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Neurobiology of Generalized Fear-Conditioning & Avoidance in Anxiety Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03033056
Recruitment Status : Recruiting
First Posted : January 26, 2017
Last Update Posted : May 26, 2021
Information provided by (Responsible Party):
University of Minnesota

Brief Summary:
Anxiety disorders are among the most prevalent, costly, and disabling mental illnesses. One central, yet largely understudied, abnormality in anxiety disorders is the heightened tendency to display fear and avoidance in reaction to benign or safe events that resemble feared situations. The current project maps brain circuits associated with this abnormality in order to contribute to future brain-based diagnosis and treatments for clinical anxiety.

Condition or disease Intervention/treatment
Anxiety Disorders Behavioral: Test of fear conditioning

Detailed Description:
The objective of this project is to neurally, behaviorally, psychologically, and clinically characterize fundamental Pavlovian and instrumental dimensions of potential threat through which emotional and behavioral responses to threat cues generalize to resembling, safe stimuli. Such generalization is aligned with the potential threat construct due to the threat ambiguity, or uncertain threat value, inherent in these safe 'generalization' stimuli. The Pavlovian dimension of interest is generalization of conditioned fear: a fundamental Pavlovian process through which fear transfers, or generalizes, to safe stimuli resembling a conditioned threat-cue (CS+). The targeted instrumental dimension is generalized avoidance: active decisions to withdraw from safe stimuli resembling the CS+ that are motivationally prompted by Pavlovian generalization. Given lab-based findings have linked heightened Pavlovian generalization to a variety of traditional anxiety disorders, overgeneralization represents a promising dimension of potential threat with relevance across traditional anxiety disorders. One central aspect of this project is testing personality and psychiatric factors (e.g., trait fear, internalizing, externalizing) that may account for the relevance of generalization and its neurobiology across traditional anxiety disorders. A second key aspect, is studying neural processes by which Pavlovian generalization evokes instrumental generalized avoidance of benign stimuli (resembling danger cues), which, when excessive, is likely to impair day-to-day functioning in anxiety patients. Unfortunately, human fear-conditioning experiments in clinical samples, have focused almost exclusively on passive-emotional, Pavlovian conditioning, to the virtual exclusion of studying active-behavioral, instrumental avoidance. The current neuroimaging project fills this gap by applying a novel Pavlovian-instrumental generalization paradigm to neurally and behaviorally elucidate Pavlovian processes leading to generalized instrumental avoidance. Personality moderators (e.g., dispositional resilience) of relations between Pavlovian and instrumental generalization will also be examined. The studied adult samples will display a wide range of symptom severity across traditional anxiety disorders and will include anxiety-clinic patients and healthy comparisons (N=159). Central goals of this proposal include: 1) elucidating the neurobiology of Pavlovian and instrumental generalization and their interaction, 2) testing relations between neural substrates of Pavlovian and instrumental generalization and broad psychiatric dysfunction (Aims2-3); and 3) assessing the degree to which relations between these dimensions of generalization and broad dysfunction are driven by psychometrically validated personality traits relevant across traditional anxiety disorders. This third and final goal is critical to the project, because individual difference measures capturing empirically-validated psychological constructs will likely track relations between fundamental conditioning processes (e.g., generalization) and general dysfunction, better than traditional, polythetic, diagnostic entities, that, by and large, do not reflect any single coherent psychological process.

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Study Type : Observational
Estimated Enrollment : 159 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Neurobiology of Generalized Fear-Conditioning & Avoidance in Anxiety Disorders (Community Anxiety Response Study)
Actual Study Start Date : July 17, 2017
Estimated Primary Completion Date : August 1, 2021
Estimated Study Completion Date : August 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Group/Cohort Intervention/treatment
Anxiety Clinic Patients
Adult males and females being treated at the anxiety disorders clinic at the University of Minnesota predominantly for clinical anxiety.
Behavioral: Test of fear conditioning
Behavioral and brain correlates of conditioned fear generalization and avoidance will be assessed using fMRI and related to levels of anxiety related psychopathology.

Healthy Comparisons
Sex, age, and socioeconomically matched healthy controls
Behavioral: Test of fear conditioning
Behavioral and brain correlates of conditioned fear generalization and avoidance will be assessed using fMRI and related to levels of anxiety related psychopathology.

Primary Outcome Measures :
  1. Functional magnetic resonance imaging [ Time Frame: Years 1-4 ]
    Blood oxygenation level dependent responses elicited during the fear conditioning paradigm

Secondary Outcome Measures :
  1. Behavioral measures [ Time Frame: Years 1-4 ]
    Online behavioral responses elicited during the fear conditioning paradigm

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Male and female adults presenting with anxiety symptoms at the Anxiety Disorders Clinic in the Department of Psychiatry at U of MN, as well as demographically matched healthy comparisons

Inclusion Criteria:

A. Diagnosis: No psychiatric diagnosis is required, but recruitment will be guided by the goal of attaining a sample with wide-ranging levels of both anxiety symptom severity and individual differences in anxiety-related states and traits.

B. Caffeine and tobacco use: Participants will abstain from caffeine and tobacco one hour preceding testing

Exclusion Criteria:

A. Psychiatric health: Current or past history of any psychotic disorder, bipolar disorder, delirium, dementia, amnestic disorder, or mental retardation; comorbid depression if accompanied by current, significant suicide risk; substance use disorder presently or for the six months preceding testing.

B. Current use of any medication that alters central nervous system function including antidepressants, benzodiazepines, anti-psychotics, mood stabilizers,anti-parkinsonian agents, anti-convulsants, sleep medications, pain medications, and anti-hypertensives.

C. Medical health: Current or past medical illnesses which in the investigator's opinion may confound study results, or place the participant at risk.

D. Pregnancy status: Females who are, or may be, pregnant. Recruitment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03033056

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Contact: Ashley Wright, BA 612-624-3395

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United States, Minnesota
University of MInnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Ashley Wright, BA    612-624-3395   
Principal Investigator: Shmuel Lissek, PhD         
Sponsors and Collaborators
University of Minnesota
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Principal Investigator: Shmuel Lissek, PhD U of MN
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Responsible Party: University of Minnesota Identifier: NCT03033056    
Other Study ID Numbers: 1610M96641
First Posted: January 26, 2017    Key Record Dates
Last Update Posted: May 26, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Minnesota:
behavioral avoidance
anxiety disorders
Additional relevant MeSH terms:
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Anxiety Disorders
Pathologic Processes
Mental Disorders