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 #
4U01AA021692-05
Application #
9069366
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Matochik, John A
Project Start
2012-09-01
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
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
Nguyen-Louie, Tam T; Courtney, Kelly E; Squeglia, Lindsay M et al. (2018) Prospective changes in neural alcohol cue reactivity in at-risk adolescents. Brain Imaging Behav 12:931-941
Peterson, Eric T; Kwon, Dongjin; Luna, Beatriz et al. (2018) Distribution of brain iron accrual in adolescence: Evidence from cross-sectional and longitudinal analysis. Hum Brain Mapp :
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Sullivan, Edith V; Lane, Barton; Kwon, Dongjin et al. (2017) Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity. Brain Imaging Behav 11:1302-1315
Jacobus, Joanna; Squeglia, Lindsay M; Escobar, Silvia et al. (2017) Changes in marijuana use symptoms and emotional functioning over 28-days of monitored abstinence in adolescent marijuana users. Psychopharmacology (Berl) 234:3431-3442
Sullivan, Edith V; Brumback, Ty; Tapert, Susan F et al. (2017) Effects of prior testing lasting a full year in NCANDA adolescents: Contributions from age, sex, socioeconomic status, ethnicity, site, family history of alcohol or drug abuse, and baseline performance. Dev Cogn Neurosci 24:72-83
Squeglia, Lindsay M; Ball, Tali M; Jacobus, Joanna et al. (2017) Neural Predictors of Initiating Alcohol Use During Adolescence. Am J Psychiatry 174:172-185

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