Glutamate Activity in Depression (GLADE)
NCT Number: NCT06482606
Acronym: GLADE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Depression
Interventions: OTHER: Flickering Checkerboard Stimulation
Sponsor: University of Oxford
Collaborators: National Institute for Health Research, United Kingdom
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: BASIC_SCIENCE
Start Date: 2024-06
Completion Date: 2025-06
Locations: University of Oxford, Oxford, Oxfordshire, OX3 7JX, United Kingdom

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.

Primary Outcome Measures: 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 Outcome Measures: Brain Glutamate Baseline Change in the Visual Cortex, Determining if the baseline glutamate concentration levels in the rest block is different between patients recovered from depression and healthy controls (without the influence of a functional task to produce a dynamic change)., Acute (0-60 minutes)|Excitatory-Inhibitory Ratio Change in the Visual Cortex, Using the glutamate and GABA concentrations quantified from the fMRS data, we will calculate the Glu/GABA ratio to assess the excitatory-inhibitory ratio and determine whether this ratio is different within participants recovered from depression and controls., Acute (0-60 minutes)|Brain Resting State Connectivity, Brain resting state connectivity change measured via blood oxygenation level-dependent resting-state functional Magnetic Resonance Imaging (BOLD-rs-fMRI) 7T, comparing activity between participants recovered from depression and controls., Acute (0-60 minutes)|Exploratory Analysis of Other Metabolite Concentrations at Baseline or Changes After Stimulation In the Visual Cortex, Other metabolites captured from the fMRS STEAM sequence will be analysed to assess whether there are differences between participants recovered depression and controls concentrations, at baseline or after stimulation., 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, Data collected on demographic factors like age and sex and clinical variables like PHQ-9 depression scores will be asessed to determine if they significantly influence metabolite levels., Acute (0-60 minutes)