1277 lines
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<meta name="description" content="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." />
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<title>NIH Researchers Identify OCD Risk Gene | National Institute on Alcohol Abuse and Alcoholism (NIAAA)</title>
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NIH Researchers Identify OCD Risk Gene
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<p><time datetime="2006-03-29T12:00:00Z">Wednesday, March 29, 2006</time>
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<p>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.</p>
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<p>“Improved knowledge of SERT‘s role in OCD raises the possibility of improved screening, treatment, and medications development for that disorder,” said Ting-Kai Li, M.D., Director, National Institute on Alcohol Abuse and Alcoholism. “It also provides an important clue to the neurobiologic basis of OCD and the compulsive behaviors often seen in other psychiatric diseases, including alcohol dependence.”</p>
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<p>Approximately 2 percent of U.S. adults (3.3 million people) have OCD, the fourth most prevalent mental health disorder in the United States. Individuals with OCD have intrusive, disturbing thoughts or images (obsessions) and perform rituals (compulsions) to prevent or banish those thoughts. Many other individuals demonstrate obsessive-compulsive behaviors that do not meet OCD diagnostic criteria but alter the individuals’ lives.</p>
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<p>Drs. David Goldman, Chief, and Xianzhang Hu, Research Scientist, in NIAAA’s Laboratory of Neurogenetics discovered the linkage aided by new functional analyses of the SERT genetic variant. The researchers first compared the genotypes of 169 OCD patients to those of 253 controls in a large U.S. patient population [i] and found that the OCD patients were twice as likely to have the variant. Then they studied transmission and non-transmission of the variant in a Canadian population [ii] of 175 OCD parent-child trios (two healthy parents and a child with OCD) and found that the risk variant was twice as likely to be transmitted from a parent to a child with OCD. Specifically, of 86 informative trios, 48 children carried the new risk variant and 26 did not.</p>
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<p>“Whereas most genetic diseases are caused by variations that lead to reduced gene function, we found that a common SERT variant that increases SERT activity also increases risk for OCD,” said Dr. Goldman. The same research team previously identified a rare gain-of-function variant at a different location in SERT. It, too, is linked to OCD but has been studied only in two families with a severe, treatment-resistant form of the disease. “That earlier study suggested that we should test the common gain-of-function variant for OCD linkage,” Goldman said.</p>
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<p>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.</p>
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<p>“The gain-of-function L alleles appear to inhibit connections between emotion and repetitive behaviors and such executive brain functions as task-switching,” Goldman said. “These neurobiology relationships should be further tested in combined genetic-neuroimaging studies.”</p>
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<p>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 at <a href="http://www.ajhg.org">www.ajhg.org</a>. It will be published in the May 2006 print issue (Volume 78, Number 5). For an interview with Dr. Goldman, please contact the NIAAA Press Office: 301-443-3860.</p>
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<p><strong>Reference</strong><p>
|
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<p>[i] Obsessive Compulsive Disorder Case Control Study, conducted by Dennis Murphy, M.D., Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health<br>
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[ii] The Toronto OCD Parent/Child Trio Study, conducted by James L. Kennedy, M.D. , Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto</p>
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The National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, diagnosis, prevention, and treatment of alcohol use disorder. NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at <a href="/" rel="nofollow noreferrer">www.niaaa.nih.gov</a>.</p>
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NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit <a href="https://www.nih.gov/" rel="noreferrer noopener">www.nih.gov</a>.</p>
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