Glutamate Activity in Depression (GLADE)

NCT06482606 | Not Yet Recruiting

• 1 other identifier: R91876/RE001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

A brain chemical (neurotransmitter) called glutamate is thought to play an important role in the causation and treatment of depression. It is possible to measure glutamate in the brain in people, using safe magnetic resonance imaging but results of studies of glutamate levels in people with depression and those at risk of depression have been inconclusive. We have devised a method whereby viewing a flashing light for a few minutes provides a measure of stimulated glutamate release. We believe that this kind of functional measure is more relevant physiologically because studies in animals show that glutamate release evoked by sensory stimulation represents release of glutamate as a neurotransmitter rather than glutamate in intermediate metabolism. Therefore, the use of functional magnetic resonance spectroscopy (fMRS) may provide a more useful measure of neural glutamate activity in people with depression and those at risk of depression. The aim of this study is to look at the effect of a flashing light on glutamate release in people who have recovered from depression and compare it to people who have not experienced depression. We hope from this to discover whether changes in glutamate activity might be a risk factor for the development of depression. This could be helpful both for diagnostic purposes and for the development of medications that can relieve depression by modifying glutamate release.

Conditions

Depression

Keywords

Depression; Recovered depression; Remitted depression; Glutamate; fMRS; Magnetic resonance spectroscopy; Flickering checkerboard; Visual cortex; Resting state; fMRI

Outcome Measures

Primary Outcomes (1)

• Brain Glutamate Dynamic Change in the Visual Cortex

  From the functional magnetic resonance spectroscopy (fMRS), calculating the glutamate concentration change in response to flickering checkerboard stimulation (by the concentration difference between rest and the stimulation block). This dynamic glutamate change will be compared between individuals recovered from depression and healthy control group.

  Acute (0-60 minutes)

Secondary Outcomes (5)

• Brain Glutamate Baseline Change in the Visual Cortex

  Acute (0-60 minutes)

• Excitatory-Inhibitory Ratio Change in the Visual Cortex

  Acute (0-60 minutes)

• Brain Resting State Connectivity

  Acute (0-60 minutes)

• Exploratory Analysis of Other Metabolite Concentrations at Baseline or Changes After Stimulation In the Visual Cortex

  Acute (0-60 minutes)

• Exploratory Investigation of the Influence of Age, Gender, and PHQ-9 Depression Scores on Metabolite Concentration Change In the Visual Cortex

  Acute (0-60 minutes)

Study Arms (2)

Participants with recovered depression

ACTIVE COMPARATOR

Participants with recovered depression will be experiencing flickering checkerboard stimulus.

Other: Flickering Checkerboard Stimulation

Healthy control participants

PLACEBO COMPARATOR

Healthy control participants will be experiencing flickering checkerboard stimulus.

Other: Flickering Checkerboard Stimulation

Interventions

Flickering Checkerboard Stimulation OTHER

This visual stimulation is a succession of alternating black and white squares on a small monitor in the scanner, the black and white checkerboard creates the effect of flickering lights.

Healthy control participants; Participants with recovered depression

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For recovered depression:
• Participant is willing and able to give informed consent for participation in the research;
• Male or female, age 18-70;
• Have at least two previous episodes of depression, and have been recovered from the most recent episode of depression for 3 months;
• Free of antidepressant medication for at least 3 months;
• Current PHQ-9 score \< 10 (the cut off for DSM major depression)
• For healthy control group:
• Participant is willing and able to give informed consent for participation in the research;
• Male or female, age 18-70

You may not qualify if:

• For recovered depression:
• Any current significant DSM-5 psychiatric disorder;
• Any previous episode of a severe mental illness, other than Depressive Disorder, for example current mood or anxiety disorder, post-traumatic stress disorder, obsessive compulsive disorder. Comorbid Anxiety disorders will be allowed;
• Any significant current medical condition likely to interfere with conduct of the study or analysis of data in the opinion of the clinical investigator;
• Ongoing psychopharmacological treatment for depression, including hypnotics;
• High consumption of illicit substances and also legal substances (like alcohol, caffeine, nicotine) to an extent that would make complying with study protocol challenging;
• Past history of dependence to illicit substances, and any consumption of illicit substances in the three months prior to the study;
• Current or past sufferer of epilepsy or photosensitive migraines;
• Currently pregnant or breast feeding;
• Any contra-indications to MRI scanning
• For healthy control group:
• History of, or current significant psychiatric disorder, for example current mood or anxiety disorder, post-traumatic stress disorder, obsessive compulsive disorder;
• History of, or current neurological disorder (e.g. epilepsy);
• History of, or current, severe migraines;
• History of, or current general medical conditions that in the opinion of the Investigator may interfere with the safety of the participant or the scientific integrity of the study;

Sponsors & Collaborators

• University of Oxford: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

University of Oxford

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

Related Publications (3)

• Bhagwagar Z, Wylezinska M, Jezzard P, Evans J, Ashworth F, Sule A, Matthews PM, Cowen PJ. Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol Psychiatry. 2007 Mar 15;61(6):806-12. doi: 10.1016/j.biopsych.2006.08.048. Epub 2007 Jan 8.

  PMID: 17210135 BACKGROUND

• Ip IB, Berrington A, Hess AT, Parker AJ, Emir UE, Bridge H. Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain. Neuroimage. 2017 Jul 15;155:113-119. doi: 10.1016/j.neuroimage.2017.04.030. Epub 2017 Apr 19.

  PMID: 28433623 BACKGROUND

• Wu F, Lu Q, Kong Y, Zhang Z. A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges. Neurosci Bull. 2023 Sep;39(9):1426-1438. doi: 10.1007/s12264-023-01052-7. Epub 2023 Mar 30.

  PMID: 36995569 BACKGROUND

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Central Study Contacts

Wendy Howard

CONTACT

01865618286; wendy.howard@psych.ox.ac.uk

Diana Verley

CONTACT

01865618212; diana.verley@psych.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2 groups of participants, both undergoing flickering checkerboard stimulus. Patient group (participants with recovered depression) and a healthy control group.

Study Record Dates

• First Submitted: June 25, 2024
• First Posted: July 1, 2024
• Study Start: June 1, 2024
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: July 1, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)