MIT Scientists Decode Reasons Behind OCD, Hint At Future Treatments
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Obsessive compulsive disorder (OCD) affects close to one percent of the U.S. population, of which nearly all receive anti-anxiety medication, antidepressants, or behavioral therapy. OCD can manifest itself in the compulsion to perform actions such as handwashing repeatedly, biting nails, and even Tourette's syndrome, among others. Because the need to perform actions is bypassing a normal consciously controlled mechanism, patients feel helpless and out of control.
New research published today from a lab at the Massachusetts Institute of Technology (MIT) sheds some light on the mechanisms behind OCD and possible treatments for the future. In a series of experiments, scientists utlized mice that have a gene mutation that predispose them to OCD behavior and trained them to acquire humanlike OCD behavior. The team then employed cutting-edge brain neuron-activating technology to better understand the basis of the condition.
The researchers trained normal mice and then mice lacking a gene called Sapap3 — which is expressed in neurons of the striatum, an area of the brain connected with addiction and repetitive behavioral problems in addition to decision making and planning — to groom themselves when they received two types of stimulus: hearing a tone then receiving a drop of water on their nose. This type of conditioning was actually developed using human OCD patients for therapeutic purposes. After hundreds of trials, both types of mice became conditioned to groom themselves when they heard the tone.
But, the behaviors of the two different types of mice then diverged. The normal mice continued to wait until just before the water drop to groom themselves, while the mice lacking the Sapap3 gene immediately began grooming themselves after the tone was heard. This showed that mice lacking the key gene were unable to suppress their compulsive behavior.
The researchers then turned to a very new and cutting-edge technology developed at MIT to activate specific parts of the brain using light. They made use of so-called 'optogenetics,' where a gene is inserted into mice that makes their neurons sensitive to certain light frequencies and become activated. By piping in light through fiber optics to specific regions of the brain, scientists can turn on certain brain neurons and see what they do.
The researchers theorized that the issue in OCD is a lack of communication between the striatum, the habit center of the brain, and the neocortex, which dictates higher brain functions and can block simple, more basic behaviors. When the scientists activated cortical cells that facilitate communication to the striatum, they found that after the tone, the mice lacking the gene stopped grooming themselves in response to the tone only. The mice were still able to groom themselves when the water drop hit their nose, which is normal mouse behavior.
The research suggests that the cure for the compulsive behavior resulted from a downstream activation of neurons, which inhibit the reaction to the compulsive behavior signals.
Deep brain stimulation with electric signals is a current treatment for some patients who are unable to control their OCD. This study is a step forward in understanding the signaling that results in OCD behavior and will eventually lead to better and more precise delivery of brain stimulation to people who suffer from the disease. "You don't have to stimulate all the time. You can do it in a very nuanced way," said Ann Graybiel, an Institute Professor at MIT, a member of MIT's McGovern Institute for Brain Research and the senior author of a science paper describing the study. Research is ongoing to find the early brain activity that is the hallmark of OCD behavior.
Source: Ahmari S, Spellman T, Douglass N, et al. Repeated Cortico-Striatal Stimulation Generates Persistent OCD-Like Behavior. Science. 2013.