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Chronic Disease

New UNC Research Shines Light on Schizophrenia

A decade’s worth of research is yielding information about genetic changes that lead to the development of schizophrenia.

By Stephanie Soucheray

Sandy Lovett, 47, is getting her medicine switched this month.

Lovett has schizophrenia, and her symptoms aren’t being fully controlled by her current cocktail of mood stabilizers and atypical antipsychotics.

“I’m still getting some auditory hallucinations,” she said.

When she was 19, Lovett was diagnosed with schizophrenia. Suicidal, she spent six months in a mental hospital, where she said she was overmedicated.

For the next 20 years, Lovett, with the support of her mother, battled not only her mental illness but also drug addiction.

Now data from a decade-long study on the DNA of people with schizophrenia has shown 22 genetic differences between study subjects with the disease and controls. Thirteen of these genetic differences were previously unknown to researchers.

In the multi-stage genome-wide association study, titled “Genome-wide association analysis identifies 13 new risk loci for schizophrenia” and published in the latest edition of Nature Genetics, researchers used the DNA from 21,000 people with schizophrenia and thousands of healthy controls to identify genetic variances.

“These are really 22 clues about what causes schizophrenia,” said Patrick Sullivan, the director of the psychiatric genomics department at UNC. “This is the biggest study of its kind.”

Sullivan has led the research on this project for the last decade. “We’re making progress and are getting able to explain why some people have schizophrenia and other’s don’t,” he said.

About 1 percent of the population has schizophrenia, the symptoms of which include paranoia, auditory and visual hallucinations, delusions and disorganized thinking. Its sufferers describe the disease as a “break” from reality.

Like Lovette, most people with schizophrenia begin to battle the disease in their early 20s, and many are hospitalized throughout their lives. Schizophrenia is treated with typical and atypical antipsychotics. There is no known cure.

“There’s no poster child for schizophrenia,” said Sullivan. “As a consequence, this field and this disease don’t get the attention they deserve.”

Sullivan said people with schizophrenia have a shorter lifespan than the average (usually by 10 to 15 years) because of higher rates of comorbidities such as obesity, substance abuse and suicide. And she said the disease can cost upwards of $1.4 million to treat over a patient’s lifetime.

Sullivan said that when he began collecting DNA samples 10 years ago, he added “a couple of zeroes” to increase his study sample size. Every genome was measured in more than a million different places, and the 22 areas of difference offer some novel understandings of the disease.

He said that the role of calcium, the essential mineral needed for nerve functions in the brain, is one of the areas that show a difference between schizophrenics and controls.

“We have the idea from this study that calcium signaling is important in schizophrenia,” said Sullivan. The paper describes differences between schizophrenics and health controls in the calcium pathway, which includes the genes CACNA1C and CACNB2.

The paper estimates that there are more than 8,000 SNPs (single nucleotide polymorphisms, or DNA sequence variations) that could contribute to a risk for developing schizophrenia in one-third of the patient population.

For years, researchers have been debating whether schizophrenia was caused by a few rare, but strong, genetic mutations or by several hundred smaller mutations that combine to form the disease state. Sullivan said his study points to the later hypothesis, and is a step toward fully understanding schizophrenia.

“Once we fully understand the disease, we have an agenda for moving forward,” he said.

Staying sober, and employed, is hard for Sandy Lovett. But one place that helps is Threshold, a clubhouse in Durham where adults with severe mental illnesses can learn skills, manage club functions and continue their educations. Lovett comes to Threshold a few days a week, one of the 55 adults who gather each day at the clubhouse in East Durham.

Susie Deter is Threshold’s executive director. She said that there are only six or seven such clubhouses (where employees and members decide rules, agendas and perform tasks) in North Carolina. Ten years ago, there were 11 or 12.

Deter said the clubhouse model, even with a shoestring budget and a complicated alphabet-soup system for reimbursements, is one of the only successful models for people with schizophrenia.

“We have the best rehospitalization rate,” said Deter. “Ninety-two to 93 percent of our members stay out, because we offer the whole package of support.”

Meanwhile, researchers continue to look for ways to make places like Threshold a thing of the past.

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