TCD Researchers Identify Genes that may Play a Key Role in the Development of Schizophrenia and Bipolar Disorder

Posted on: 23 March 2010

Trinity College Dublin researchers have identified genes that may be susceptible to the development of schizophrenia and bipolar disease in a study recently published in the journal Molecular Psychiatry.

The genes identified are those belonging to the Cell Adhesion Molecule (CAM) pathway. A pathway is a group of genes which are involved in key biological processes. In the case of the Cell Adhesion Molecule (CAM) pathway, it is involved in neuronal cell adhesion, helping brain cells to connect, which is critical for synapse formation and in normal cell signalling.

Schizophrenia and bipolar disorder, which together affect about one in fifty Irish adults, present with perceptual disturbances, mood symptoms and changes in cognition and behaviour. Treatments are available, but the response is variable and the underlying biology remains elusive. Identifying the molecular basis of these disorders as a means of advancing diagnostics and developing new treatments is a key goal in mental health research.

The study, led by TCD  researchers compared hundreds of thousands of genetic markers between cases and controls in a sample of almost 15,000 individuals.

The authors applied a novel method of molecular pathway analysis developed by the TCD Psychosis Research Group. The approach involved examining 212 different pathways, comprising groups of genes which are involved in key biological processes,  to see whether they carried genetic variants that increased risk of developing a psychotic disorder. This identified the Cell Adhesion Molecule (CAM) pathway as being significantly associated with risk of developing either schizophrenia or bipolar disorder. The CAM genes identified are known to be involved in neuronal cell adhesion, helping brain cells to connect. At an individual gene level, the effect on risk was small and not applicable as a diagnostic test, but the work opens important new avenues for researchers. The TCD researchers are now intensively focussing on how this normal process is being disrupted and whether this effect can be reversed.

Commenting on the significance of the findings, Dr Aiden Corvin, Science Foundation Ireland Principal Investigator and Head of the Psychosis Research Group at Trinity College Dublin said: “This is a really intriguing finding, which suggests that regulation of brain wiring is playing a significant role in schizophrenia and bipolar disorder. What is surprising is that some of the genes contributing to this effect have previously been implicated in disorders of language and autism, suggesting that this regulatory process is critical to the development of many different neurodevelopmental disorders which until now we have considered separately.”

The study involved substantial cooperation from researchers across Europe and the US, in particular from the International Schizophrenia Consortium, Genetic Association Information Network and Wellcome Trust Case Control Consortium.

The research was funded by Science Foundation Ireland and the Health Research Board.

Notes to Editor:

The Trinity College Dublin Psychosis Research Group (Principal Investigators, Dr Derek Morris, Dr Gary Donohoe and Dr Aiden Corvin) is part of the Neuropsychiatric Genetics Research Group (NRG), headed by Professor Michael Gill (https://www.tcd.ie/medicine/psychiatry/research/neuropsychiatric-genetics/) at the university. Work at the NGRL in schizophrenia, bipolar disorder, autism and attention deficit hyperactivity disorder (ADHD)  funded by Science Foundation Ireland, the Health Research Board, the Wellcome Trust, Autism Speaks, and others is focusing on identifying and characterizing the biological processes that contribute to psychiatric diseases.