One in fifty Irish adults lives with a major psychotic disorder. These are challenging and enigmatic brain conditions as they affect how a person perceives reality and interprets the world around them. The two commonest conditions, schizophrenia and bipolar disorder, typically emerge in early adulthood and can have a long-term course characterized by episodic, or continuous illness, with significant functional impairment. Psychotic disorders are poorly understood, but are heritable and this was the starting point for our work. Since 1996 with the help of more than 3,000 Irish participants we have made significant progress in understanding the molecular/genetic basis of these conditions with the aim of developing better diagnostics and treatment.
Psychosis Research Group
Funded by Wellcome, Science Foundation Ireland (SFI), the Health Research Board (HRB) and the National Institute of Health, US (NIH) we have assembled an experienced multi-disciplinary research team of clinicians, geneticists, biostatisticians, psychologists and biologists dedicated to identifying and understanding how psychosis develops at a molecular and biological level. The group, led by Professor Aiden Corvin, is based at the Department of Psychiatry and Trinity Translational Medicine Institute (TTMI) at the St James’s Hospital campus in Dublin. We collaborate widely through our prominent role in the international Psychiatric Genomics Consortium and on individual projects with NUI Galway, Virginia Commonwealth University (US), Oxford University (UK), Cold Spring Harbor Laboratory (US) and the Broad Institute of MIT/Harvard (US).
Over the last two decades we have contributed to significant advances in the field. We have identified that it is likely that hundreds of small genetic effects contribute to genetic risk of these disorder in most of the people affected. This risk is shared between schizophrenia and bipolar disorder, suggesting that shared molecular mechanisms are involved. Prof Corvin recently co-headed an international effort demonstrating that there is in fact substantial genetic overlap across many psychiatric conditions (e.g. schizophrenia, bipolar disorder, depression, ADHD), a genetic risk that is not shared with neurological conditions. We have found evidence implicating more than one hundred genes in schizophrenia susceptibility and shown that these genes cluster in pathways involved in how neuronal cells communicate and interact to bring about learning within the brain. We have also shown that for a small number of people, rare genetic mutations have a much larger impact on their risk of developing illness and these may represent key ‘hub’ genes within the molecular pathways involved.
Our gene discovery work currently has two main areas of focus. First, in large-scale genome sequencing to look in much greater depth at genes to investigate how they disrupt normal genomic function. Second, as a lead site with the Psychiatric Genomics Consortium (PGC), to examine genome sequences from families who are densely affected with mental illness to find out if particular key genes are important in translating shared genetic risk into the development of illness. Our work in understanding the biology and other aspects of psychosis are described in the Cognitive Neuroscience, Functional Genetics and Bioinformatics sections of our website.