Thyroid Dysfunction and the Risk of Clinically Relevant Depression: A Longitudinal Cohort Study

To examine the association between thyroid function, measured via thyrotropin level, and depression, assessed by the Patient Health Questionnaire-9 (PHQ-9), in a longitudinal cohort.

We conducted a longitudinal cohort study of euthymic and euthyroid adults at baseline (PHQ-9 score, <5; thyrotropin level, >0.3-4.2 mIU/L) from January 1, 2000, through August 30, 2021, with thyrotropin level and PHQ-9 assessed within 6 months and at least 2 paired measurements per participant. Data included demographics, medical comorbidities, thyroid function, psychotropic medications, thyroid disorders, hormone replacement, and mood disorder diagnoses (International Classification of Diseases, Tenth Revision, Clinical Modification). Thyroid dysfunction was classified as low thyrotropin level (≤0.3 mIU/L) or high thyrotropin level (>4.2 mIU/L) based on the first occurrence of abnormal values. The primary outcome was clinically relevant depression (CRD; PHQ-9 score, ≥10). Cox proportional hazards models assessed the association between time-varying thyroid dysfunction and time to CRD, including sex-based differences in the onset of thyroid dysfunction or CRD.

Among 6191 adults (mean age, 50.2 years, 67% female, 92.4% White), thyroid dysfunction was significantly associated with an increased CRD risk (hazard ratio [HR], 1.33; P<.001). Low (HR, 1.57; P<.001) and high (HR, 1.25; P=.005) thyrotropin levels were both linked to elevated CRD risk. Females had a higher incidence and earlier onset of thyroid dysfunction and CRD.

Thyroid dysfunction is associated with an increased risk of CRD, with females showing a higher incidence and earlier onset of both conditions, underscoring the need for depression screening in affected individuals. Further research is needed to validate these findings in diverse populations.