Mood and anxiety disorders confer marked personal and fiscal cost. Current therapeutic efforts show only moderate efficacy, and little is known about the characteristics of those who respond to specific treatment regimens. The lack of objective descriptors of symptom severity and reliable predictors of illness outcome contributes to limited diagnostic and treatment success. Here, we have begun to develop a normative neurobehavioral database of responses to affective stimuli by combining functional magnetic resonance imaging (fMRI), with comprehensive behavioral assessment and quantitative analyses of neural responses to standard emotional cues. These data reveal robust and distinct neural patterns between two groups with similar low self-reported depression and anxiety, and one group with high depression and anxiety scores. This and related strategies may be used to identify covert phenotypes associated with psychiatric illness and resilience.