Fear Conditioning Interventions for PTSD

Recruiting at 1 trial location

Overseen By Isabel Moallem, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Neuroleptics

Disqualifiers: Neurologic disease, Suicidal ideation, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

300 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using neuroleptics, you must not have taken them within one year prior to the study.

What data supports the effectiveness of the treatment Avoidance conditioning, Fear Conditioning, and related therapies for PTSD?

Research shows that fear conditioning and extinction-based therapies, like exposure therapy, can reduce fear symptoms in PTSD patients, although some may experience a return of fear. Combining these therapies with approach-avoidance training may further reduce fear and prevent its return. ^{1 2 3 4 5}

Is fear conditioning therapy safe for humans?

The research does not provide specific safety data for fear conditioning therapy, but it is commonly used in exposure therapy for anxiety and PTSD, suggesting it is generally considered safe in clinical settings. ^{1 3 6 7 8}

How does the fear conditioning treatment for PTSD differ from other treatments?

Fear conditioning treatment for PTSD is unique because it focuses on understanding and modifying the fear learning processes, such as fear extinction and inhibition, which are often impaired in PTSD. This approach uses experimental paradigms to study and potentially improve the way individuals with PTSD respond to fear-related cues, offering a novel method compared to traditional therapies that may not specifically target these underlying fear mechanisms. ^{1 9 10 11 12}

Research Team

Mohammed Milad, PhD

Principal Investigator

The University of Texas Health Science Center at Houston (UTHealth Houston)

Eligibility Criteria

This trial is for adults aged 18-70 with current PTSD, diagnosed through specific assessments (CAPS and SCID). It's also open to trauma-exposed healthy controls without any history of psychiatric disorders or PTSD. Participants must be willing to undergo experiments involving avoidance of stimuli.

Inclusion Criteria

I have been diagnosed with PTSD as my primary condition.

I am either female or male.

You are someone who has been diagnosed with PTSD.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Initial assessment visit to establish baseline measures before experimental visits

1 day

1 visit (in-person)

Experimental Visits

Participants undergo an emotional learning paradigm and fMRI scan over two consecutive days

2 days

2 visits (in-person)

Follow-up

Participants are monitored for any delayed responses or effects post-experiment

4 weeks

Treatment Details

Interventions

• Avoidance conditioning
• Fear Conditioning
• Pavlovian fear extinction learning
• Willingness to pay to avoid shock

Trial Overview The study tests how people with PTSD learn to avoid things that scare them. It involves measuring brain responses and feelings during tasks like paying to avoid shocks, learning about fear, avoiding conditioned stimuli, and overcoming learned fears.

Participant Groups

Group I: Emotional learning paradigm Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

The review highlights various classical conditioning paradigms, such as extinction learning and fear generalization, which are crucial for understanding the development and treatment of PTSD, supported by case examples from patients with severe symptoms.

It discusses the neurobiological mechanisms involved in conditioning and extinction across different populations, suggesting that biological, behavioral, and cognitive factors play significant roles in how PTSD symptoms are learned and treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical applications and practical relevance of human conditioning paradigms for posttraumatic stress disorder. Zuj, DV., Norrholm, SD.[2019]

In a study of 110 military personnel and veterans, higher PTSD severity was linked to lower availability of environmental and hedonic rewards, suggesting that individuals with PTSD may struggle to find positive reinforcement in their lives.

The research supports a behavioral economic model of PTSD, indicating that those with the disorder may have a short-sighted focus on immediate rewards rather than future benefits, which could contribute to their symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The associations between posttraumatic stress disorder and delay discounting, future orientation, and reward availability: A behavioral economic model. Olin, CC., McDevitt-Murphy, ME., Murphy, JG., et al.[2022]

Combining fear extinction therapy with an Approach-Avoidance Task (AAT) did not significantly enhance the reduction of conditioned fear or prevent the return of fear symptoms in participants, suggesting limited effectiveness of this approach.

Despite modifying approach-avoidance tendencies, no significant differences in subjective fear or physiological arousal were observed between groups during follow-up tests, indicating that the addition of AAT may not improve outcomes of traditional exposure therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Approach-Avoidance Training on the Extinction and Return of Fear Responses. Krypotos, AM., Arnaudova, I., Effting, M., et al.[2018]

The innovative treatment framework called Multi-modular Motion-assisted Memory Desensitization and Reconsolidation (3MDR) combines personalized virtual reality, multi-sensory input, and physical activity to enhance engagement and reduce avoidance in veterans with treatment-resistant PTSD.

3MDR aims to optimize treatment effectiveness by changing the therapeutic setting from a sedentary position to an active context, allowing patients to walk towards trauma-related images in a virtual environment, which may improve memory retrieval and learning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Innovative Framework for Delivering Psychotherapy to Patients With Treatment-Resistant Posttraumatic Stress Disorder: Rationale for Interactive Motion-Assisted Therapy. van Gelderen, MJ., Nijdam, MJ., Vermetten, E.[2020]

Identifying individual differences in risk for PTSD can be more effectively achieved using weaker learning situations that involve uncertainty, as opposed to strong situations with clear cues.

Studies show that behaviorally inhibited individuals and animals exhibit enhanced learning responses, such as increased eyeblink conditioning and avoidance behavior, which may indicate a higher risk for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weaker situations: Uncertainty reveals individual differences in learning: Implications for PTSD. Allen, MT.[2023]

In a study of 502 firefighters, avoidance learning responses were similar to those of individuals with low anxiety, indicating that this population may not exhibit maladaptive avoidance typically associated with PTSD.

The research found no significant association between avoidance learning and PTSD symptoms at baseline or over a 24-month follow-up, suggesting that avoidance learning may not be a predictive factor for PTSD in this low-symptomatic group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoidance learning as predictor of posttraumatic stress in firefighters. de Haart, R., Mouthaan, J., Vervliet, B., et al.[2021]

The paper argues that existing theories of avoidance learning in humans do not adequately explain how phobias are acquired and maintained, suggesting a new model that emphasizes the role of Pavlovian conditioning rather than instrumental learning.

It critically evaluates the common belief that Pavlovian conditioning has a minimal role in the development of fears, highlighting its significant implications for understanding and treating human phobias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoidance learning, Pavlovian conditioning, and the development of phobias. Siddle, DA., Bond, NW.[2019]

Acceptance and Commitment Therapy (ACT) can help improve treatment engagement for veterans with PTSD by addressing avoidance behaviors that often hinder participation in traditional therapies.

ACT techniques, such as cognitive defusion and values clarification, have shown promise in enhancing engagement with cognitive-behavioral treatments, suggesting they could be beneficial as adjuncts to standard PTSD treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using acceptance and commitment therapy techniques to enhance treatment engagement in veterans with posttraumatic stress disorder. Phillips, MA., Chase, T., Bautista, C., et al.[2021]

Fear conditioning experiments reveal the complex neurobiological mechanisms behind PTSD, highlighting different fear-related dimensions such as fear extinction and generalization, which can inform targeted treatment strategies.

These paradigms not only enhance our understanding of PTSD but also serve as a platform for developing new pharmacological and non-pharmacological interventions, emphasizing the need for further research to optimize their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors. Briscione, MA., Jovanovic, T., Norrholm, SD.[2021]

Latent inhibition (LI) is a phenomenon where repeated exposure to a neutral cue without any negative associations reduces the fear response when that cue is later paired with an aversive stimulus, suggesting a mechanism for how we can learn to ignore certain threats.

Understanding LI could have important clinical applications, particularly for enhancing resilience in individuals frequently exposed to trauma, like healthcare workers and first responders, and may help in treating psychiatric disorders characterized by heightened fear responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral and neural mechanisms of latent inhibition. Miller, DB., Rassaby, MM., Collins, KA., et al.[2023]

The study found that women with interpersonal violence-related PTSD showed disrupted model-based reinforcement learning processes during fear conditioning, which may contribute to their impaired ability to learn about fear and safety.

Reduced activity in visual processing areas during model-based updating was linked to higher PTSD symptoms, suggesting that these neural mechanisms could influence treatment responses, such as the effectiveness of exposure therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value estimation and latent-state update-related neural activity during fear conditioning predict posttraumatic stress disorder symptom severity. Letkiewicz, AM., Cochran, AL., Privratsky, AA., et al.[2023]

A study involving 84 firefighters found that deficits in extinction learning, measured before trauma exposure, can predict the severity of posttraumatic stress symptoms after experiencing trauma.

Specifically, reduced ability to extinguish a conditioned emotional response was linked to 31% of the variance in posttraumatic stress severity, suggesting that this impairment may be a risk factor for developing PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extinction learning before trauma and subsequent posttraumatic stress. Guthrie, RM., Bryant, RA.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

The clinical applications and practical relevance of human conditioning paradigms for posttraumatic stress disorder. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

The associations between posttraumatic stress disorder and delay discounting, future orientation, and reward availability: A behavioral economic model. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of Approach-Avoidance Training on the Extinction and Return of Fear Responses. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

An Innovative Framework for Delivering Psychotherapy to Patients With Treatment-Resistant Posttraumatic Stress Disorder: Rationale for Interactive Motion-Assisted Therapy. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Weaker situations: Uncertainty reveals individual differences in learning: Implications for PTSD. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Avoidance learning as predictor of posttraumatic stress in firefighters. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Avoidance learning, Pavlovian conditioning, and the development of phobias. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Using acceptance and commitment therapy techniques to enhance treatment engagement in veterans with posttraumatic stress disorder. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Behavioral and neural mechanisms of latent inhibition. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Value estimation and latent-state update-related neural activity during fear conditioning predict posttraumatic stress disorder symptom severity. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Extinction learning before trauma and subsequent posttraumatic stress. [2022]