Neurophysiological Correlates of Neuroanatomical Dimensions in Major Depressive Disorder: Electroencephalographic Markers of Brain Function and Treatment Outcome.

Background:Major depressive disorder (MDD) is heterogeneous in clinical presentation and treatment response. The COORDINATE-MDD consortium identified two magnetic resonance imaging (MRI)-derived neuroanatomical profiles: dimension 1 (D1), with relatively preserved gray and white matter, and dimension 2 (D2), showing widespread reductions aligned with immunometabolic profile. Profiles were associated with distinct responses to selective serotonin reuptake inhibitor (SSRI) antidepressant and placebo (PLA). In this study, we examined electrophysiological correlates of the neuroanatomical profiles and their relationship to treatment outcome. Methods:Baseline resting-state, eyes-closed electroencephalography (EEG) was acquired from 237 medication-free participants with MDD who were in a current depressive episode (155 women; mean age [SD] = 37.47 [13.36] years) from CAN-BIND (Canadian Biomarker Integration Network in Depression) (SSRI) and EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) (SSRI or PLA). EEG features included spectral power, frontal alpha asymmetry (FAA), multiscale sample entropy, and intersite phase clustering. Effects of profile (D1 and D2) and clinical outcome (responder, nonresponder; defined as ≥50% symptom improvement) were examined with age, sex, and site as covariates. Results:No significant electrophysiological differences were observed after covariate adjustment. However, among participants who subsequently responded to treatment, D1 showed greater baseline alpha power in frontal and central regions and lower relative delta posteriorly compared with D2. In PLA-treated responders, D2 showed spectral slowing, elevated low-frequency power, reduced gamma, and coarse-scale entropy compared with D1. Baseline FAA was lower in responders than nonresponders, independent of the neuroanatomical profile. Conclusions:EEG differences between MRI-defined neuroanatomical profiles emerged in relation to clinical outcome. D1 was associated with electrophysiological patterns consistent with flexible, globally regulated cortical dynamics in SSRI responders, whereas D2 showed a distinct pattern in PLA responders, indicating partially separable neural mechanisms underlying pharmacological and PLA treatment effects.