Deficiencies in reward and punishment processing are theoretical cornerstones of alcohol and substance dependence, addiction, and other psychopathology. However, most research ignores the fact that contemporary cognitive theory emphasizes two processing modes: a reflective mode where processing is under conscious control and predominantly frontally-mediated, and a reflexive mode that is not under conscious control and is predominantly striatally-mediated. In addition, a detailed understanding of the genetic underpinnings of dual processing modes of reward and punishment is critical to improving our theories of addiction and psychopathology and to translational work focused on developing interventions. Dopamine and serotonin genes are hypothesized to affect reflexive and reflective reward and punishment processing and are therefore the focus of this proposal. The overall goal of this project is to test specific hypotheses regarding dopaminergic and serotonergic genetic variation on reflexive and reflective reward and punishment processing. We use classification learning tasks for which the optimal mode of processing (reflective or reflexive) can be defined rigorously and for which the research team has over 20 years of experience. The proposed studies will also complement a single nucleotide polymorphism approach with a haplotype strategy, which will determine whether additional variants in these dopaminergic and serotonergic genes also influence reward and punishment processing. We will also account for population stratification by testing and statistically controlling for occult population substructure.
Aim 1 examines associations between genetic variation in dopaminergic and serotonergic systems with reward and punishment processing when optimal performance is mediated by the reflexive system or by the reflective system.
Aim 2 examines the effects of "reflexive system" genetic variation on reflective-optimal task performance, and "reflective system" genetic variation on reflexive-optimal task performance.
Aim 3 examines the influence of stress on reflexive reward and punishment processing. The proposed studies are the first to attempt to characterize the interactive effects of serotonin, dopamine and stress on cognitive processing of rewards and punishment using contemporary cognitive frameworks. This integrative, interdisciplinary research approach will provide the critical foundation needed for future translational work that examines how these processes go awry in clinical disorders.

Public Health Relevance

Deficiencies in reward and punishment processing are theoretical cornerstones of alcohol and substance dependence, addiction, and other psychopathology, yet little is known about these are affected by task goals, genetic variation or stress. The overall goal of the proposed research is to provide a detailed understanding of the genetic underpinnings of dual processing modes of reward and punishment which is critical to improving our theories of addiction and psychopathology and to translational work focused on developing interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA032457-03
Application #
8599762
Study Section
Special Emphasis Panel (ZRG1-BBBP-L (04))
Program Officer
Gordon, Harold
Project Start
2012-04-01
Project End
2017-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
3
Fiscal Year
2014
Total Cost
$396,264
Indirect Cost
$103,503
Name
University of Texas Austin
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Gorlick, Marissa A; Worthy, Darrell A; Knopik, Valerie S et al. (2015) DRD4 long allele carriers show heightened attention to high-priority items relative to low-priority items. J Cogn Neurosci 27:509-21
Xie, Zilong; Maddox, W Todd; Knopik, Valerie S et al. (2015) Dopamine receptor D4 (DRD4) gene modulates the influence of informational masking on speech recognition. Neuropsychologia 67:121-31
Chandrasekaran, Bharath; Van Engen, Kristin; Xie, Zilong et al. (2015) Influence of depressive symptoms on speech perception in adverse listening conditions. Cogn Emot 29:900-9
Maddox, W Todd; Chandrasekaran, Bharath (2014) Tests of a Dual-systems Model of Speech Category Learning. Biling (Camb Engl) 17:709-728
Maddox, W Todd; Chandrasekaran, Bharath; Smayda, Kirsten et al. (2014) Elevated depressive symptoms enhance reflexive but not reflective auditory category learning. Cortex 58:186-98
Worthy, Darrell A; Maddox, W Todd (2014) A Comparison Model of Reinforcement-Learning and Win-Stay-Lose-Shift Decision-Making Processes: A Tribute to W.K. Estes. J Math Psychol 59:41-49
Ellis, Alissa J; Wells, Tony T; Vanderlind, W Michael et al. (2014) The role of controlled attention on recall in major depression. Cogn Emot 28:520-9
Wells, Tony T; Clerkin, Elise M; Ellis, Alissa J et al. (2014) Effect of antidepressant medication use on emotional information processing in major depression. Am J Psychiatry 171:195-200
Worthy, Darrell A; Cooper, Jessica A; Byrne, Kaileigh A et al. (2014) State-based versus reward-based motivation in younger and older adults. Cogn Affect Behav Neurosci 14:1208-20
Pearson, Rahel; McGeary, John E; Beevers, Christopher G (2014) Association between serotonin cumulative genetic score and the Behavioral Approach System (BAS): Moderation by early life environment. Pers Individ Dif 70:140-144

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