The panoply of cognitive, affective, motivational, and social functions that underpin everyday human experience requires precisely choreographed patterns of interaction between networked brain regions. Perhaps not surprisingly, diverse forms of psychopathology are characterized by breakdowns in these interregional relationships. Here, we discuss how functional brain imaging has provided insights into the nature of brain dysconnectivity in mental illness. Synthesizing work to date, we propose that genetic and environmental risk factors impinge upon systems-level circuits for several core dimensions of cognition, producing (...) transdiagnostic symptoms. We argue that risk-associated disruption of these circuits mediates susceptibility to broad domains of psychopathology rather than discrete disorders. (shrink)