Thyroid-Stimulating Hormone Levels and Incident Depression

Results From the ELSA-Brasil Study

Ana C. Varella; Isabela M. Benseñor; Carolina C.P.S. Janovsky; Alessandra C. Goulart; Marina G. Birck; Itamar S. Santos; Andre R. Brunoni; Paulo A. Lotufo


Clin Endocrinol. 2021;94(5):858-865. 

In This Article

Abstract and Introduction


Objective: This study aimed to prospectively evaluate whether TSH levels at baseline were associated with incident depression after four years of follow-up in a cohort of middle-aged adults, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methods: TSH and free-thyroxine (FT4) levels were evaluated at baseline. Depression diagnoses were performed using the Clinical Interview Schedule—Revised (CIS-R) at baseline and after a 4-year follow-up. Poisson regression models (95% Confidence Intervals) were built to evaluate the association between TSH quintiles at baseline and incident depression. All analyses were stratified by sex. Models were presented crude, adjusted for age and sex; and further adjusted for race, education, BMI, smoking, alcohol consumption, use of antidepressants/benzodiazepines, kidney function and comorbidities.

Results: Mean age was 51.5 years, and 51.2% were women. Overall, low TSH levels (1st quintile) were associated with incident depression (adjusted RR = 1.36, 95% CI 1.02–1.81), remaining significant for women (adjusted RR = 1.64, 95% CI 1.15–2.33), but not for men. The same results were found when restricting analysis to euthyroid participants (adjusted RR = 1.46, 95% CI 1.08–1.99), also significant for women only (adjusted RR = 1.63, 95% CI 1.12–2.38).

Conclusions: Our results showed that low TSH levels were positively associated with incident depression, particularly among women. Similar results were found when restricting the analysis to euthyroid participants. In contrast, high TSH levels were inversely associated with incident depression, also among women.


Thyroid and psychiatric disorders in adults usually share common clinical symptoms and characteristics. In both conditions, patients might present apathy, fatigue, psychomotor alterations, cognitive and sleep disturbances, weight variation, mania and acute psychosis.[1,2] However, the association between subclinical thyroid dysfunction and depression has not yet been confirmed.[3]

To assess the possible relationship between subclinical thyroid dysfunction and depression, studies have focused on thyroid-stimulating hormone (TSH) levels. In cross-sectional analysis, studies reported an association between low TSH levels and depression in men[4,5] and women.[5] Furthermore, high TSH levels were associated with lower risk of depression in men[6] and women.[6,7] In contrast, the latter study also showed that higher TSH levels were associated with higher prevalence of depression among men.[7] One study showed no association between TSH levels and depression for both sexes.[8]

Few studies have prospectively analysed the association between TSH levels and depression among individuals with subclinical thyroid dysfunction and/or euthyroidism. A retrospective cohort study found that higher TSH levels were associated with an increased risk of depression among women, even among euthyroid participants.[9] A prospective analysis in men found no association between TSH levels and depression.[10] Similarly, a large prospective study reported no association between TSH levels among euthyroid individuals and incident depression.[11]

Due to the varied findings observed so far, we aimed to prospectively investigate the association between TSH levels and incidence of depression using a large Brazilian sample. Our hypothesis was that the association of subclinical thyroid diseases and depression would consist of a U-shaped curve, with greater risk of depression appearing towards the lowest and highest TSH levels, even within the normal range. As both thyroid disorders and depression are more common in women,[12] we also hypothesized that this association would be stronger for women.