Executive Functions in Adult Offspring of Alcohol‐Dependent Probands: Toward a Cognitive Endophenotype?

Gierski, Fabien; Hubsch, B.; Stefaniak, Nicolas; Benzerouk, Farid; Cuervo-Lombard, Christine-Vanessa; Bera‐Potelle, Céline; Cohen, Renaud F.; Kahn, Jean‐Pierre; Limosin, Frédéric · 2012 · OpenAlex-citations

DOI: 10.1111/j.1530-0277.2012.01903.x

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Summary

This study investigates whether executive function (EF) impairments in non-alcoholic adult offspring of alcohol-dependent individuals represent a cognitive endophenotype for alcohol dependence (AD). While EF deficits in AD patients are often attributed to alcohol’s neurotoxic effects, the authors hypothesize that these impairments may predate disease onset and serve as a genetic vulnerability factor. Previous research on this topic was limited primarily to children and adolescents; this study addresses that gap by examining adults, whose frontal lobes are fully mature, to determine if EF weaknesses are heritable traits associated with familial risk for AD. The researchers recruited 155 healthy, non-alcoholic Caucasian adults: 55 with a family history of AD (FHP, specifically offspring of AD fathers) and 100 without such history (FHN). Participants were matched for age, gender, and education. They underwent clinical assessments using the Diagnostic Interview for Genetic Studies and the Barratt Impulsiveness Scale-11 (BIS-11). Neuropsychological testing focused on inhibition and set shifting using the Wisconsin Card Sorting Test, Stroop Color Word Test, Trail Making Test, and Arithmetic Switching Task. Statistical analyses included principal component analysis to derive a composite executive factor score and hierarchical regression to identify predictors of EF performance while controlling for confounding variables like psychiatric history and smoking. Results indicated that FHP participants exhibited significantly higher self-reported impulsiveness and poorer performance on neuropsychological tests assessing inhibition and set shifting compared to FHN controls. Specifically, FHP individuals made more perseverative errors on the Wisconsin Card Sorting Test and had longer completion times on the Trail Making Test and Arithmetic Switching Task. A composite executive factor score confirmed significantly lower EF performance in the FHP group. Hierarchical regression analysis revealed that the number of AD relatives was a significant predictor of EF deficits, even after controlling for age, education, IQ, psychiatric history, and smoking. Notably, self-reported impulsiveness did not significantly predict EF scores, suggesting that impulsivity and executive dysfunction are distinct neurobehavioral systems. The findings support the hypothesis that executive function weaknesses constitute a cognitive endophenotype for alcohol dependence. The study demonstrates that EF impairments exist in unaffected adult relatives, independent of alcohol exposure, and correlate with familial density of the disorder. This suggests that deficits in prefrontal-mediated processes, such as inhibition and set shifting, may be heritable risk factors contributing to the pathogenesis of AD. The results imply that EF assessments could aid in identifying individuals at high genetic risk for alcoholism and highlight the need to consider familial history in clinical evaluations of mood and anxiety disorders.

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• cognitive impairment