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Understanding the biological basis of bipolar disorder

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 are using state-of-the-art DNA sequencing, genomics and neuroimaging technologies to understand the biological basis of bipolar disorder risk, and response to pharmaceutical treatments. This will help to determine whether future risk can be predicted in young people who are at increased genetic risk of bipolar disorder.

Finding genes which contribute to bipolar disorder
Using large scale “next-generation” sequencing, our team is finding that rare DNA variants which affect the function of brain-expressed genes relates to earlier symptom onset. Our studies indicate that genes expressed in the synapse, the molecular communication system between neurons, carry more rare DNA variants than expected, thereby increasing risk of disease. The teams’ contribution to international genomics consortia are further elucidating the genetic architecture of bipolar disorder, identifying several new risk genes, and providing additional support for genes previously identified.

Predicting treatment response Lithium is the most commonly prescribed mood-stabilising drug used for the treatment for bipolar. However, the drug works effectively in only 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.

Early identification of those at future risk of bipolar disorder
As part of a multi-site collaboration with four universities in the United States, NeuRA is involved in a unique longitudinal study of young kids and siblings of patients with bipolar, who are at high risk of developing bipolar themselves in the future. The team follow these participants over time to identify predictors which may give an early indication as to which “high risk” individuals will ultimately develop bipolar. Identification of accurate predictors would open up the opportunity for early intervention, to slow or even prevent illness in individuals identified as “high risk”.