The primary aim of the current application is to test a novel model of how the relative responsiveness of reward- and threat-related neural circuits interact with life stress to predict drug use in a large cohort of adolescents and young adults. The application also aims to identify genetic profiles representing variability in key neuromodulatory pathways that predict these interactions. To address these specific aims the application will collect measures of: 1) core behavioral processes that serve as risk factors for drug use and abuse, 2) brain circuits supporting threat and reward responsiveness as well as behavioral control, 3) the experience of stressful life events and 4) DNA sequence variation in 600 18-22 year old undergraduates. All measures will be collected using the existing extensive research infrastructure of the Duke Neurogenetics Study. Innovative analytic strategies for modeling individual differences will be applied to these data in the service of identifying behavioral, neurobiological, environmental and genetic mechanisms mediating variability in risk behaviors. The predictive utility of our findings for informing developmental trajectories of drug use, abuse, and dependence will be tested through federated studies. These studies are collecting overlapping measures in both community samples as well as longitudinal samples of patients and individuals at high risk (e.g., low SES, positive family history). Data federation wil also provide replication data sets and/or additional power for testing novel associations between neural, genetic, and environmental variation and the emergence of psychopathology. Furthermore, existing collaborations with investigators using animal models of human behavior and disease as well as those conducting epidemiological gene-environment interaction research will facilitate unique translational projects based on our findings. These collaborations will allo for identification of both detailed molecular mechanisms and broader clinical relevance. Collectively, the research proposed will reveal mechanisms and pathways that predict psychopathology with a focus on drug use and the transition to abuse, which represents a major thrust of current research supported by NIDA and is consistent with the Research Domain Criteria (RDoC) emphasis on classifying psychopathology based on dimensions of observable behavior and neurobiological measures.
The proposed research offers a unique opportunity to identify specific markers of brain function, genetics, experience, and behavior that: 1) predict an individual's risk for drug use, 2) inform the likelihood of transitioning from use to abuse and 3) highlight new targets for better treatment and prevention of drug abuse and comorbid mental illnesses.
|Swartz, J R; Hariri, A R; Williamson, D E (2016) An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents. Mol Psychiatry :|
|Hyde, Luke W; Shaw, Daniel S; Murray, Laura et al. (2016) Dissecting the role of amygdala reactivity in antisocial behavior in a sample of young, low-income, urban men. Clin Psychol Sci 4:527-544|
|Waller, Rebecca; Corral-FrÃas, Nadia S; Vannucci, Bianca et al. (2016) An oxytocin receptor polymorphism predicts amygdala reactivity and antisocial behavior in men. Soc Cogn Affect Neurosci 11:1218-26|
|Bogdan, Ryan; Pagliaccio, David; Baranger, David Aa et al. (2016) Genetic Moderation of Stress Effects on Corticolimbic Circuitry. Neuropsychopharmacology 41:275-96|
|Nelson, E C; Agrawal, A; Heath, A C et al. (2016) Evidence of CNIH3 involvement in opioid dependence. Mol Psychiatry 21:608-14|
|Nikolova, Y S; Knodt, A R; Radtke, S R et al. (2016) Divergent responses of the amygdala and ventral striatum predict stress-related problem drinking in young adults: possible differential markers of affective and impulsive pathways of risk for alcohol use disorder. Mol Psychiatry 21:348-56|
|Gorka, Adam X; LaBar, Kevin S; Hariri, Ahmad R (2016) Variability in emotional responsiveness and coping style during active avoidance as a window onto psychological vulnerability to stress. Physiol Behav 158:90-9|
|Demers, Catherine H; Drabant Conley, Emily; Bogdan, Ryan et al. (2016) Interactions Between Anandamide and Corticotropin-Releasing Factor Signaling Modulate Human Amygdala Function and Risk for Anxiety Disorders: An Imaging Genetics Strategy for Modeling Molecular Interactions. Biol Psychiatry 80:356-62|
|Corral-FrÃas, N S; Pizzagalli, D A; CarrÃ©, J M et al. (2016) COMT Val(158) Met genotype is associated with reward learning: a replication study and meta-analysis. Genes Brain Behav 15:503-13|
|Victor, Elizabeth C; Hariri, Ahmad R (2016) A neuroscience perspective on sexual risk behavior in adolescence and emerging adulthood. Dev Psychopathol 28:471-87|
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