Relatives of Patients With PD at Higher Risk for Depression, Anxiety

December 7, 2007 — New research has found that first-degree relatives of patients with Parkinson's disease (PD) have approximately a 50% increased risk of developing depression or anxiety, suggesting that these psychiatric conditions may share a genetic link to Parkinson's, a neurologic disorder.
Another explanation for this increased risk is that first-degree relatives share something other than genes with their brother or sister with PD — perhaps an environmental exposure, according to Walter A. Rocca, MD, MPH, from the Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic in Rochester, Minnesota, and principal investigator for the study, which appears in the December issue of the Archives of General Psychiatry.
The study, part of the Mayo Clinic Family Study of Parkinson's Disease, included 1000 first-degree relatives of 162 patients with PD and 850 first-degree relatives of 147 age- and sex-matched controls. The presence of dementia, any other neurologic disease, or any psychiatric disorder was not an exclusion criterion for controls. The study excluded relatives younger than 40 years because parkinsonism is so rare in this age group. The patients and controls were from Olmsted County in Minnesota.
Relatives Observed From Birth
All of the relatives were followed up from birth to onset of psychiatric disorders, death, telephone interview for the study, or last medical record information. For relatives who were deceased or incapacitated, the researchers contacted the most knowledgeable person in the family. Documentation of psychiatric disorders was obtained through telephone interviews that involved a structured questionnaire for depressive disorders; an open-ended question about other psychiatric disorders, including anxiety disorders; and administration of the Geriatric Depression Scale. The relatives were also studied through review of medical records.
The relatives, interviewers, and clinicians were kept uninformed of the relationship of the relatives to patients with PD or controls.
Relatives at Increased Risk
The study showed that compared with relatives of controls, relatives of patients with PD had an increased risk for depressive disorder (hazard ratio [HR], 1.45), anxiety disorder (HR, 1.55), somatoform disorders (HR, 3.93), and adjustment disorders (HR, 2.16). The somatoform and adjustment disorders had limited statistical power.
The researchers conducted an analysis excluding the 72 relatives who developed parkinsonism. "By doing that, you make sure that the people who have depression and anxiety are not the same that were already at risk of Parkinson disease," Dr. Rocca told Medscape Neurology and Neurosurgery. "We tried to address that overlap concern." In that analysis, the risk for depression and anxiety remained approximately the same.
In the study, relatives of patients with earlier age at onset of PD (≤ 66 years) had a particularly increased risk for depressive disorders. Researchers found an increasing risk for depressive disorders in relatives with decreasing age at onset of PD, but the trend for anxiety disorders in relatives was less pronounced.
Increased Risk "Sizable but Not Huge"
The 50% increased risk for some psychiatric conditions among relatives of patients with PD should not be a major concern, said Dr. Rocca, noting that this disease is still relatively rare. He pointed out that the cumulative risk for depression at approximately age 80 years is roughly 25% among relatives of someone with PD vs 20% among relatives of someone who does not have this disorder. The difference in cumulative risk for anxiety is 10% vs 7%. "So the jump is sizable but is not huge," said Dr. Rocca.
At first glance, it looks like the results of this and other research suggest that certain families have the same gene variants that predispose them to develop PD and other neurologic and psychiatric conditions, but the issue is likely more complex than that. "You have to remember that the brother and sister were also eating the same food, drinking the same water, living in the same neighborhood and had the same socioeconomic level, so there may be other factors involved," said Dr. Rocca. "It's too simplistic to say it's just the genes."
Neurologic and Psychiatric Conditions as a Continuum
In the past, researchers had shown that close relatives of people with PD are at increased risk of developing that disease and conditions such as essential tremor and dementia. They also knew that some people are depressed or anxious before developing PD or become depressed after being diagnosed with PD. They had also observed that neurologic and psychiatric disorders sometimes appear on a continuum.
"Some patients were anxious when they were young, then a little bit depressed when they were an adult, then they become parkinsonian, then they become demented," said Dr. Rocca. "When all these come in the same person, then you start wondering, what about brothers and sisters?"
This new study goes a long way toward answering that question. "It's kind of good news and bad news; the good news is that the effect is not gigantic; the bad news is that some families seem to have a package deal of things going on that may manifest in different ways," said Dr. Rocca.
The research was supported by grants from the National Institutes of Health. Dr. Rocca is employed at Mayo Clinic. Coauthor Dr. Maraganore has disclosed a US provisional patent application for a method of treating neurodegenerative disease, which has been licensed to Alnylam Pharmaceutical Inc, a provisional application for PD-related compositions and methods, which is owned by Perlegen Sciences Inc, and a provisional patent application for predicting PD, which is owned by the Mayo Foundation for Medical Education. Dr. Maraganore has also consulted for Merck and Pfizer, for which he received no compensation.
Arch Gen Psychiatry. 2007;64:1385-1392.