This study investigates structural and functional brain changes in Hashimoto’s thyroiditis (HT), hypothyroidism, and healthy controls – both with and without major depression (MDD) – using GMV, CT, and fMRI analyses. The most prominent findings were observed in functional activation during the episodic memory task, with a significant interaction effect between somatic diagnosis (HT/hypothyroidism/no thyroid disorder) and MDD. The group with combined MDD and HT (MDDHa) consistently showed reduced activation, particularly in the superior frontal gyrus, parahippocampus, and hippocampus—areas belonging to the Default-Mode and Central-Executive Networks, which are typically altered in depression. Despite hormone replacement therapy, patients with HT still exhibited functional changes, and in the MDDHa group, TPO and TG antibodies negatively correlated with activation and cortical thickness, suggesting a potential autoimmune-mediated mechanism. Overall, the findings confirm a link between HT/hypothyroidism and depressive symptoms but highlight the need for further research into the neurobiological underpinnings of these associations.
