Infralimbic prefrontal cortex structure affects therapy response dynamics in depressive disorder across clinical diagnostic entities

Most imaging studies on the limbic system in affective disorders focus on case/control differences and not on the large variability within patients. Pre-treatment differences of prefrontal brain responses have already shown to hold potential to predict therapeutic outcome. We used voxel based morphometry in 167 in-patients with depressive disorders, cross-validated by manual landmark setting in the infralimbic region, to determine if variability of prefrontal and limbic cortex structures indeed influences therapy response in depression. Response was dissected into independent severity and therapy response dynamic components from initial and 5 further weekly HAM-D ratings. Eventually, episode severity, an overall linear component and quadratic/cubic components, useful to quantify early fast responses and response stability, were available. General linear models with total gray matter, gender and age were set up in combination with all and with separated response components. We found that subgenual/paraterminal and posterior orbitofrontal cortex volumes relate to overall therapy response with high local specifity. Episode severity independently related to left lateral prefrontal regions. Interaction analysis revealed that larger subgenual volumes rather stabilized the response course, while larger volume in hippocampal subregions were coupled to better early response. Results should foster the development of tests for an individuals' infralimbic prefrontal functional status.