Imaging synaptic plasticity in therapeutic sleep deprivation for major depression

Patients with major depression benefit from therapeutic sleep deprivation. The causality of this clinically effective therapeutic measure is unknown; there is particularly only rare information about the underlying molecular mechanisms. We hypothesize that prolonged wakefulness is associated with an increase in synaptic strength, and that the synaptic dysregulation is affecting long term potentiation in patients with major depression. The aim of the project is to examine the synaptic basis of the antidepressant effect of therapeutic sleep deprivation by Positron Emission Tomography (PET) imaging of the synaptic vesicle protein 2A (SV2A) as a measure of synaptic density in patients and healthy subjects as well as animal models of depression. Since both anesthesia and sleep are subject to compromise biologically valid outcomes when studying the synaptic basis of therapeutic sleep deprivation, a fully quantitative PET imaging method for awake animals will be developed.
We are convinced that synaptic density determined with PET has the power to become an indicator for the success of therapeutic sleep deprivation and thus providing means for future stratifications of different therapies in major depression. Identifying and understanding the mechanisms that mediate the effects of sleep restriction is necessary to develop effective interventions. This project will test a model that can be used to improve schedule design.

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