Understanding the relationship between thyroid hormone action and psychological well-being through common genetic variation

A relationship between thyroid hormones and psychological well-being has been assumed for a long time with little or no evidence from large studies in unselected populations. Recent negative findings from such studies have brought this association into question. Our understanding of thyroid hormone action throughout the body and at a tissue and cellular level has increased markedly in recent years, providing us with tools to further investigate this association and the mechanisms involved. Hypothesis: Commonly inherited genetic markers in genes associated with thyroid hormone action can clarify the relationship between thyroid function and psychological well-being and the mechanisms behind this. Aims: To investigate the relationship between serum thyroid hormone and TSH levels and psychological well-being in both subjects on thyroid hormone replacement and the general population, using common genetic variation as an interrogation tool. Scope: We investigated the association between serum thyroid hormone levels and psychological well-being in the HUNT 2 cohort from Norway and the DEPTH cohort from Bristol and confirmed an excess of psychological morbidity in thyroxine (T4)-treated subjects compared with the general population. Furthermore the relationship between serum thyroid hormones and psychological wellbeing differed between T4-treated subjects and the general population, with an inverse relationship in the former, and a neutral or slightly positive relationship in the latter. We investigated a behavioural explanation for this difference in the DEPTH cohort where we discovered that subjects with low mood in primary care were being tested for thyroid function and speculate that this results in many subjects with mood disorders being commenced inappropriately on T4 for this.