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.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAA1-CC (06))
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Matochik, John A
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Squeglia, L M; Jacobus, J; Brumback, T et al. (2014) White matter integrity in alcohol-naive youth with a family history of alcohol use disorders. Psychol Med 44:2775-86
Jacobus, Joanna; Squeglia, Lindsay M; Sorg, Scott F et al. (2014) Cortical thickness and neurocognition in adolescent marijuana and alcohol users following 28 days of monitored abstinence. J Stud Alcohol Drugs 75:729-43
Squeglia, Lindsay M; Rinker, Daniel A; Bartsch, Hauke et al. (2014) Brain volume reductions in adolescent heavy drinkers. Dev Cogn Neurosci 9:117-25
Squeglia, Lindsay M; Jacobus, Joanna; Sorg, Scott F et al. (2013) Early adolescent cortical thinning is related to better neuropsychological performance. J Int Neuropsychol Soc 19:962-70
Squeglia, Lindsay M; McKenna, Benjamin S; Jacobus, Joanna et al. (2013) BOLD response to working memory not related to cortical thickness during early adolescence. Brain Res 1537:59-68