TSH, FT3, and FT4 were measured using chemiluminescence.
RESULTS: The prevalence of the study-defined higher-TSH subgroup was 13.6 % (140/1026) and was significantly higher in women (15.3 %) than in men (10.3 %) (p = 0.027). In sex-specific logistic regression models conducted separately in men and women, higher systolic blood pressure and greater psychotic symptom severity were independently associated with this higher-TSH subgroup in both sexes. Among women, a history of suicide attempts was independently associated with membership in this subgroup, and its combination with systolic blood pressure yielded only a small, exploratory gain in discrimination compared with systolic blood pressure alone.
CONCLUSIONS: Overweight/obese female patients with FEDN-MDD are more likely than men to develop the study-defined higher-TSH subgroup. Thyroid screening, combined with cardiovascular and symptom monitoring, is warranted in this population.
PMID:41475570 | DOI:10.1016/j.jad.2025.121068
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