NeuRA Magazine #21

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 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.

See what’s going on at NeuRA

FEEL THE BUZZ IN THE AIR? US TOO.

Cortical activity during balance tasks in ageing and clinical groups using functional near-infrared spectroscopy

Prof Stephen Lord, Dr Jasmine Menant Walking is not automatic and requires attention and brain processing to maintain balance and prevent falling over. Brain structure and function deteriorate with ageing and neurodegenerative disorders, in turn impacting both cognitive and motor functions.   This series of studies will investigate: How do age and/or disease- associated declines in cognitive functions affect balance control? How is this further impacted by psychological, physiological and medical factors (eg. fear, pain, medications)? How does the brain control these balance tasks?     Approach The experiments involve experimental paradigms that challenge cognitive functions of interest (eg.visuo-spatial working memory, inhibitory function). I use functional near-infrared spectroscopy to study activation in superficial cortical regions of interest (eg. prefrontal cortex, supplementary motor area…). The studies involve young and older people as well as clinical groups (eg.Parkinson’s disease).   Studies Cortical activity during stepping and gait adaptability tasks Effects of age, posture and task condition on cortical activity during reaction time tasks Influence of balance challenge and concern about falling on brain activity during walking Influence of lower limb pain/discomfort on brain activity during stepping   This research will greatly improve our understanding of the interactions between brain capacity, functions and balance control across ageing and diseases, psychological, physiological and medical factors, allows to identify targets for rehabilitation. It will also help identifying whether exercise-based interventions improve neural efficiency for enhanced balance control.
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