Examination of Glutamate and mGluR5 in Psychiatric Disorders
| Status: | Recruiting |
|---|---|
| Conditions: | Depression, Depression, Major Depression Disorder (MDD), Psychiatric, Psychiatric, Psychiatric, Psychiatric, Bipolar Disorder |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 1/11/2018 |
| Start Date: | August 2011 |
| End Date: | August 2020 |
| Contact: | Sarah O, MA |
| Phone: | 203-737-7066 |
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.
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.
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.
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.
Inclusion Criteria:
General inclusion criteria:
- Subjects will be between the ages of 18-65 years old
- English speaking
- No other DSM-IV diagnosis present, besides required as below
Inclusion criteria for acute depressed subjects:
- Clinical diagnosis of a current depressive episode
- Medication-free for at least 2 weeks or medicated with a permissible medication
Inclusion criteria for PTSD subjects:
- Clinical diagnosis of current PTSD as per DSM-IV
- Medication free for at least 2 weeks or medicated with a permissible medication
Inclusion criteria for healthy controls:
- No current, or history of, any DSM-IV diagnosis
Exclusion Criteria:
- Have a current or past significant medical, neurological or metabolic disorder or loss
of consciousness for 5 minutes or more
- Have active, significant suicidal ideation
- Have implanted metallic devices or any MR contraindications
- Are women who are pregnant or breastfeeding
- Met DSM-IV criteria for alcohol/illicit substance dependence in past year or met
alcohol/illicit substance abuse within past 6 months
- Have history of prior radiation exposure for research purposes within the past year
such that participation in this study would place them over FDA limits for annual
radiation exposure. This guideline is an effective dose of 5 rem received per year
- Have given a blood donation within eight weeks of the start of the study
- Have history of a bleeding disorder or are currently taking anticoagulants (such as
Coumadin, Heparin, Pradaxa, Xarelto)
We found this trial at
1
site
New Haven, Connecticut 06519
Principal Investigator: Irina Esterlis, PhD
Phone: 203-737-7066
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