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OBJECTIVE: Several studies have established links between thyroid gland dysfunction and mood disorders, in particular major depressive disorder (MDD). Preliminary evidence also suggests that thyroid hormone gene variants influence grey matter (GM) volume, which is reportedly altered in patients with MDD. This study tested for associations of single nucleotide polymorphisms (SNPs) in two thyroid hormone transporter genes with regional GM volume differences in a large sample population of patients with recurrent MDD and healthy volunteers. METHODS: High-resolution T1-weighted magnetic resonance images were acquired at the Max Planck Institute, Munich, Germany. After quality control procedures were applied to images and genotypes, data for 134 patients and 144 well-matched controls were included in a stringent voxel-based morphometry analysis using non-stationary cluster-based inference. We first tested for associations between 10 candidate SNPs and regional GM volume differences across the combined sample population. We then tested for group-by-genotype interactions (i.e., differential associations determined by group status). RESULTS: No significant associations were found between SNPs and regional GM volume when testing across the combined sample population. However, group-by-genotype interactions for two highly correlated SNPs (rs496549 and rs479640) revealed co-localised association clusters in the left occipital cortex (P-values 0.002 and 0.004, respectively, after full correction for whole brain and multiple SNP testing). The effect magnitudes within the average modulated GM clusters were greater in the control group relative to the MDD group. This study provides supporting evidence to the existing literature that thyroid-related gene variants influence regional GM volume. We propose that future studies should consider neuroimaging phenotypes when investigating the effects of thyroid hormones on brain structure and function.

Original publication




Journal article



Publication Date





929 - 934


Alleles, Anxiety Disorders, Case-Control Studies, Depressive Disorder, Major, Female, Genome-Wide Association Study, Genotype, Humans, Hydrocortisone, Magnetic Resonance Imaging, Male, Monocarboxylic Acid Transporters, Occipital Lobe, Polymorphism, Single Nucleotide, Prealbumin