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Previous high-risk family designs in psychiatry have focused largely on offspring of affected parents. We take a pedigree-based approach and examine the social, psychological, and psychiatric features of offspring from extended pedigrees selected for high-densities of alcohol use disorder (AUD) or drug abuse (DA). We identified, from the Swedish population, 665,715 pedigrees containing a mean of 17.9 parents, aunts/uncles, grandparents, and cousins of a core full-sibship we term the pedigree offspring. We then derived 13 empirical classes of these pedigrees based on the density of cases of AUD and DA. High rates of AUD or DA in the pedigrees were associated in the offspring with lower levels of school achievement, educational attainment, and resilience, and higher rates of psychiatric illness, neighborhood deprivation, unemployment, social welfare, early retirement, and criminal convictions. Effect sizes were large in the offspring of the highest density pedigrees and were stronger in high-density DA than in high-density AUD pedigrees. Sensitivity to the pathogenic effects of membership in these high-risk sibships was substantially attenuated by high levels of school attainment and resilience, female sex, and absence of parental divorce. Offspring of pedigrees with a high density of AUD or DA are multiply disadvantaged and typically suffer from educational difficulties, social deprivation, socio-economic dysfunction, personality problems, and elevated rates of both psychiatric disorders and externalizing syndromes. Despite these difficulties, personal strengths, including improved school achievement and resilience, and an intact parental marriage can substantially buffer these adverse effects and might form a basis for prevention efforts.

molecular psychiatry

The risk for drug abuse, alcohol use disorder, and psychosocial dysfunction in offspring from high-density pedigrees: its moderation by personal, family, and community factors