Knowledge about SLITRK5 may advance a precision medicine-based cure for common mental health disorder
New genetic research has created the first ever opportunity to provide precision medicine treatments for obsessive-compulsive disorder (OCD). OCD is a mental health disorder that is characterized by unreasonable thoughts that lead to uncontrolled, compulsive behaviors. The behaviors are often repetitive or follow certain patterns and are uncontrollable by the person who has OCD.
OCD affects 1% to 2% of the general population in the United States and is known to run in families, indicating a strong genetic component to the disease. While many clinicians believe that the risk of OCD is strongly impacted by genetics, the identity of the genes potentially influencing the development of OCD is not known.
What Genes Influence OCD
New research, performed by Columbia University Vagelos College of Physicians and Surgeons in collaboration with other institutions, set out to solve the mystery of what genes influence OCD. The initiative used a new method of study that had not been implemented before in OCD research.
Previous OCD genetic research focused on specific individual genes thought to potentially be related to OCD, then examining patients with OCD to determine which genes do, in fact, increase the risk of the disorder.
“The solution to the problem is to study all the genes in the genome at the same time and ask whether any of them have significant evidence of influencing risk. That had not been done yet at scale in OCD,” said David B. Goldstein, PhD, in a recent press release. Goldstein is the director of the Institute for Genomic Medicine at Columbia University and a senior author on the new paper, “Exome Sequencing in Obsessive-Compulsive Disorder Reveals a Burden of Rare Damaging Coding Variants,” published recently in Nature Neuroscience.
Recent Genomics Research into OCD
With improvements in genomic sequencing technologies, automation processes, and computing, the price of genomic sequencing is falling. As a result, genome projects continue to proliferate. This project used whole exome sequencing to investigate the genes that encode protein, in relation to OCD.
Goldstein’s team, in collaboration with Gerald Nestadt, MBBCh, MPH, a psychiatrist at Johns Hopkins University, used a genome-wide approach, analyzing the entire genome of OCD patients using a combination of high-throughput sequencing that provided full genomic data on patients, and computational biology techniques that identified relevant genes.
“Many neurological diseases are influenced by strongly acting mutations which can cause disease by themselves,” explained Goldstein about the reasons for the research. “These mutations are individually very rare but important to find because they can provide a starting point for the development of therapeutics that target precise underlying causes of disease.”
Toward Personalized Medicine, One Gene Strongly Correlated With OCD
Researchers were able to identify several rare genetic mutations linked to OCD in the 1,300 patients that were involved in the study. One gene in particular, called SLITRK5, was strongly correlated with the development of the disorder. This may prove valuable in providing a potential target for precision medicine OCD treatments for the debilitating condition.
Having a treatment for OCD has the potential to impact a significant percentage of those with mental illness. “OCD is a disabling disorder that is twice as common as schizophrenia,” said H. Blair Simpson, MD, PhD, in a Columbia University press release. Simpson was not a member of the research team, but is a well-recognized professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons and director of the Center for OCD and Related Disorders at New York State Psychiatric Institute.
Serotonin reuptake inhibitor medications and cognitive-behavioral therapy are the two most commonly used OCD treatments. These treatments are only effective in about half of patients with OCD, Simpson explains. “Thus, these genetic findings are very exciting; they indicate that the promise of precision medicine could include OCD, ultimately transforming how we diagnose and treat this disorder.”
Clinical site teams that treat OCD should be aware of the recent advances in understanding what genetic mutations do and, therefore, should watch for precision medicine-focused advances in developing new treatments for OCD.
As physicians and health systems focus on preventive healthcare, and on translating clinical research advances into practical applications for patients, screening and care models that incorporate elements of precision medicine-based personalized care will become clearer. The new genetic breakthrough related to OCD will support the development of promising treatments for individuals that have previously not responded well to conventional treatments.