Distinct Biotypes of Visual Perception in Major Depressive Disorder

Previous studies showed abnormalities in both visual motion perception (VMP) and occipital cortex activity in subjects suffering from major depressive disorder (MDD). Can the psychophysical and/or neural markers of visual perception serve for clinical identification of MDD subgroups? To address this yet unresolved issue, we develope a novel analytical framework combining visual perceptual measurement with machine learning clustering to identify MDD subgroups. Within a cohort of 272 individuals with acute MDD, this approach reveals a VMP-positive (VMP-P) biotype characterized by impaired VMP. Clinically, this biotype exhibits significant cognitive deficits. We validate the robustness of this biotype through cross-validation and confirm its generalizability in an independent sample (n = 63). Furthermore, 7T MRI implicate aberrant neural activity in the occipital cortex as a mechanism underlying the VMP-P biotype. Our findings establish a novel, clinically translatable path for stratifying MDD, which can guide treatment development and advance precision medicine.