TCD Researchers Contribute to Important Genetic Findings in Schizophrenia and Bipolar Affective Disorder

Posted on: 31 July 2008

The Psychosis Research Group in Trinity College Dublin, in collaboration with international colleagues, has made a series of important breakthroughs in understanding the genetics of schizophrenia and bipolar affective disorder. These advances in identifying the genes associated with both disorders have long been a research priority to understand disease processes better and potentially offer new avenues for treatment.

The Trinity research group, led by Dr Aiden Corvin, of TCD’s Institute of Molecular Medicine and Department of Psychiatry, is a member of the International Schizophrenia Consortium. The consortium’s findings, the largest and most complete study to date, were published online on 30 July 2008 in the international journal Nature.

Schizophrenia and bipolar affective disorder are common mental disorders, affecting about one person in 100 of the adult Irish population. Their underlying causes are poorly understood. Both disorders, characterised by delusions and hallucinations, are known to involve inherited and environmental risk factors and they may share common risk mechanisms.

In Nature, the International Schizophrenia Consortium reports that people suffering from schizophrenia are far more likely to carry rare chromosomal structural changes of all types, particularly those that have the potential to alter gene function. In addition, the study uncovered two new specific genomic areas that, when altered, significantly increase the risk of developing the disease. 

“This has been an extraordinary, rewarding, and collaborative effort by leading international researchers which heralds real progress in our understanding of these devastating disorders,” stated Dr Aiden Corvin, Senior Lecturer in Psychiatry at Trinity College Dublin. “The next step of the research will be to understand why there is an excess of rare chromosomal structural changes and to identify which genes are most critical in the development of the disorder.”

Formed in 2006, the International Schizophrenia Consortium is led by senior researchers from 11 institutes in Europe and the USA. Major funding bodies include the Wellcome Trust, Science Foundation Ireland and the UK Medical Research Council.  The TCD Psychosis Research group is also involved in two other large collaborative studies. The separate reports, published in the journal Nature Genetics, identify specific risk genes. In bipolar disorder, the identified genes are known to be involved in sodium and calcium channel function at cell membranes, supporting a role for ion channel dysfunction in the pathogenesis of bipolar disorder (Ferreira et al, in press). In schizophrenia, three regions were strongly implicated, most significantly at a gene known to have a role in regulating other genes. Further studies of this gene, in bipolar disorder, suggest that it may be involved in a mechanism common to both disorders (O’Donovan et al, in press).

In addition to following up these findings, the Psychosis Research Group, with colleagues at Virginia Commonwealth University (US) and Queens University Belfast, is now conducting a genome-wide association study of both disorders to better understand the genomics of complex disease, specifically in the Irish population, as part of a larger international research effort, The Wellcome Trust Case Control Consortium. The group, Dr Aiden Corvin, Dr Derek Morris and Dr Gary Donohoe, is part of the Neuropsychiatric Genetics Laboratory in TCD headed by Professor Michael Gill. This work is funded by Science Foundation Ireland, the Health Research Board and the Wellcome Trust (UK).  

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