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Objective <p>The triglyceride-glucose (TyG) index, linked to insulin resistance (IR), is implicated in depression, but its association with anxiety in major depressive disorder (MDD) is unclear. Subclinical hypothyroidism (SCH) is independently associated with metabolic issues and anxiety in MDD. This study aimed to (1) validate the TyG-anxiety link in first-episode, drug-naïve (FEDN) MDD patients and (2) explore SCH’s interactive role.</p> Methods <p>This cross-sectional study involved 1,654 FEDN MDD patients. Demographics, clinical data, and biochemical markers (including the TyG index) were collected. Depression and anxiety severity were assessed using HAMD-17 and HAMA-14 scales. Multivariable linear regression evaluated the TyG-anxiety association. Stratified analyses by SCH status and interaction tests were conducted.</p> Results <p>Of 1,654 MDD patients, 79.6% (1,316) had anxiety distress (HAMA-14 ≥ 18). In a fully adjusted model, each 1-unit TyG index increase was associated with a 0.67-point higher anxiety score (β = 0.67, 95% CI: 0.33–1.01). Patients in the highest TyG quintile (Q5: 9.42–10.27) showed a 0.75-point increase versus the lowest quintile (Q1: 6.64–8.59) (<i>P</i> &lt; 0.05). This association was significant in patients with SCH (β = 1.15, 95% CI: 0.68–1.61), not in those without SCH (β = 0.05, 95% CI: -0.44-0.53) (<i>P</i> for interaction&lt;0.05).</p> Conclusions <p>The TyG index is independently associated with anxiety symptoms in FEDN MDD patients, particularly in those with comorbid SCH. This suggests that the interaction between thyroid function and metabolism is associated with anxiety symptoms, highlighting a potential biological interplay that warrants further investigation. Clinicians should pay attention to anxiety levels in patients with MDD who also present with metabolic disturbances and SCH. Future longitudinal and basic studies are needed to confirm causality and mechanisms.</p>

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Association of triglyceride-glucose index with anxiety in first-episode, drug-naïve major depressive disorder: role of subclinical hypothyroidism

  • 期刊论文

  • 发表日期：

    2025年12月8日

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  • Xue Tian,
  • Yan Zhou,
  • Yuying Qiu,
  • Meijuan Li,
  • Jie Li,
  • Xiang-Yang Zhang

摘要

Objective

The triglyceride-glucose (TyG) index, linked to insulin resistance (IR), is implicated in depression, but its association with anxiety in major depressive disorder (MDD) is unclear. Subclinical hypothyroidism (SCH) is independently associated with metabolic issues and anxiety in MDD. This study aimed to (1) validate the TyG-anxiety link in first-episode, drug-naïve (FEDN) MDD patients and (2) explore SCH’s interactive role.

Methods

This cross-sectional study involved 1,654 FEDN MDD patients. Demographics, clinical data, and biochemical markers (including the TyG index) were collected. Depression and anxiety severity were assessed using HAMD-17 and HAMA-14 scales. Multivariable linear regression evaluated the TyG-anxiety association. Stratified analyses by SCH status and interaction tests were conducted.

Results

Of 1,654 MDD patients, 79.6% (1,316) had anxiety distress (HAMA-14 ≥ 18). In a fully adjusted model, each 1-unit TyG index increase was associated with a 0.67-point higher anxiety score (β = 0.67, 95% CI: 0.33–1.01). Patients in the highest TyG quintile (Q5: 9.42–10.27) showed a 0.75-point increase versus the lowest quintile (Q1: 6.64–8.59) (P < 0.05). This association was significant in patients with SCH (β = 1.15, 95% CI: 0.68–1.61), not in those without SCH (β = 0.05, 95% CI: -0.44-0.53) (P for interaction<0.05).

Conclusions

The TyG index is independently associated with anxiety symptoms in FEDN MDD patients, particularly in those with comorbid SCH. This suggests that the interaction between thyroid function and metabolism is associated with anxiety symptoms, highlighting a potential biological interplay that warrants further investigation. Clinicians should pay attention to anxiety levels in patients with MDD who also present with metabolic disturbances and SCH. Future longitudinal and basic studies are needed to confirm causality and mechanisms.