Shared and distinct neural signatures in major depressive disorder and comorbid post-traumatic stress disorder:...

Major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are highly prevalent psychiatric disorders that frequently co-occur, yet the neural mechanisms underlying their shared and distinct pathophysiology remain unclear. This study aimed to delineate the shared and disorder-specific structural and functional neural alterations in individuals with MDD and comorbid post-traumatic stress disorder (MDD-PTSD), which may potentially improve diagnostic precision and inform targeted interventions.

Neuroimaging data were collected from 63 participants, including 18 MDD, 17 MDD-PTSD, and 28 healthy controls matched for age, sex, and education. Symptom severity was assessed using the 24-item Hamilton Depression Rating Scale and PTSD Checklist-Civilian Version. Structural MRI and functional connectivity analyses were conducted to identify neural alterations. Canonical correlation analysis was used to link connectivity patterns with clinical symptoms.

Structural analyses revealed hippocampal atrophy and cortical thinning in the anterior cingulate cortex and insula as key features of MDD, whereas MDD-PTSD exhibited additional reductions in cerebellar and para-hippocampal volumes. Functional connectivity analysis identified default mode network disruptions in MDD and hyperconnectivity in motor, sensory, and cerebellar-prefrontal circuits in MDD-PTSD. Canonical correlation analysis highlighted distinct neural components associated with depressive and trauma-specific symptoms, emphasizing default mode network and hippocampal alterations in MDD and motor-prefrontal and cerebellar circuits in PTSD.

This study uncovers shared and distinct neural signatures in MDD and MDD-PTSD, offering potential biomarkers for targeted interventions. These findings deepen our understanding of the neural basis of trauma-related psychiatric disorders and suggest potential new avenues for precision medicine in MDD and PTSD.