Different genes influence smoking risk during adolescence and adulthood

There is growing evidence that the risk factors for addiction change throughout the lifespan.

The risk factors for developing addiction in adolescence are the most intensively studied because this life phase is associated with the highest addiction risk. Traits linked to addiction risk during adolescence include pleasure-seeking, behavioral disinhibition, and devaluation of the future negative consequences of behavior. In contrast, the development of substance use among adults is more commonly associated with high levels of stress, anxiety, and depression.

Thus, perhaps it is not surprising that different sets of genes are now implicated in the risk for addiction in adolescence and adulthood.

In a new study published in Biological Psychiatry, researchers found that teenagers carrying variants in two gene regions were three times more likely to become regular smokers in adolescence and twice as likely to be persistent smokers in adulthood, compared to non-carriers.

Variation in a set of dopamine-related genes was associated with a person’s risk of starting smoking, and these genes had a stronger impact on smoking initiation in adolescents than in adults. Individuals carrying the risk variants had a 1.3-fold increased risk of starting smoking in their teenage years.

The other set of genes coded for subunits of the nicotinic cholinergic receptors, the brain targets for nicotine inhaled during smoking. Variation in these genes influenced the likelihood of smokers continuing the habit into adulthood, as it had a stronger influence on the smoking habits of adults than of adolescents. Those carrying these variants had a 1.3-fold increased risk of becoming a heavy and persistent smoker in adulthood.

“These findings seem to make some sense. The dopamine-related genes may be more closely associated with the risk for addiction within the context of thrill-seeking, while cholinergic receptors, which have been implicated in mood and cognition as well as addiction, might contribute to self-medication models of addiction,” commented Dr. John Krystal, Editor of Biological Psychiatry.

The researchers say the findings could help develop genetic testing for those wishing to know their susceptibility to nicotine dependence and tobacco-related disease. It could also pave the way for targeted drugs that influence an individual’s response to nicotine. However, further research is necessary before these goals could be implemented.

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Notes to Editors

The article is “TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 Influence Different Pathways Leading to Smoking Behavior from Adolescence to Mid-Adulthood” by Francesca Ducci, Marika Kaakinen, Anneli Pouta, Anna-Liisa Hartikainen, Juha Veijola, Matti Isohanni, Pimphen Charoen, Lachlan Coin, Clive Hoggart, Jesper Ekelund, Leena Peltonen, Nelson Freimer, Paul Elliott, Gunter Schumann, and Marjo-Riitta Järvelin. The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article.

The article appears in Biological Psychiatry, Volume 69, Number 7 (April 1, 2011), published by Elsevier.

John H. Krystal, M.D. is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available at http://journals.elsevierhealth.com/webfiles/images/journals/bps/Biological-Psychiatry-Editorial-Disclosures-7-22-10.pdf.

Full text of the article mentioned above is available upon request. Contact Chris J. Pfister at .(JavaScript must be enabled to view this email address) to obtain a copy or to schedule an interview.

About Biological Psychiatry

This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length reports of novel results, commentaries, case studies of unusual significance, and correspondence judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise reviews and editorials that focus on topics of current research and interest are also published rapidly.

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