Gains and Losses: Reward Processing in Pediatric Major Depressive Disorder

Washington University, Saint Louis MO

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): This proposal explores how the neural and behavioral mechanisms involved in reward/punishment processing may be affected in pre-puberty onset Major Depressive Disorder (MDD). Problems experiencing pleasure, anhedonia, is one of the core components of MDD. It is thought that this symptom is related to changes in processing within the reward circuitry. Namely adults and adolescents with MDD show attenuated response to reward in brain regions such as the dorsal and ventral striatum, orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (PFC), all known to be involved in reward processing. There is less evidence for alterations in punishment processing at the neural level, but girls at increased risk for developing MDD show increased insula activity when receiving punishments, which aligns with behavioral evidence that individuals with MDD are hypersensitive to punishment. While it seems clear that adolescents and adults with MDD, and even adolescents at risk for MDD, experience changes in reward processing, it has yet to be determined whether pre- puberty cases of MDD are characterized by similar reward/punishment processing deficits. Regions involved in reward processing such as the OFC and striatum undergo significant development over the course of puberty and some researchers have hypothesized that this developmental process could contribute to the rapid rise in incidence of MDD through adolescence. The current proposal tests the hypothesis that pre-puberty children (7-10 years) with MDD, prior to adolescent development of reward systems, are hyper-responsive to punishments and hypo-responsive to rewards compared to healthy peers. We will test this hypothesis both behaviorally and at the neural level in a two-session experiment (using state-of-the-art functional magnetic resonance imaging methods and analytical techniques) that examines whether these children are able to adjust their behavior based on reward/punishment feedback and whether activity within brain regions associated with reward/punishment processing is different between groups during receipt of candy rewards and punishments. Success in this work would provide important information about the continuity of the neurobiological and behavioral symptoms of MDD over the course of development. This information could impact development of future treatment options tailored to the specific developmental and clinical needs of this population struggling with MDD.