Scientists seek causes of Parkinson’s neuropsychiatric symptoms
$3M Department of Defense grant is funding multiteam research in US
New U.S. Department of Defense-funded research at Binghamton University in New York is investigating the underlying causes of neuropsychiatric symptoms — those that result from medical conditions involving both neurologic and psychiatric components — in people with Parkinson’s disease.
The four-year grant, totaling $3 million, is shared between Binghamton, part of the State University of New York, the Barrow Neurological Institute in Arizona, and the University of Illinois in Chicago, and is intended to support research into the teams’ hypothesis that the brain’s compensatory processes in Parkinson’s disease may cause diverse psychiatric issues. Among the resulting symptoms, according to the researchers, are depression, anxiety, sleep issues, cognitive changes, and, in some cases, psychosis.
The three institutions have been working together on such research for more than three years.
“It’s a truly collaborative effort; none of us would be able to do this by ourselves,” Christopher R. Bishop, PhD, a professor at Binghamton University, said in a university news story about the ongoing research.
Parkinson’s disease is best known for motor-related symptoms caused by a loss of brain cells that produce dopamine, an important molecule for communication between nerve cells in the brain.
However, many patients also experience serious nonmotor symptoms, including cognitive changes and mental health problems, that are less well-understood. In fact, as many as 70% of all Parkinson’s patients may be affected by psychosis at some point during the course of their disease.
Investigating neuroplasticity as a cause of neuropsychiatric symptoms
Military veterans have been found to experience higher rates of Parkinson’s than the general population. Given that, the Department of Defense is now funding research that investigates how psychiatric symptoms in Parkinson’s patients may be caused by unexpected changes in the brain — a process known as neuroplasticity.
Prior research has found that nerve cells that typically produce a different molecule used in nerve cell communication, called serotonin, can become unexpectedly capable of producing dopamine when exposed to levodopa, commonly used as a Parkinson’s treatment. Levodopa is a molecule that can be converted to dopamine in the brain.
However, when these serotonin nerve cells produce dopamine, they do so in an uncontrolled way, often causing significant side effects, including psychiatric symptoms.
“It’s almost as if the systems get hijacked and tip over into aberrant neuroplasticity,” Bishop said.
Signs of aberrant neuroplasticity can be detected in animal models of Parkinson’s disease and in postmortem human brain samples. These researchers have been investigating how these unexpected changes occur in regions of the brain involved in neuropsychiatric, cognitive, and sleep function.
According to Bishop, the changes represent a “global compensatory mechanism … in the disease.”
Now, the researchers are using new technologies and techniques that allow them to modify cell types in animal models of Parkinson’s, and to selectively stimulate certain cell types with chemicals to see how these changes impact the brain and downstream behavior. They’ve found that animals with specific cellular changes exhibit increased levels of anxiety.
The researchers also have identified several medications they believe could be repurposed to address the maladaptive plasticity in serotonin-producing nerve cells.
One currently approved treatment for Parkinson’s-related psychosis, Nuplazid, targets serotonin receptors throughout the nervous system to reduce hallucinations and delusions. Management of depression and anxiety in Parkinson’s patients may also include treatment with anti-depressants and anti-anxiety medications.
The team noted their partnership with the Muhammad Ali Parkinson Center, a NeuroNEXT clinical trial site, as aiding in their work. The collaboration provides clinical researchers with expertise in clinical trials access to a large population of people with Parkinson’s disease.
According to Binghamton University, “long-term, [this] research could ultimately improve the lives of [Parkinson’s] patients and the management of symptoms.”
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