Thyroid Function Within the Normal Range and the Risk of Depression: A Population-Based Cohort Study

Context: Overt hypo- and hyperthyroidism are associated with an increased risk of depression. Little is known about the effects of variation in thyroid function within the normal range on the risk of depression. Objective: The objective of the study was to examine the association between normal-range thyroid function and the risk of depression. Design, Setting, and Participants: This was a cohort study in 1503 Dutch men and women, aged 70.6 (7.3) (mean [SD]) years. At baseline, serum TSH, thyroperoxidase antibody levels, and depressive symptoms [Center for Epidemiologic Studies Depression Scale (CES-D)] were assessed. A CES-D of 16 or greater is indicative of a depressive disorder. During follow-up (mean 8.0 y), participants were continuously monitored for the occurrence of incident depressive syndromes (n = 156). Results: Cross-sectionally, persons in the lowest TSH tertile (0.3-1.0 mU/L) had more depressive symptoms [CES-D score (mean): 7.95 vs 6.63, P = .014] as well as an increased risk of a CES-D of 16 or greater [10.7% vs 5.0%, odds ratio (95% confidence interval) 2.22 (1.18-4.17)], compared with persons in the highest normal range TSH tertile (1.6-4.0 mU/L). In the prospective analyses, persons in the lowest TSH tertile who were depression free at baseline had a higher risk of incident depressive syndromes [12.3% vs 7.6%, odds ratio (95% confidence interval) 1.85 (1.10-3.11)]. Thyroid autoimmunity (thyroperoxidase antibody positivity) was not associated with CES-D scores or incident depressive syndromes. Conclusions: Elderly persons with low-normal TSH levels have more concurrent depressive symptoms as well as a substantially increased risk of developing a depressive syndrome in the subsequent years. This study identifies low-normal TSH as an important risk factor for depression in the elderly.