Genes' link to disease examined

Arthur Smith sat back in a chair in the office of psychiatrist Hany Elia at Serenity Behavioral Health Systems and reflected on his family's history of schizophrenia.

His dad had told him his uncle "was like that," said Mr. Smith, 59. "It must have been passed down. Right, Dr. Elia?"

"It can run in the family," Dr. Elia said.

Exactly how Mr. Smith's genes might have led to his illness is something Dr. Elia is now helping to figure out. Mr. Smith will be among 10,000 schizophrenia patients nationwide whose genome will be compared to 10,000 healthy subjects in an effort to further narrow down how the disease develops on the genetic level.

"It certainly is one of the largest coordinated collections designed to become a resource for the field," said Carlos N. Pato, a co-principal investigator for the five-year study, and head of the Department of Psychiatry and Behavioral Sciences at the University of Southern California, where the study is based.

Medical College of Georgia is one of eight sites around the country that will help to enroll patients, in conjunction with some of the state's community mental health centers, including Serenity, said Peter F. Buckley, the chairman of the Department of Psychiatry and Health Behavior at MCG and principal investigator for the Augusta arm of the study.

"We're the leading enrolling site across the country," he said. "That's because of the support from the public mental health system. And the institutions, each of them, have really gotten behind us."

As of last week, 104 patients and health controls had been enrolled, and eventually MCG will contribute 1,000, said Edna Stirewalt, the clinical research manager for the Department of Psychiatry and Health Behavior.

The work builds on a study of 3,400 schizophrenics and a similar number of control subjects that found three deletions in the genome led to developing the illness, Dr. Pato said. More important, published in the same volume of the journal Nature , was a parallel study out of Iceland that pinpointed the exact same deletions, he said.

"So this is a critical scientific breakthrough in the sense that not only were we able to clearly identify them but almost simultaneously, in a different population, these were replicated," Dr. Pato said. "And that is something that, in terms of these very complex types of inherited disorders, with not a single gene that is causing them, one looks for."

Surveying an even larger sample then is critical, he said.

"We really need very large samples and we need to see that the signals we're seeing are actually found across the board," Dr. Pato said. "What these studies did is I think they lead us to be extremely optimistic about how we're going to be able to move forward."

Genetic material from patients such as Mr. Smith, along with relevant clinical information, will form the basis of a large repository that will lend itself to other scientific collaborations and follow-up studies down the road, Dr. Pato said.

That will not only allow researchers to see how the genetic changes happen over time but also how they are affected by treatment, and hopefully lead to better care and potentially even prevention, Dr. Pato said.

"Can we divert the development of illness if we learn more about those things that happen in concert that lead to the unfortunate appearance of illness in an individual?" he asked.

That is the hope of Dr. Elia at Serenity, who noted that those who are treated earlier tend to do better long-term.

"If we can identify the patients that are prone to schizophrenia, then we can look at certain stressors that can bring on the condition, and then how we can avoid it," he said.

In a previous MCG study, determining whether patients carried a genetic variation allowed researchers to predict whether the patient would gain weight from a certain drug, Dr. Buckley said. Being able to tailor treatments based on a patient's genetic makeup would be ideal, he said.

"Today, if you go to see a psychiatrist, you may have the best psychiatrist at Serenity or at MCG, but it's still a trial and error basis" in deciding which drugs to try first," Dr. Buckley said. "So being able to predict for the level of the individual person is really where our field wants to go. Because if we could personalize treatment, we would make a real leap forward."

It is that kind of impact, maybe years down the road, that Mr. Smith is hoping to have by offering up his blood and his time to the study.

"It can help my family and a lot of other people, too, by me volunteering like that," he said. "I think it is a good idea."

Reach Tom Corwin at (706) 823-3213 or tom.corwin@augustachronicle.com.