Brain volume analysis-guided basic research in psychiatry

Magnetic resonance imaging (MRI) volumetric analysis is among the few tools able to probe the living human brain, offering a route from clinical findings back to basic neuroscience. Here we propose a reverse-translational framework for psychiatric research that links human MRI findings to their underlying molecular mechanisms in model animals. The framework rests on three "liaisons": a species liaison, confirming that a volume change identified in humans is also observed in mice using the same imaging and analytical method; a scale liaison, in which a histological pipeline explains the macroscopic volume change in terms of cell number and cell volume; and a causal liaison, in which molecular or cell-biological intervention converts correlative histological findings into causal evidence by inducing or reversing the volume change. We further propose that unbiased, whole-brain MRI volumetric analysis in mice can serve as an exploratory region-screening method, identifying disease- or treatment-related regions without a predefined region of interest, and capturing the maintained structural outcome of an intervention rather than its immediate functional trace. Together, the three-liaison framework and the region-screening approach outline a general strategy by which MRI-guided reverse and forward translation can uncover the structural and molecular basis of psychiatric diseases and their treatments.