Missing protein causes OCD behaviour in mice

German researchers have discovered what they believe to be the underlying cause of obsessive-compulsive disorder (OCD) — an illness which until now had no clear trigger.

According to Professor Kai Schuh and his team at the Julius-Maximilians-Universität (JMU) Würzburg, OCD-like behaviour was exhibited in mice that were deficient in the protein SPRED2. Writing in the journal Molecular Psychiatry, they explained that this deficiency triggered an overactive molecular signal pathway in the brain region known as the amygdala.

Occurring in all cells of the body, SPRED2 is found in particularly high concentrations in regions of the brain, namely in the basal ganglia and the amygdala. Normally the protein inhibits an important signal pathway of the cell, the so-called Ras/ERK-MAP kinase cascade. When it is missing, this signal pathway is more active than usual.

“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,” said study co-author Dr Melanie Ullrich.

In the JMU study, SPRED2 knockout (KO) mice were found to partake in excessive self-grooming, which resulted in facial skin lesions. This is not unlike the behaviour of many human OCD patients, who develop such an obsession with washing and cleaning that they are unable to stop — even after causing skin irritation or damage.

The researchers found that they were able to treat the OCD in their mouse models with antidepressants, similarly to standard therapy in humans. More excitingly, however, they found an improvement in symptoms after administering an inhibitor to attenuate the overactive signal cascade. Their study thus opens up new targets for therapy, as drugs that inhibit this cascade are already available and some are approved for cancer treatment.

“So 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,” said Dr Ulrich.

Image courtesy of mitramirae under CC BY 2.0