Ignite Creation Date:
2024-05-06 @ 1:26 AM
Last Modification Date:
2024-10-26 @ 11:03 AM
Study NCT ID:
NCT01800383
Status:
COMPLETED
Last Update Posted:
2023-04-04
First Post:
2013-02-14
Brief Title:
Cerebral GABA and Fear Conditioning in PTSD
Sponsor:
Isabelle Rosso
Organization:
Mclean Hospital
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 with the trauma ie 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 brains 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
1 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
2 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
3 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
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 brains 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
1 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
2 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
3 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None