Stress Disorders, Post-TraumaticNCT01800383
Cerebral GABA and Fear Conditioning in PTSD
An observational study of Stress Disorders, Post-Traumatic, run by Isabelle Rosso at 1 site in United States.
Trial summary
Posttraumatic stress disorder (PTSD) is a common and debilitating neuropsychiatric disorder in which an acute fear response to a traumatic event does not abate. This failure to recover from trauma is thought to be due at least in part to a deficit in learning not to fear situations and stimuli previously associated… Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Stress Disorders, Post-Traumatic
- Type of treatment
- Injection or infusion
- How many people
- 126 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Subjects will be between the ages of 20 and 50 years. These will include 31 subjects meeting DSM-IV criteria for PTSD, 31 trauma-exposed healthy subjects, and 31 healthy comparison (HC) subjects without any trauma exposure.
Who may be able to join
- 20-50 years of age
- right-handed
- DSM-IV diagnosis consistent with group assignment
- groups to be matched for age, sex, education, race/ethnicity
- ability to provide written informed consent
- groups to be matched on proportion of female subjects in follicular/luteal menstrual phases.
Who cannot join
- Medical condition that would confound results
- history of seizures or head trauma with loss of consciousness
- exposure to psychotropic medications within 4 weeks of study (8 weeks for fluoxetine)
- metal implants, claustrophobia or other Magnetic Resonance Imaging (MRI) exclusions
- positive urine toxicology or human chorionic gonadotropin (HCG) status on scan day
- history of psychotic disorder, bipolar disorder, eating disorder, mental retardation, or pervasive developmental disorder; history of meeting full criteria for non-PTSD anxiety disorder.
- PTSD and trauma subjects will be matched in terms of comorbid depressive disorder, not to exceed 50%. Trauma-exposed subjects will have a history of trauma exposure and will not meet criteria for PTSD. Non-traumatized healthy subjects will have no history of Axis I psychiatric disorder and no trauma exposure.
Trial locations and contacts
1 site in 1 country.
About this study
Posttraumatic stress disorder (PTSD) is a common and debilitating neuropsychiatric disorder in which an acute fear response to a traumatic event does not abate. This failure to recover from trauma is thought to be due at least in part to a deficit in learning not to fear situations and stimuli previously associated with the trauma (i.e., specifically due to a failure of extinction recall). Pavlovian fear conditioning can be simulated and measured experimentally in humans using a 2-day fear conditioning paradigm developed by our group, wherein conditioning and extinction learning phases are conducted on Day 1, and extinction recall is tested on Day 2.
Recent functional magnetic resonance imaging (fMRI) evidence indicates that PTSD is associated with hyper-responsivity of the insular cortex and hyporesponsivity of the ventromedial prefrontal cortex (VMPFC) during exposure to fear-inducing stimuli, consistent with altered excitability of brain regions mediating fear conditioning and extinction. As the brain's principal inhibitory neurotransmitter, GABA exerts a prominent role in modulating neuronal excitability. Interestingly, there are reports that adjunctive treatment with GABA-enhancing antiepileptics is efficacious in PTSD. There is also evidence, albeit inconsistent, that lower serum GABA levels predict a more chronic course of the illness. However, it is unclear whether serum levels accurately reflect brain GABA, which may contribute to inconsistency of serum findings. Moreover, it is possible that GABA alterations may vary in their presence, nature and significance across brain regions implicated in PTSD. The proposed study will examine the relationship of PTSD symptoms and behavioral fear conditioning deficits with regional brain gamma-aminobutyric acid (GABA) using proton magnetic resonance spectroscopy (1H-MRS).
Read more
We have the following aims and hypotheses:
- To determine whether GABA alterations are associated with the categorical diagnosis of PTSD and not merely exposure to trauma. It is hypothesized that PTSD will be associated with higher GABA in VMPFC and lower GABA in the right insula.
- To determine whether GABA levels are significantly associated with dimensional measures of PTSD symptom severity and individual symptom dimensions. It is predicted that higher GABA in the VMPFC and lower GABA in the right anterior insula will be associated with greater total symptom severity.
- To determine whether GABA in VMPFC and right anterior insula are significantly associated with measures of extinction recall failure and anxiety sensitivity in PTSD. It is hypothesized that VMPFC GABA will be positively correlated with skin conductance response to a conditioned stimulus that had previously been extinguished and insula GABA will be negatively correlated with anxiety sensitivity.
- Conditions
- Stress Disorders, Post-Traumatic
- Keywords
- posttraumatic stress disorder, fear conditioning, proton magnetic resonance spectroscopy, GABA
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Control | No Axis I psychiatric disorder and no trauma exposure | |
| Trauma-Exposed Normal Control | History of trauma exposure and subthreshold PTSD symptoms. | |
| PTSD | Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of PTSD as determined by the Structured Clinical Interview for DSM-IV-Text Revised |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regional brain gamma-aminobutyric acid (GABA) levels in the ventromedial prefrontal cortex (VMPFC), right anterior insula, and right posterior temporal cortex
Single voxel 3T H-MRS cortex using a MEGAPRESS sequence will be used to detect and quantify GABA in these brain regions.
Measured: Measured on the day of the MRI scan
Regional brain glutamate metabolism in the ventromedial prefrontal cortex (VMPFC), right anterior insula, and right posterior temporal cortex
Single voxel 3T H-MRS cortex using a 2DJPRESS sequence at 3T will be used to detect and quantify glutamate and glutamine in these brain regions.
Measured: Measured on the day of the MRI scan
Regional brain neuronal integrity in the ventromedial prefrontal cortex (VMPFC), right anterior insula, and right posterior temporal cortex
Single voxel 3T H-MRS cortex using a 2DJPRESS sequence at 3T will be used to detect and quantify N-acetyl aspartate in these brain regions.
Measured: Measured on the day of the MRI scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionFeb 2018
- Study completionDec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stress Disorders, Post-TraumaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- Isabelle Rosso
- Sponsor type
- University, hospital or other
- Collaborators
- Mclean Hospital
- Responsible party
- Sponsor-investigator, Isabelle Rosso, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01800383
- Sponsor's protocol ID
- MH096987-01A1
- Status last verified
- Mar 2023
- First submitted
- 14 Feb 2013
- Last updated
- 4 Apr 2023
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cerebral GABA and Fear Conditioning in PTSD
- ClinicalTrials.gov ID
- NCT01800383
- Acronym / sponsor ID
- MH096987-01A1
- Conditions
- Stress Disorders, Post-Traumatic
- Keywords
- posttraumatic stress disorder, fear conditioning, proton magnetic resonance spectroscopy, GABA
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- Isabelle RossoUniversity, hospital or other
- Collaborators
- Mclean Hospital
- Study start
- Feb 2013 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Dec 2022 (actual)
- First posted
- 27 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Posttraumatic stress disorder (PTSD) is a common and debilitating neuropsychiatric disorder in which an acute fear response to a traumatic event does not abate. This failure to recover from trauma is thought to be due at least in part to a deficit in learning not to fear situations and stimuli previously associated with the trauma (i.e., specifically due to a failure of extinction recall). Pavlovian fear conditioning can be simulated and measured experimentally in humans using a 2-day fear conditioning paradigm developed by our group, wherein conditioning and extinction learning phases are conducted on Day 1, and extinction recall is tested on Day 2.
Recent functional magnetic resonance imaging (fMRI) evidence indicates that PTSD is associated with hyper-responsivity of the insular cortex and hyporesponsivity of the ventromedial prefrontal cortex (VMPFC) during exposure to fear-inducing stimuli, consistent with altered excitability of brain regions mediating fear conditioning and extinction. As the brain's principal inhibitory neurotransmitter, GABA exerts a prominent role in modulating neuronal excitability. Interestingly, there are reports that adjunctive treatment with GABA-enhancing antiepileptics is efficacious in PTSD. There is also evidence, albeit inconsistent, that lower serum GABA levels predict a more chronic course of the illness. However, it is unclear whether serum levels accurately reflect brain GABA, which may contribute to inconsistency of serum findings. Moreover, it is possible that GABA alterations may vary in their presence, nature and significance across brain regions implicated in PTSD. The proposed study will examine the relationship of PTSD symptoms and behavioral fear conditioning deficits with regional brain gamma-aminobutyric acid (GABA) using proton magnetic resonance spectroscopy (1H-MRS).
We have the following aims and hypotheses:
- To determine whether GABA alterations are associated with the categorical diagnosis of PTSD and not merely exposure to trauma. It is hypothesized that PTSD will be associated with higher GABA in VMPFC and lower GABA in the right insula.
- To determine whether GABA levels are significantly associated with dimensional measures of PTSD symptom severity and individual symptom dimensions. It is predicted that higher GABA in the VMPFC and lower GABA in the right anterior insula will be associated with greater total symptom severity.
- To determine whether GABA in VMPFC and right anterior insula are significantly associated with measures of extinction recall failure and anxiety sensitivity in PTSD. It is hypothesized that VMPFC GABA will be positively correlated with skin conductance response to a conditioned stimulus that had previously been extinguished and insula GABA will be negatively correlated with anxiety sensitivity.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | – | –No Axis I psychiatric disorder and no trauma exposure |
| Trauma-Exposed Normal Control | – | –History of trauma exposure and subthreshold PTSD symptoms. |
| PTSD | – | –Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of PTSD as determined by the Structured Clinical Interview for DSM-IV-Text Revised |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Subjects will be between the ages of 20 and 50 years. These will include 31 subjects meeting DSM-IV criteria for PTSD, 31 trauma-exposed healthy subjects, and 31 healthy comparison (HC) subjects without any trauma exposure.
Key inclusion criteria (6 listed)
- 20-50 years of age
- right-handed
- DSM-IV diagnosis consistent with group assignment
- groups to be matched for age, sex, education, race/ethnicity
- ability to provide written informed consent
Key exclusion criteria (7 listed)
- Medical condition that would confound results
- history of seizures or head trauma with loss of consciousness
- exposure to psychotropic medications within 4 weeks of study (8 weeks for fluoxetine)
- metal implants, claustrophobia or other Magnetic Resonance Imaging (MRI) exclusions
- positive urine toxicology or human chorionic gonadotropin (HCG) status on scan day
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Regional brain gamma-aminobutyric acid (GABA) levels in the ventromedial prefrontal cortex (VMPFC), right anterior insula, and right posterior temporal cortex
Time frame: Measured on the day of the MRI scan
Single voxel 3T H-MRS cortex using a MEGAPRESS sequence will be used to detect and quantify GABA in these brain regions.
Regional brain glutamate metabolism in the ventromedial prefrontal cortex (VMPFC), right anterior insula, and right posterior temporal cortex
Time frame: Measured on the day of the MRI scan
Single voxel 3T H-MRS cortex using a 2DJPRESS sequence at 3T will be used to detect and quantify glutamate and glutamine in these brain regions.
Regional brain neuronal integrity in the ventromedial prefrontal cortex (VMPFC), right anterior insula, and right posterior temporal cortex
Time frame: Measured on the day of the MRI scan
Single voxel 3T H-MRS cortex using a 2DJPRESS sequence at 3T will be used to detect and quantify N-acetyl aspartate in these brain regions.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Stress Disorders, Post-Traumatic, run by Isabelle Rosso at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Regional brain gamma-aminobutyric acid (GABA) levels in the ventromedial prefrontal cortex (VMPFC), right anterior insula, and right posterior temporal cortex (time frame: Measured on the day of the MRI scan). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2023; AzTrials last refreshed its copy on 6 Nov 2026.