Regulation of Arginine-vasopressin (AVP)

Not Applicable

Completed

• Conditions: Schizophrenia; Depression
• Interventions: Other: Procedural

• Registration Number: NCT02626832
• Lead Sponsor: Yale University

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2010-02
• Primary Completion: 2013-11
• Study Completion: 2014-12
• Study First Submitted: 2015-11-04
• Status Verified: 2015-12
• Study First Submitted QC: 2015-12-08
• Last Update Submitted: 2015-12-08
• Study First Posted: 2015-12-10
• Last Update Posted: 2015-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy Control	Procedural	This group is represented by healthy controls
Schizophrenia	Procedural	This experimental group is represented by subjects with schizophrenia
Depression	Procedural	This experimental group is represented by subjects with depression
Prodromal subjects	Procedural	This experimental group is represented by subjects with prodromal symptoms for schizophrenia

Primary Outcome Measures

Name	Time	Method
AVP response to plasma osmolality as measured by slopes between the two variables	Within 3 months

Trial Locations

Locations (2)

The John Pierce Laboratory; 🇺🇸 New Haven, Connecticut, United States

VA Connecticut Healthcare System; 🇺🇸 West Haven, Connecticut, United States