When most people think of Parkinson's disease, they think of its physical symptoms, including tremors and difficulty moving. However, the disorder also takes a toll on mental health, with up to half of Parkinson's patients developing depression, according to the National Institutes of Health. Both the mental and the physical symptoms of the disease may be set off by gradually decreasing dopamine production, as that neurotransmitter helps the brain coordinate physical movements and create sensations of pleasure.

Although no medications target the underlying processes of Parkinson's, researchers are attempting to better understand the disease's mental effects in hopes of creating better treatments for them. One such team at the University of Florida's Movement Disorders Center is finding that the depression of Parkinson's patients can look quite different from depression experienced by otherwise healthy people, or even people with other movement disorders. For instance, an article in press at Neurology by University of Florida clinical psychology graduate student Lindsey Kirsch-Darrow shows that close to 30 percent of those with Parkinson's disease show a pattern of mental symptoms better described as "apathy" than "depression."

"With apathy, there aren't the feelings of worthlessness or guilt you have in depression sometimes," says Kirsch-Darrow.

Parkinson's patients with apathy show a general lack of motivation and, instead of feeling sad, experience no mood, says paper co-author Dawn Bowers, PhD, a University of Florida clinical and neuropsychology professor. What's more, Parkinson's patients' lack of interest in things such as physical therapy can decrease their ability to manage their symptoms and put a strain on those who take care of them, she says.

"If you are with someone who feels 'blah' all the time, who never wants to do anything, it can cause secondary caregiver depression," says Bowers. "It can also influence their relationship with physicians and other health-care providers."

And while current treatments for depression-including cognitive-behavioral therapy and selective serotonin reuptake inhibitors-are fairly effective for people with Parkinson's, they may not address the symptoms of apathy, says Bowers.

"The first step is getting a handle on what apathy is," says Bowers. "The next step is to devise some clinical trials and see if we can do something to help these patients."

Pure apathy

To take that first step, Kirsch-Darrow and her colleagues compared the mental state of people with Parkinson's with that of people with dystonia, another movement disorder. Both groups of patients experience symptoms including rigidity, and so the two groups have a similar experience of disability, Kirsch-Darrow says.

The researchers recruited 80 Parkinson's patients and 20 dystonia patients during routine medical examinations at a movement disorder clinic. The participants then completed the Beck Depression Inventory and the Apathy Evaluation Scale. Typical items on the depression questionnaire include "I feel I have failed more than the average person" and "I feel sad." The apathy evaluation asked participants, for example, whether they "are interested in learning new things" and "feel neither happy nor sad, just in between."

About half of the people with Parkinson's disorder showed the symptoms of apathy, compared with 20 percent of people with dystonia. What's more, 29 percent of people with Parkinson's had "pure apathy"-that is, apathy without depression-but none of the people with dystonia did.

This suggests that, like slowed movement, apathy may be a defining feature of Parkinson's disorder, says Michael Okun, MD, medical director of the National Parkinson Foundation.

"It has been on our radar screen, but most people haven't recognized there is a difference between apathy and depression," says Okun. "That distinction is important and has clinical implications."

Treatment horizons

Parkinson's specialist Katrina Gwinn-Hardy, MD, a program director at the National Institute of Neurological Disorders and Stroke, hasn't formally made the distinction between apathy and depression in her clinical work. But she has noticed that a flat mood and a lack of motivation are common among her patients.

"A lack of motivation can be a sign of depression, but once we treat a patient with antidepressants, that apathy may not go away," says Gwinn-Hardy.

Adding evidence to the hypothesis, Gwinn-Hardy notes that many of the people in Kirsch-Darrow's study were taking antidepressants, and yet they still experienced symptoms of apathy.

Unfortunately, there are no drugs that have proven effective at treating apathy among Parkinson's patients, though dopamine agonists-which mimic the effect of dopamine in the brain-have shown promise treating apathy among people without Parkinson's disease.

The drugs' effects appear to be moderate, and they will probably work best in combination with cognitive-behavioral therapy, says Bowers. The shape an intervention might take is far from determined, she says, but could include helping patients to feel hopeful about their lives and encouraging them to re-engage with the activities they used to enjoy.

"Treating the mental symptoms of Parkinson's is critical to improving [patients'] quality of life," says Bowers. "It is just as critical as treating their physical ones."