Research led by the Institute of Psychiatry (IoP) at King’s College London has identified genetic variants linked to signaling pathways in the brain likely to be involved in causing bipolar disorder.

Dr. Gerome Breen, senior author of the study published in Biological Psychiatry and Senior Lecturer at the IoP at King’s, says: ‘Our study provides some of the first evidence to show the biochemical and developmental processes involved in causing risk for developing this life-long and costly illness. We have highlighted potential new avenues for new drug treatments and intervention.’

Certain disorders, like Huntington's disease, are caused by the mutation of a single gene. However, the biology and genetics of bipolar disorder are much more complex and the exact causes of bipolar disorder, which affects approximately 1 in 100 people in the UK, are not well understood.

Researchers combined the results of three genome-wide association studies (GWAS), which examined the genetic variation throughout the genome of thousands of patients with bipolar disorder and healthy controls from the UK, Germany and the USA, and a study of gene expression patterns in post-mortem brain tissue from people who had been diagnosed with bipolar disorder. The findings were also combined with information from protein databases (Human Protein Reference Database) to identify networks of genes and proteins in the brain that are key in the development of bipolar disorder.

The findings revealed genes involved in several neural signaling pathways, including the Notch pathway, important in neurogenesis, and the Wnt signaling pathway which helps ensure genes are switched on. Together, the pathways are key processes in neurotransmission and brain development and the findings indicate they are also likely to be involved in causing bipolar disorder.

“None of our research approaches provides us with sufficient information, by itself, to understand the neurobiology of psychiatric disorders. This innovative paper wrestles with this challenge in a creative way that helps us to move forward in thinking about the neurobiology of bipolar disorder,” commented Dr. John Krystal, Editor of Biological Psychiatry.

This research was supported by the European Community Health Seventh Framework Programme. The authors received funding from the National Institute for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, Kings College London, the Medical Research Council, the Wellcome Trust, National Alliance for Research on Schizophrenia and Depression, and Biotechnology and Biological Sciences Research Council.

Full paper

Pedroso, I. et al. “Common Genetic Variants and Gene-Expression Changes Associated with Bipolar Disorder Are Over-Represented in Brain Signaling Pathway Genes” Biological Psychiatry, Volume 72, Issue 4 (August 15, 2012) http://dx.doi.org/10.1016/j.biopsych.2011.12.031