br Conflict of interest br Acknowledgements This study
Conflict of interest
Acknowledgements This study was supported by the Dutch Health Care Research Organization (ZON-Mw; 60-600-97-172) and a Vici grant 453-08-001 from the Dutch National Science Foundation (N.W.O.) awarded to prof. Dr. Reinout W. Wiers.
Introduction Alcohol use typically begins during adolescence, a time during which the still-maturing raas inhibitor may be particularly vulnerable to its neurotoxic effects. However, while a number of differences in brain structure and function associated with early alcohol drinking have been identified (Squeglia et al., 2009), it remains unclear whether such neurological changes are antecedent or consequent to adolescent alcohol use. A family history of alcoholism (FH) constitutes a major risk factor for the development of alcohol use disorders (Conway et al., 2003). Thus, neuroimaging studies of adolescents with family histories of alcoholism can help identify neurobiological risk factors for alcohol use disorders and can help distinguish potential precursors of alcoholism from its sequelae. A number of neurobiological and behavioral differences have been identified between youth who are family history positive (FH+) for alcoholism and family history negative (FH−) peers, including increased impulsivity (Gierski et al., 2013) and differences in recruitment of regulatory brain regions during inhibitory demands, as revealed by functional magnetic resonance imaging (fMRI) (DeVito et al., 2013; Hardee et al., 2014; Silveri et al., 2011). While the role of neurochemistry in older adults with alcohol use disorders has been investigated (Meyerhoff et al., 2013, 2014; Sullivan and Pfefferbaum, 2014), neurochemical correlates of family history of alcoholism in youth has remained largely unstudied to date. To this end, the current study employed magnetic resonance spectroscopy (MRS) to investigate the glutamatergic system, including turnover of the general metabolic pool, as indexed by the ratio of glutamine (Gln) to glutamate (Glu) (Öngür et al., 2008; Yüksel and Öngür, 2010) in FH− and FH+ adolescents and emerging adults. Relationships between Gln/Glu and impulsivity were also examined in these populations. Maturation of frontal brain regions, including the anterior cingulate cortex (ACC), supports normative reductions in impulsivity during adolescence, as regulatory brain circuitry follows a protracted developmental course that extends well into early adulthood (Casey et al., 2008; Gogtay et al., 2004; Luna and Sweeney, 2004; Rubia et al., 2006). Difficulty in regulation of impulsive actions during this age period may contribute to experimentation with alcohol, drinking binges, and alcohol abuse in youth. Furthermore, inhibitory control is prominent among the cognitive abilities most vulnerable to disruption by alcohol (Sher et al., 1997), leaving adolescents who drink alcohol at an enhanced risk for reckless decision-making and continued substance misuse. Moreover, age of initiation, magnitude of use, and prevalence of alcohol use disorders are influenced by genetic vulnerability, as early onset and greater use and abuse have been linked with having a positive family history of alcoholism among adolescents and young adults (Biederman et al., 2000; Conway et al., 2003; Hill et al., 2000). Although intellectual functioning in this at-risk population typically falls within the healthy range (Alterman et al., 1989), children of alcoholics demonstrate deficits in abstract reasoning and planning, lower IQ scores, and poorer spelling and math performance compared to children of non-alcoholics (Poon et al., 2000). Further, altered executive functioning has been reported in FH+ youth in conjunction with increased self-report ratings of impulsivity (Gierski et al., 2013) and fMRI studies have identified numerous brain areas that are differentially recruited by FH+ and FH− individuals during tasks requiring cognitive control. For instance, studies have reported increased ACC activation in FH+ versus FH− participants during inhibitory control on classic tasks such as the Stroop Color–Word Interference task (Silveri et al., 2011) and the Go–NoGo task (Hardee et al., 2014; Jamadar et al., 2012). Collectively, prior data suggest that differential ACC functioning may have an influential role in elevating risk for substance use and abuse in FH+ compared to FH− youth.