Fear Conditioning for Anxiety and Post-Traumatic Stress Disorder
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Texas at Austin
Must not be taking: Benzodiazepines, Psychotropics
Disqualifiers: Major illness, Neurological disorder, Pregnancy, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
The purpose of this research is to use functional magnetic resonance imaging (fMRI) to investigate how the brain forms associations between neutral and negative stimuli. The ultimate goal is to understand the neural systems involved in regulating negative emotional responses to fearful stimuli.
Will I have to stop taking my current medications?
The trial requires that participants with PTSD must be stable on their current medications, so you may not need to stop taking them. However, the protocol does not specify for other participants, so it's best to discuss your specific situation with the study team.
What data supports the effectiveness of the treatment Fear Conditioning, Exposure Therapy, and Behavioral Therapy for Anxiety and Post-Traumatic Stress Disorder?
Is exposure therapy safe for treating anxiety and PTSD?
How is fear conditioning treatment different from other treatments for anxiety and PTSD?
Fear conditioning treatment is unique because it focuses on understanding and modifying the way fear memories are formed and recalled, using techniques like exposure therapy to help patients learn to manage their fear responses. This approach is different from other treatments as it targets the underlying learning processes of fear, rather than just reducing symptoms.1011121314
Eligibility Criteria
This trial is for individuals with PTSD and those without any psychiatric disorders. Participants should not have major medical or neurological issues, significant head trauma, a history of substance abuse, or be at immediate suicide risk. Pregnant women and people with certain metal implants that affect MRI safety are also excluded.Inclusion Criteria
I have PTSD and may also have a mood or anxiety disorder, but not bipolar disorder.
I do not have metal implants or conditions that prevent me from undergoing an MRI.
I have PTSD diagnosed by specific symptom severity and criteria.
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Exclusion Criteria
Individuals considered an immediate suicide risk based on the Columbia Suicide Severity Scale (C-SSRS) or who would likely require hospitalization during the course of the study
Volunteers meeting DSM-5 criteria for history of or current psychotic or bipolar affective disorders, a current eating disorder (bulimia, anorexia nervosa), or dissociative identity disorder
Volunteers meeting DSM-5 criteria for another substance use disorder, with the exception of caffeine or nicotine, within the past 12 months
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2 weeks
1 visit (in-person)
Baseline and Assessment
Participants undergo baseline assessments and are scheduled for MRI visits
2 weeks
1 visit (in-person)
Treatment
Participants undergo a learning paradigm inside the MRI scanner over 3 days, with the first two days consecutive and the third visit 1 month later
1 month
3 visits (in-person)
Follow-up
Participants are monitored for changes in physiological arousal and MRI data
1 month
Treatment Details
Interventions
- Fear conditioning (Behavioral Intervention)
Trial OverviewThe study uses fMRI to explore how the human brain forms memories associated with fear and safety. It aims to understand the neural mechanisms involved in emotional response regulation when encountering fearful stimuli.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: PTSD groupExperimental Treatment1 Intervention
Participants will be screened and diagnosed using typical screening procedures and diagnostic criteria (e.g., the clinically administered PTSD scale). Participants also screened for contraindications for MRI. The learning paradigm inside the MRI scanner occurs over 3 days. The first two days are consecutive (back-to-back) and the third MRI visit is 1 month later. Participants are asked to look at a screen and listen to simple tones over headphones, while the experimenter measures brain activity and physiological measures of arousal (e.g., sweating from sensors on the hand). These visits will be scheduled within two weeks from the baseline and assessment visit.
Group II: Healthy control groupExperimental Treatment1 Intervention
Participants will be healthy adults without a history of psychiatric illness. Participants also screened for contraindications for MRI. The learning paradigm inside the MRI scanner occurs over 3 days. The first two days are consecutive (back-to-back) and the third MRI visit is 1 month later. Participants are asked to look at a screen and listen to simple tones over headphones, while the experimenter measures brain activity and physiological measures of arousal (e.g., sweating from sensors on the hand). These visits will be scheduled within two weeks from the baseline and assessment visit.
Fear conditioning is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Exposure Therapy for:
- Anxiety Disorders
- Post-Traumatic Stress Disorder (PTSD)
- Obsessive-Compulsive Disorder (OCD)
🇪🇺 Approved in European Union as Exposure Therapy for:
- Anxiety Disorders
- Post-Traumatic Stress Disorder (PTSD)
- Obsessive-Compulsive Disorder (OCD)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of Texas at AustinAustin, TX
Biomedical Imaging CenterAustin, TX
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Who Is Running the Clinical Trial?
University of Texas at AustinLead Sponsor
References
Predictors and Outcomes of Growth Mixture Modeled Trajectories Across an Exposure-Based PTSD Intervention With Veterans. [2019]Exposure-based psychotherapies for posttraumatic stress disorder (PTSD) are effective for many, but not all patients. It is important to determine for whom these treatments work and to examine predictors of success.
Correction to Rauch et al. (2021). [2023]Reports an error in "An intensive outpatient program with prolonged exposure for veterans with posttraumatic stress disorder: Retention, predictors, and patterns of change" by Sheila A. M. Rauch, Carly W. Yasinski, Loren M. Post, Tanja Jovanovic, Seth Norrholm, Andrew M. Sherrill, Vasiliki Michopoulos, Jessica L. Maples-Keller, Kathryn Black, Liza Zwiebach, Boadie W. Dunlop, Laura Loucks, Brittany Lannert, Monika Stojek, Laura Watkins, Mark Burton, Kelsey Sprang, Lauren McSweeney, Katie Ragsdale and Barbara O. Rothbaum (Psychological Services, 2021[Nov], Vol 18[4], 606-618). In the original article, in the second sentence of the paragraph under "Baseline to Post-Treatment Change in Symptoms" in the Results section, changes were needed to match the information given in Table 3. The sentence "Posttreatment scores were not available for 11 of the 77 completers on the PCL-5 and one of the 77 completers on the PHQ-9 due to administrations error, so baseline to posttreatment change in PCL-5 was calculated based on 68 veterans and for the PHQ-9 on 76 patients" should have said "Posttreatment scores were not available for 9 of the 77 completers on the PCL-5 due to administrations error, so baseline to posttreatment change in PCL-5 was calculated based on 68 veterans. N = 77 for all other measures." These changes do not alter the conclusions of this article. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2020-50253-001). High rates of drop-out from treatment of PTSD have challenged implementation. Care models that integrate PTSD focused psychotherapy and complementary interventions may provide benefit in retention and outcome. The first 80 veterans with chronic PTSD enrolled in a 2-week intensive outpatient program combining Prolonged Exposure (PE) and complementary interventions completed symptom and biological measures at baseline and posttreatment. We examined trajectories of symptom change, mediating and moderating effects of a range of patient characteristics. Of the 80 veterans, 77 completed (96.3%) treatment and pre- and posttreatment measures. Self-reported PTSD (p < .001), depression (p < .001) and neurological symptoms (p < .001) showed large reductions with treatment. For PTSD, 77% (n = 59) showed clinically significant reductions. Satisfaction with social function (p < .001) significantly increased. Black veterans and those with a primary military sexual trauma (MST) reported higher baseline severity than white or primary combat trauma veterans respectively but did not differ in their trajectories of treatment change. Greater cortisol response to the trauma potentiated startle paradigm at baseline predicted smaller reductions in PTSD over treatment while greater reductions in this response from baseline to post were associated with better outcomes. Intensive outpatient prolonged exposure combined with complementary interventions shows excellent retention and large, clinically significant reduction in PTSD and related symptoms in two weeks. This model of care is robust to complex presentations of patients with varying demographics and symptom presentations at baseline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Cognitive processes during fear acquisition and extinction in animals and humans: implications for exposure therapy of anxiety disorders. [2018]Anxiety disorders are highly prevalent. Fear conditioning and extinction learning in animals often serve as simple models of fear acquisition and exposure therapy of anxiety disorders in humans. This article reviews the empirical and theoretical literature on cognitive processes in fear acquisition, extinction, and exposure therapy. It is concluded that exposure therapy is a form of cognitive intervention that specifically changes the expectancy of harm. Implications for therapy research are discussed.
Posttraumatic stress disorder: conceptualization and treatment. [2007]After a long history of both scientific and political debate, the notion that extreme psychological traumatic experiences, in and of themselves, could result in a severe, even malignant, psychiatric disorder is now established. In 1980 posttraumatic stress disorder finally became an officially classified anxiety disorder. Since then, the few controlled treatment outcome studies that have been carried out appear to indicate that the most effective treatment for PTSD is some form of exposure therapy. This is not surprising in light of the fact that several other types of anxiety disorders respond well to this form of behavioral treatment. However, PTSD may be more complex than the other types of anxiety disorders, especially with regard to the variety of symptoms involved. In its chronic form or in combat-related PTSD, no one type of treatment tested so far has been successful in reducing all the symptoms of the disorder. Psychophysiological overarousal to imaginal facsimiles of the traumatic event is especially difficult to influence with treatment. Identifying techniques that reduce or at least control this arousal will likely be grist for the research mill for many years. Theoretical and conceptual formulations regarding both the etiology and treatment of the disorder are in early stages of development. It is hoped that these efforts will eventually mature our understanding of the disorder as researchers explore important issues such as (1) predisposing factors; (2) how the nature and intensity of the stressor relates to the severity of the disorder; and (3) how biological, psychological, social, and cultural variables interact to result in PTSD and to either ameliorate or exacerbate its symptoms.
Exposure therapy for post-traumatic stress disorder. Four case studies. [2019]Four cases of PTSD, and their treatment, are described. Symptoms responded differently to two behavioural approaches. In-vivo exposure was effective for phobic anxiety while imaginal exposure improved dysphoria and some phobic symptoms. Audio-taped imaginal exposure may be important as part of treatment.
Acquisition, extinction, and return of fear in veterans in intensive outpatient prolonged exposure therapy: A fear-potentiated startle study. [2023]Prolonged exposure (PE) therapy is a first-line treatment for posttraumatic stress disorder (PTSD) and involves repeated presentation of trauma-related cues without aversive outcomes. A primary learning mechanism of PE is fear extinction (new learning that a dangerous cue is now safe) and its retention (maintaining this new learning over time). Extant research suggests extinction is impaired in PTSD patients. In this study, we employed an established fear-potentiated startle-based paradigm to examine fear acquisition, extinction learning and retention before and after completion of intensive outpatient treatment. First, PTSD patients undergoing PE (n = 55) were compared to trauma-exposed patients without PTSD (n = 57). We identified excessive fear in PTSD patients during acquisition and extinction before treatment compared to non-PTSD patients. At post-treatment, we examined the return of fear after extinction in PTSD patients showing high or low treatment response to PE (≥50% change in PTSD symptom severity vs.
Exposure therapy for posttraumatic stress disorder. [2018]Exposure therapy is a well-established treatment for Posttraumatic Stress Disorder (PTSD) that requires the patient to focus on and describe the details of a traumatic experience. Exposure methods include confrontation with frightening, yet realistically safe, stimuli that continues until anxiety is reduced. A review of the literature on exposure therapy indicates strong support from well-controlled studies applied across trauma populations. However, there are many misconceptions about exposure therapy that may interfere with its widespread use. These myths and clinical guidelines are addressed. It is concluded that exposure therapy is a safe and effective treatment for PTSD when applied as directed by experienced therapists.
Integrated exposure-based therapy for co-occurring posttraumatic stress disorder and substance dependence: a randomized controlled trial. [2022]There is concern that exposure therapy, an evidence-based cognitive-behavioral treatment for posttraumatic stress disorder (PTSD), may be inappropriate because of risk of relapse for patients with co-occurring substance dependence.
Exposure Therapy Beliefs and Utilization for Treatment of PTSD: A Survey of Licensed Mental Health Providers. [2021]Exposure-based therapies for posttraumatic stress disorder (PTSD) and anxiety disorders remain underutilized, despite their effectiveness and widescale dissemination efforts. This study surveyed a broad range of licensed providers (N = 155) to examine rates at which prolonged exposure (PE) and other interventions are used to treat PTSD and to investigate provider characteristics linked to exposure beliefs and utilization. While 92.3% of clinicians reported understanding of or training in exposure, only 55.5% of providers reported use of PE to treat PTSD. Clinicians with current cognitive behavioral therapy (CBT) orientation, CBT training orientation, a doctoral degree, and training in PE endorsed greater likelihood of exposure utilization for PTSD (ps
Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors. [2021]Post-traumatic stress disorder (PTSD) is a heterogeneous disorder that affects individuals exposed to trauma (e.g., combat, interpersonal violence, and natural disasters). It is characterized by hyperarousal, intrusive reminders of the trauma, avoidance of trauma-related cues, and negative cognition and mood. This heterogeneity indicates the presence of multiple neurobiological mechanisms underlying the development and maintenance of PTSD. Fear conditioning is a robust, translational experimental paradigm that can be employed to elucidate these mechanisms by allowing for the study of fear-related dimensions of PTSD (e.g., fear extinction, fear inhibition, and generalization of fear) across multiple units of analysis. Fear conditioning experiments have identified varying trajectories of the dimensions described, highlighting exciting new avenues of targeted, focused study. Additionally, fear conditioning studies provide a translational platform to develop novel interventions. The current review highlights the versatility of fear conditioning paradigms, the implications for pharmacological and non-pharmacological treatments, the robustness of these paradigms to span an array of neuroscientific measures (e.g., genetic studies), and finally the need to understand the boundary conditions under which these paradigms are effective. Further understanding these paradigms will ultimately allow for optimization of fear conditioning paradigms, a necessary step towards the advancement of PTSD treatment methods.
The clinical applications and practical relevance of human conditioning paradigms for posttraumatic stress disorder. [2019]The classical conditioning paradigm of fear learning has spawned a number of experimental variations for the explanation of posttraumatic stress disorder (PTSD) etiology. These paradigms include extinction learning and recall, fear inhibition, fear generalization, and conditioned avoidance. As such, each of these paradigms have significant applications for understanding the development, maintenance, treatment, and relapse of the fear-related features of PTSD. In the present review, we describe each of these conditioning-based paradigms with reference to the clinical applications, and supported by case examples from patients with severe PTSD symptoms. We also review the neurobiological models of conditioning and extinction in animals, psychiatrically healthy humans, and PTSD patients, and discuss the current balance of evidence suggesting a number of biological, behavioral, and cognitive mechanisms/moderators of the conditioning and extinction process in experimental and clinical contexts.
Optimizing inhibitory learning during exposure therapy. [2022]Prevailing models of exposure therapy for phobias and anxiety disorders construe level of fear throughout exposure trials as an index of corrective learning. However, the evidence, reviewed herein, indicates that neither the degree by which fear reduces nor the ending fear level predict therapeutic outcome. Developments in the theory and science of fear extinction, and learning and memory, indicate that 'performance during training' is not commensurate with learning at the process level. Inhibitory learning is recognized as being central to extinction and access to secondary inhibitory associations is subject to influences such as context and time, rather than fear during extinction training. Strategies for enhancing inhibitory learning, and its retrieval over time and context, are reviewed along with their clinical implications for exposure therapy and directions for future research.
Extinction learning before trauma and subsequent posttraumatic stress. [2022]Fear conditioning theories propose that persistent stress reactions may occur as a result of impaired extinction learning, and a poor capacity for extinction learning may predispose some individuals to posttraumatic stress disorder development. This study indexed the extent to which deficits in extinction learning before trauma exposure are a risk factor for persistent posttraumatic stress after trauma exposure.
The M-Maze task: An automated method for studying fear memory in rats exposed to protracted aversive conditioning. [2019]Fear conditioning (FC) in rodents is the most used animal model to investigate the neurobiology of posttraumatic stress disorder (PTSD). Although research using FC has generated a better understanding of fear memories, studies often rely on mild or moderate FC training and behavioral analysis generally focuses on measuring freezing responses within few test sessions.