Processes and Circuitry Underlying Threat Sensitivity as a Treatment Target for Co-morbid Anxiety and Depression
Laureate Institute for Brain Research, Inc.
Summary
This mechanistic study uses an anti anxiety drug and brain imaging to study the threat processing system and associated brain circuits in people with depression, anxiety disorders and comorbid depression and anxiety disorders. In a double blind, placebo controlled crossover design, up to 65 individuals will be recruited who will have a diagnosis of major depressive disorder (MDD) and at least one anxiety disorder (AD) (AD-MDD group), up to 65 participants will have a diagnosis of MDD and no diagnosis of an AD and up to 65 participants will have no diagnosis of MDD and a diagnosis of at least one AD will be enrolled to participate in an two session study to obtain 150 completers (50 per group). All participants will receive a single dose of Lorazepam and placebo (order randomized) taken orally. After the \~2.5 hr screening session, participants will complete two identical \~5 hr experimental sessions, each of which include a 30 min eyeblink startle session and a 1.5 hr functional magnetic resonance imaging (MRI) brain scan session. The total time involved in the study is approximately 10.5 hours. The main questions the study seeks to answer are: * are people with comorbid depression and anxiety different than those with depression alone in terms of their eyeblink startle response to threat? * are people with comorbid depression and anxiety different than those with depression alone in terms of their brain activation in response to threat? * are people with comorbid depression and anxiety different than those with depression alone in terms of their responses to anxiety drugs?
Description
This mechanistic study of major depressive disorder (MDD), anxiety disorders (AD) and comorbid anxiety and depression (AD-MDD) aims to break down threat sensitivity into acute threat (AT) and potential threat (PT). A well validated startle task (Neutral, Predictable, Unpredictable or NPU-threat task) and a cutting-edge computational functional magnetic resonance imaging (fMRI) probe of predator escape decisions (Flight Initiation Distance or FID task) will be used to determine whether AD-MDD show increased PT or AT and how the behavioral dynamics of escape decisions are most impaired in AD-MDD…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- No
An individual must meet the following criteria to be considered eligible to participate in the study: Inclusion Criteria: All subjects: * Female or male sex assigned at birth; * Age 18-65; * Normal or corrected to normal vision/hearing, as protocol elements may not be valid otherwise; * Fluent English speaker, capable of providing written informed consent MDD and AD-MDD subjects: * Current major depressive episode assessed by clinician with guidance from the MINI; * Minimum score of 55 on PROMIS Depression scale AD and AD-MDD subjects: * Current anxiety disorder (generalized anxiety dis…
Interventions
- DrugLorazepam
1mg of Lorazepam will be prepared by pharmacy (Barnes, Tulsa) in capsule form
- OtherPlacebo
placebo will be prepared by pharmacy (Barnes, Tulsa) in capsule form
Location
- Laureate Institute for Brain ResearchTulsa, Oklahoma