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Systems Biology of Alcohol Addiction: Modeling and validating disease state networks in human and animal brains for understanding pathophysiolgy, predicting outcomes and improving therapy

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Brain networks could hold key to treating addiction

Achieving a better understanding of the brain mechanisms involved in addiction could help researchers identify vulnerability to alcoholism early, and lead to more personalised and effective treatments.

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Alcohol addiction represents a significant burden in many parts of the world, but nowhere more so than in Europe. The EU currently has the highest consumption of pure alcohol per person of any region across the globe – 11 litres per year – and it is estimated that nearly 20 million Europeans suffer from some form of alcohol use disorder. While progress has been made in understanding the psychological and neurobiological processes that underlie addictive disorders, translating this scientific knowledge into clinical treatment has not always been straightforward. To address this, the EU-funded SyBil-AA project integrated fragmented research efforts on alcoholism across Europe, and combined this with cutting-edge mathematical modelling.

New approaches to addiction

Crucially, the SyBil-AA project sought to bridge the gap between scientific knowledge and the treatment of alcoholism. “We wanted to look at all brain regions simultaneously and logically, to see if we could uncover some potential new targets for treatment, or find new configurations of complex neural networks,” explains project coordinator Wolfgang Sommer, Head of the Research Group at the Central Institute of Mental Health in Mannheim, Germany. Sommer’s view is that all neurological interactions should be analysed together, and that the societal and behavioural implications of addiction must also be taken into account. Such an approach could lead to a better understanding of the different trajectories people take into alcohol addiction, enabling practitioners to define more targeted treatments. To achieve this, models of the ‘relapse-prone’ state of the brain were built. This helped researchers to get a more detailed picture of the neural characteristics that make people with alcohol use disorders relapse when they attempt to quit. The models enabled researchers to test new, non-invasive therapies for alcoholism, as well as new pharmacological candidate compounds.

Understanding alcohol disorder

“We managed to obtain results in a relatively short period of time,” says Sommer. “We found particular regions of the brain that looked promising for further research, while others offered no response. This will help researchers in the future to focus on the more promising parts of the brain.” For example, the project team identified parts of the brain that continue to deteriorate when patients stop consuming alcohol. This suggests that the brain needs longer to recover after addiction and could have important implications for treatment. The project also identified certain brain alterations that could point to novel alcoholism treatments, as well as biomarkers that could be used to test for clinical efficacy. Although officially completed in December 2019, SyBil-AA will continue to have a positive impact on the way addiction research is carried out. A total of 18 pre- and post-doctoral researchers – 13 of them female – worked on the project and are now pursuing promising academic careers. “Although the project is finished, analysing all the data we mined together will continue for a few years,” adds Sommer. “Many of the collaborations we made have become very deep.”

Keywords

SyBil-AA, alcohol, addiction, brain, neural, alcoholism, neurological, pharmacological

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