Correlation between cognitive dysfunction and amygdala connectivity in first-episode, treatment-naïve patients with...

Anxiety symptoms often co-occur in major depressive disorder (MDD), defining a clinical subtype known as anxious MDD (aMDD). Cognitive dysfunction is prevalent in aMDD patients and may arise from aberrant brain functional activity. This study explores amygdala-based functional connectivity (FC) alterations in aMDD patients and their correlation with cognitive function.

We recruited 62 first-episode MDD patients, including 34 aMDD and 28 non-anxious MDD (naMDD), along with 52 matched healthy controls (HCs). The 17-item Hamilton Depression Rating Scale was utilized to evaluate the severity of anxiety and depression symptoms in MDD patients. All participants underwent the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) for cognitive assessment and MRI scanning. FC analysis was conducted using bilateral amygdala as seed regions. Partial correlation analysis was employed to investigate the correlation between aberrant FC and cognitive function.

Compared to naMDD patients, aMDD patients exhibited more severe depressive symptoms and speed of processing (SOP) deficits, plausibly driven by comorbid anxiety. We found for the first time that, aMDD patients showed increased FC between the left amygdala and left cerebellum lobule VIII. This hyperconnectivity was positively correlated with SOP scores. Furthermore, aMDD patients demonstrated decreased FC between the left amygdala and the left superior temporal pole, which exhibited a positive correlation with Visual Learning (VIS) scores. These findings indicate that anxiety-related pathophysiology may induce circuit-specific connectivity disturbances that influence cognitive performance in aMDD.

These aberrant FC patterns may be attributable to comorbid anxiety symptoms and cognitive dysfunction in MDD patients. This research provides fresh neurobiological insights for developing targeted interventions aimed at improving cognitive dysfunction in aMDD patients.