Developmental considerations have been nearly absent in the literature on endophenotypes [131], although it has been noted that one of the more prominent candidate endophenotypes for AUD—P3 amplitude reduction—is more pronounced in adolescence compared to young adulthood in males with a high-risk paternal history of externalizing disorders [132]. Another promising example of a developmental candidate endophenotype comes from a recent fMRI study of spatial working memory. It found that the pattern of functional brain connectivity in early adolescents (12–14 years) with a family history of AUD was less similar to that of older adolescents/young adults (16–20 years) compared to a control sample of early adolescents without a family history [133]. The pattern of findings suggests that neural connectivity is less mature in adolescents with a family history of AUD. Interestingly, this may represent a neuromaturational lag that can only be detected in adolescence. Additional data are needed to determine whether this neurodevelopmental lag in adolescence is indeed associated with subsequent AUD, but this example illustrates that novel candidate endophenotypes that have “sleeper effects” for AUD may be used in gene finding studies.
