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Clinical Trial Summary

This research study is designed to look at the involvement of the glutamate system in depression. Each subject will undergo a screening appointment to determine study eligibility. Thereafter, the study will take 2 or 3 visits depending on schedule availability and will consist of one MRI scan, and PET scan. Subjects will also participate in cognitive testing. Depending on camera time, staff availability and subject schedule, total study participation may last 1-2 months.


Clinical Trial Description

With the recent advancements in positron emission tomography (PET) and radioligand development, the investigators are now able to image and quantify the metabotropic glutamatergic system (mGluR5) in vivo in human subjects. The study proposes a novel investigation of mGluR5 in depression to obtain critical data to advance understanding of the etiology of depression and its associated symptoms of cognitive dysfunction. Aim 1: To determine mGluR5 availability in individuals with mood disorders compared to healthy controls as measured with PET brain imaging. Hypothesis 1: The study hypothesizes a decrease in mGluR5 availability in individuals with mood disorders in regions responsible for emotional and cognitive processes, including the amygdala, hippocampus, thalamus, anterior cingulate, and frontal cortices. Aim 2: To determine if glutamate cycling in individuals with mood disorders is altered as compared to healthy controls as measured with [1H]MRS and [13C]MRS. Hypothesis 2: The study hypothesizes an increase in glutamate number in individuals with mood disorders as compared to controls. Aim 3: To determine if the PET alterations in the glutamatergic system of depressed individuals are associated with cognitive deficits observed in depression, including concentration, attention, and memory. Hypothesis 3: The study hypothesizes a positive relationship between mGluR5 availability and cognitive functioning, such that individuals with higher receptor availability will perform better on tests of concentration, attention, and memory than individuals with lower receptor availability. Aim 4: To determine mGluR5 availability in individuals with anxiety and schizophrenia compared to healthy controls as measured with PET brain imaging. Hypothesis 4: Anxiety disorders such as obsessive compulsive disorder, and delusional disorders such as schizophrenia are frequently comorbid with mood disorders, and the glutamatergic system has been observed to be compromised in these individuals as well. This study will examine if there are regional differences in mGluR5 availability between individuals with depression, bipolar disorder, obsessive compulsive disorder, and schizophrenia. Aim 5: To examine whether changes in mGluR5 availability are dependent on state, or whether the lower availability is due to trait. Hypothesis 5: Due to changes in endogenous GLU shown with MRS studies, this study hypothesizes normalization (or increase) in mGluR5 availability in euthymia as compared to depressed state. Aim 6: To compare SV2A availability in individuals with MDD, healthy control individuals, and individuals with PTSD using APP311 and PET. Hypothesis 6: The study hypothesizes lower SV2A density in MDD and PTSD in the prefrontal cortex. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02727972
Study type Interventional
Source Yale University
Contact Sarah O, MA
Phone 203-737-7066
Status Recruiting
Phase N/A
Start date August 2011
Completion date August 2025

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