An interventional study of Procedural in Schizophrenia and Depression, sponsored by Yale University. Completed at 2 sites in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2015-12-10.
Sponsored by Yale University · Not applicable, Interventional, and Diagnostic
This study aims to develop a method for the assessment of central NMDA receptor functioning in patients with depression and schizophrenia. For this purpose a transitional approach is used based on preclinical studies that show a dose-dependent relationship between the activity of hypothalamic NMDA receptor and plasma AVP response to increasing plasma osmolality. Patients with schizophrenia, depression and healthy controls participated in this study. The Investigators found that in a subgroup of patients with schizophrenia the AVP response was low and that in a subgroup of subjects with depression the AVP response was high compared to healthy controls.
Evidence suggests that altered N-methyl-D-aspartate (NMDA) receptor activity and glutamate signaling may underlie the pathogenesis of both schizophrenia and depression at least in subgroups of patients. In schizophrenia, pharmacologic modeling, postmortem and imaging data suggest reduced NMDA signaling. In contrast, recent clinical trials demonstrating the efficacy of the NMDA antagonist ketamine in severely depressed patients suggest increased NMDA receptor signaling. The Investigators have conducted a proof of concept study to assess whether there is any in vivo evidence for an inverse association in depression and schizophrenia with respect to the NMDA receptor function. For this purpose the investigators used a translational approach, based on findings from animal studies that NMDA receptor is a key mediator of arginine-vasopressin (AVP) release into the bloodstream. Using hypertonic saline to induce AVP release, as done in animal studies, it was found that in a subgroup of depressed patients, NMDA receptor mediated AVP release was significantly increased, whereas in a subgroup of schizophrenia patients, the same response was abnormally low. Previous research has demonstrated that this response is well conserved. These findings are consistent with implicated NMDA receptor related abnormalities in depression and schizophrenia in subgroups of patients, and provide the first in vivo evidence towards this dichotomy.
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Inclusion criteria for healthy controls:
Exclusion criteria for healthy controls:
Inclusion criteria for patients with schizophrenia:
Exclusion criteria for patients with schizophrenia
Inclusion criteria for patients with depression:
Exclusion criteria for patients with depression:
Inclusion criteria for patients from the PRIME Clinic:
Exclusion criteria for patients from the PRIME Clinic:
This group is represented by healthy controls
Other: Procedural
This experimental group is represented by subjects with depression
Other: Procedural
This experimental group is represented by subjects with schizophrenia
Other: Procedural
This experimental group is represented by subjects with prodromal symptoms for schizophrenia
Other: Procedural
All subjects receive intravenous hypertonic saline and serial blood samples are drawn for AVP concentrations
AVP response to plasma osmolality as measured by slopes between the two variables
Time frame: Within 3 months
This study is completed, as verified in Dec 2015. You cannot join it, but the record below documents what was studied.
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Yale University