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Targeting One Symptom of Schizophrenia May Help Relieve Others

A new study suggests that targeting one particular symptom of schizophrenia may have a positive effect on other symptoms, offering significant promise for treating an aspect of schizophrenia that currently has no pharmaceutical options.

The study, published in the journal Schizophrenia Bulletin, reveals that successfully treating the negative symptom avolition — reduced motivation — has a positive effect on other negative symptoms of the debilitating disorder.

The negative symptoms of schizophrenia “take away” from the patient’s personality. These may include the inability to show emotions, apathy, difficulties communicating and withdrawing from social situations. These are in contrast to the “positive” symptoms of schizophrenia, such as hallucinations or delusions, which are the targets of antipsychotic medications.

The results are based on a trial of the compound roluperidone by Minerva Neurosciences.

“This could be the first drug that receives an indication for negative symptoms of schizophrenia from the Food and Drug Administration, which is perhaps the biggest need in the field of psychiatry,” said Dr. Gregory Strauss, assistant professor in the Franklin College of Arts and Sciences at the University of Georgia.

“It would be a monumental benefit to the lives of people with schizophrenia.”

Research has shown that schizophrenia is the leading medical cause of functional disability worldwide. People with functional disability struggle to hold a job, build social relationships and maintain the independent activities of daily living.

In the U.S., it can also mean receiving government-supported disability funds.

“The government spends a tremendous amount of money every year on functional disability,” Strauss said. “Negative symptoms are the strongest predictor of functional disability, but no medication has received FDA approval for treating them. Therefore, they are a critical treatment target.”

Strauss has published more than 125 studies investigating the symptoms of schizophrenia. A 2018 paper published in JAMA Psychiatry demonstrated that negative symptoms are not a singular construct, as has long been assumed, but reflect five distinct domains: avolition; anhedonia (reduced pleasure); asociality (reduction in social activity); blunted affect (reduction in outwardly expressed emotion in the face and voice); and alogia (reduced speech). Each domain constitutes a separate treatment target.

In a 2019 study published in Schizophrenia Bulletin, Strauss sought to identify which domain is most critical to target in treatment trials.

Historically, researchers have looked at how symptoms function in isolation, but network analysis has revealed that they can significantly affect each other. Even if a drug doesn’t decrease the severity of a symptom, it may serve a valuable function in changing the interactions among symptoms, Strauss said.

The findings indicate that avolition is a highly central domain within the negative symptom construct, suggesting that the other negative symptoms are tightly woven to this domain, and if it is treated successfully, the entire range of negative symptoms might improve.

Strauss’ most recent study conducted network analysis on Minerva Neurosciences’ clinical trial data. In the clinical trial, the company observed that roluperidone had a significant reduction on negative symptoms. The team’s analysis of the data revealed that avolition was the most central domain for the active treatment group, suggesting that when the drug improved avolition, all other negative symptoms improved as a result.

“This study suggests that future drug development should target mechanisms of avolition in particular,” Strauss said. “If that domain is successfully improved, it might be possible to improve all negative symptoms and subsequently reduce functional disability.”

Strauss serves as a consultant with Minerva Neurosciences. He co-developed and validated the key clinical outcome measure used in their trial but was not involved with developing roluperidone.

Source: University of Georgia

Targeting One Symptom of Schizophrenia May Help Relieve Others

Traci Pedersen

Traci Pedersen is a professional writer with over a decade of experience. Her work consists of writing for both print and online publishers in a variety of genres including science chapter books, college and career articles, and elementary school curriculum.

APA Reference
Pedersen, T. (2020). Targeting One Symptom of Schizophrenia May Help Relieve Others. Psych Central. Retrieved on November 30, 2020, from
Scientifically Reviewed
Last updated: 29 Jan 2020 (Originally: 29 Jan 2020)
Last reviewed: By a member of our scientific advisory board on 29 Jan 2020
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