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Targeting Motivation Could Improve Other Negative Symptoms in Schizophrenia

February 05, 2020

Successfully treating reduced motivation, or avolition, in patients with schizophrenia has a positive effect on other negative symptoms, according to a study published online in Schizophrenia Bulletin. 

“This study suggests that future drug development should target mechanisms of avolition in particular,” said researcher Gregory Strauss, PhD, an assistant professor at the University of Georgia, Athens. “If that domain is successfully improved, it might be possible to improve all negative symptoms and subsequently reduce functional disability.”

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In 2018, Dr. Strauss and colleagues published a paper in JAMA Psychiatry demonstrating that negative symptoms in schizophrenia are not a singular construct but represent 5 distinct domains—avolition, anhedonia, asociality, blunted affect, and alogia, or reduced speech—with each constituting a separate treatment target. 

In a Schizophrenia Bulletin paper published last year, Dr. Strauss was part of a team that ran a network analysis and found negative symptoms do not function in isolation but interact with one another. Successful treatment of avolition, that study suggested, may improve the entire constellation of negative symptoms in schizophrenia. 

The most recent study involved a network analysis of data from a phase 2b trial in which the compound roluperidone by Minerva Neurosciences significantly reduced negative symptoms. The analysis by Dr. Strauss and colleagues found that avolition was the most central domain for the active treatment group. When the drug improved avolition, the analysis found, all other negative symptoms improved as a result. 

“There’s a lot of hope that Minerva’s phase 3 trial will show a similar improvement in negative symptoms,” Dr. Strauss said. “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. It would be a monumental benefit to the lives of people with schizophrenia.”

A consultant with Minerva Neurosciences, Dr. Strauss codeveloped and validated the key clinical outcome measure used in the phase 2b trial. He was not, however, involved with the development of roluperidone.

—Jolynn Tumolo


Strauss GP, Zamani Esfahlani F, Sayama H, et al. Network analysis indicates that avolition is the most central domain for the successful treatment of negative symptoms: evidence from the roluperidone randomized clinical trial. Schizophrenia Bulletin. 2020 January 28;[Epub ahead of print].

Mann A. Research offers promise for treating schizophrenia. University of Georgia. Published January 28, 2020. Accessed February 5, 2020.

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