Fatt CRC, Jha MK, Cooper CM, et al. - Via this study, researchers investigated the predictive value of patterns of resting-state connectivity between brain regions for the differential outcome to antidepressant medication (sertraline) compared with placebo. At baseline, structural and resting-state functional MRI was performed on participants in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care study. Then, they randomized the participants to receive either sertraline or placebo treatment for 8 weeks (N = 279). Using a region of interest–based approach, computation of functional connectivity between brain regions was done. The analysis revealed specific functional network–based moderators of treatment outcome involving brain networks known to be affected by major depression. They identified the involvement of several within- and between-network connectivity patterns in prediction of response to sertraline. In general, better outcomes were predicted by higher connectivity within the default mode network specifically for sertraline, as well as by greater between-network connectivity of the default mode and executive control networks. In contrast, between-network hippocampal connectivity predicted both placebo and sertraline outcomes (in opposite directions). Hence,