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Obsessive-Compulsive Disorder: A Gene Variant Linked to Risk

 
  April, 10 2006 19:06
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Scientists at the National Institutes of Health's(NIH) National Institute on Alcohol Abuse and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual’s risk for obsessive-compulsive disorder (OCD). The new functional variant, or allele, is a component of the serotonin transporter gene (SERT), site of action for the selective serotonin reuptake inhibitors (SSRIs) that are today’s mainstay medications for OCD, other anxiety disorders, and depression.

The new variant is located at a well-recognized site in the SERT gene. Also known as HTTLPR, the site is the most heavily studied polymorphic site (those that may display differing DNA sequences) in psychiatric genetics. For years, HTTLPR has been known to have two variants — S and L — that alter expression of the SERT gene and are common across all human populations. The loss-of-function S variant exerts a small effect on a person’s risk for anxiety, depression, and suicidality, especially in response to environmental stressors. The S allele exerts a larger effect on the intermediate neurobiology of anxiety and depression, specifically, by disrupting the structure and functional coupling of key brain regions. The gain-of-function L allele, on the other hand, enhances SERT activity and functional coupling. The current study differentiates the L variant into two — LA and LG — and shows that LA exerts a greater influence on SERT expression.

The study entitled "Serotonin Transporter Promoter Gain-of-Function Genotypes Are Linked to Obsessive-Compulsive Disorder" appears in the current online version of the American Journal of Human Genetics It will be published in the May 2006 print issue (Volume 78, Number 5).


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