Association between 5-HTTLPR genotypes and persisting patterns of anxiety and alcohol use: results from a 10-year longitudinal study of adolescent mental health

Abstract

The serotonin transporter gene (5-HTT) encodes a transmembrane protein that plays an important role in regulating serotonergic neurotransmission and related aspects of mood and behaviour. The short allele of a 44 bp insertion/deletion polymorphism (S-allele) within the promoter region of the 5-HTT gene (5-HTTLPR) confers lower transcriptional activity relative to the long allele (L-allele) and may act to modify the risk of serotonin-mediated outcomes such as anxiety and substance use behaviours. The purpose of this study was to determine whether (or not) 5-HTTLPR genotypes moderate known associations between attachment style and adolescent anxiety and alcohol use outcomes. Participants were drawn from an eight-wave study of the mental and behavioural health of a cohort of young Australians followed from 14 to 24 years of age (Victorian Adolescent Health Cohort Study, 1992 -present). No association was observed within low-risk attachment settings. However, within risk settings for heightened anxiety (ie, insecurely attached young people), the odds of persisting ruminative anxiety (worry) decreased with each additional copy of the S-allele (B30% per allele: OR 0.77, 95% CI 0.62-0.97, P ¼ 0.029). Within risk settings for binge drinking (ie, securely attached young people), the odds of reporting persisting high-dose alcohol consumption (bingeing) decreased with each additional copy of the S-allele (B35% per allele: OR 0.74, 95% CI 0.64-0.86, Po0.001). Our data suggest that the S-allele is likely to be important in psychosocial development, particularly in those settings that increase risk of anxiety and alcohol use problems. Molecular Psychiatry (2005) 10, 868-876.

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

“…However, the current study found no significant relationships between 5-HTT genotype and age of onset of alcoholism, which is consistent with family-based studies reporting no differential association of the L or S allele with early onset of alcoholism in offspring (Samochowiec et al, 2006). Previous reports have suggested that the SS genotype is associated with increased anxiety and affective liability (Olsson et al, 2005) and may be associated with subtypes of alcoholism complicated by a comorbid psychiatric condition (Feinn et al, 2005). Though the current study included only patients without psychiatric comorbidity, we have reported, in another study of this population, that anxiety reduction is associated with a favorable treatment outcome (Sloan et al, 2003).…”

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

“…Ten studies estimating the associations of an interaction between the 5-HTTLPR genotype and an environmental factor with alcohol use and misuse were found, two that examined rhesus monkeys [28,30] and eight that examined humans [29,[31][32][33][34][35][36][37]. Descriptions of the studies are presented in Tables 1 and 2.…”

“…Three studies were longitudinal: one followed a sample from 15 to 22 years [31]; another followed a sample from 15.5 to 24 years [35]; and the final study followed participants from age 15 to 19 [33]. One study did not report the age of participants [32].…”

“…Four of the eight studies of humans were longitudinal [31][32][33]35], and four cross-sectional [29,34,36,37]. One study was a family based study design [32].…”

“…Studies recruited participants through flyers, advertisements, emails [34,36], questionnaires on youth psychosocial health [29,31,33,35], and from treatment programs [32,37]. Four of the eight studies of humans were longitudinal [31][32][33]35], and four cross-sectional [29,34,36,37].…”