Depression May Be Harbinger of Parkinson’s

Fran Lowry

May 28, 2015

Depression may be a very early prodromal symptom of Parkinson’s disease, a large Swedish study suggests.

"The link between depression and subsequent Parkinson’s disease appears to be strongest in the few years before the onset of motor symptoms, but depression may exist earlier," senior researcher Peter Nordström, PhD, from the Department of Community Medicine and Rehabilitation, Geriatrics, Umeå University, Sweden, told Medscape Medical News.

"We saw this link between depression and Parkinson’s over a timespan of more than 2 decades, so depression may be a very early symptom of the disease, or a risk factor," Dr. Nordström said.

He and his group also looked at siblings and found no link between a sibling having depression and the other having Parkinson’s disease.

"This finding gives us more evidence that these two diseases are linked. If the diseases were independent of each other but caused by the same genetic or early environmental factors, then we would expect to see the two diseases group together in siblings, but that didn’t happen," he said.

The research, which is based on a large Swedish cohort, was published online May 26 in Neurology.

Dr Peter Nordström

Strong, Supportive Data

"The connection between depression and Parkinson’s disease is well known," commented Samuel Frank, MD, from Boston University Medical Center, Massachusetts, who was asked by Medscape Medical News to comment on the study.

"The authors reference a number of previous articles, so it is not a surprise to me that they are supporting previous research on the link between Parkinson’s and depression. But what is important is that these are really long-term data in a closed population that has been followed very well, so I agree when they say that these are strong, prospective, long-term data to support this known link," Dr Frank said.

Dr Samuel Frank

"In addition, their discovery that there is a higher risk of developing Parkinson’s more proximal to the diagnosis of depression but that the risk continues over decades, is also why the study is so important," he said.

For this analysis, Dr Nordström and his group started with all Swedish citizens age 50 years and older at the end of 2005. They found 140,688 cases of depression diagnosed from 1987 to 2012 and matched them with 421,718 controls who had not been diagnosed with depression.

The total cohort consisted of 562,631 participants (61.6% women), with a median age of 62.9 years at enrollment. The median follow-up time was 6.8 years (range, 0 to 26.0 years).

The researchers also followed a subcohort of 540,811 sibling pairs to investigate a potential familial coaggregation of depression and Parkinson’s disease.

In all, 3260 (0.5%) participants were diagnosed with Parkinson’s disease at a median of 4.5 (range, 0 to 24.9) years after enrollment.

Of these, 1485 (1.1%) had been diagnosed with depression, compared with 1775 (0.4%) of the control participants (P < .001).

Participants with depression also had significantly more diagnoses of diabetes, stroke, traumatic brain injury, and alcohol abuse compared with controls (P < .001 for all) and lower education level compared with controls (P < .001).

The increased risk for Parkinson’s disease among participants with depression weakened over time but remained significant during the entire follow-up period.

The odds ratios decreased from 3.21 (95% confidence interval [CI], 2.50 - 4.11) within 1 year of enrollment to 1.47 (95% CI, 1.08 - 2.00) after 15 to 25 years.

Results were similar for men and women.

People with more serious cases of depression were also more likely to develop Parkinson’s disease. Those who were hospitalized for depression five or more times were 40% more likely to develop Parkinson’s than people who had been hospitalized for depression only one time.

People who had been hospitalized for depression were also 3.5 times more likely to develop Parkinson’s disease than those who had been treated for depression as outpatients.

In the sibling cohort, which consisted of 540,811 sibling pairs, siblings’ depression was not significantly associated with Parkinson’s disease risk in index persons (odds ratio, 1.1; 95% CI, 0.9 - 1.4).

Study Aids in the Understanding of PD

"This study has no direct clinical implication since, although we can show that depression is a risk factor for PD, only a minority of those with depression develop PD," Dr Nordström said.

"This study is more of the kind that helps us understand the nature of PD, and that risk factors are present decades before diagnosis. In a quite recent study, also published in Neurology, we also found that low muscle strength already at 18 years of age is a risk factor for PD 30 years later," he said.

Dr Nordström hypothesized that depression could induce stress and somehow damage the brain and thus start the neurodegenerative process of Parkinson’s.

"Or, depression could be an early prodromal sign of PD. Actually, we have the same situation with Alzheimer’s dementia, which is also a neurodegenerative disorder of unknown cause in most cases. But again, most of those with depression will not develop PD," he said.

People who are diagnosed with depression in adulthood should be monitored for Parkinson’s disease, said Dr Frank.

"The causal link between depression and Parkinson’s disease is still not known," he said.

"Studies like this showing that even long term the risk remains are important and may help us to understand why these 2 diseases are connected, but right now we do not know the reason why. Nor do we know of any steps we can take to ward off the disease. But we can certainly monitor people with depression, particularly adult onset. If someone develops depression in their 50s or 60s, they should definitely be monitored for Parkinson’s disease," Dr Frank said.

The study was supported by the Swedish Research Council. Dr Nordström and Dr Frank have disclosed no relevant financial relationships.

Neurology. Published online May 20, 2015. Abstract

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