SysMedAlcoholism

Alcohol Addiction: A Systems-Oriented Approach

"It is inherently impossible to explain alcoholism by pursuing only the analytical study of alcohol interactions with the nervous system at ever finer levels of molecular structure and function”

Harold Kalant, 2010, Addiction

Following Aristotle’s idea of “The whole is greater than the sum of its parts“, with our here presented consortium of a systems-oriented approach to alcohol addiction we aim to integrate all systems levels from genes to molecules to neuronal ensembles to large neuronal networks and finally to behavior. Our mission is to better understand the ethiology of alcohol addiction, to define risk factors in young people for alcohol-use disorders later in life, and to provide better treatments to our patients.

According to the WHO, about 2 billion people drink alcohol. Excessive alcohol consumption can result in alcohol addiction, which is one of the most prevalent neuropsychiatric diseases afflicting our society today. Prevention and intervention of alcohol binging in adolescents and treatment of alcoholism are major unmet challenges affecting our health care system and society alike. In this program we intend to define (i) individual neurobehavioral risk profiles in adolescents that are predictive of alcohol use disorders later in life and (ii) identify new pharmacological treatment approaches. To achieve these goals we will apply existing infrastructure, common databanks and multiple omics-derived datasets that have been supported by NGFN and EU programs, and combine them with excellent expertise in biostatistics, mathematical modeling and neuroimaging. Our consortium will thus use information from epigenomics, genomics, transcriptomics, neurodynamics, and neuroimaging to feed mathematical prediction modules provided by two Bernstein Centers for Computational Neurosciences (Berlin and Heidelberg/Mannheim), the results of which will subsequently be functionally validated in independent clinical samples and appropriate animal models. This approach will help to deliver early intervention strategies and identify innovative molecules for relapse prevention that will be tested in experimental human studies. Our interdisciplinary consortium consists of mathematicians, physists, computational neuroscientists, molecular biologists, geneticists, and clinicians. In 3 project modules - central resources, mathematical predictions, and functional validation - 12 subprojects have been implemented in a highly integrative manner. The e:Med program will ultimately help in consolidating excellent addiction research clusters in Germany that can effectively conduct large clinical trials, implement early intervention strategies and impact political and healthcare decision makers.

Achievements:

  • 1. Identification of a further primary molecular target of alcohol: nicotinic acetylcholine receptor (EU Patent Application No 14155868.4)
  • 2. Variant of the µ-opioid receptor (A118G) modulates alcohol reinforcement effects (Bilbao et al., 2015)
  • 3. Identification of a “neuronal ensemble” within the infralimbic cortex encoding for alcohol-craving (Pfarr et al., 2015)
  • 4. New in silico prediction module (embedded into a user-friendly software) allows to predict whole brain neurochemical changes following acute and chronic drug treatment or of any compound of interest (EU Patent Application No 14161717.5)
  • 5. Striking finding: Individual history as romantic events and early drinking onset contributes most to later alcohol binging (Whelan et al., 2014)