FORT MYERS, FLA— The mood of individuals with Parkinson's disease (PD) frequently fluctuates dramatically over the course of a day, and researchers and clinicians have generally assumed that these variations occur in tandem with patients' motor fluctuations. However, a study reported at the 11th Annual Meeting of the American Neuropsychiatric Association suggests that on most days, patients' mood and motor function appear to be largely independent.

Mood disturbances are a common problem in PD; depression or dysthymia may affect as many as half of patients. Often, however, these disorders are less disconcerting to patients than the mood swings that, in extreme cases, may shift from feelings of euphoria to suicidal urges within the same day. "For some people, it's their predominant complaint, more so than the motor fluctuations," said study author Irene Hegeman Richard, MD, an assistant professor of neurology and psychiatry at the University of Rochester Medical Center. "When their emotions are literally out of control, it's very disturbing to them." Approximately two thirds of patients with advanced PD and motor fluctuations also experience mood fluctuations.

DAILY DIARIES AND HOURLY ASSESSMENTS

In the new study, Dr. Richard, along with coauthors Anne Justus and Roger Kurlan, MD, investigated mood fluctuations in 17 patients with idiopathic PD. For one week, participants kept a diary in which they used a visual analog scale to record their mood, anxiety level, and motor function at hourly intervals. Subjects also completed formal measures of depression and anxiety the day before starting the diary and provided detailed psychiatric histories. Eight patients (47%) had scores of 10 or more on the Geriatric Depression Rating Scale, and 11 patients (65%) were currently using one or more antidepressants—findings that "speak to the prevalence of anxiety and depression in this disorder," Dr. Richard noted.

Statistical analyses allowed the researchers to determine if, for each patient, there was a significant correlation between the hourly mood and motor ratings on a given day. When correlations did occur, they were generally positive, such that patients experienced depressed mood at times of poor mobility; in one patient, mood and motor fluctuations were closely associated on all seven days of the study (figure 1). In most patients, however, mood and motor fluctuations were correlated on no more than one or two of the seven days—and in some instances, there was a negative correlation between mood and motor fluctuations (figure 2). Similarly, motor fluctuations did not consistently correlate with subjects' anxiety levels.

Figure 1: MOOD AND MOTOR FLUCTUATATIONS POSITIVELY CORRELATED.

Figure 2: MOOD AND MOTOR FLUCTUATATIONS NEGATIVELY CORRELATED.

Some experts have suggested that the mood fluctuations in PD are either a psychologic reaction to patients' motor fluctuations or result from changing brain levels of dopamine. Alternatively, separate neurobiologic mechanisms could underlie the mood and motor fluctuations, a possibility supported by the lack of correlation observed in most patients. Because of the study's findings, Dr. Richard suspects that several different mechanisms may lead to mood fluctuations, with each operating in a subgroup of PD patients.

"The patient in whom there was a perfect correlation between mood and motor fluctuations every day had no history of psychiatric problems and was taking no psychoactive medicine," she noted. "That might be a person in whom a reactive process is occurring." In cases in which there was no correlation, however, "the underlying mechanism may be something different," perhaps involving neurotransmitters other than dopamine.

HOW SHOULD MOOD FLUCTUATIONS BE TREATED?

Because no treatment trials of mood fluctuations have been conducted, little is known about the management of the problem. Dr. Richard suggests that clinicians first try to optimize a patient's motor status in case his or her fluctuations are a reactive phenomenon or an independent result of changing brain dopamine; they may wish to add a dopamine agonist or catechol-O-methyltransferase inhibitor to the patient's regimen. Dr. Richard notes that although the relationship between mood fluctuations and more pervasive emotional disorders remains unclear, a detailed evaluation to ensure that the patient does not have a depressive or anxiety disorder would be prudent. For patients whose mood fluctuations are particularly dramatic, she said, "I would consider using an antidepressant, because it might decrease the degree of dysphoria the patient experiences." There is no evidence that antidepressants induce mania in this population.

Dr. Richard recently received funding for a study that may provide further clues on how to treat the phenomenon. She and her colleagues will be giving patients levodopa, alternating oral medication with infusions, "to see whether or not their mood fluctuations are reduced when we ameliorate their motor fluctuations." Subjects will again use visual analog scales to rate their motor and mood fluctuations, although the study will also include objective measures of motor function. In addition, a group of elderly controls will keep similar mood diaries to help determine how mood varies in normal populations. The results, Dr. Richard hopes, will indicate whether a single mechanism underlies motor and mood fluctuations—at least in some patients.

And perhaps, she added, the study will provide a window into how mood homeostasis is disrupted in persons without PD. "It might," she speculated, "even give some insight into what causes mood fluctuations within primary psychiatric disorders," such as bipolar disorder and major depression.

—Peter Doskoch

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