Fear and Avoidance in PTSD Patients

Neural Correlates of Active Avoidance Learning and Their Interactions With Fear Extinction Mechanisms in PTSD Patients

The purpose of this research study is to study how the brain learns to avoid certain stimuli or situations using an experimental paradigm. The big goal is to measure brain responses and subject's feelings and expectations when they are learning to actively avoid experimental stimuli, and how fear extinction learning and monetary cost can change how and when subjects are to avoid.

Study Overview

• Status: Recruiting
• Conditions: Post Traumatic Stress Disorder
• Intervention / Treatment: Behavioral: Fear Conditioning; Other: Avoidance conditioning; Other: Pavlovian fear extinction learning; Other: Willingness to pay to avoid shock

Detailed Description

This study aims to study the neural correlates of avoidance learning using a recently validated conditioning and active avoidance paradigm (CAAP). The overarching objective is to measure the neural correlates of active avoidance, and how fear extinction learning and monetary cost modulate these avoidance responses. Participants will include healthy controls (HC), trauma-exposed healthy controls (TEHC), and participants with post-traumatic stress disorder (PTSD). Avoidance is common and often hinders the progression and success of extinction-based exposure therapy in PTSD. The data to be gathered in this study will enable us to probe neural mechanisms of avoidance, extinction, and decision-making to avoid or not, in addition to understanding the impact of cost on avoidance decision-making. These data will provide a more integrated platform for the understanding of the mechanisms of avoidance in both trauma-exposed healthy controls and PTSD psychopathology, which has important implications for treatment.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohammed Milad, PhD; Phone Number: 713-486-2754; Email: Mohammed.R.Milad@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77054
      • Recruiting
      • UTHealth Houston
      • Contact: Mohammed R. Milad, PhD; Email: Mohammed.R.Milad@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 18 - 70 years of age
2. Female or Male

3. Inclusion Criteria: PTSD Subjects

   a. Diagnosis of current PTSD

4. Inclusion Criteria: Trauma-exposed healthy controls (TEHC)

   1. SCID diagnosis consistent with no current psychiatric disorders, and no current PTSD
   2. History of trauma exposure

5. Inclusion Criteria: Healthy controls (HC)

   1. SCID diagnosis consistent with no current psychiatric disorders ("Axis I" disorders).
   2. No history of trauma exposure
6. Willing and able to provide informed consent.

Exclusion Criteria for ALL subjects:

1. History of neurologic disease (e.g. tic disorder)
2. Current significant suicidal ideation, plan or intent or suicidal behavior in past 6 months based on CSSRS or Self-injurious behavior that involves suicidal intent, requires medical attention, or occurs daily
3. History of seizure or significant head trauma
4. History of the serious/significant psychiatric diagnosis ("Axis I" disorders)
5. Use of neuroleptics within one year prior to study
6. Current substance use (assessed by urine toxicology; positive urine toxicology screen for any substance, with the exception of THC). Per PI judgement and approval: if urine toxicology is positive for a substance, participant may be eligible to proceed with study provided their urine toxicology (or saliva test for THC) is negative at experimental visit(s)
7. Pregnancy (to be ruled out by urine ß-HCG)
8. Metallic implants or devices contraindicating magnetic resonance imaging

9. High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process

   Additional exclusion criteria for Trauma-exposed healthy controls (TEHC) group and Healthy controls (HC) group:

10. Current psychiatric diagnosis ("Axis I" diagnoses)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Emotional learning paradigm; After the initial screening / baseline assessment visit, participants will undergo two Experimental Visits, which include participation in an emotional learning paradigm and an fMRI scan over the course of two consecutive days. Participants will be asked to look at pictures on a computer screen to measure physiological response physiological response (skin conductance response) and brain responses using a functional Magnetic Resonance Imaging (fMRI) machine. These two visits will be scheduled within a month from the baseline assessment visit.

Behavioral: Fear Conditioning; Participants will be administered increasing intensities of mild electric shock via electrodes connected to the foot. New Biopac stimulators that can deliver higher shock intensity, provided participants agreement will be used to assure adequate conditioning levels. Stimulation is measures in milliamps (mA), and each delivered stimulation will be 0.5 seconds long (500 milliseconds). To colored (blue, red, & yellow) light stimuli (CS). The light stimulus is followed by a shock or no shock depending on color.; Other: Avoidance conditioning; Via button pressing. Only one stimulus-CS will enable control over experiencing the shock: the participant can press the button during the first 2 seconds of the light presentation to avoid the shock.; Other: Pavlovian fear extinction learning; After avoidance conditioning, the CS+ associated with avoidance responding appears with no button to press and no shock is administered.; Other: Willingness to pay to avoid shock; On the next day, participants receive a monetary stipend to use to pay to guarantee that they are not to receive any shocks if they press a button from the CS+. This and all previously described experimental phases noted above will occur inside of the fMRI scanner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin Conductance Response (SCR)	Skin Conductance Response (SCR) assesses the stress/seat level, or level of anxiety in a particular moment, or in response to a specific cue. SCR will be reported in microsiemens.	Experimental Day 1, Experimental Day 2
Functional MRI (fMRI) responses	fMRI data, including blood-oxygen-level-dependent (BOLD) responses, is used in neuroimaging studies assess neural correlate activations and observe the increase/decrease in activation of a particular brain area in response to a specific cue.	Experimental Day 1, Experimental Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Anxiety	State-Trait Anxiety Inventory STAI (State) The State-Trait Anxiety Inventory (STAI) is a psychological inventory based on a 4-point Likert scale and consists of 40 questions on a self-report basis. The STAI measures two types of anxiety - state anxiety, or anxiety about an event, and trait anxiety, or anxiety level as a personal characteristic.	Experimental Day 1, Experimental Day 2
Change in Emotional Stress tolerance	Distress Tolerance Scale (DTS) is a 15 item self-report measure of emotional distress tolerance. Individuals select on a 1-5 likert scale. (Strongly Disagree, Mildly Disagree, Feel Neutral, Mildly Agree, Strongly Agree) about each of the 16 statements about distress.	Experimental Day 1, Experimental Day 2
Change in shock expectancy	Shock expectancy questionnaire is a self reported questionnaire that measures what they expect to see certain colors and whether they expected to feel shocks in the study.	Experimental Day 1, Experimental Day 2
Ratings of Pleasantness in Conditioned Stimuli and Unconditioned Stimulus	Pleasantness Rating of relief scale measures participants sense of the relief they felt when no shock was given, on a scale from 1 to 5 (1=neutral, 5=extremely pleasant)	Experimental Day 1, Experimental Day 2
Ratings of Unpleasantness in Conditioned Stimuli and Unconditioned Stimulus	Rating of Conditioned Stimuli(CS) and Unconditioned Stimulus (US) Unpleasantness measures participants sense of the unpleasantness they felt when the CS was given, on a scale from 1 to 5 (1=neutral, 5=extremely pleasant)	Experimental Day 1, Experimental Day 2

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Mohammed Milad, PhD, The University of Texas Health Science Center at Houston (UTHealth Houston)

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 25, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: HSC-MS-23-0495; R01MH123736 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will have access and give upon reasonable request. Requests should be directed to Mohammed.R.Milad@uth.tmc.edu. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No