Serotonin transporter genotype by environment: Studies on alcohol use and misuse in non-human and human primates

Much evidence indicates that gene-by-environment interactions (GxE) play a role in alcohol misuse. It has been proposed that interactions between serotonin and stress confer vulnerability for alcohol misuse. The present review examined studies of the interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) genotype and stressful life events and alcohol-related phenotypes, in rhesus monkeys and humans. Ten studies were found that had investigated the interaction of 5-HTTLPR and various measures of stress and alcohol use or misuse, two studies of rhesus monkeys, and eight of humans. The results are contradictory. Important differences were reported in study samples, experimental designs, measures used to assess environmental variables, definitions and measurements of alcohol-related phenotypes, and in the statistical analyses. These differences may explain the contradictory results. Guidelines for future studies are suggested. Results are discussed in light of findings from molecular, non-human animal, and clinical studies. The review highlights the need for future studies examining associations of interactions between the serotonin transporter gene and environmental factors and alcohol misuse, especially in samples followed over time.