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Medically unexplained illnesses provide a unique forum to examine mind-body factors and how culture and gender can influence symptoms, psychologists and others say.

In her book "Medically Unexplained Illness: Gender and Biopsychosocial Implications," behavioral neuroscientist Susan K. Johnson, PhD, of the University of North Carolina at Charlotte, summarizes multidisciplinary research on a range of conditions that have received media attention in the past few decades, including chronic fatigue syndrome (CFS), fibromyalgia and irritable bowel syndrome. Rife with debilitating symptoms, without known organic causes, and correlated with states such as anxiety and depression, they challenge researchers to consider complex causes as a likely possibility, says Johnson.

These conditions share a range of commonalities: They tend to first appear in women in their early 30s, and to remain as they age, though symptoms may become less intense over time. They are highly disabling, yet lack hard-core biological markers such as tumors, viruses or slipped disks. They have many common symptoms, including fatigue, insomnia, trouble concentrating, headaches and diffuse pain. "Some researchers think they are all one syndrome, showing up in the systems that people have most trouble with," says Johnson. For example, someone with a history of intestinal problems might develop irritable bowel syndrome, while a person with a pain history might develop fibromyalgia.

In addition, Johnson says, people who have these conditions often aren't receptive to psychological explanations. "There is a lot of pressure to find a medical explanation and treatment. Yet I've been in this field for 20 years and it doesn't seem like we've gotten very far in discovering causes," she says.

One promising theory is the multifactorial "central sensitivity hypothesis," which posits that as a result of early trauma such as childhood abuse, childhood illness or a childhood accident, some people are highly sensitive to sensory stimuli and have a low tolerance for pain. In turn, "that sets up a dysregulation of your stress system, so you feel symptoms more intensely," Johnson says.

That theory was underscored by research unveiled at the American College of Rheumatology's annual meeting in November by medical researcher Richard Harris, PhD, of the University of Michigan, who presented imaging studies showing that people with fibromyalgia have a down-regulation in opioid receptor activity that may exaggerate their sensitivity to pain.

Other researchers are seeking strictly biological explanations for some of these debilitating disorders. Among them is DePaul University psychologist Leonard Jason, PhD, who discovered during 10 years of epidemiological research that chronic fatigue syndrome was more likely to afflict low-income minorities than it was the wealthy whites who spawned the syndrome's nickname, "the yuppie flu." In research reported in the Archives of Internal Medicine in 1999, he also found it was twice as common as previously thought.

Since then, he and others have been developing a case definition of the illness, which Jason believes is biologically based. The researchers will be working in the next few years to support the definition by analyzing large samples of people with CFS symptoms. In an article in press in Fatigue: Biomedicine, Health & Behavior, for instance, Jason and colleagues compare three case definitions of CFS in more than 500 people with the condition.

Such a definition should make it easier for researchers to accurately distinguish between CFS and another disorder it's often conflated with, major depressive disorder, Jason says. "If you ask the right questions, you can get a high degree of differentiation between these groups," he says.

That said, there continues to be plenty of disagreement about the disorder, with physicians' groups, researchers and patient advocates promoting different names, diagnostic criteria, etiologies and treatments.

Meanwhile, University of Manchester psychologist Richard Brown, PhD, ClinPsyD, has been conducting studies showing that all physical illnesses seen as emotionally based — what were called "somatoform" disorders in earlier versions of the DSM — aren't necessarily so. Early theories held that these symptoms were the result of unexpressed bereavement or trauma, while more recent hypotheses suggest that people with these conditions have heightened anxiety that makes them feel normal bodily sensations more intensely.

"While those things are perfectly possible in many cases," says Brown, "my take is that it can also be a basic perceptual problem — that the brain can make a mistake about what is going on in the body." A common example is someone who feels her cell phone vibrating in her pocket when it is not. Brown is using a similar paradigm to conduct a series of studies asking people to gauge whether they feel a faint vibration or not. So far, he's finding that, on average, people tend to experience false vibrations about 20 percent of the time, and that those who experience more false vibrations tend to report more physical symptoms in everyday life.

The findings suggest "you don't necessarily have to be emotionally unwell to have a symptom," he says.

In the end, it doesn't really matter whether your symptoms are "all in your head" or "all in your body" — the fact is they're all ultimately expressions of the integration of information by your brain, no matter what their cause, adds psychiatric researcher Michael Sharpe, MD, of the University of Oxford.

In fact, there's a joke he likes to share with his medical students. "There's one organ I can remove that I promise will abolish all of your symptoms," he says.

Tori DeAngelis is a writer in Syracuse, N.Y.