Biological mechanisms for common psychiatric disorders

27 January 2015

Research from the Psychiatric Genomics Consortium, which includes researchers from CTGlab, has found that common psychiatric disorders such as schizophrenia, bipolar disorder and major depression share genetic risk factors related to immune function and DNA regulation.

Thousands of genetic differences across the human genome act together to increase the risk for psychiatric conditions such as schizophrenia. However, until now, it has not been clear how these genetic changes affect different biological processes that then go on to alter brain function.

The research was led by Dr. Gerome Breen, MRC Centre for Social Genetic and Developmental Psychiatry at King’s, and Professor Peter Holmans, MRC Centre for Neuropsychiatric Genetics & Genomics, University of Cardiff, together with their colleagues including Professor Danielle Posthuma. They analyzed genetic data from over 60,000 participants, including individuals with schizophrenia, bipolar disorder, major depression, autism spectrum disorders and attention deficit hyperactivity disorder, as well as healthy individuals. Their aim was to identify the biological and biochemical pathways involved in causing risk for these disorders.

Dr. Breen said: ‘When we grouped the genetic data together, we found that genes relating to histone methylation – molecular changes that alter DNA expression – and immune function are risk factors associated with the development of these disorders. Biological pathways are important as they are much broader drug targets than single genes or proteins.’

Colm O`Dushlaine (formerly Stanley Centre, Broad Institute and joint first author) continues: ‘The histone pathways we found have previously been studied in cancer and the immune pathway in infectious disease. We now have evidence of their involvement in the etiology of complex psychiatric phenotypes, a critical step towards understanding how best to develop novel therapeutic approaches.’

Professor Danielle Posthuma (VU/VUmc) commented: ‘The successful identification of these novel pathways for multiple psychiatric disorders underscores the importance of pathway and network analysis in psychiatry.’

These are exciting findings in the study of psychiatric disease as they represent a first step in identifying shared biological mechanisms that act across disorders. This will help in developing treatments that target these mechanisms, and are thus effective for a range of psychiatric illness, irrespective of exact diagnosis.’

‘It is only thanks to the huge sample sizes that we are finally able to make sense of underlying pathways for psychiatric disorders’ adds Professor Danielle Posthuma.

The study is the result of many years of work by hundreds of investigators worldwide in the Psychiatric Genomics Consortium (PGC,, an international, multi-institutional collaboration founded in 2007 to conduct broad-scale analyses of genetic data for psychiatric disease. The PGC is currently genotyping new samples to further study these and additional psychiatric diseases, including anorexia and PTSD.

Core funding for the Psychiatric Genomics Consortium comes from the U.S. National Institute of Mental Health (NIMH), along with numerous grants from governmental and charitable organizations, as well as philanthropic donations.

The study was published online January 19th in Nature Neuroscience.
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