Thyroid function and the natural history of depression: Findings from the Caerphilly Prospective Study (CaPS) and a meta-analysis

Objective : Low thyroid function has been associated with depression in clinical populations. We have examined whether thyroid function in the normal range is associated with minor psychiatric morbidity. Design : Prospective cohort study of 2269 middle aged men (45-59 years) with thyroid function (total T ₄ only, TSH unavailable) measured between 1979 and 1983 and with repeat measures of minor psychiatric morbidity (GHQ-30) over a mean of 12·3 years follow-up. We also undertook a systematic review and meta-analysis of population-based studies examining thyroid function and mood. Results : There was a positive association between total T ₄ and chronic psychiatric morbidity (odds ratio 1·21, 95% CI 1·02-1·43, P = 0·03), but this was consistent with chance after adjusting for social class, alcohol and smoking behaviours. The association with incident and recovery from psychiatric morbidity was weaker and consistent with chance. We identified seven eligible studies, from our systematic review and included six studies, including our own, in a meta-analysis. The pooled estimate showed a positive association (odds ratio 1·12, 95% CI 1·02-1·22, P-value = 0·01) between depression and T ₄ and an inverse association with TSH (odds ratio 0·92, 95% CI 0·88-0·97, P = 0·0007) with no evidence of heterogeneity or publication bias. Conclusion : The results from CaPS and our meta-analysis are consistent and suggest that, if anything, higher levels of thyroxine in the normal range are associated with increased risk of depression. The effects of thyroid hormone on mood may differ in normal populations and patients with clinical thyroid dysfunction.