ReHo-Based RVI May Serve as a Sensitive Functional Biomarker for MDD
Regional homogeneity (ReHo)–magnetic resonance imaging (MRI) cortical deficit patterns may serve as a sensitive functional biomarker for major depressive disorder (MDD), according to a case-control study published in JAMA Psychiatry.
“The similarity in regional pattern for ReHo and regional cerebral blood flow (RCBF), as well as the regional vulnerability index (RVI) analysis that intends to concisely capture the regional pattern, provide corroborative evidence that the regional ReHo deficits in MDD form a replicable pattern consistent with hypoperfusion in a regionally specific manner in MDD,” wrote first author Peter Kochunov, Department of Psychiatry and Behavioral Sciences, UTHealth Houston School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, TX, and study coauthors.
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The study included 15501 participants from 4 datasets that collected ReHo, cortical thickness, or RCBF measures: the UK Biobank (UKBB) sample (N = 4810; 2220 with recurrent MDD and 2590 controls), the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) Consortium sample (N = 10115; 2148 with MDD and 7957 healthy controls), the Amish Connectome Project (ACP) sample (N = 372; 68 with a lifetime diagnosis of MDD and 136 controls), and the Ament Clinic Inc (ACI) sample (N = 204; 296 with recurrent MDD and 76 controls). To understand whether cortical ReHo patterns offered a more sensitive biomarker than reduced cortical thickness in MDD, the researchers measured and compared the regional ReHo effect sizes in MDD with the corresponding effect sizes in structural measurements. They also assessed if ReHo deficit patterns reflected RCBF deficit patterns, and whether these data could be used to calculate RVIs that provide a brain pattern-based biomarker of MDD.
According to the analysis, patients with MDD had lower cortical ReHo in the frontal lobe, superior temporal lobe, and cingulum, but no significant differences in cortical thickness. The regional pattern of ReHo MDD effect sizes was significantly correlated with the effect sizes of RCBF data collected from 2 independent datasets (Pearson r = 0.52 and Pearson r = 0.46; P < 10−4). The ReHo and RCBF functional RVIs resulted in numerically stronger effect sizes (Cohen d = 0.33-0.90) than the structural RVIs (Cohen d = 0.09-0.20). An elevation in ReHo-based RVI-MDD values in MDD patients was also associated with higher depressive symptom severity across all cohorts.
“Results of this case-control study suggest that the ReHo MDD deficit pattern reflected cortical hypoperfusion and was regionally specific in MDD,” the authors wrote.
While further research is needed to better assess disease specificity, the impact of MRI protocols, and reproducibility in more diverse populations, the findings point to a novel biomarker to aid in the study of MDD. “ReHo as a resting-state functional MRI technique may open new doors to the study of brain perfusions in future etiological and interventional studies of neuropsychiatric conditions,” the researchers concluded.
Reference
Kochunov P, Adhikari BM, Keator D, et al. Functional vs structural cortical deficit pattern biomarkers for major depressive disorder. JAMA Psychiatry. 2025;82(6):582–590. doi:10.1001/jamapsychiatry.2025.0192
