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 (∼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 (∼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.
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Acknowledgements
This work was in part funded by a grant from the Australian Alcohol Education Fund. Dr Craig Olsson is supported by a National Alliance for Research on Schizophrenia and Depression (NARSAD) Post Doctoral Fellowship. Dr Graham Byrnes is supported by a National Health and Medical Research Council Capacity Building Grant in Population Health (251533). We thank Ms Carolyn Coffey, Ms Diana Crocker, Ms Denise Becker and Dr Max Watson for assistance in this research. We also acknowledge Professor Glenn Bowes and Dr Sue Forrest for their seminal role in the development of this work.
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Olsson, C., Byrnes, G., Lotfi-Miri, M. et al. Association between 5-HTTLPR genotypes and persisting patterns of anxiety and alcohol use: results from a 10-year longitudinal study of adolescent mental health. Mol Psychiatry 10, 868–876 (2005). https://doi.org/10.1038/sj.mp.4001677
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DOI: https://doi.org/10.1038/sj.mp.4001677
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