A Neuroimaging-based Precision Medicine Framework for Depression

ABSTRACT Objective Developing a neuroimaging-based precision medicine framework for depression. Methods The study was conducted in two stages at two sites: development of a neuroimaging-based subtyping and precise repetitive transcranial magnetic stimulation (rTMS) strategy for depression at Center 1 and its clinical application at Center 2. Center 1 identified depression subtypes and subtype-specific rTMS targets based on amplitude of low frequency fluctuation (ALFF) in a cohort of 238 major depressive disorder patients and 66 healthy controls (HC). Subtypes were identified using a Gaussian Mixture Model, and subtype-specific rTMS targets were selected based on dominant brain regions prominently differentiating depression subtypes from HC. Subsequently, one classifier trained per Center 1 findings for subtyping and subtype-specific rTMS targets were employed to deliver two-week precise rTMS to 72 hospitalized, depressed youths at Center 2. MRI and clinical assessments were obtained at baseline, midpoint, and treatment completion for evaluation. Results Two neuroimaging subtypes of depression, archetypal and atypical depression, were identified based on distinct frontal-posterior functional imbalance patterns as measured by ALFF. The dorsomedial prefrontal cortex was identified as the rTMS target for archetypal depression, and the occipital cortex for atypical depression. Following precise rTMS, ALFF alterations were normalized in both archetypal and atypical depressed youths, corresponding with symptom response of 90.00% in archetypal depression and 70.73% in atypical depression. Conclusions A precision medicine framework for depression was developed based on frontal-posterior functional imbalance and implemented with promising results. Future randomized controlled trials are warranted. Chinese Clinical Trial Registry identifier: ChiCTR2100045391