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.)

Public Health Relevance

This project has high relevance for the understanding and future treatment of childhood Major Depressive Disorder (MDD). Investigating reward and punishment processing within pre- pubertal MDD cases will give information regarding the continuity of changes in behavioral and neural responses to reward/punishment within adolescent and adult MDD. This is of particular importance given that the neuro-circuitry involved in reward/punishment processing undergoes significant development over adolescence. Understanding whether changes in reward processing occurs in MDD cases prior to the neural development associated with puberty will provide a more complete view of childhood MDD which is critical given the lack of safe and effective treatment options for this population. This information may help drive the development of more effective interventions in this population.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F02A-J (20))
Program Officer
Sarampote, Christopher S
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Washington University
Schools of Arts and Sciences
Saint Louis
United States
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Luking, Katherine R; Neiman, Jamie S; Luby, Joan L et al. (2017) Reduced Hedonic Capacity/Approach Motivation Relates to Blunted Responsivity to Gain and Loss Feedback in Children. J Clin Child Adolesc Psychol 46:450-462
Gilbert, Kirsten; Luking, Katherine; Pagliaccio, David et al. (2017) Dampening, Positive Rumination, and Positive Life Events: Associations with Depressive Symptoms in Children at Risk for Depression. Cognit Ther Res 41:31-42
Luking, Katherine R; Pagliaccio, David; Luby, Joan L et al. (2016) Depression Risk Predicts Blunted Neural Responses to Gains and Enhanced Responses to Losses in Healthy Children. J Am Acad Child Adolesc Psychiatry 55:328-37
Pagliaccio, David; Luking, Katherine R; Anokhin, Andrey P et al. (2016) Revising the BIS/BAS Scale to study development: Measurement invariance and normative effects of age and sex from childhood through adulthood. Psychol Assess 28:429-42
Gilbert, Kirsten Elizabeth; Luking, Katherine Rose; Pagliaccio, David et al. (2016) Dampening Positive Affect and Neural Reward Responding in Healthy Children: Implications for Affective Inflexibility. J Clin Child Adolesc Psychol :1-11
Luking, Katherine R; Pagliaccio, David; Luby, Joan L et al. (2016) Do losses loom larger for children than adults? Emotion 16:338-48
Luking, Katherine R; Pagliaccio, David; Luby, Joan L et al. (2015) Child Gain Approach and Loss Avoidance Behavior: Relationships With Depression Risk, Negative Mood, and Anhedonia. J Am Acad Child Adolesc Psychiatry 54:643-51
Luking, Katherine R; Luby, Joan L; Barch, Deanna M (2014) Kids, candy, brain and behavior: age differences in responses to candy gains and losses. Dev Cogn Neurosci 9:82-92
Luking, Katherine R; Barch, Deanna M (2013) Candy and the brain: neural response to candy gains and losses. Cogn Affect Behav Neurosci 13:437-51