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

• Published in: Molecular psychiatry Vol. 10; no. 9; pp. 868 - 876
• Main Authors: OLSSON, C. A, BYRNES, G. B, LOTFI-MIRI, M, COLLINS, V, WILLIAMSON, R, PATTON, C, ANNEY, R. J. L
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.09.2005
• Subjects: Addictive behaviors; Adolescent; Adult; Adult and adolescent clinical studies; Alcohol Drinking - genetics; Alcohol use; Alcoholism; Alleles; Anxiety; Anxiety - genetics; Anxiety - physiopathology; Biological and medical sciences; Child & adolescent mental health; Cohort Studies; Drinking behavior; Female; Follow-Up Studies; Gene deletion; Gene polymorphism; Genotype; Humans; Insertion; Longitudinal Studies; Male; Medical sciences; Membrane Glycoproteins - genetics; Membrane Transport Proteins - genetics; Nerve Tissue Proteins - genetics; Neurotransmission; Psychology, Adolescent; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Serotonin; Serotonin Plasma Membrane Transport Proteins; Serotonin transporter; Sex Characteristics; Substance use; Teenagers; Transcription; Human; alcohol; Affect affectivity; 5-HTTLPR; Alcoholism; Mental health; gene-environment interaction; Genotype; Alcoholic beverage; Genotype environment interaction; Follow up study; Adolescent; Risk factor; adolescence; Developmental stage; Anxiety
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4001677

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.