ARTICLE IN BRIEF
Investigators in the Netherlands reported that factors unrelated to Parkinson's disease also significantly influence the risk for depression, and are greater predictors of risk than factors that are related inherently to the movement disorder.
The same types of risk factors that make people susceptible to depression — life stressors, gender, prior episodes or family history of anxiety or depression — can tip the diagnostic scale in patients with neurodegenerative conditions. Many diseases — including stroke, Parkinson's and Huntington's diseases — are associated with high rates of depressive disturbances.
Researchers and clinicians continue to debate the causes for the increased risk — whether it is sadness and grief over the diagnosis itself or something innate in the neurodegenerative disease process that triggers biochemical mood and behavior changes. Adding to the dialogue, a team of scientists in the Netherlands, as part of a multinational study, tested a model for depressive symptoms in patients with Parkinson's disease (PD). They reported in a paper published online ahead of the Sept. 17 print edition of Neurology that non-PD factors also significantly influence the risk for depression, and are greater predictors of risk than factors that are related inherently to the movement disorder.
STUDY DESIGN, RESULTS
The researchers, led by Albert F. G. Leentjens, MD, PhD, a scientist in the department of psychiatry at Maastricht University Medical Center, set out to look for all the possible contributing factors of depression in PD, both related to the disease and to general risk factors for depressive disorders.
In developing a model to assess the factors that increase a patient's risk for depression, the investigators looked at a cross-sectional dataset of 342 patients and looked at a dozen factors, settling on nine, that could be used to help explain the risk for depression. Three were specific to PD and most, six, were not. This same dataset was used in previous studies of anxiety disorders in PD.
For the study, demographic and disease-related variables were gathered during a clinical interview. PD-related symptoms were assessed with the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed with the Mini-Mental State Examination and activities of daily living with the Lawton Instrumental ADL scale. The Hamilton Depression Rating (HAM-D) Scale was used to determine the severity of depressive symptoms.
Based on the Mini International Neuropsychiatric Inventory (MINI), a structured interview for DSM-IV disorders, and the HAM-D, 14 percent of the patients had a current major depressive disorder, 5.6 percent had a mild depression, and 19 percent had “clinically relevant depressive symptoms.”
The variables that were related to motor aspects of PD — increased disease duration (based on when the motor symptoms were apparent); more severe motor symptoms; and response to levodopa — were not as strong predictors for the risk for depression as six non-PD specific risk factors, including female gender, history of mood disorders, problems carrying out activities of daily living, and worse cognitive status.
Non-specific risk factors — those things that put anyone at greater risk for depression — had a three times higher impact on the model than PD-specific risk factors. The scientists concluded that clinicians need to “examine a wider scope of factors” to assess depression in the PD patient. Experts say you could make the same case for other neurodegenerative conditions that share a greater likelihood for depression.
The variables in the experimental model accounted for risk for depression in 41 percent of the patients. The neuropathological processes of PD are known to affect areas of the brain involved in mood regulation as well as motor function, thus making any individual with PD at higher risk for developing a mood disorder. These data suggest that the non-PD factors further enhance that vulnerability.
“Depression is a common and complex disorder,” said Laura Marsh, MD, executive director of the Mental Health Care Line at the Michael DeBakey VA Medical Center in Houston and a professor of psychiatry and neurology at Baylor College of Medicine. She is a co-investigator of the study. “Depressive disorders comprise a whole constellation of symptoms. It's not surprising that a brain disease will put people at risk for biochemical changes linked to mood and behavior.”
Dr. Marsh said PD patients who develop depression often say that their mood symptoms arrived before the more obvious motor signs. “Clinicians often confuse depressive disturbances with emotional reactions to the diagnosis of PD and other central nervous system diseases. There is a difference between a grief reaction following a diagnosis and the more persistent and disabling symptoms of depression — changes in sleep and eating, loss of energy, and inability to feel pleasure, problems concentrating, feeling worthless. Depressive disturbances trump coping and, therefore, make coping with the motor symptoms of PD much more difficult. In addition, study after study shows that depression alters quality of life measures as well as motor and cognitive deficits. Overall, patients with untreated or under-treated depressive disturbances do worse.”
When depression is properly identified and treated, she added, “patients feel a lot better, even though they still have PD.” Education helps patients understand what they can expect from treatment of depression, she added, such as having more energy and wanting to resume activities and actually enjoying them, despite whatever limitations PD may impose.
She said that depression is often missed during the initial diagnostic period because clinicians (and patients) are often paying attention to the motor signs, and may be reluctant to ask about changes in mood or behavior, or consider them a reaction to the motor problems. But the high prevalence for depression in PD — some estimate that 35 percent of patients will have symptoms of a mood disorder — means that early diagnosis and treatment are critical. Depression should be addressed and treated, and since depressive illnesses can remit with treatment, symptoms should be tracked over time to determine whether the treatment approach is adequate, she said.
Dr. Marsh said that the clinical message in the model is simple: Ask questions about depression that you would also ask any patient without a neurological disease. In addition to family history of movement disorders, inquire about family history of mood and other psychiatric disorders. See whether they have had any changes in activities that they have previously enjoyed. Ask about any current life events that may have tipped the emotional scales, especially if there are hints of mood problems.
“First, you have to recognize depression in your patients,” she added. “And then you have to treat it.”
“The authors state that many factors lead to depression. But in my view,” said Marshal Folstein, MD, a psychiatrist who co-authored the Mini-Mental State Examination with his wife Susan Folstein, MD, “some cases are more or less genetically and neurologically based.”
“Not every case of Parkinson's disease has the same degree of degeneration in the locus coeruleus, for example,” said Dr. Folstein, professor of psychiatry emeritus at Tufts University and voluntary professor of psychiatry at the University of Miami. “Family history of depression was common but not found in all cases in the PD patients, so in some cases there is more genetic influence than others.”
But, he added, neurologists “should be skilled at identifying depression from all causes in the patients and thoroughly evaluating and treating them with appropriate psychiatric consultation, if needed. The important point is that not all cases are depressed so evaluation is necessary to identify treatable cases. More research is needed to identify the most effective treatment of depression in all neurological disorders.”
Christopher G. Goetz, MD, professor and associate chairman of the department of neurological sciences at Rush University Medical Center in Chicago, said that the depressive symptoms he sees among PD patients are not the same as those observed in a true psychiatric diagnosis, especially early in the disease when the patient has just learned of his or her diagnosis.
But, said Dr. Goetz, “the biochemistry itself likely triggers depressive system, and trying to distinguish these two causes is a constant challenge.
“Working with a psychiatrist who specializes in the behavioral issues of Parkinson's disease is a strong advantage, both for distinguishing these two entities and for designing the best therapeutic approach.
“Reactive depression can often be treated with counseling and education, whereas a biochemical imbalance usually needs to be addressed with medications,” he continued. “We really don't spend enough time talking about depression and monitoring it throughout the course of Parkinson's disease,” said Dr. Goetz. “With a lack of recognition, we do not treat depression enough in our Parkinson's disease practices.”
Mark Gudesblatt, MD, chief of neurology at Brookhaven Hospital and director of the Comprehensive MS Comprehensive Care Center at South Shore Neurologic Associates, agreed. “Most clinicians don't ask about depression because they are looking at tremors and rigidity and walking. They look at the obvious. Neurologists need to be more inclusive and exhaustive in their search for depression. Not getting treatment for depression certainly makes things worse for the patient with a neurodegenerative condition.”