Moderate Level Fetal Alcohol Exposure and Serotonin Transporter Gene Promoter Polymorphism Affect Neonatal Temperament and Limbic-Hypothalamic-Pituitary-Adrenal Axis Regulation in Monkeys

Abstract

A length polymorphism in the serotonin (5-HT) transporter gene promoter region in humans and rhesus monkeys affects functional characteristics of the brain 5-HT system. Prenatal alcohol exposure (FA-exposure) can have an impact on brain and psychosocial development that could interact with genetic endowment. This study determined whether moderate FA-exposure interacts with polymorphism in the 5-HT transporter gene to increase the incidence or severity of fetal alcohol effects in rhesus monkeys. The offspring of monkeys who did or did not consume moderate amounts of alcohol during pregnancy were assessed for temperament as neonates and adrenocorticotropic hormone (ACTH) and cortisol (CORT) in response to mother-infant separation at 6 months of age. Serotonin promoter region genotypes (homozygous s/s or heterozygous s/l versus homozygous l/l) were determined. Prenatal alcohol exposed carriers of the s allele exhibited increased neonatal irritability and increased ACTH and CORT compared with FA-exposed monkeys homozygous for the l allele and monkeys that were not FA-exposed regardless of genotype. The s allele of the 5-HT transporter increases the probability of neonatal irritability and increased stress responsiveness in FA-exposed monkeys, and this gene-environment interaction may affect psychosocial development. It is probable that FA-exposure contributes to 5-HT transporter gene-environment interactions in humans.