Bipolar disorder is a severe and debilitating psychiatric condition, for which the specific causes remain largely obscure. The disorder is ranked in the top 20 most disabling disorders, and leads to severe social impacts, increased suicide risk, and poor general medical health for the approximately 250,000 Australians affected. In Australia alone, the financial costs to government and societal sectors exceed $3.3 billion per annum.
Dr Jan Fullerton and her team at NeuRA are conducting a number of studies to understand the biological basis of bipolar, to identify genetic signatures which may predict response or non-response to pharmaceutical treatments, and to determine whether future risk of bipolar can be predicted in young people who are at increased genetic risk.
Finding genes which contribute to bipolar disorder
Using large scale “next-generation” DNA sequencing, Jan’ team is identifying and characterising rare DNA variants in the genomes of people with bipolar. The objective is to find that genes expressed in the synapse, the molecular communication system between neurons, which are enriched for damaging rare DNA variants in people with this condition. Together with collaborators at the Garvan Institute, the team is relating rare DNA variants to functional changes in the way genes are expressed using RNA-sequencing. Working with international collaborators, the team are also conducting studies to identify genes carrying common DNA variants which increase an individuals’ risk of bipolar. These studies are elucidating the genetic architecture of bipolar, and have identified several new risk genes, as well as providing additional support to the involvement of genes previously identified.
Predicting treatment response
Lithium is the most commonly prescribed mood stabilising drug used for the treatment for bipolar. However, the drug only works effectively in about a third of patients, and we currently cannot predict which patients are likely to respond. As part of the International Consortium on Lithium Genetics, we are actively pursuing the identification of genetic signatures which will facilitate targeted pharmaceutical therapies, enabling faster and improved medication response.
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