Processes and Circuitry Underlying Threat Sensitivity as a Treatment Target for Co-morbid Anxiety and Depression

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?

Conditions

• Depression, Anxiety
• Fear
• Depression
• Anxiety and Fear
• Anxiety Disorders
• Anxious Depression

Interventions

DRUG

Lorazepam

1mg of Lorazepam will be prepared by pharmacy (Barnes, Tulsa) in capsule form

OTHER

Placebo

placebo will be prepared by pharmacy (Barnes, Tulsa) in capsule form

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  collaborator NIH

• California Institute of Technology

  collaborator OTHER

• Laureate Institute for Brain Research, Inc.

  lead OTHER

Principal Investigators

• Maria Ironside, DPhil · Laureate Institute for Brain Research

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-11-08

Primary Completion

2027-12-31

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States

Study Locations