How Optogenetics Could Shine a Light on the Causes and Treatment of OCD

Pulsing light on genetically modified neurons revealed a link between specific brain cells and compulsive behaviour.

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Nov 24 2015, 12:50pm

Image: Merydolla/Shutterstock

Obsessive compulsive disorder is an oft-misunderstood illness. Frequently used as flippant shorthand for "tidy" or "organised," OCD can, in reality, be deeply debilitating for sufferers; the World Health Organisation describes it as causing "considerable suffering and disease burden."

As the name suggests, OCD encompasses thoughts or behaviours that are considered compulsive. This can include anything from compulsive checking or hand washing to hoarding or intrusive thoughts and impulses. These thoughts are often disturbing and uncontrollable and can significantly inhibit a person's life. According to charity group OCD UK, up to 12 people in every 1,000 are affected by OCD.

Until recently, not much was known about the biology of OCD. But in 2013, a paper was published in Science that posited a new way of looking at the brain's role in obsessive behaviours, and that could shine a light—literally—on its treatment.

"This kind of optogenetic approach ... could help us identify new treatment targets."

The research was one of the first major studies in the relatively new field of optogenetics, a technique that uses light to control genetically-modified neural cells. In typical neuroscience research, neurons have been analysed and altered by tiny electrodes—a method that has poor precision in terms of targeting individual cells. But by genetically modifying cells that can be "switched on and off" by bursts of light, optogenetics allows them to be individually examined, leading to a better understanding of how the brain works as a whole. This is particularly significant for patients with neurological or psychiatric disorders.

Susanne Ahmari, who researches how optogenetics can be used to understand and treat psychiatric disorders, is hopeful that it could be used to help change the chemistry of the brain; she compares it to deep brain stimulation, which is already used to treat Parkinson's and depression.

"This kind of optogenetic approach could be used to understand the circuit mechanisms underlying deep brain stimulation and other treatments, and it could help us identify new treatment targets," she explained.

The 2013 study was interesting for understanding OCD specifically. Using these optogenetic techniques, the research team was able to isolate an area of the brain responsible for compulsive behaviours—in mice, at least. The study used a number of knockout mice (lab mice who have had an existing gene replaced or disrupted) who had had a synaptic protein replaced. Without this protein, the mice display obsessive grooming behaviour; so much so that they often develop facial lesions.

The team found that, using the optogenetic "on" and "off" switch, they could control the neural cells of the mice

The mice were shown a pulse of laser light before receiving a drop of water to their forehead, which irritates both knockout mice and normal control mice and makes them groom. After a few rounds, the normal mice would stop grooming in anticipation of the light, but the knockout mouse would start to groom as soon as it pulsed—essentially, by switching the neuron "on," the mice experienced obsessive behaviour. It's of course not the same as the intrusive thoughts experienced by OCD sufferers, but it is a model of compulsive behaviour.

The team found that, using the optogenetic "on" and "off" switch, they could control the neural cells of the mice and control their behaviour. By switching the cells off, the compulsive grooming of the knockout mouse almost completely ceased. The implications are obvious. Optogenetics could help isolate the cells that play a role in compulsive behaviour. And if we can isolate them and genetically modify them, maybe we can also turn them off.

It's obviously more complex in humans. Ahmari said it's difficult to understand cause and effect in human illness, and stressed that the study isn't definitive.

"There's been a big debate in the field," added Satinder Kaur Singh, who studies the molecules involved in disorders like OCD at Yale University. "But what these studies show is that it [the relationship between the genetically modified brain cells and compulsive behaviour] is causative."

Elsewhere, researchers are using optogenetics to study bipolar disorder and drug addiction

It's too early to say that optogenetics could inform the treatment of OCD in humans. But the research could enact changes on our models of mental illness. Elsewhere, researchers are using optogenetics to study bipolar disorder and drug addiction.

It's important to remember, however, that OCD is a psychological illness as well as a biological one. As with other psychiatric illnesses, there's the ever present "nature vs. nurture" debate. Most experts now posit that a combination of genetics, biology, and environment are the cause of mental illness. So even if the research has isolated a biological root of OCD, it wouldn't account for all aspects of the disease. But understanding part of the cause would have an undeniably huge impact on treatment.

Scott Rauch, professor of psychiatry at McClean Hospital, is hopeful. "Delineating a pathway for compulsive behaviours in a more refined way than we've ever been able to do is exciting," he told The Scientist at the time of the study.

"It points us in the direction of pathogenesis and pathophysiology of the disorder, but also means we have new targets for potential intervention."

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