Discovering The Genetic Cause For Obsessive-Compulsive Disorder

Of all psychiatric conditions, obsessive-compulsive disorder, or OCD as it’s more commonly known, is perhaps the most widely known and also, misunderstood. Colloquially, this term is used to describe anyone with a penchant for a obsessive nature. Yet, this ailment, which only affects about 2% of the population, is quite difficult to both diagnose and manage.
Understanding the underlying cause for OCD has been a challenge for researchers as the wide spectrum of symptoms suggests no one single answer. In general, there appears to be some genetic component as the condition appears to be hereditary. Yet little has been known about what the contributions actually are.

One particular hypothesis for a genetic link to OCD involves a phenomenon known as copy number variation Normally we have two copies of every gene, but this is not always the case. Parts of our DNA may either lose or duplicate copies of either whole genes or segments of them. This may alter the function of certain proteins and eventually lead to imbalance in the individual. As a result, copy number variation has been implicated in certain mental health conditions.
In 2007, a study attempting to associate autism with copy number variation revealed a link in up to ten percent of those studied. In 2011, an examination of links to attention deficit hyperactivity disorder found approximately eight percent of patients had these variations.  In that same year, a review of over 15,750 children revealed a quarter of individuals suffering from developmental delay and intellectual disability possessed these copy number variations.
Due of these apparent links between variation and cognitive disorders, a group of researchers led by Dr. Stephen Scherer at The Hospital For Sick Children, wanted to find out if similar associations existed with OCD. If they were correct, they could at least highlight certain genetic elements prone to variation leading to this condition. Their results are now available in the Journal of Neurodevelopmental Disorders.
The team examined 307 individuals diagnosed with OCD and collected their genetic material. As a control, they used already available human genomics databases. In each case, the genetic code was analyzed in the hopes of finding copy number variation.
Once the variations were collected, common ones appearing in over 0.5% of the population were excluded. The team was only interested in rare alterations within the genome. This left them with eighteen CNVs identified. This number was reduced down to eight as the team only wanted variations from areas involved in the production of proteins, known as exons.
With these eight variations identified, the next step of the process was to determine which, if any, might play a role in the development of OCD symptoms. The team examined the various proteins encoded by the areas in the hopes of finding possible associations with psychiatric disorders. As expected, in some of the cases, the genes had no links to any psychiatric disorder. However, there were some changes already known to be involved in certain conditions such as ASD, Tourette’s syndrome, and even OCD itself.
The next stage involved examining the genetic makeup of parents to determine whether these alterations were inherited or had happened spontaneously. Unfortunately, there was no constant pattern. In some cases, the same type of copy number variation was inherited while in others, it occurred spontaneously.
The wide-spanning nature of the results revealed the delicate nature of copy number variation in relation to this psychiatric illness. Only a fraction of the total number of cases could be associated with copy number variation. Yet, despite this low occurrence, the effect of these mutations cannot be ignored.
This study, while small, reveals the need for greater study of the role of genetic mutations, such as copy number variations, in human health. Although the number of people encountering diseases as a result of these changes in the genetic code, from a public health perspective, having this knowledge may be of significant use for diagnosis and treatment. Moreover, for those who are suffering from the debilitating symptoms of this disorder and other psychiatric illnesses, knowing the cause may not only offer information but also may provide a certain peace of mind.

Original research article:

Gazzellone MJ, Zarrei M, Burton CL, Walker S, Uddin M, Shaheen SM, Coste J, Rajendram R, Schachter RJ, Colasanto M, Hanna GL, Rosenberg DR, Soreni N, Fitzgerald KD, Marshall CR, Buchanan JA, Merico D, Arnold PD, Scherer SW.
Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation. J Neurodev Disord. 2016 Oct 18;8:36.