Brain Reward System Dysfunction in Adolescence: Current, Cumulative, and Developmental Periods of Depression.

Abstract

Reward system dysfunction is a well-known correlate and predictor of depression in adults and adolescents, with depressed individuals showing blunted (hyporeactive) striatal response to monetary rewards. Furthermore, studies of remitted depression suggest network-wide hyporeactivity of striatal (caudate, putamen, nucleus accumbens) and cortical (insula, anterior cingulate cortex [ACC]) regions even in the absence of current symptoms. Thus, it remains unclear which patterns of hyporeactivity represent a trait-like indicator of depression and which represent a current depressed state. The authors examined the relationships between regions of a cortico-striatal circuit supporting reward processing and both current depression and cumulative depression history. Using a functional MRI monetary reward task, the authors measured brain response to monetary gains and losses in a longitudinal sample of adolescents (N=131) who had been annually assessed for psychiatric symptoms since ages 3-5 years. Current depression severity was associated with hyporeactivity exclusively in the nucleus accumbens in response to the anticipation of a reward, while cumulative depression severity was associated with blunted response to anticipation across a cortico-striatal circuit (striatum, ACC, insula). Follow-up analyses investigating the effects of depression on reward processing at different developmental stages revealed a similar pattern: recent depression severity during adolescence was associated with more focal hyporeactivity in the nucleus accumbens, while depression severity during early childhood (i.e., preschool) was associated with more global hyporeactivity across the cortico-striatal circuit. The study findings indicate important distinctions between disruptions in reward system neural circuitry associated with a history of depression (particularly early-onset depression) and current depression. These results have implications for understanding the etiology and treatment of reward processing deficits in depression.