Jillian E Hardee1, Barbara J Weiland2, Thomas E Nichols3, Robert C Welsh4, Mary E Soules1, Davia B Steinberg1, Jon-Kar Zubieta5, Robert A Zucker1, Mary M Heitzeg6. 1. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan; Addiction Research Center, University of Michigan, Ann Arbor, Michigan. 2. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan; Addiction Research Center, University of Michigan, Ann Arbor, Michigan; Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado. 3. Department of Statistics & Warwick Manufacturing Group, University of Warwick, Coventry, United Kingdom. 4. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan; Department of Radiology, University of Michigan, Ann Arbor, Michigan. 5. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan; Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan. 6. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan; Addiction Research Center, University of Michigan, Ann Arbor, Michigan. Electronic address: mheitzeg@umich.edu.
Abstract
BACKGROUND: Difficulty with impulse control is heightened in children with a family history of alcohol use disorders and is a risk factor for later substance problems. Cross-sectional functional magnetic resonance imaging studies have shown altered impulse control processing in adolescents with a positive family history, yet developmental trajectories have yet to be examined. METHODS: Longitudinal functional magnetic resonance imaging was conducted in children of alcoholic families (family history positive [FH+]; n = 43) and children of control families (family history negative [FH-]; n = 30) starting at ages 7-12 years. Participants performed a go/no-go task during functional magnetic resonance imaging at intervals of 1-2 years, with two to four scans performed per subject. We implemented a repeated-measures linear model fit across all subjects to conduct a whole-brain search for developmental differences between groups. RESULTS: Performance improved with age in both groups, and there were no performance differences between groups. Significant between-group differences in linear age-related activation changes were found in the right caudate, middle cingulate, and middle frontal gyrus. Post hoc analyses revealed significant activation decreases with age in the caudate and middle frontal gyrus for FH- subjects and a significant increase with age in middle cingulate activation for FH+ subjects. Group differences were evident at age 7-12 years, even in alcohol- and drug-naïve participants, with FH+ subjects showing significantly blunted activation at baseline compared with FH- subjects. CONCLUSIONS: Differences in response inhibition circuitry are visible in FH+ individuals during childhood; these differences continue into adolescence, displaying trajectories that are inconsistent with development of normal response inhibition. These patterns precede problem drinking and may be a contributing factor for subsequent substance use problems.
BACKGROUND: Difficulty with impulse control is heightened in children with a family history of alcohol use disorders and is a risk factor for later substance problems. Cross-sectional functional magnetic resonance imaging studies have shown altered impulse control processing in adolescents with a positive family history, yet developmental trajectories have yet to be examined. METHODS: Longitudinal functional magnetic resonance imaging was conducted in children of alcoholic families (family history positive [FH+]; n = 43) and children of control families (family history negative [FH-]; n = 30) starting at ages 7-12 years. Participants performed a go/no-go task during functional magnetic resonance imaging at intervals of 1-2 years, with two to four scans performed per subject. We implemented a repeated-measures linear model fit across all subjects to conduct a whole-brain search for developmental differences between groups. RESULTS: Performance improved with age in both groups, and there were no performance differences between groups. Significant between-group differences in linear age-related activation changes were found in the right caudate, middle cingulate, and middle frontal gyrus. Post hoc analyses revealed significant activation decreases with age in the caudate and middle frontal gyrus for FH- subjects and a significant increase with age in middle cingulate activation for FH+ subjects. Group differences were evident at age 7-12 years, even in alcohol- and drug-naïve participants, with FH+ subjects showing significantly blunted activation at baseline compared with FH- subjects. CONCLUSIONS: Differences in response inhibition circuitry are visible in FH+ individuals during childhood; these differences continue into adolescence, displaying trajectories that are inconsistent with development of normal response inhibition. These patterns precede problem drinking and may be a contributing factor for subsequent substance use problems.
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