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Sunday, April 28, 2013

Autism, Schizophrenia and Other Psychiatric Disorders Share Genetic Underpinnings

From the Boston.com Blog "Science in Mind"

By Carolyn Y. Johnson, Globe Staff
February 27, 2013

An international consortium, including researchers from Boston, has for the first time discovered a handful of common genetic underpinnings for five distinct psychiatric illnesses, providing evidence that disorders such as schizophrenia and autism overlap—and may share fundamental biological causes.

The study is one step in an ambitious effort that could ultimately redraw or blur the boundary lines between psychiatric illnesses, based on a precise understanding of the underlying biology.

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Read HealthDay.com's Report on This HERE.

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Over the past five years, many teams have focused on analyzing genetic variants—spots in the genome that commonly differ among people—to pinpoint the risk factors for particular disorders. In the new work, published Wednesday in The Lancet, researchers examined genetic data from people with autism, depression, schizophrenia, bipolar disorder, and attention deficit-hyperactivity disorder, and found clues that genes involved in signaling within the brain may go awry in a broad set of psychiatric illnesses.

“This is the first time we’ve seen specific genetic variants that seem to confer risk across traditional boundaries, to a broad range of child- and adult-onset disorders,” said Dr. Jordan Smoller, a professor of psychiatry at Mass. General Hospital and Harvard Medical School, and a leader of the study.

“Each one of them, by themselves, still accounts for a small amount of the risk. The fascinating thing is there might be such variants that cross our clinically-distinct syndromes.”

Smoller and colleagues analyzed genetic data from more than 33,000 people with the five disorders and compared them with nearly 28,000 people without mental illness. They found four spots in the genome that were more common among those with psychiatric disease, two of which occurred in genes involved in communication between brain cells.

They also found that genetic risk factors for bipolar disorder and schizophrenia had the most overlap. Interestingly, autism, a disorder that emerges in childhood, overlapped with both disorders, which typically emerge in adulthood.

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See More on the NBC News "Vitals" Blog HERE.

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Those are tantalizing clues for scientists, who now have a range of starting points for teasing out more about the shared biological basis of these psychiatric diseases—a way to pry open the black box of illnesses that are poorly understood.

What the new study cannot do is provide a way of predicting mental illness with a gene test; all of the genetic variants are very weak risk factors.

Dr. Daniel Weinberger, director of the Lieber Institute for Brain Development, a nonprofit research institution based in Maryland, compared deciphering the genetics of psychiatry to trying to divine what causes something with a diverse array of causes, such as car accidents.

“What you would discover, across a diverse population of car accidents, is a factor common to most of them, which may in any individual case not explain much risk,” Weinberger said. “What you end up with is a driver’s license.”

But he added that such an approach is helping to elucidate mechanisms and the biology behind disorders.

“They are the first objective clues as to what mental illnesses are at a basic biological level,” Weinberger said.

Dr. Judith Rapoport, chief of the child psychiatry branch at the National Institute of Mental Health, the agency that funded the research, said the work resonated with her own.

Rapoport studies a rare form of schizophrenia that occurs in childhood. She has looked at “copy-number variations,” in which DNA segments are repeated an unusual number of times in samples taken from patients.

Strikingly, in her samples, she has seen copy-number variations associated with intellectual disability, schizophrenia, autism, and epilepsy.

“There’s a sense in psychiatry there may be some very common genetic variants that, let’s say hypothetically, very early on affect very early brain development. Then, maybe environment, or interactions with other genes” causes a particular illness to develop, Rapoport said.

She said the new study also may help explain why a person with one psychiatric disease is often at risk of developing other problems.

The next step will be to investigate further the gene variants flagged by the study, to see whether scientists can understand what role they might play—and whether they might reveal new targets for treatments. The researchers also hope to include more disorders in their sample to see whether other shared risk factors emerge.

About Science in Mind

Science in Mind chronicles the discoveries, ideas, inventions, and people that make Boston a scientific hub. Like scientists, we're driven by curiosity. Carolyn Y. Johnson joined the Health team as a science writer in 2008. She also has covered telecommunications and tech culture for the Business section. Johnson was a physics and English major at Amherst College, and earned her master’s degree in science writing from MIT. Contact her at cjohnson@globe.com or follow her on Twitter @carolynyjohnson.

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