We Know We’re Sick Even If Medical Tests Don’t

What you say when a doctor asks how you feel is as good—or perhaps even better—than any test to predict long-term illness or death.

“A couple of years ago there was a boom of work in psychology and medicine about what we call patient-reported outcomes, the idea that what patients actually feel like and say they feel like seems to be more prognostic of morbidity and mortality than all the cholesterol ratings and blood tests we get from doctors’ offices,” says Christopher Fagundes, assistant professor of psychology at Rice University.

“That was an odd finding,” he says. “You would think that objective markers like blood pressure would be more accurate. The way people generally report how they feel is more often linked to a future disease or mortality than what the doctor accesses.

“As psychologists, we think, ‘They’re sensing something. There’s something going on here.’ That’s what took us to this paper.”

Feelings and fate

For the study in the journal Psychoneuroendocrinology, researchers set out to find evidence that would connect the dots between feelings and fate.


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They found it in existing data that established solid links between self-rated health and rising levels of herpesvirus activity, an important marker of poor cellular immunity that promotes high levels of inflammation.

Fagundes has a long-standing collaboration with a team at the University of Texas Medical Branch at Galveston and was able to take advantage of a dataset it gathered a decade ago for the Texas City Health and Stress Study.

That study assessed the relationship between stress and health in the community that hosts petrochemical industries at the mouth of the Houston Ship Channel.

The survey gathered residents’ self-assessments (through a 36-item questionnaire) and blood samples for nearly 1,500 individuals. Those samples were analyzed for levels of active herpesviruses and biomarkers for inflammation.

“Doctors have ignored them for years, saying, ‘It’s in your head.’ Well, it’s in your head, but there’s a reason.”

“We found that self-rated health was associated with reactivation of herpesviruses,” says postdoctoral researcher Kyle Murdock. “We’re not talking about the sexually transmitted disease, but viruses that are associated with things like cold sores that are ubiquitous among adults.”

“Herpesvirus activity is a very good functional marker of cellular immunity, because almost everybody has been exposed to one type of the virus or another,” Fagundes says.

“It doesn’t mean you’re sick; it’s probably been dormant in your cells for most of your life. But because it reactivates at a cellular level and prompts the immune system to fight it, it becomes a great marker of how the system is working.

“You can imagine that when the immune system’s fighting something, you get more inflammation throughout the body, and inflammation contributes to disease. That’s it in a nutshell,” he says.

Not just ‘in your head’

Previous studies have demonstrated the link between herpesvirus activation and inflammation. While patients may not be aware of active herpesviruses or inflammation, the researchers suspected a mechanism stronger than mere instinct was responsible for their expressions of discomfort.

“We found that poor self-rated health was associated with more reactivation of these latent herpesviruses, which was associated with higher inflammation, and we know those two things are associated with morbidity and mortality, as well as some cancers, type 2 diabetes, and cardiovascular disease,” Murdock says.

After eliminating data for 251 individuals who showed no sign of herpesvirus, the team wound up with a snapshot that clearly showed those who reported feeling in good health had low virus and inflammation levels, while those who said they felt poorly were high on the virus and inflammation scales.

Primary care physicians are highly unlikely to check for herpesvirus activity or inflammation, Fagundes says. “It’s too hard an assay to do clinically and takes too much time.”

“They look at things like white blood cell counts in cancer patients but would never do a herpesvirus latency test, and tests for inflammation would be rare. These are good markers for long-term health, but not for things that are going to impact you tomorrow.”

Scientists haven’t yet identified the channel that gives people a sense of impending illness. One theory is that fatigue is a marker.

“I’ve heard many primary care physicians say they’ve never seen anyone with a disease that wasn’t associated with fatigue,” Fagundes says. Another possibility is a sense of imbalance in the gut microbiome, another avenue of future study.

But doctors should still pay close attention to what patients report. “When a patient says, ‘I don’t feel like my health is very good right now,’ it’s a meaningful thing with a biological basis, even if they don’t show symptoms.”

“When I go to patient-advocate conferences, people say they’re grateful we’re finding biological mechanisms because they feel like doctors have ignored them for years, saying, ‘It’s in your head.’ Well, it’s in your head, but there’s a reason.”

Other researchers from Rice and from the University of Texas Medical Branch at Galveston, and Microgen Laboratories in La Marque, Texas are coauthors of the study.

The National Cancer Institute and the National Heart, Lung and Blood Institute supported the work.

Source: Rice University

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