Obsessive-compulsive disorder (OCD) can be a debilitating condition, as persistent anxious thoughts lead sufferers to repeat an action to the point where it interferes with their everyday life. The cause of the disorder is thought to be a murky combination of biological and environmental factors, but now, researchers in Germany have singled out a protein called SPRED2, the absence of which can cause a key signal pathway in the brain to go into hyperdrive, leading to obsessive compulsive behavior in mice.
Anxiety takes many forms, and OCD can be a particularly visible one. People suffering from the condition can be plagued with fears of germs or an obsession with things having a set order or pattern to them, and will act on those concerns with compulsive behaviors, like constant hand-washing or repeatedly checking things. Since the cause is largely unknown, treatment options usually fall under the wider umbrella of mental illnesses encompassing anxiety, depression and eating disorders.
But the new research, from Julius Maximilian University (JMU) of Würzburg, has narrowed down the list of possible suspects to one: SPRED2. This protein is common throughout the body but is particularly concentrated in the basal ganglia and amygdala regions of the brain. There, SPRED2 normally inhibits a cell signal pathway called the Ras/ERK-MAP kinase cascade, but when the protein is absent or deficient, that pathway becomes too active. That creates the obsessive worries and, in turn, the compulsive behaviors that so many people struggle with.
"It is primarily the brain-specific initiator of the signal pathway, the receptor tyrosine kinase TrkB, that is excessively active and causes the overshooting reaction of the downstream components," says Dr. Melanie Ullrich, an author of the study.
The team found that mice engineered to be deficient in SPRED2 would excessively groom themselves, to the point of inflicting facial lesions on themselves – similar to the injuries that extreme OCD sufferers can cause. But these destructive behaviors improved when the researchers administered an inhibitor to control the overactive signal pathways. Making the connection between the condition and that particular cell pathway could open up a new avenue of more targeted treatments.
"We were able to show in mouse models that the absence of the protein SPRED2 alone can trigger an excessive grooming behavior," says Kai Schuh, lead researcher on the study. "Our study delivers a valuable new model that allows the disease mechanisms to be investigated and new therapy options for obsessive-compulsive disorders to be tested."
An antidepressant was found to reduce OCD symptoms, but interestingly, existing drugs currently used to fight cancer – and already approved by the US Food and Drug Administration – could also be potential treatments for the disorder. That's because a hyperactive Ras/ERK-MAP kinase cascade has already been identified as a cancer trigger, but applying it to OCD still needs more study.
"We are wondering whether such drugs could also be effective in the treatment of obsessive-compulsive disorders and whether they are beneficial in terms of side effects," says Ullrich.
The research was published in the journal Molecular Psychiatry.
Source: JMU Würzburg
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