New genetic variants linked to bipolar disorder

Scientists have gained new understanding of the origin of bipolar disorder by identifying genetic variants linked to signalling pathways in the brain likely to be involved in causing the neurological disease. Researchers from the Institute of Psychiatry at King’s College London combined the results of three genome-wide association studies which examined the genetic variation in the genomes of thousands of patients with bipolar disorder (BD) and healthy controls from the UK, USA and Germany. This was pooled with gene expression patterns in post-mortem brain tissue from people diagnosed with BD and information from protein databases.

“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,” said Dr Gerome Breen, senior author and Senior Lecturer at King’s. “We have highlighted potential new avenues for new drug treatments and interventions.”

Their aim was to identify networks of genes and proteins in the brain that are linked to the development of BD. The findings uncovered genes involved in several neural signalling pathways including the Notch pathways – important in neurogenesis – and the Wnt signalling pathway which ensures genes are switched on.

These pathways are key processes in neurotransmission and brain development, and the findings – published in Biological Psychiatry – indicate that they are also likely to be involved in causing BD.

The study provides evidence of associations of networks involving several interlinked signalling pathways, and has identified genes as promising candidate to generate animal models and pharmacological treatments.

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