In response to RFA-AA-12-006, this application proposes the UCSD Research Component of the National Consortium on Alcohol and Neurodevelopment in Adolescence (N-CANDA) to determine the effects of alcohol use on the developing adolescent brain. Recruited at ages 12 through 21, a high risk enhanced community sample of 170 San Diego subjects (N=680 from all 4 sites) will complete a baseline assessment and undergo three annual follow-up assessments in an accelerated longitudinal design. At each visit, a multimodal magnetic resonance imaging (MRI) protocol, comprehensive neuropsychological battery, and assessments of alcohol and other substance use and related problems, mental health symptomatology, and substance use disorder risk factors will be measured. Brain imaging includes state-of-the-art high-resolution structural MRI (sMRI), diffusion tensor imaging (DTI), and resting state MRI (rsMRI). The examination of alcohol consequences will focus on structural and functional maturation of brain areas that actively develop during adolescence, are involved in psychological regulation, respond to rewards, and appear vulnerable to neurotoxic effects of alcohol. In addition, our Research Component will collaborate on two additional studies. First, we will collaborate with the Duke University site to study recovery of these abnormalities. Specifically, we will examine the degree to which targeted heavy drinking related neurocognitive and brain integrity deficits remit over 4 weeks of monitored abstinence. Second, we will collaborate with the SRI International site to study the default mode network. In particular, we will examine the influence of adolescent heavy drinking on default mode network integrity, and the extent to which this mediates cognitive performance, using functional connectivity analyses during a Stroop Match to Sample task in conjunction with resting state fMRI data acquired both before and after the task. Studied in the context of risks and baseline brain characteristics, we will determine both the effects of alcohol exposure on the developmental trajectory of the adolescent human brain, and identify preexisting psychobiological vulnerabilities that may put an adolescent at elevated risk for an alcohol use disorder.

Public Health Relevance

Successful completion of the above aims will demonstrate that adolescent alcohol involvement disrupts brain development. This project represents a critical step in understanding neurobiological risks for accelerated alcohol use and alcohol effects on brain development in adolescence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA021692-03
Application #
8695257
Study Section
Special Emphasis Panel (ZAA1-CC (06))
Program Officer
Matochik, John A
Project Start
2012-09-01
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
$798,422
Indirect Cost
$283,311
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Squeglia, Lindsay M; Ball, Tali M; Jacobus, Joanna et al. (2016) Neural Predictors of Initiating Alcohol Use During Adolescence. Am J Psychiatry :appiajp201615121587
Jacobus, Joanna; Castro, Norma; Squeglia, Lindsay M et al. (2016) Adolescent cortical thickness pre- and post marijuana and alcohol initiation. Neurotoxicol Teratol 57:20-29
Brumback, T Y; Worley, Matthew; Nguyen-Louie, Tam T et al. (2016) Neural predictors of alcohol use and psychopathology symptoms in adolescents. Dev Psychopathol 28:1209-1216
Pfefferbaum, Adolf; Rohlfing, Torsten; Pohl, Kilian M et al. (2016) Adolescent Development of Cortical and White Matter Structure in the NCANDA Sample: Role of Sex, Ethnicity, Puberty, and Alcohol Drinking. Cereb Cortex 26:4101-21
Pohl, Kilian M; Sullivan, Edith V; Rohlfing, Torsten et al. (2016) Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study. Neuroimage 130:194-213
Brumback, T; Castro, N; Jacobus, J et al. (2016) Effects of Marijuana Use on Brain Structure and Function: Neuroimaging Findings from a Neurodevelopmental Perspective. Int Rev Neurobiol 129:33-65
Nguyen-Louie, Tam T; Tracas, Ashley; Squeglia, Lindsay M et al. (2016) Learning and Memory in Adolescent Moderate, Binge, and Extreme-Binge Drinkers. Alcohol Clin Exp Res 40:1895-904
Sullivan, Edith V; Brumback, Ty; Tapert, Susan F et al. (2016) Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: Contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction. Neuropsychology 30:449-73
Squeglia, Lindsay M; Sorg, Scott F; Jacobus, Joanna et al. (2015) Structural connectivity of neural reward networks in youth at risk for substance use disorders. Psychopharmacology (Berl) 232:2217-26
Brumback, Ty; Squeglia, Lindsay M; Jacobus, Joanna et al. (2015) Adolescent heavy drinkers' amplified brain responses to alcohol cues decrease over one month of abstinence. Addict Behav 46:45-52

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