What causes the neuropsychiatric problems seen in Parkinson’s disease?

Parkinson’s disease is most known for its movement-related symptoms: tremors and rigidity, slowness and falls, caused by the loss of the brain’s dopamine-producing neurons.

However, about half of Parkinson’s patients also experience neuropsychiatric problems, including cognitive and sleep issues, depression, anxiety, even psychosis, according to Binghamton University Psychology Professor Christopher R. Bishop.

Bishop is part of a collaborative research team that recently received a four-year grant from the Department of Defense to investigate the underlying cause of neuropsychiatric symptoms in Parkinson’s disease (PD).

The $3 million is split among researchers at Binghamton, the Barrow Neurological Institute in Arizona and the University of Illinois in Chicago. The team began working together more than three years ago on a National Institutes of Health-funded project focused on the brain’s compensatory processes in PD and includes experts in neuroanatomy, neuroimaging, neurophysiology and neurochemistry.

“It’s a truly collaborative effort; none of us would be able to do this by ourselves,” said Bishop.

Veterans tend to develop Parkinson’s at a higher rate than the general population, which is why the DOD funds research of this type, he said.

Changes in serotonin-producing neurons have often been linked to PD in clinical studies, and research has found that serotonin neurons are unexpectedly capable of producing dopamine when exposed to L-DOPA, a common PD treatment. However, the serotonin neurons release dopamine in an uncontrolled way, leading to significant side effects.

“It’s almost as if the systems get hijacked and tip over into aberrant neuroplasticity,” Bishop explained. “The severity of the disease is the tipping point and adding treatment on top of disease progression.”

Due to the development of new techniques, researchers can directly modify specific cell types in animal models and study or stimulate those cell types with chemo-genetic tools. So far, they have been able to demonstrate that animals subject to specific cellular changes show increased levels of anxiety.

Long-term, their research could ultimately improve the lives of PD patients and the management of symptoms.

In fact, the researchers have identified several medications that could be repurposed to treat serotonin dysfunction in PD, should their hypothesis prove true. Thanks to a partnership with the Muhammad Ali Parkinson Center, a NeuroNEXT clinical trial site, they also have access to a large PD population, as well as extensive expertise in clinical trials.

“Non-motor symptoms of PD clearly come from an organic source,” Bishop said. “As we investigated it further using our animal models and even postmortem human brains, we noticed the same plasticity in the movement system in the areas involved in neuropsychiatric, cognitive and sleep-related functions. There is a more global compensatory mechanism involved in the disease.”