Neurobiological Insights into Psychotic Depression from Magnetic Resonance Imaging: A Systematic Review

Abstract

Psychotic depression (PD) is increasingly recognized as a distinct psychiatric condition with unique neurobiological features. To identify neuroimaging biomarkers of PD, we systematically reviewed evidence across structural magnetic resonance imaging (MRI), functional MRI, diffusion tensor imaging, and magnetic resonance spectroscopy, following PRISMA guidelines. PubMed, MEDLINE, and Embase were searched through December 2025; 28 of 1195 records met PICOS-based inclusion criteria. PD showed distinct structural and functional abnormalities versus healthy controls and non-psychotic depression, particularly involving lower gray matter volume in prefrontal, insular, anterior cingulate, and temporal regions; aberrant temporoparietal and frontoparietal function; altered dorsal anterior cingulate metabolism; and default mode network-cortical hypoconnectivity. Pharmacological and electroconvulsive therapies may partially reverse frontotemporal and visual network abnormalities. Evidence for subcortical volume changes was inconsistent. Despite small, heterogeneous studies precluding meta-analysis, symptom-correlated fronto-insular-limbic and precuneus alterations may represent potential biomarkers warranting further investigation.