Researchers in 'most powerful genetic studies of psychosis to date'

Two genome wide studies involving more than 50,000 participants have identified new genetic risk factors for schizophrenia and bipolar disorder. The research was conducted by over 250 scientists from more than 20 countries – one of the largest collaborative efforts in psychiatry to date.

The results of the Psychiatric Genome-Wide Association Study (GWAS) Consortium were published in two research papers in the October issue of Nature Genetics.  

The schizophrenia study found a total of seven locations on the genome to be implicated in the disease, five of which had not been identified before. The bipolar GWAS study revealed four locations on the genome associated with the disorder, one of which has not been previously identified. Combining the findings from both studies revealed that three gene locations were involved in both disorders, confirming the genetic overlap between schizophrenia and bipolar disorder.

Schizophrenia and bipolar disorder are common and often devastating brain disorders. Some of the most prominent symptoms of schizophrenia are hallucinations and delusions. Bipolar disorder is characterized by severe, episodic mood swings. The conditions are known to be caused by a combination of genetic and environmental risk factors.

Professor David Collier from the Institute of Psychiatry at King’s College London, who was involved in both studies says: ‘Although we have known that psychiatric disorders such as schizophrenia and bipolar disorder have a strong genetic basis, it has proven very difficult to identify the genetic risk factors involved. This is because the causes of these illnesses are highly complex, with many different genes and environmental factors involved. In order to try and solve this puzzle, hundreds of scientists researching schizophrenia have pooled their research results resulting in a major and unprecedented research cooperation, involving tens of thousands of volunteer patients.'

Prof Collier adds: ‘These are the most powerful genetic studies of psychosis to date, and have enabled us to identify a host of new genetic risk factors. These include one gene, a ‘micro RNA’ which may be acting as a master regulator, influencing the biological pathways in the brain, which once perturbed lead to schizophrenia.

‘Our findings are a significant advance in our knowledge of the underlying causes of psychosis - especially in relation to the development and function of the brain. Unravelling the biology of these disorders brings great hope for the development of new therapies – we can attempt to develop therapeutic drugs which target the molecules in the brain involved in the development of psychosis.’

IoP researchers at the MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre who contributed to the bipolar GWAS study included Professor Anne Farmer, Professor Peter McGuffin, Dr Gerome Breen, Amanda Elkin and Richard Williamson and Professor David Collier who also contributed to the schizophrenia GWAS study.

The research was funded by over 40 US National Institutes of Health grants and a similar number of government grants from many countries involved, along with substantial private and foundation support.

Notes to editors:

Sklar, P. at el. ‘Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4’, Nature Genetics (October 2011) doi:10.1038/ng.943
http://www.nature.com/ng/journal/v43/n10/full/ng.943.html

Gejman, P.V. et al. ‘Genome-wide association study identifies five new schizophrenia loci’, Nature Genetics (October 2011) doi:10.1038/ng.940 http://www.nature.com/ng/journal/v43/n10/full/ng.940.html

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Watchdog Halts Action on Researchers

The federal Office for Human Research Protections announced on Wednesday that it would suspend action against the University of Alabama at Birmingham, which it said in March did not adequately inform parents about the risks to their premature infants of enrollment in a large research trial.

In a letter dated Tuesday, the watchdog office still maintained that researchers had not properly informed parents, and that it could still require that the university and 22 other trial sites, which include many of the country’s top research universities, take corrective action. But it also acknowledged that federal guidelines about a researcher’s obligations needed to be clarified and issued. On the office’s Web site, the federal Department of Health and Human Services announced that a public meeting to debate such guidelines was forthcoming.

The timing of the letter coincided with the publication on the Web site of The New England Journal of Medicine of an opinion article by leaders of the National Institutes of Health that took issue with the agency’s initial condemnation of the Surfactant, Positive Pressure, and Oxygenation Randomized Trial, widely known as Support. Both the agency and the N.I.H. are branches of Health and Human Services.

The Journal also published a letter, signed by 46 doctors and scholars, that criticized the office’s initial action as overreaching and having a potentially chilling effect on essential research.

At the center of the uproar, which has engendered commentary from scientists, is whether researchers needed to disclose to parents the risks of a randomized trial of higher and lower oxygen levels administered to premature infants. The levels of oxygen concentration given to the infants were within the range of 85 percent to 95 percent, the standard treatment recommended by the American Academy of Pediatrics. Researchers wanted to pinpoint more precisely the level at which the risks of eye damage or neurological damage, or even death, were abated.

There were risks to the infants at either end of the narrow band. The results, published in The New England Journal of Medicine in 2010, showed that lowering the oxygen levels led to greater mortality rates than expected.

But as the office wrote, “Some physicians, recognizing the particular concerns about risks near the low (85 percent) and high (95 percent) ends of that range, might choose to avoid one or both of those regions.”

Dr. Joel E. Frader, a pediatrician and professor of medical humanities and bioethics at Northwestern, who signed the letter in The Journal, felt that the office initially did overreach, but also that the researchers did not properly inform parents of all risks. Because there was a band of oxygen saturation levels, he said, there was no clear standard of care for these infants, only an “acceptable range.” And parents should have been told that, he said.

“It’s the obligation of investigators to say, ‘Here’s the debate, here’s how we’re trying to answer the question, and that involves the possibility that there is an additional risk with being a research subject,’ ” he said.

He applauded the effort to clarify guidelines for disclosure, even in standard-of-care trials. Researchers should not shy away from fully informing subjects, he said. “There is no empirical evidence that transparency and clarity decreases participation in clinical research,” he said.

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