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

• We assessed the relationship between thyroid-stimulating hormone level and risk of depression.
• Relationships between thyroid function and depressive symptoms were different by gender.
• Low normal thyroid function was associated with the development of depression in females.

SummaryObjectiveThis 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.MethodsThis 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.ResultsThe 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).ConclusionsOur finding suggests that suboptimal thyroid function increases vulnerability to the occurrence of depressive symptom and represents a modifiable risk factor for depression in females.