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Shared Genes May Link ADHD, Autism and Depression
Date:2/28/2013

By Steven Reinberg
HealthDay Reporter

WEDNESDAY, Feb. 27 (HealthDay News) -- Autism, attention-deficit/hyperactivity disorder (ADHD), major depression, bipolar disorder and schizophrenia may all share common genetic risk factors, a new study says.

In this largest study of its kind, researchers spotted gene variations governing brain function that may raise the risk for these often devastating mental woes. In the future, these gene variants might become key targets for prevention or treatment, the scientists said.

"This study, for the first time, shows that there are specific genetic variants that influence a range of childhood and adult-onset psychiatric disorders that we think of as clinically different," said lead researcher Dr. Jordan Smoller, a professor of psychiatry at Harvard Medical School in Boston.

"We also found that there was significant overlap in the genetic components of several disorders, especially schizophrenia with bipolar disorder and depression, and to a lesser extent autism with schizophrenia and bipolar disorder," he said.

The researchers don't yet understand exactly how these variants are involved in the disorders, he noted. "This is the first clue that specific genes and pathways may cause a broader susceptibility to a number of disorders. Now the important work will be to figure out how this actually happens," said Smoller, who is also associate vice chair of the department of psychiatry at Massachusetts General Hospital.

Dr. Alessandro Serretti, from the Psychiatry Institute at the University of Bologna in Italy, wrote an accompanying journal editorial on the study. He believes that "we are now able to understand what are the pathways to [these] psychiatric disorders."

There are potential clinical applications, both in the classification of disorders, predicting who's most at risk, and perhaps new and better drug therapies, Serretti said. However, there's no immediate clinical application for these findings, he added.

The report was published Feb. 28 in the online edition of The Lancet.

To look for common genetic markers, called nucleotide polymorphisms, that might be risk factors for the five disorders, the Psychiatric Genomics Consortium scanned the genes of more than 33,000 people suffering from these disorders and nearly 28,000 people without such issues. This is the largest study of the genetics of psychiatric illness yet conducted, the researchers said.

Smoller's group found four gene areas that all overlapped with the five disorders, two of which regulate calcium balance in the brain.

These overlapping gene variants appear to increase the risk for bipolar disorder, major depressive disorder and schizophrenia in adults, the researchers said.

Further analysis found that genes governing calcium channel activity in the brain might also be important in the development of all five disorders, autism and ADHD included.

Smoller noted these genetic risk factors may only account for a very small part of the risk driving these disorders, and just how big a share they account for isn't yet known.

So, looking for these genes in an individual now would not be considered a diagnostic tool. "They are not enough to predict any individual's risk. And you might carry all of these variants and never develop a psychiatric disorder," Smoller said.

However, the new findings add to the understanding of these conditions and may help in developing new treatments, he explained.

"It could also change the way we define and diagnose these disorders, based on the biological causes," Smoller said. "Some of the disorders we think of as clinically distinct actually have more of a relationship than we might have thought."

Two experts not connected to the study agreed.

"This is the first genome-wide evidence showing that neuropsychiatric diseases share genetic risk factors," said Eva Redei, professor of psychiatry at the Feinberg School of Medicine at Northwestern University in Chicago.

She noted that all five of the conditions tackled in the study can share certain clinical features and symptoms, including variation in mood, mental impairments, and even psychosis.

"Therefore, the question is whether the identified shared genetic risk factors are related to the diseases or to the shared clinical symptoms," Redei said. "Shared genetic contribution can identify some key regulators in the brain, and can also help to find new drug targets," she said.

Simon Rego, director of psychology training at Montefiore Medical Center at the Albert Einstein College of Medicine in New York City, agreed that the findings are "an important next step" in understanding mental illness.

As more gene studies are conducted and analyzed, scientists will "be in a better place to identify shared cause of psychiatric disorders at a molecular level," he said. "Ultimately, [this could] generate new models for drug interventions and possibly even prevention."

More information

For more information on mental disorders, visit the U.S. National Institute of Mental Health.

SOURCES: Jordan Smoller, M.D., professor of psychiatry, Harvard Medical School, associate vice chair, department of psychiatry, Massachusetts General Hospital, Boston; Simon Rego, Psy.D., director, psychology training, Montefiore Medical Center/Albert Einstein College of Medicine, New York City; Alessandro Serretti, M.D., Ph.D., Psychiatry Institute, University of Bologna, Italy; Eva Redei, Ph.D., David Lawrence Stein Professor of Psychiatry, Feinberg School of Medicine Northwestern University, Chicago; Feb. 28, 2013, The Lancet, online


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