An “increase-decrease-increase” pattern: TSH levels and anxiety symptoms in treatment-naïve first-episode patients with major depressive disorder

12/04/2026

J Affect Disord. 2026 Apr 9:121778. doi: 10.1016/j.jad.2026.121778. Online ahead of print.

ABSTRACT

BACKGROUND: Whether thyroid-stimulating hormone (TSH) concentrations are related to anxiety symptoms in major depressive disorder (MDD) has not yet been clearly established and remains inconclusive. Therefore, the association between TSH concentrations and anxiety symptoms in treatment-naïve, first-episode (TNFE) MDD patients was explored.

METHODS: About 1718 TNFE MDD patients were included. The association between TSH concentrations and anxiety symptoms was analyzed using multivariate logistic regression. To identify a possible inflection point and examine nonlinearity, piecewise logistic regression was conducted, and subgroup analyses were also performed to identify potential effect modifiers.

RESULTS: Both univariate and multivariate analyses showed consistent results that TSH concentrations were positively correlated with anxiety symptoms (adjusted OR = 1.31, 95% CI: 1.19-1.43) in TNFE MDD patients. At the same time, smoothing plot results indicated nonlinear relationships between TSH concentrations and anxiety symptoms, with inflection points at 4.30 and 6.90 μIU/mL. TSH concentrations <4.30 μIU/mL (OR = 2.72, 95% CI: 1.59-4.65) and TSH concentrations ≥6.90 μIU/mL (OR = 1.72, 95% CI: 1.39-2.12) were positively correlated with anxiety, whereas a negative association was observed in TNFE MDD patients with TSH concentrations of 4.30-6.90 μIU/mL (OR = 0.67, 95% CI: 0.48-0.93). Moreover, subgroup analysis indicated that sex, marital status, suicide, and psychotic symptoms were not effect modifiers of the above association (interaction P>0.05).

CONCLUSIONS: The results indicated that TNFE MDD patients exhibited a significant nonlinear association between TSH concentrations and anxiety symptoms, suggesting that assessment of TSH may contribute to understanding anxiety symptoms in patients with MDD.

PMID:41966231 | DOI:10.1016/j.jad.2026.121778

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