TP5 - SysMedSUDs

Examining the excitatory/inhibitory neurotransmitter balance in SUD patients by MR spectroscopy

Substance use disorders are the third most frequent group of psychiatric diagnoses in Germany. Taking nicotine dependence into account, they are even the most common group of psychiatric diagnoses. The same diagnostic criteria are used for different substance dependences. At the same time, the mechanisms of how substances affect the brain can be very different.
Studies suggest an imbalance between neurotransmitters in the brain (the activating glutamate (Glu) and the inhibiting gamma-Aminobutyric acid (GABA)) as an important mechanism in the development of substance use disorders. However, there is no direct verification of this dysregulation yet. For this reason, we want to use magnetic resonance spectroscopy (MRS) to measure the concentration of the neurotransmitters Glu and GABA in two brain regions that are relevant in the development of substance use disorders. We want to do this in patients with different substance dependencies (opiates, cannabis and nicotine) and in healthy control participants. In addition, we want to measure the resting state activity of the brain with functional magnetic resonance imaging (fMRI) in order to analyse its properties and possible associations to the local neurotransmitter concentration. Furthermore, we want to collect bio matters (blood and feces) from the study participants in order to examine genetic factors, epigenetic variations and other biological factors (inflammatory parameters, gut bacteria). Additionally, we want to measure the performance of the cognitive functions that humans use to control their behavior (the so called “executive functions”) in order to make comparisons between the different substance use disorders and to be able to detect associations between these functions and the neurobiological parameters.
The goal of our study is to increase the understanding of the neurobiological mechanisms that are specific for different substance use disorders and on those they have in common. This may ultimately contribute to the diagnosis and treatment of substance use disorders.
Our central hypothesis is that there is an association between executive functioning and the balance between the neurotransmitters Glu and GABA in the brain. In addition, we want to investigate the following hypotheses:

• The neurotransmitter balance differs between the different substance use disorders.
• There is correlation between the neurotransmitter balance and executive functioning test performance.
• The neurotransmitter balance effects are specific for the different substance use disorders.

Keywords: Substance use disorders, opiate dependency, cannabis dependency, nicotine dependency, fMRT, excitatory/inhibitory balance, glutamate, GABA, Resting-State, Insula, mPFC, executive functions