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Anxiety emerges early in patients with Parkinson’s Disease, and not just as an emotional response to a difficult diagnosis.

And the qualities of this anxiety can change over the course of the disease. While some patients may experience generalized anxiety — for example, they may feel uncomfortable in social situations — they may also experience autonomic symptoms, such as sweating, a racing heart or physical nervousness.

“We have evidence from clinical pathology as well as some unique features of anxiety to suggest that it is organic and not simply a perception driven by disease diagnosis,” explained �����о�Ժ���� Psychology Professor Christopher Bishop, who recently received a grant from the Michael J. Fox Foundation to study the neurobiology of anxiety related to Parkinson’s Disease.

Prior to this latest grant, Bishop has conducted research into non-motor problems linked to Parkinson’s, such as psychosis.

Some patients experience anxiety even before the motor symptoms characteristic of Parkinson’s emerge, Bishop said. Coupled with the development of recent biomarkers, anxiety symptoms may help predict the future progression of the disease.

Recently, the Michael J. Foundation has been promoting a powerful assay that can detect markers for Parkinson’s in cerebral spinal fluid, Bishop said. Bishop’s collaborative research partner, Fredric Manfredsson at the Barrow Neurological Institute in Arizona, has a novel model of the disease that produces this same pathological protein marker. Together, they will look at the emergence of anxiety during the course of the disease and key regions of the brain that may produce this behavior.

The role of the amygdala

In addition to collaborators at Barrow, Bishop’s lab is working with �����о�Ժ���� Professor Marvin Diaz, an expert in electrophysiology and behavior with a focus on the amygdala, a part of the brain connected with fear and anxiety.

“He knows the connectivity of the amygdala very well. We saw that as a perfect marriage with our project because Parkinson’s patients display pathology in the amygdala fairly early on,” Bishop said. “That led us to believe that this was a place that needs a closer look.”

The research uses Manfredsson’s alpha-synuclein-based model, which refers to a protein involved in the release of neurotransmitters. In Parkinson’s, abnormal versions of this protein can accumulate within neurons, including in the amygdala. The question: How do these functional changes translate to behaviors?

The project relies on animal models, specifically rodents. A researcher, for example, may put a rat in a new situation and then monitor their behavior to infer their psychological state. A non-anxious animal placed in an unfamiliar environment will feel concerned, but eventually their curiosity kicks in and they will begin to explore. An anxious rat is more hesitant to engage in exploration, Bishop explained.

Bishop’s senior graduate student, Natalie Lipari, has already completed the first round of studies, which is part of her doctoral dissertation project.

“We are seeing the emergence of that anxiety phenotype in our rat model,” he said.

And while they’re seeing functional changes in how the amygdala responds, they aren’t seeing cell loss in the amygdala itself; this area of the brain is not believed to degenerate.

“That means two things: If they’re not degenerating, those cells are still available; they’re just not working as they should,” Bishop said. “The upside of that is because they’re still there, we may be able to modulate them with treatment.”