This Mentored Research Scientist Development Award will support the candidate in establishing an independent research career using longitudinal developmental neuroimaging to investigate genetic risk for substance use disorders (SUDs). Career development training areas include: 1) Functional magnetic resonance imaging (fMRI) methods and statistical analyses with a particular focus on pediatric neuroimaging;2) The genetic basis of complex behaviors, and gene-brain-behavior relationships;3) Theoretical constructs regarding risk of psychopathology;and 4) Longitudinal research methods and statistical analyses. The proposed research plan is to examine the contribution of specific genetic polymorphisms and early-life stress on the neural correlates of SUD risk in children using fMRI. Both behavioral and emotional dysregulation at an early age are strong predictors of SUDs later in life. A complex neuronal circuit, including the striatum, amygdala and prefrontal cortex, regulates these processes. The proposed research plan will investigate these neural systems cross-sectionally in a sample of 7 to 11 year old boys and girls (n=60) from the ongoing UM/MSU Longitudinal Study (R37 AA07065), and longitudinally in this sample at 2-year intervals. The cross-sectional study will investigate effects of, and interactions between, early stress and genetic variants (COMT, SLC6A4, MAO-A, TPH, BDNF) on brain responses to tasks designed to probe behavioral risk for SUDs. The longitudinal study will investigate the effects of early stress and genetic variants on the maturation of brain functional responses to these same tasks. It will also begin to address the influence of drug use on brain development, as well as the predictive value of early brain functional responses in identifying risk for later substance abuse problems. The proposed training and research activities will provide a solid foundation for the candidate to become an independent investigator specializing in longitudinal developmental neuroimaging studies of risk for SUDs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DA020088-05
Application #
7667428
Study Section
Special Emphasis Panel (ZDA1-MXS-M (06))
Program Officer
Boyce, Cheryl A
Project Start
2005-08-01
Project End
2011-01-31
Budget Start
2009-08-01
Budget End
2011-01-31
Support Year
5
Fiscal Year
2009
Total Cost
$149,430
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Psychiatry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Weiland, Barbara J; Zucker, Robert A; Zubieta, Jon-Kar et al. (2017) Striatal dopaminergic reward response relates to age of first drunkenness and feedback response in at-risk youth. Addict Biol 22:502-512
Cope, Lora M; Hardee, Jillian E; Soules, Mary E et al. (2016) Reduced brain activation during inhibitory control in children with COMT Val/Val genotype. Brain Behav 6:e00577
Hardee, Jillian E; Weiland, Barbara J; Nichols, Thomas E et al. (2014) Development of impulse control circuitry in children of alcoholics. Biol Psychiatry 76:708-16
Weiland, Barbara J; Korycinski, Steven T; Soules, Mary et al. (2014) Substance abuse risk in emerging adults associated with smaller frontal gray matter volumes and higher externalizing behaviors. Drug Alcohol Depend 137:68-75
Glaser, Yi G; Zubieta, Jon-Kar; Hsu, David T et al. (2014) Indirect effect of corticotropin-releasing hormone receptor 1 gene variation on negative emotionality and alcohol use via right ventrolateral prefrontal cortex. J Neurosci 34:4099-107
Weiland, Barbara J; Heitzeg, Mary M; Zald, David et al. (2014) Relationship between impulsivity, prefrontal anticipatory activation, and striatal dopamine release during rewarded task performance. Psychiatry Res 223:244-52
Heitzeg, Mary M; Villafuerte, Sandra; Weiland, Barbara J et al. (2014) Effect of GABRA2 genotype on development of incentive-motivation circuitry in a sample enriched for alcoholism risk. Neuropsychopharmacology 39:3077-86
Heitzeg, Mary M; Nigg, Joel T; Hardee, Jillian E et al. (2014) Left middle frontal gyrus response to inhibitory errors in children prospectively predicts early problem substance use. Drug Alcohol Depend 141:51-7
Weiland, Barbara J; Welsh, Robert C; Yau, Wai-Ying Wendy et al. (2013) Accumbens functional connectivity during reward mediates sensation-seeking and alcohol use in high-risk youth. Drug Alcohol Depend 128:130-9
Villafuerte, S; Heitzeg, M M; Foley, S et al. (2012) Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism. Mol Psychiatry 17:511-9

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