Researchers identify OCD risk gene
Scientists at the National Institutes of Healths (NIH) National Institute on Alcohol Abuse and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individuals 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 todays mainstay medications for OCD, other anxiety disorders, and depression.
"Improved knowledge of SERTs 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."
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.
Drs. David Goldman, Chief, and Xianzhang Hu, Research Scientist, in NIAAAs 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 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 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.
"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.
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 persons 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 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."
Ann Bradley | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...