UC San Diego

BACKGROUND: A positive family history (FHP) of alcohol use disorders (AUD) is linked to increased risk for personal AUD, but mechanisms behind this risk are unclear. FHP adolescents tend to be different from family history negative (FHN) youth on electrophysiological, brain volumetric, and neuropsychological measures. These differences diminish by young adulthood, suggesting that a subtle neurodevelopmental lag may contribute to AUD risk. HODS: Neural networks of blood oxygen level dependent (BOLD) response to a spatial working memory (SWM) task were examined for markers of neuromaturational delay across FH groups. It was hypothesized that FHP adolescents (n=24, ages 12-14), as compared to matched FHN youth (n=26, ages 12-14), would show less similarity to brain activity patterns observed in older adolescents (OA; n=35, ages 16- 20). Structural equation modeling tested the fit of brain response in FH groups against the OA model. The influence of physiological noise was also examined using a filter to isolate task related response. RESULTS: Connectivity between key regions for SWM response was similar between FH groups, but FHN connectivity resembled OA patterns more than FHP adolescents did. FHP youth demonstrated higher bilateral association between right posterior and left frontal brain regions (rs=.49 v .22, p<.05) than FHN youth, and had a link between more superior posterior activation and poorer SWM accuracy (r=-.40, p<.05, r²=.16) not observed in other groups. Applying filters to model sources of noise did not alter results. CONCLUSIONS: Developmental stage of adolescence and FH status influenced functional connectivity to a SWM task. A bilateral brain connection was characteristic of FHP young adolescents but not to OA model fit, suggesting this as a less mature brain response pattern, and providing additional support for the notion of a neuromaturational lag in FHP youth. Protracted neuromaturation may be a mechanism by which FH increases risk for alcohol dependence, and this less mature neural connectivity pattern may provide a novel endophenotype for identifying youth at risk for drinking problems.