This R21 proposal aims to capitalize on the landmark Adolescent Brain Cognitive Development (ABCD) study1, through the addition of imaging methods that will add vital neurotransmitter data to the study outcomes. Enhancing the existing ABCD dataset with cross-sectional, in vivo measures of ?-Aminobutyric acid (GABA) and glutamate (Glu), supports the National Institute on Drug Abuse (NIDA) 2016-2020 Strategic Plan, Goal 2, Objective 2.1: ?Determine the mechanisms that underlie individual risk and resilience and comorbidities.? As described in PA-18-078, substance use disorders (SUDs) affect 8.1% of the U.S. population aged >12 years. Yet while the brain abnormalities associated with chronic drug exposure have been well-studied, critical gaps remain in our knowledge of brain changes in the initial stages of drug and alcohol exposure, including the premorbid predictors of SUDs, and the transition from volitional to compulsive use. Thus, the goal of this proposal is to establish the feasibility of adding measures of GABA and Glu in an ABCD add-on study. In addition, data from this study would break new ground by establishing a baseline, i.e. by documenting the excitatory-inhibitory neurotransmitter balance prior to both adolescence, and to illicit drug exposure. This research would extend previous findings that strongly implicate GABA and Glu in SUDs. We will run a pilot/feasibility study and employ state-of-the art proton (1H) MRS methods to acquire GABA and Glu data from the anterior cingulate cortex (ACC) as well as the parietal-occipital cortex (POC) in 10-11 year-old children returning to the University of Utah site for their 12-month follow-up ABCD visit. We will acquire 1H MRS data from participants known to have either low- or high traits of impulsivity, which will be established using subscales taken their baseline UPPS-P assessments. To minimize motion artifacts, and to enhance the quality of 1H MRS data obtained, this feasibility pilot study will make use of motion analytics from ABCD baseline neuroimaging data, and we will exclude subjects who are likely to display unfavorable motion metrics during spectroscopy. We will pursue the following Specific Aims: 1. To Conduct a Pilot/Feasibility Study of 1H MRS GABA and Glutamate Neurotransmitter Metabolism in High- and Low-Trait Impulsivity ABCD Subjects. We anticipate successful demonstration of feasibility, and hypothesize that (a) lower ACC GABA, and higher ACC Glu, will be present in High- versus Low-Trait Impulsivity youth, and (b) lower ACC GABA, and higher ACC Glu, are associated with greater baseline UPPS-P impulsivity scores across both groups. 2. To Utilize ABCD Baseline Imaging Data for Refinement of High- and Low Trait Impulsivity Youth with Favorable Motion Analytics. This exploratory aim will use ABCD resting-state neuroimaging data recorded at baseline, to identify subjects exhibiting minimal motion, and to further refine the High- versus Low-Trait Impulsivity samples targeted for enrollment in pursuit of Specific Aim 1.
Substance use disorders (SUDs) affect 8.1% of the U.S. population aged >12 years, yet, while the brain abnormalities associated with chronic drug exposure have been well-studied, critical gaps remain in our knowledge of brain changes in the initial stages of drug and alcohol exposure, including the premorbid predictors of SUDs, and the transition from volitional to compulsive use. The proposed study will investigate brain chemistry in 10-11 year-old children with a specific focus on metabolites that are critically involved in healthy brain development, and strongly implicated in SUDs. Data from this study will break new ground by establishing a baseline, i.e. documenting a brain chemical imbalance prior to both adolescence, and to illicit drug exposure.
