Individualized Computational Assessment of the Effects of GABA Receptor Modulation in Posttraumatic Stress Disorder
VA Office of Research and Development
Summary
A substantial majority of Veterans with posttraumatic stress disorder (PTSD) continue to suffer even with the best current medications. Progress in developing more effective medications is hampered by the substantial variability within Veterans with PTSD, meaning the most effective medication likely varies from individual to individual. New scientific tools to help identify distinct subgroups of Veterans with PTSD who are likely to respond to specific medications could help improve treatment in this population. Research has indicated that a specific subgroup of Veterans with PTSD with a high level of anxious arousal may benefit from medications which boost signaling of the neurotransmitter gamma-aminobutyric acid (GABA). This project aims to validate a clinical test to identify these individuals using new computational and neuroimaging methods combined with the medication lorazepam, a positive GABA modulator. The ultimate goal is to use these methods in future clinical trials of new medications to target the best treatments to individual Veterans with PTSD.
Description
Heterogeneity in Veterans with PTSD has been identified as a major obstacle in developing effective treatments for this population. Research suggests that a PTSD subgroup characterized by elevated arousal, relative to general negative affect, may benefit from novel medications that positively modulate inhibitory gamma aminobutyric acid (GABA) signaling. An objective, functional phenotypic marker for this subgroup could therefore enable targeted treatment and improve clinical outcomes. The investigators propose a computational goal-directed control paradigm as a novel clinical assessment based…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: Inclusion Criteria: 1. Veteran; 2. 18-65 years of age, inclusive; 3. Participants must be willing to abstain from alcohol 24 hours prior to and 24 hours after the testing session; 4. Participants must be able to participate and willing to give written informed consent and to comply with the study restrictions; Additional Inclusion Criteria for PTSD Group: (a) Current diagnosis of PTSD based on CAPS-5. Exclusion Criteria: Exclusion Criteria: 1. Has uncontrolled, clinically significant neurologic (including seizure disorders), cardiovascular, pulmonary, hepatic, renal,…
Interventions
- DrugLorazepam 1 mg tablet
Lorazepam is an oral medication which is FDA approved to treat anxiety.
- DrugPlacebo tablet
Placebo will match the study drug in mode of administration, color, size, and taste.
Location
- VA San Diego Healthcare System, San Diego, CASan Diego, California