March 20, 2007

Researchers Identify Risk Gene for Schizophrenia and Immune System (PAR1)

A team of schizophrenia scientists in New York State has scanned the entire human genome for evidence of genes that play a role in schizophrenia and has discovered an strongly associated spot near two genes that regulate the immune system.

Psychiatric researchers at The Zucker Hillside Hospital campus of The Feinstein Institute for Medical Research have uncovered evidence of a new gene that appears to increase the risk of developing schizophrenia. The Newsday newspaper talked to leaders in the research field:

"It's interesting work," said Dr. Robert Yolken, a professor of pediatrics and director of the Stanley Neurovirology Laboratory at Johns Hopkins University School of Medicine. "It fits with the prediction that Dr. Fuller Torrey [a schizophrenia researcher] and I made that genes discovered in schizophrenia will be associated with an immune response.

"It would make sense that some of the genes are determinants of the response to infection."

Working in conjunction with researchers at the Harvard Medical School Partners Center for Genetics and Genomics in Boston, MA, the Zucker Hillside team utilized a cutting-edge technology called whole genome association (WGA) to search the entire human genome in 178 patients with schizophrenia and 144 healthy individuals. WGA technology was used to examine over 500,000 genetic markers in each individual, the largest number of such markers examined to date, and the first published study to utilize WGA technology in a psychiatric illness. Previous studies have been much more limited in scope, often incorporating less than 10 markers.

Of the 500,000 genetic markers, the researchers found that the most significant link with schizophrenia came from a marker located in a chromosomal region called the pseudoautosomal region 1 (PAR1), which is on both the X and Y chromosomes. The marker was located adjacent to two genes, CSF2RA and IL3RA, which previously were thought to play a role in inflammation and autoimmune disorders. Those two genes produce receptors for two cytokines, GM-CSF and interleukin-3. Cytokines are involved in the body's response to infection, and may play a role in the brain's response to injury.

By then examining the DNA sequence of those genes in a separate group of patients with schizophrenia and healthy individuals, the research team working in conjunction with PGx Health in New Haven, CT -- observed multiple gene abnormalities in patients with schizophrenia that were not found, or were found much less commonly, in healthy individuals.

"WGA technology allowed us to shine a light across virtually the entire genome, rather than looking at just one gene at a time," said Todd Lencz, PhD, the first author of the study, and an investigator at Zucker Hillside and The Feinstein Institute. "Using WGA, we found genes that had not been previously considered in studies of schizophrenia." Dr. Lencz added that "the critical next step is confirming these results in independent datasets."

Anil Malhotra, MD, also of Zucker Hillside and The Feinstein, and senior investigator of the study, noted: "If these results are confirmed, they could open up new avenues for research in schizophrenia and severe mental illness. A role for cytokines could help explain why prenatal exposure to viruses is a risk factor for schizophrenia, thus providing a bridge between genetic risk and environmental exposures."

In a related announcement, Clinical Data Inc., a biotechnology firm reports the company's genetic research with the aforementioned medical academics could eventually lead to a test to determine a patient's risk of developing schizophrenia.

The company reports its study showed a novel link between a cytokine receptor gene region and schizophrenia. The division contributed to the research the results from a study of its test to predict patient responses to schizophrenia drug Clozapine.

PGxHealth has applied for patents on the study results and may try to use the findings to develop diagnostic tests for schizophrenia, officials said.

The study results are scheduled to be published online in Molecular Psychiatry .

The study was funded by a private donation from the Donald and Barbara Zucker Foundation, an award from the KeySpan Energy, and grants from the National Institute of Mental Health; NARSAD, the Mental Health Research Association (formerly known as National Alliance for Research on Schizophrenia and Depression); and the Stanley Medical Research Institute.

(Thanks Tim for pointing us to this release)


I can say as a mother of a dear child at the age of thirteen was diagnosed as having Schizophrenia you do have to look deeper than that!! Oddly he had what appeared to be Acanthosis Nigricans on the back of his neck a year or several months before psychosis began. Well it turns out my son is not diabetic typically seen with AN and ended up having Confluent and Reticulated Papillomatosis this is a very rare skin condition and mostly happens in people of color my son is white. This stuff has basically taken over his whole upper part of his body finally after seeing several specialist with no clue of what he had, we took him to USF and the doctor came in with a diagnosis, well our son and us will be attending a meeting with twenty doctors, and in my eyes I hope this will be helpful to other parents that are faced with the unknown. I think my son has an autoimmune problem that is attacking his brain, we have seen three different times what antibiotics can do for him mentally and thinking this could be a part of PANDAS we are just not sure and after two years we are still fitting the piece to the puzzle.

Thank you for posting this!!

Very concerned mother!

Posted by: tina at March 21, 2007 08:26 PM

Post a comment

Please enter this code to enable your comment -
Remember Me?
(you may use HTML tags for style)
* indicates required