Exploring the interaction effects of subclinical hypothyroidism and major depressive disorder on brain networks

Major depressive disorder (MDD) often presents alongside physical illnesses, such as a high incidence of subclinical hypothyroidism (SHypo) in patients, highlighting the common occurrence of these comorbidities. Recent research has indicated that the presence of comorbid SHypo in individuals diagnosed with MDD may result in notable alterations in both brain structure and function. This study aimed was to investigate the neurological mechanisms underlying this co-occurrence using a data-driven approach to analyze brain activity patterns.

Twenty-nine patients diagnosed with MDD without any comorbid conditions (nSHypo-MDD) were included in the study, along with 29 MDD patients who also had SHypo (SHypo-MDD), 26 patients with SHypo only, and 29 healthy individuals as controls (HCs). Each participant received resting-state functional magnetic resonance imaging scans and underwent neuropsychological evaluations.

We found significantly altered functional connectivity (FC) within the resting-state networks (RSNs) of the ventral and dorsal sensorimotor network (VSMN and DSMN) and occipital pole visual network (PVN) (p < 0.05, FDR corrected). A vital interaction effect between SHypo and MDD was detected in the PVN, showing that SHypo-MDD patients had higher FC values in the left cuneus than nSHypo-MDD patients. Serum-free triiodothyronine (FT3) levels in SHypo-MDD patients demonstrated an inverse relationship with FC values of the right supplementary motor area (SMA.R) (r = - 0.563, p = 0.003). Furthermore, the FC values in the left cuneus are positively associated with the Digit Symbol Substitution Test (DSST) scores (r = 0.507, p = 0.008).

Our study reveals significant FC changes in SHypo-MDD patients, particularly in the PVN, VSMN, and DSMN, suggesting compensatory mechanisms that mitigate cognitive deficits and highlighting the need for integrated management of SHypo and MDD to improve cognitive outcomes.