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Health Sentinel: New methods offer hope for early diagnosis of mental illnesses

Monday, November 26, 2012 - 12:01 am

A few days before Thanksgiving, I was discussing with a friend his family's holiday plans.

Children and grandchildren were coming for dinner, everyone except one adult son. Despite multiple invitations and offers for a ride to the family gathering, everyone knew he would decline. This son has a serious mental illness and avoids such get-togethers, preferring to stay in his apartment alone.

Getting an accurate diagnosis for a mental illness is a challenge. No X-ray or blood test can confirm it.

Schizophrenia, which affects about one in every 100 U.S. adults, is one of the most challenging mental illnesses to diagnose and treat. I've heard many accounts from families with a loved one who has seen multiple psychiatrists and been prescribed numerous medications in a trial-and-error treatment plan before finally getting symptoms stabilized. Those symptoms can include delusions, hallucinations, paranoia, withdrawal, social isolation and depression, to name the more common ones.

But improved diagnostic methods are in the works, with identifying key biomarkers at the forefront of research. This month in the journal Biological Psychiatry, researchers at Kings College, Aberdeen, Scotland, published findings from their studies using simple, inexpensive eye tests to diagnose schizophrenia with accuracy between 89 percent and 98 percent. Dr. Philip Benson, lead author of the study, points out other diagnostic methods have at best a 60 percent to 70 percent accuracy rate.

The eye tests track how people follow a slowly moving object with their eyes, how they scan a picture and how they stare at a fixed object. In each test, people with diagnosed schizophrenia had abnormal movement patterns of their eyes compared to their healthy same-age peers.

“These results stayed stable even after taking into account sex, use of medication and whether or not the participant was a smoker,” the journal article states.

Holding further promise is that the same eye tests are being used in clinical trials for differentiating between major mental illnesses, such as bi-polar and schizophrenia, and the Scottish researchers are finding eye movement abnormalities specifically vary with different mental illnesses.

Psychiatrist Dr. Alexander B. Niculescu III is director of Indiana University School of Medicine's Laboratory of Neurophenomics which, along with collaborative work of other U.S. neuroscience labs, has identified the group of genes most predictive of schizophrenia.

Once specific genes were identified, Niculescu's research team looked at where they were located, how they were combined and for presence of mutations. Tissue samples were obtained from individuals with and without schizophrenia to compare gene expression data. In the past, scientists focused more on individual mutations rather than looking at the bigger picture of the genetic linkage factor.

Their findings were published in May in the journal Molecular Psychiatry. These genes, which include a long list spread across the human genome map, “have most to do with how the brain is built and organized and how neurons connect to each other,” Niculescu says. “Based on these genes, we put together a genetic risk score. We can identify subjects at high risk or lower risk for schizophrenia,” with accuracy in about two-thirds of cases.

For families with a history of schizophrenia, these tests will help predict whether individual members are at risk for developing the illness.

“Potentially, these tests could be given at birth, but that doesn't mean if the person has a higher score they will develop schizophrenia,” Niculescu points out. “They need to be watched more closely, and early intervention may prevent full-blown disease. For most people, it is useful to know about higher risk.

“Genetic risk doesn't mean you will for sure develop the disease,” he says. “It is not a life sentence, but in the case of complex disorder, having some of the mutations in the higher genetic risk means you can be aware and intervene earlier.”

In tandem, the tests looking at gene linkage, gene expression and mutations and the predictive eye tests are a win-win for individuals with undiagnosed or misdiagnosed mental illnesses and for people who are symptom free but who have a family history of mental illness.

As data unfolds to improve the ability of doctors to differentiate illnesses and treat earlier, the hit-and-miss pharmacological treatment approach may be replaced with a more personalized medicine approach.

“There is a lot of symptom overlap between many disorders,” says Dr. Gladys Beale, a psychiatrist with Parkview Behavioral Health. “Also, the specific clinical symptoms manifested can differ between individuals. Some disorders like schizophrenia have a long period (called a prodromal) where signs of dysfunction are marginal. It is only after a major psychotic break that retrospectively the prodrome is identified.

“The eye test, if very specific for a disorder, would be valuable,” Beale says. “A biomarker is more concrete so that the diagnosis is readily more likely to be accepted by the patient. Eye tests would be invaluable if they could identify schizophrenia before the first psychotic break. Since the neurodegenerative process is quite severe at the time of presentation, earlier detection could be preventative.”

Niculescu concurs, though he says in his evaluation of the data outlined by Benson and his colleagues, the 98 percent predictability rate is “inflated.” Still, the eye tests hold great promise for changing the trajectory of early diagnosis of schizophrenia and other mental illnesses.

“It should be studied in children and adolescents who are quite at high risk and in people with relatives with schizophrenia,” Niculescu says, to determine, “how well does it catch symptoms early on before the disorder develops?”

With the potential of major reductions in funding for medical research due to federal budget cuts, I am encouraged that researchers such as Niculescu and IU's Laboratory of Neurophenomics and the Scottish scientists are taking a collaborative approach rather than operating in solo efforts.

“We're actually looking at combining some of the eye tests at our clinic and how they correlate with the genetic findings,” Niculescu says.

When I read headlines of people with undiagnosed mental illness going on shooting sprees in a theater or hearing less dramatic but still heart-wrenching stories of families torn apart by serious mental illness, such as my friend's, these collaborative research projects are a win-win for all of us.

This column is the personal opinion of the writer and does not necessarily reflect the views or opinion of The News-Sentinel.