Variation in the gene encoding the serotonin transporter is associated with a measure of sociopathy in alcoholics

The present study examined the association between a measure of sociopathy and 5-HTTLPR genotype in a sample of individuals from Project MATCH, a multi-center alcohol treatment trial. 5-HTTLPR, an insertion-deletion polymorphism in SLC6A4, the gene encoding the serotonin transporter protein, results in functionally distinct long (L) and short (S) alleles. The S allele has been associated with a variety of psychiatric disorders and symptoms including alcohol dependence, but it is unknown whether 5-HTTLPR increases the risk for co-morbid sociopathy among those with alcohol dependence. Eight hundred sixty-two subjects diagnosed with alcohol dependence completed the California Psychological Inventory, a psychological assessment that includes a measure of socialization, which was used as a proxy measure of sociopathy. Subjects were genotyped for the insertion-deletion polymorphism, as well as a single nucleotide polymorphism (A→G) that is located in the inserted region. Regression analysis revealed that after controlling for age, which was negatively related to socialization score, 5-HTTLPR genotype interacted with sex to determine socialization score (P < 0.001). Males with the L'L' genotype (i.e. those homozygous for the L(A) allele) had lower socialization scores (i.e. greater sociopathy) than males who were carriers of the S' allele (P = 0.03). In contrast, women with the S'S' genotype had lower socialization scores than women with two L' alleles (P = 0.002) and tended to have lower Socialization Index of the California Psychological Inventory scores than women with one copy of the L' allele (P = 0.07). Among individuals with alcohol use disorders, the tri-allelic 5-HTTLPR polymorphism had opposite effects on socialization scores in men than women. The basis for this finding is unknown, but it may have implications for sub-typing alcoholics.