A Multimodal Neuroimaging Study of Brain Activation Patterns Under Ketamine
Status:
Completed
Trial end date:
2018-12-01
Target enrollment:
Participant gender:
Summary
The aim of the project is to establish a multimodal imaging approach for the investigation of
the neural mechanisms underlying neuroreceptor regulation, glutamatergic metabolism and brain
function that are of particular relevance for major depressive disorder (MDD) and that can be
translated into clinical applications.
There is growing evidence for imbalance with regard to glutamatergic neurotransmission in
stress-related affective disorders. Further support for the hypothesis that dysfunctional
glutamatergic signaling underlies major depressive disorder, and indeed that its reversal
constitutes a potential efficacious mechanism of action, is provided by the evidence that
pharmacological compounds active at the N-methyl-D-aspartate (NMDA) ionotropic glutamate
receptor such as ketamine exert rapid antidepressant effects. As a tool compound ketamine
enables the safe investigation of the brain region-specific effects of NMDA receptor
antagonism in terms of glutamatergic neurotransmission, brain function and the association of
these neural changes with emotional state, thereby allowing for increased understanding of
the therapeutic mechanism of action.
The possibility to simultaneously study brain perfusion (arterial spin labeling), functional
brain activity (fMRI) and connectivity (resting state fMRI), neurometabolism (proton magnetic
resonance spectroscopy) and metabotropic glutamate receptor densities (positron emission
tomography) will unravel their functional interplay in the mechanisms underlying the
regulation of mood and cognition. Combining those imaging modalities with treatment
interventions in healthy subjects and depressed patients, this project aims at providing
insight into the neuropharmacological effects of ketamine and its antidepressant properties.