Relationship between thyroid-stimulating hormone levels and risk of depression among the general population with normal free T4 levels

Objective: This study assessed the relationship between thyroid-stimulating hormone (TSH) level and risk of depressive symptom in a population with no clinical or laboratory evidence of thyroid dysfunction.

Methods: This retrospective cohort study included 13,017 subjects (7913 males and 5104 females), 17-84 years of age, who underwent health examinations at the hospital. Subjects had a Beck Depression Inventory (BDI) total score of ≤9 and fell within the normal range of free T4 levels at baseline. The association between gender-specific serum TSH tertile at baseline and the development of clinically significant depressive symptom (i.e., ≥19 BDI total score) on the follow-up visit was evaluated using the Cox proportional hazards model, with adjustment for demographic and life style factors.

Results: The risk of depressive symptom was increased among subjects with the highest tertile TSH level (adjusted hazard ratio [HR], 2.236; 95% confidence interval [CI], 1.443-3.466; p<0.001) as compared with subjects with the lowest tertile in females, but not in males. Even among patients with normal TSH levels, females in the lowest-normal TSH tertile had a higher risk of depressive symptoms (adjusted HR, 2.279; 95% CI, 1.456-3.567; p<0.001) than did those in the highest tertile. The TSH level as a continuous variable significantly predicted the depressive symptoms in females (adjusted HR, 1.402; 95% CI, 1.002-1.812; p=0.027).

Conclusions: Our finding suggests that suboptimal thyroid function increases vulnerability to the occurrence of depressive symptom and represents a modifiable risk factor for depression in females.