The relentless itch of rituals stemming from obsessive-compulsive disorder (OCD) interfere with the lives of some 80 million people worldwide, and now we may have the best explanation yet for the cause.
An international team of Canadian, American and European researchers, led by Harvard and MIT computational biologist, Hyun Ji Noh, have linked four genes – all from the same neural circuit – to OCD. The work could explain why people who have relatives diagnosed with the disease also develop it.
Living with OCD can be seriously debilitating. Casual use of the term in popular culture and lazy analogies spreads misinformation about the condition’s true complexity and gravity (not least of all in the media). For sufferers, it means putting up with intrusive thoughts and powerful urges to repeat tasks which can result in extreme anxiety attacks if the task isn’t performed.
Rituals extend beyond well-known ones like hand-washing, however. Excessively contacting loved ones to ensure they’re OK; double, triple, quadruple checking locks when unnecessary, and spending large portions of the day cleaning are all common examples.
Dogs and mice provide clues through similar behaviour
The discovery was made using three sets of DNA linked with compulsive behaviour – but it wasn’t just humans who were studied. Mice and dogs also made the cut because of the similarities between their brains and that of people, as well as the existing body of work on compulsive behaviour in these species.
“Dogs, it turns out, are surprisingly similar to people,” said co-author Elinor Karlsson, speaking with NPR. “They’re chasing their own tail or chewing themselves or chasing shadows like normal, but they’re doing it for hours. They literally can’t stop.”
Researchers compared over 600 genes in 592 people with OCD and 560 without the disease. They found four genes consistent in people with the condition that were mutated in some manner – NRXN1, HTR2A, CTTNBP2, and REEP3.
This does not mean that having mutations in these four genes equals a guaranteed OCD diagnosis, but the chances of developing it are higher.
“OCD is a really complicated disease. All we can say is if you have variations in these genes, you are more likely to have OCD,” says Karlsson.
Environmental factors are still an important factor to consider.
Stuck in a loop: the mental reality of OCD
These four genes are part of the cortico-striatal loop – a system of pathways thought to control actions. Previous evidence from brain imaging suggests that hyperactivity in this circuit is part of the dysfunctionality of OCD.
The striatum, a brain structure associated with learning, communicates with the decision-making cortex via the thalamus, and the authors suggest that it is a breakdown of control in this circuit that leads to OCD behaviour. The mutations could disrupt proper synapse development and hamper the neural pathways that rely on them.
In a nutshell, healthy brains can recognize when a thought has gone through the loop, but for those with OCD, the loop may be lacking a ‘stop’ mechanism and the thought can’t end.
This is an exciting find. A conclusive discovery of the mechanism behind OCD could be the basis of new and more effective treatments.
Currently, SSRIs play a big role in OCD treatment, with up to 60% in reduction of symptoms according to the International Obsessive Compulsive Disorder Foundation. One of the four genes identified here – HTR2A – is involved in serotonin signalling, and Noh believes it is therefore possible that OCD sufferers have problems with regulating serotonin in their brains.
Thinking long-term, the team hopes to eventually supersede current treatments using their ground-breaking research: “We would like to develop a drug that reverses the effects, either by targeting the gene itself or the pathway it regulates,” says Noh.