Meta-analysis finds mixed MRI patterns in subgenual cingulate cortex in medication-free MDD patientsWhat does depression look like in the brain? The picture is complicated

BACKGROUND: This systematic review aims to synthesize anatomical and functional magnetic resonance imaging (MRI) findings in the subgenual anterior cingulate cortex (sgACC) and associated network among medication-free patients with major depressive disorder (MDD) compared to healthy controls. METHODS: A search for published studies was performed through Ovid (MEDLINE, Embase, APA PsycINFO) on 18 April 2024. The JBI Critical Appraisal Tools and a modified version of the specialist protocol for MRI research were used for the quality assessment. Random-effects and activation likelihood estimation (ALE) meta-analyses were applied to studies reporting numerical and stereotactic data, respectively. RESULTS: Forty-two publications were reviewed. There was an equal split between the number of studies (n = 5) reporting reduced sgACC GM volume vs. no difference in MDD, with both findings supported by significant ALE clusters with peaks in the right sgACC (p ≤ .0005). Four task-based activity studies reported overactive sgACC in MDD, whereas 6 reported no difference. Both findings were supported by two significant ALE clusters with peaks in the right sgACC (p ≤ .00001). Eleven studies highlighted the global reduced resting-state network coherence of the sgACC in MDD, and reduced coherence with ventromedial prefrontal cortex (p = .00004) and right insula (p = .00002) was replicated across several reports. CONCLUSIONS: Results highlight laterality and voxel-wise differences across subregions of the sgACC, displaying non-uniform GM volume, activity, and network coherence patterns in MDD. High-resolution parcellation of the sgACC should be considered in future MRI investigations.