A new study conducted by researchers from the Vanderbilt University has identified a potential target for novel treatments of schizophrenia.
Schizophrenia, which affects approximately one percent of the global population, has been historically difficult to treat. Current clinically approved antipsychotics are effective at reducing "positive symptoms" like hallucinations and delusions in some patients, but they fail to treat "negative symptoms," such as social withdrawal, lack of motivation and cognitive deficits associated with the disease.
Schizophrenia is thought to occur when a region of the brain called the prefrontal cortex becomes abnormally active because interneurons, which connect neuron circuits or neuron groups, become dysfunctional and stop regulating neuronal activity.
The team led by James Maksymetz, sought to modulate the activity of those cells, and identifyedGlu1—metabotropic glutamate receptor subtype 1—as a potentially druggable target. Then, they tested it with a compound that enhances its function: a positive allosteric modulator or PAM like the "Diazepam," "Alprazolam," and "Chlordiazepoxide". The researchers found that these compounds selectively increased the activity of specific inhibitory interneurons.
These findings, published on Wednesday in the Cell Reports journal, suggest that using a PAM to enhance mGlu1 activity is an effective treatment for schizophrenia.
"Schizophrenia is an important clinical and societal concern. Inadequate treatment responses and failures to address 'negative symptoms' and cognitive deficits result in poor patient outcomes. And they incur a huge financial burden on the US and global economies," Maksymetz said.
Researchers hope that this novel treatment strategy may eventually provide relief for patients, allow them to reintegrate into and contribute to society, and diminish the burden on our health care systems.
To translate these findings to the clinic, scientists will need to investigate the efficacy of PAMs when used chronically rather than in the short term, and evaluate potential side-effects.
