Fatt CRC, Jha MK, Cooper CM, et al. - In this study, researchers examined the predictive value of patterns of resting-state connectivity between brain regions for the differential outcome to antidepressant medication (sertraline) compared with placebo. In the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study, structural and resting-state functional MRI was performed on participants at baseline. Then, either sertraline or placebo treatment was provided for 8 weeks (N = 279) to participants. In general, higher connectivity within the default mode network was comparable to greater between-network connectivity of the default mode and executive control networks in predicting better outcomes, particularly for sertraline. In contrast, between-network hippocampal connectivity predicted both placebo and sertraline outcomes (in opposite directions). These outcomes suggest a likely significant role of functional connectivity patterns of brain regions between and within networks in recognizing a favorable response for a drug treatment for major depressive disorder.