Association between 5-HTTLPR genotypes and persisting patterns of anxiety and alcohol use: results from a 10-year longitudinal study of adolescent mental health.
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 (approximately 30% per allele: OR 0.77, 95% CI 0.62-0.97, P=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 (approximately 35% per allele: OR 0.74, 95% CI 0.64-0.86, P<0.001). 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.
Olsson
C A
CA
Centre for Adolescent Health, Murdoch Childrens Research Institute, Royal Children's Hospital, The University of Melbourne, Victoria, Australia. craig.olsson@rch.org.au
Byrnes
G B
GB
Lotfi-Miri
M
M
Collins
V
V
Williamson
R
R
Patton
C
C
Anney
R J L
RJ
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000297:Psychology, Adolescent; D050486:Serotonin Plasma Membrane Transport Proteins; D012727:Sex Characteristics
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins