Differential associations of sex and D2 dopamine receptor (DRD2) genotype with negative affect and other substance abuse risk markers in children of alcoholics.

Children of alcoholics have increased risk for substance abuse problems. Self-medication of negative affect may be one developmental path to future substance abuse. Because the 146 young (adolescent) children of alcoholics in the current sample had not used enough abused substances to study substance use directly, the relation of substance abuse risk markers to negative affect was assessed. Because the D2 dopamine receptor (DRD2) A1 allele has been associated with alcoholism and other substance use disorders, negative affect, measured by the Beck Depression Inventory (BDI), was determined in four groups of children: boys and girls with the A1+ allele (A1A1 and A1A2 genotypes) and with the A1- allele (A2A2 genotype). The other risk markers were stress, low amplitude of the P300 evoked potential, poor visuospatial functioning, novelty seeking (NS), and harm avoidance (HA). Stress was correlated with BDI scores in all groups. In contrast, low P300 was associated with BDI scores only in boys with the A1+ allele (P = .04), NS was associated with BDI scores only in girls with the A1+ allele (P = .02), and HA was associated with BDI scores only in boys with the A1- allele (P = .01). In addition, boys with the A1+ allele had lower BDI (P = .05) and HA (P = .005) scores than the respective scores for boys with the A1- allele. Girls with the A1- allele had lower HA scores compared with scores for boys with the A1- allele (P = .02). Girls with the A1+ allele had lower visuospatial functioning than that of boys with the A1+ allele (P<.001). Results indicate that both sex and DRD2 genotype modify associations between negative affect and other substance abuse risk markers.