Stress, Sex, and the Generalization of Fear

NCT ID: NCT03786952

Last Updated: 2023-03-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 606 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-25
• Study Completion Date: 2022-06-30

Brief Summary

The impact of well-known risk factors for such disorders (stress, biological sex, anxiety-related dispositions) on fear generalization will be examined. Findings from this study may provide insight into how these risk factors influence the development and/or maintenance of psychological disorders that involve overgeneralization of fear and could facilitate future approaches to their treatment.

Detailed Description

Many researchers approach the etiology of trauma-, stressor-, and anxiety-related mental disorders from the perspective of classical conditioning processes gone awry. According to this view, abnormal associative relationships between neutral, conditioned stimuli (CSs) and aversive, unconditioned stimuli (USs) underlie pathological anxiety and result in unusually intense fear memories or fear memories that cannot be properly extinguished. Recent work has expanded this view by showing that many psychological disorders involving pathological anxiety are associated with an exaggerated form of the commonly adaptive classical conditioning phenomenon, stimulus generalization, leading individuals with such disorders to respond with fear and anxiety to a variety of environmental contexts and cues that should not be threatening. Few studies have been conducted in humans to better understand the process of fear generalization, and factors that might influence susceptibility to overgeneralize fear have yet to be assessed. It is well-known that stress, biological sex, and anxiety-related dispositions of an individual increase one's susceptibility for pathological anxiety and significantly impact fear learning; thus, it is possible that such factors, alone or in combination, contribute to clinical anxiety by influencing fear generalization processes. Aim 1 of the present study is to determine the effects of acute stress and its physiological correlates on fear generalization in human participants. Because acute stress profoundly impacts cognitive brain areas that underlie generalization, it is predicted that acute stress will enhance or impair fear generalization, depending on when the stressor is administered relative to fear learning. Aim 2 is to assess the role of biological sex in fear generalization and acute stress-induced changes in such processes. Females are more likely than males to develop several psychological disorders that involve pathological anxiety, and research has consistently reported sex-related differences in fear learning and stress-induced alterations of fear learning, effects that have been associated with ovarian hormones. Thus, it is predicted that females will exhibit greater fear generalization than males that will be impacted differently by stress. It is also hypothesized that the observed effects will correlate with estradiol and progesterone in females. The final aim of this project (Aim 3) is to evaluate the relationship between childhood stress, dispositional anxiety, and fear generalization. Early life stress has been repeatedly associated with altered stress responses and the development of anxiety-related phenotypes, yet the influence of childhood stress and trait anxiety on fear generalization have yet to be examined. This study will be the first to examine how several factors that are known to increase susceptibility for trauma-, stressor, and anxiety-related psychological disorders impact fear generalization in human subjects. The resulting findings will provide important insight into the etiology of such disorders, which could aid future approaches to their treatment.

Conditions

Psychological Stress

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Stress, immediate, males

Stress immediately before learning in males

Group Type: EXPERIMENTAL

Stress immediately before learning in males

Intervention Type: BEHAVIORAL

Male participants will be exposed to the socially evaluated cold pressor test immediately prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Immediately following the acute stressor, participants will undergo the acquisition phase of fear conditioning.

Stress, delayed, males

Stress 30 minutes before learning in males

Group Type: EXPERIMENTAL

Stress 30 minutes before learning in males

Intervention Type: BEHAVIORAL

Male participants will be exposed to the socially evaluated cold pressor test 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Thirty minutes following the acute stressor, participants will undergo the acquisition phase of fear conditioning.

Sham control, immediate, males

Sham control immediately before learning in males

Group Type: SHAM_COMPARATOR

Sham control immediately before learning in males

Intervention Type: BEHAVIORAL

Male participants will be exposed to the sham control condition (no stress) immediately prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Immediately following the sham control condition, participants will undergo the acquisition phase of fear conditioning.

Sham control, delayed, males

Sham control 30 minutes before learning in males

Group Type: SHAM_COMPARATOR

Sham control 30 minutes before learning in males

Intervention Type: BEHAVIORAL

Male participants will be exposed to the sham control condition (no stress) 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Thirty minutes following the sham control condition, participants will undergo the acquisition phase of fear conditioning.

Stress, immediate, females

Stress immediately before learning in females

Group Type: EXPERIMENTAL

Stress immediately before learning in females

Intervention Type: BEHAVIORAL

Female participants will be exposed to the socially evaluated cold pressor test immediately prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Immediately following the acute stressor, participants will undergo the acquisition phase of fear conditioning.

Stress, delayed, females

Stress 30 minutes before learning in females

Group Type: EXPERIMENTAL

Stress 30 minutes before learning in females

Intervention Type: BEHAVIORAL

Female participants will be exposed to the socially evaluated cold pressor test 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Thirty minutes following the acute stressor, participants will undergo the acquisition phase of fear conditioning.

Sham control, immediate, females

Sham control immediately before learning in females

Group Type: SHAM_COMPARATOR

Sham control immediately before learning in females

Intervention Type: BEHAVIORAL

Female participants will be exposed to the sham control condition (no stress) immediately prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Immediately following the sham control condition, participants will undergo the acquisition phase of fear conditioning.

Sham control, delayed, females

Sham control 30 minutes before learning in females

Group Type: SHAM_COMPARATOR

Sham control 30 minutes before learning in females

Intervention Type: BEHAVIORAL

Female participants will be exposed to the sham control condition (no stress) 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Thirty minutes following the sham control condition, participants will undergo the acquisition phase of fear conditioning.

Interventions

Stress immediately before learning in males

Male participants will be exposed to the socially evaluated cold pressor test immediately prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Immediately following the acute stressor, participants will undergo the acquisition phase of fear conditioning.

Intervention Type: BEHAVIORAL

Sham control immediately before learning in males

Male participants will be exposed to the sham control condition (no stress) immediately prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Immediately following the sham control condition, participants will undergo the acquisition phase of fear conditioning.

Intervention Type: BEHAVIORAL

Stress 30 minutes before learning in males

Male participants will be exposed to the socially evaluated cold pressor test 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Thirty minutes following the acute stressor, participants will undergo the acquisition phase of fear conditioning.

Intervention Type: BEHAVIORAL

Sham control 30 minutes before learning in males

Male participants will be exposed to the sham control condition (no stress) 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Thirty minutes following the sham control condition, participants will undergo the acquisition phase of fear conditioning.

Intervention Type: BEHAVIORAL

Stress immediately before learning in females

Female participants will be exposed to the socially evaluated cold pressor test immediately prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Immediately following the acute stressor, participants will undergo the acquisition phase of fear conditioning.

Intervention Type: BEHAVIORAL

Sham control immediately before learning in females

Female participants will be exposed to the sham control condition (no stress) immediately prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Immediately following the sham control condition, participants will undergo the acquisition phase of fear conditioning.

Intervention Type: BEHAVIORAL

Stress 30 minutes before learning in females

Female participants will be exposed to the socially evaluated cold pressor test 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Thirty minutes following the acute stressor, participants will undergo the acquisition phase of fear conditioning.

Intervention Type: BEHAVIORAL

Sham control 30 minutes before learning in females

Female participants will be exposed to the sham control condition (no stress) 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Thirty minutes following the sham control condition, participants will undergo the acquisition phase of fear conditioning.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• 18 years of age
• Registered student at Ohio Northern University in Ada, Ohio

Exclusion Criteria

• Regular use of tobacco or recreational drugs (e.g., marijuana, cocaine, heroin, etc.)
• Previous diagnosis of Raynaud's disease or peripheral vascular disease
• Previous diagnosis of skin diseases (e.g., severe psoriasis, eczema, scleroderma)
• History of syncope or vasovagal response to stress
• History of any heart conditions or cardiovascular issues (e.g., high blood pressure)
• History of severe head trauma
• Current treatment with narcotics, beta-blockers, or steroids
• Previous diagnosis of substance use disorder
• Regular nightshift work
• Hearing loss
• Consumed alcohol in past 24 hours
• Engaged in strenuous exercise in past 24 hours
• Ate or drank anything but water in past 2 hours

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Ohio Northern University

OTHER

Sponsor Role: lead

Responsible Party

Phillip Zoladz

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Phillip Zoladz, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Ohio Northern University

Locations

Ohio Northern University

Ada, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

R15MH116337

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R15MH116337-01A1

Identifier Type: NIH

Identifier Source: org_study_id

View Link