Major Depression Clinical Trial
Official title:
Effects of Mineralocorticoid Receptor Stimulation on Cognitive Bias and Social Cognition in Patients With Major Depression and Healthy Controls: What's the Role of NMDA Receptors?
The steroid hormone cortisol is released in response to stress and acts in the central
nervous system upon glucocorticoid (GR) and mineralocorticoid receptors (MR). GR are widely
distributed across the brain while MR are predominantly expressed in the hippocampus and
prefrontal cortex - two brain areas closely related to memory and executive function.
Stimulation of MR leads to an increase of glutamate that act on glutamatergic NMDA receptors
in the hippocampus and prefrontal cortex. In previous studies, the investigators have shown
that fludrocortisone, a mineralocorticoid receptor (MR) agonist, improves memory and
executive function in depressed patients and healthy controls. However, depressed patients
not only exhibit cognitive deficits in traditional neuropsychological domains such as memory
or executive function. In addition, there are depression-specific alterations such as
cognitive bias and deficits in social cognition, two clinically highly relevant areas.
Therefore, the specific aims of this renewal proposal are two-fold:
- To examine whether beneficial effects of fludrocortisone in depressed patients can be
extended to depression-specific cognitive bias and to social cognition
- To determine whether beneficial effects of fludrocortisone depend on NMDA-receptor
function and whether these beneficial effects can be enhanced by NMDA receptor
stimulation.
The investigators hypothesize that fludrocortisone will improve cognitive bias and social
cognition in depressed patients and that its beneficial effects depend on the NMDA receptor.
Therefore, the investigators further hypothesize that the effects of fludrocortisone can be
enhanced by co-administration of the partial NMDA receptor agonist D-cycloserine.
The study not only advances current knowledge by further examining the mechanism of action by
which MR stimulation exerts beneficial effects on cognition but extends these effects to
depression-specific cognitive bias and alterations in social cognition. Furthermore, a
potential interaction between MR and NMDA receptors is highly clinically relevant given the
promising results with NMDA receptor antagonists in the treatment of major depression.
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