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

Abstract

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.

Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure

“…[111][112][113][114][115][116] Carrying the short variants of the 5-HTTLPR and MAOA-uVNTR polymorphisms is likely to result in high levels of prenatal serotonin, which, due to an inhibitory effect on nerve cell growth, [117][118][119][120][121] should result in smaller, or weaker, circuits regulated by prenatal serotonin levels. 114,122 This is likely to imply, although probably in a sexdependent manner, a greater risk of vulnerability for depression, [123][124][125][126] and alcoholism, 127,128 as well as for impulsiveness and aggressiveness. 122,124,[129][130][131][132][133] This notion has recently been experimentally supported by results on rhesus monkeys.…”

Personality as an intermediate phenotype for genetic dissection of alcohol use disorder

“…It is thus plausible that high levels of serotonin and enhanced amygdala activity are the biological substrate of HA that represents a susceptibility endophenotype of AUD (Belcher et al 2014 ). However, the literature on alcohol as an outcome of the interaction between 5-HTTLPR and stress is discordant both in human and non-human primates (reviewed by Todkar et al ( 2013 ).…”

Recent Stressful Life Events (SLE) and Adolescent Mental Health: Initial Validation of the LEIA, a New Checklist for SLE Assessment According to Their Severity, Interpersonal, and Dependent Nature

“…However, the role of proximal SLEs in other areas is not so clear. For example, their connection with psychosis (Beards et al, 2013) or alcohol use (Veenstra et al, 2006) is far from completely consistent; and their moderator role on some mental disorders reported in gene–environment interaction studies (e.g., Caspi et al, 2003; Covault et al, 2007) has not always been replicated (Risch et al, 2009; Todkar, Nilsson, Oreland, Hodgins, & Comasco, 2013). One of the possible explanations of these and other inconsistencies is the psychometric deficiencies that SLE checklists often present (Beards et al, 2013; Compas, Davis, Forsythe, & Wagner, 1987; Grant et al, 2004; Monroe & Reid, 2008).…”