Genetically determined thyroid function and cerebral cortex structure: A Mendelian randomization study

A correlation between thyroid function and cognitive impairment has been well established; however, the impact of thyroid dysfunction on structural changes in the brain cortex remains largely unexplored.

The study describes a 2-sample Mendelian randomization (MR) analysis to elucidate the relationship between thyroid malfunction and brain structure and function.

Eight phenotypes of thyroid function were extracted from THYROIDOMICS consortium by determining free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels in both men and women separately and together, as well as in individuals with increased or decreased TSH levels. The results were assessed in terms of overall brain cortical thickness and the surface area (SA) of grey matter, along with 34 specific measurements for various regions. The primary method employed for the analysis was the inverse-variance weighted (IVW) approach.

The data were subjected to MR Egger regression, Cochrane's Q statistic and leave-one-out analysis to determine the correlation between the variables. The FT4 in men, women and overall was statistically associated with cortical thickness of entorhinal cortex (EC). Overall TSH and TSH in men were associated with cortical thickness of caudal anterior cingulate. Additionally, in men, TSH levels showed an association with cortical thickness in the cuneus gyrus. Increased TSH was associated with decreased SA of lateral occipital (LO) and increased SA of lateral orbitofrontal, medial orbitofrontal and superior frontal cortex. Decreased TSH was negatively associated with the SA of pars opercularis (PO) and the cortical thickness of posterior cingulate cortex. No pleiotropy was detected.

Our findings indicate a possible causal link between thyroid function and the cortical architecture of particular functional areas associated with neurodegenerative and psychiatric conditions.