Parental Family History of Alcohol Use Disorder and Neural Correlates of Response Inhibition in Children From the Adolescent Brain Cognitive Development (ABCD) Study

Background Youth whose parents have alcohol use disorder (AUD) are at higher risk for earlier initiation and greater magnitude of alcohol use, and have a higher likelihood of developing an AUD than their peers without parental history of AUD. This increased risk may be partly attributable to altered development of inhibitory control and related neural circuitry. This study examined neural activation during a motor response inhibition Stop Signal Task (SST) in substance-naive youth aged 9 to 10 years with and without parental family history of AUD. Methods Baseline cross-sectional survey and functional magnetic resonance imaging (fMRI) data were drawn from 6,898 youth in the US-based Adolescent Brain Cognitive Development Study. Generalized additive mixed models were conducted to examine the association between maternal, paternal, and parental (both mother and father) family history of AUD with neural activation during successful and failed response inhibition. Family history interactions with sex and stratification by ethnicity were explored. Results Of 6,898 participants, 951 (14%) were family history positive for any parental AUD. Paternal history of AUD was associated with greater activation for successful inhibition in the right medial orbital frontal gyrus, compared to youth with no family history. Maternal history of AUD was associated with greater activation for failed response inhibition among females in the cerebellum, compared to females with no such history. Parental history (both mother and father) of AUD was associated with greater activation during successful inhibition in the left paracentral gyri and left superior parietal lobule. Maternal history and parental history of AUD findings were accounted for by a family history of substance use disorder in general. All effect sizes were relatively small. Conclusions Substance-naive children with a parental family history of AUD exhibit greater neural activation in some regions of the fronto-basal ganglia and cerebellar networks when they successfully or unsuccessfully inhibit a response as compared to children with no such family history. This unique neural response pattern could reflect a compensatory response and may represent an inherent neurobiological vulnerability to risk-related behaviors in these youth which will be examined in future longitudinal analyses of this cohort.