The overall goal of this application for an Independent Scientist Award (K02) is to support the continuing development of the candidate as an independent scientist and facilitate the candidate's interdisciplinary research progrann aimed at a better understanding the determinants and consequences of substance use disorders (SUD). Genetic influences on the liability to addiction are well documented, however, neurobiological mechanisms by which genetic factors contribute to addictive behaviors remain poorly understood. The candidate's major theoretical premise is that genetically transmitted deficits in inhibitory self- regulation of behavior constitute a core component of addiction vulnerability. The candidate's research using quantitative EEG and event-related brain potentials (ERPs) has identified a number of heritable neurophysiological indicators of behavioral regulation, however, limited spatial resolution of electrophy- siology methods impedes the identification of the underlying neural substrates. Accordingly, the candidate's first career objective is to gain expertise in functional magnetic resonance imaging (fMRI) techniques through formal coursework, hands-on training, and developing collaborative projects with neuroimaging researchers at Washington University. The second career objective is to increase the candidate's expertise in advanced methods for the analysis of genetically informative longitudinal data such as latent growth and latent class transition modeling. The research plan draws upon the candidate's ongoing studies of adolescent and young adult twins. Specific research aims are: 1) to identify neurocognitive endophenotypes for addiction and establish their commonality versus specificity and their ability to prospectively predict substance use and abuse;2) to better characterize neural substrates of inhibitory self-regulation of behavior by adding functional neuroimaging assessments to the Pi's ongoing studies and integrating genetic, fMRI, and ERP data;3) to provide a functional validation of genetic variants implicated in addiction vulnerability using a combination EEG, ERPs, functional MRI, neuropsychological testing, and diagnostic assessments. In the long run, establishing the links between genes, brain function, and inhibitory control of behavior will lead to a better understanding of the pathways to addiction and identify targets for prevention and treatment efforts.

Public Health Relevance

Research has documented the role of genetic factors in addictions, but very little is known about how genes exert their influence'on complex behaviors. Investigating the neurobiological pathways and cognitive processes mediating genetic influences on behavior will lead to a better understanding of the pathways to addiction and identify targets for prevention and treatment efforts.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA027096-04
Application #
8278655
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Gordon, Harold
Project Start
2009-07-15
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$117,652
Indirect Cost
$8,715
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Anokhin, Andrey P; Golosheykin, Simon; Mulligan, Richard C (2015) Long-term test-retest reliability of delayed reward discounting in adolescents. Behav Processes 111:55-9
Anokhin, Andrey P (2014) Genetic psychophysiology: advances, problems, and future directions. Int J Psychophysiol 93:173-97
Mulligan, Richard C; Kristjansson, Sean D; Reiersen, Angela M et al. (2014) Neural correlates of inhibitory control and functional genetic variation in the dopamine D4 receptor gene. Neuropsychologia 62:306-18
Anokhin, Andrey P; Golosheykin, Simon; Grant, Julia D et al. (2011) Heritability of delay discounting in adolescence: a longitudinal twin study. Behav Genet 41:175-83
Anokhin, Andrey P; Golosheykin, Simon; Grant, Julia D et al. (2010) Developmental and genetic influences on prefrontal function in adolescents: a longitudinal twin study of WCST performance. Neurosci Lett 472:119-22