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Fibromyalgia, Depression May Be Part of Same Spectrum

Major depression and fibromyalgia appear to share a common genetic risk factor or factors. One such factor could be dysfunction in the serotonin neurotransmitter system.

The origin of fibromyalgia—a syndrome characterized by widespread pain and generalized tender points—is elusive. Psychologically stressful events do not seem to trigger or reawaken fibromyalgia pain, a recent study of persons impacted by the events of September 11, 2001, suggested (Psychiatric News, January 17, 2003).

In contrast, since patients with fibromyalgia often have a history of major depressive disorder, it's possible that a genetic predisposition toward depression triggers fibromyalgia. Findings pointing to this hypothesis were reported in the July issue of Pain. The study was headed by Karen Raphael, Ph.D., an associate professor of psychiatry at New Jersey Medical School.

Even as early as the 1940s, there were suspicions that fibromyalgia and depression were closely intertwined. Since then, numerous studies have found that fibromyalgia patients are at increased risk for major depression. Some researchers, in fact, are convinced that fibromyalgia is a psychiatric disorder, and some people in the field have suggested that the term "fibromyalgia" be replaced by terms such as "affective spectrum disorder" or "somatoform pain disorder."

So Raphael and her coworkers decided to investigate whether fibromyalgia and major depressive disorder share a common familial predisposition or genetic origin. They decided to limit their study to women, since fibromyalgia is markedly more prevalent in women.

First they called women in the New York-New Jersey metropolitan area to locate subjects who had fibromyalgia, a history of a major depressive disorder, both illnesses, or neither illness. They ended up with 274 individuals, whom they divided into four groups: 68 persons with both fibromyalgia and a history of major depressive disorder; 22 with fibromyalgia but no history of major depressive disorder, 144 without fibromyalgia but with a history of major depressive disorder, and 40 persons with neither fibromyalgia nor major depressive disorder.

The researchers then attempted to contact as many of the first-degree relatives of the subjects in the above four groups as possible. They made contact with 659 in all. They then looked to see how many relatives of subjects in each of the four groups had ever had a major depressive disorder and compared the numbers for the four groups. They found that the rates of major depressive disorder were elevated to a comparable level in relatives of persons in the first three groups compared with the fourth group. In other words, relatives of subjects who had fibromyalgia but no major depression turned out to have the same elevated risk of major depression as did relatives of subjects who had major depression themselves.

This finding, the researchers concluded, implies that "fibromyalgia is a depression spectrum disorder, in which fibromyalgia and major depressive disorder are characterized by shared, familially mediated risk factors.... The pattern of results leads us to reject the hypothesis that the comorbidity of fibromyalgia and major depressive disorder is due to reactive depression, as a function of the stress of living with fibromyalgia."

What are the implications of these results for psychiatrists? "Our findings don't mean that depression is a form of somatization, `masked depression,' or a psychiatric disorder itself," Raphael told Psychiatric News. "This concept is highly stigmatizing to fibromyalgia patients and not at all helpful. Although we write that our results support the view of fibromyalgia as a `depression spectrum disorder,' we shouldn't be misled by that terminology. One could just as easily say that `major depression is a fibromyalgia-spectrum disorder' or, if we could clearly identify the shared pathogenic mechanism, that both major depression and fibromyalgia are perhaps `serotonergic system dysfunction disorders.'"

Rollin Gallagher, M.D., a psychiatrist and pain medicine specialist at the University of Pennsylvania and one of the co-authors of the study, also discussed the implications of the study for psychiatrists in an interview. "It appears that chronic pain of certain types related to bodily injury of some sort or another seems to lead to depression in people who aren't even vulnerable [to depression] based on family or personal history," he said, "whereas fibromyalgia is a different story—a story of people who appear to be vulnerable based on family history to both depression and fibromyalgia. This is not surprising since there is a high rate of comorbidity, but also since fibromyalgia is a central nervous system disorder of modulation of sensation—in other words, there is a change in the perception of pain in people with fibromyalgia so nonpainful stimuli cause pain. That is a central nervous system phenomenon, not a peripheral disease."

In terms of treatment for fibromyalgia, he added, "there is some good news.... Some of the antidepressants that work for depression [such as] serotonin-norepinephrine reuptake inhibitors.. .seem to work for both fibromyalgia and depression. So psychiatrists should feel comfortable in treating fibromyalgia with that kind of medication and also supporting fibromyalgia patients in other ways."

Yet another study to see whether fibromyalgia and major depressive disorder cluster in families has been conducted by Leslie Arnold, M.D., an associate professor of psychiatry at the University of Cincinnati, and colleagues. But instead of using individuals with major depressive disorder as a comparison group, they used rheumatoid arthritis patients. They too found that fibromyalgia and major depressive disorder co-aggregate in families and reported their findings in the March Arthritis and Rheumatism.

"I was very excited to see Karen Raphael's results because they confirm our findings," Arnold told Psychiatric News. "Both studies obtained similar findings using different designs, lending support to the hypothesis that mood disorders and fibromyalgia share common familial determinates.... Future work to understand the shared determinates should command a high priority."

The study by Raphael and her team was financed by the National Institutes of Health.

An abstract of the study, "Familial Aggregation of Depression in Fibromyalgia: A Community-Based Test of Alternate Hypotheses," can be accessed online at <www.sciencedirect.com> by clicking on "Browse A-Z of journals," "P," and Pain.

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