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Stress, Sex, and the Generalization of Fear

O

Ohio Northern University

Status

Completed

Conditions

Psychological Stress

Treatments

Behavioral: Stress 30 minutes before learning in males
Behavioral: Sham control immediately before learning in males
Behavioral: Sham control immediately before learning in females
Behavioral: Stress immediately before learning in females
Behavioral: Sham control 30 minutes before learning in females
Behavioral: Stress immediately before learning in males
Behavioral: Sham control 30 minutes before learning in males
Behavioral: Stress 30 minutes before learning in females

Study type

Interventional

Funder types

Other
NIH

Identifiers

NCT03786952
1R15MH116337-01A1
R15MH116337 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

606 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Factorial Assignment

Masking

Double Blind

606 participants in 8 patient groups

Stress, immediate, males
Experimental group
Description:
Stress immediately before learning in males
Treatment:
Behavioral: Stress immediately before learning in males
Stress, delayed, males
Experimental group
Description:
Stress 30 minutes before learning in males
Treatment:
Behavioral: Stress 30 minutes before learning in males
Sham control, immediate, males
Sham Comparator group
Description:
Sham control immediately before learning in males
Treatment:
Behavioral: Sham control immediately before learning in males
Sham control, delayed, males
Sham Comparator group
Description:
Sham control 30 minutes before learning in males
Treatment:
Behavioral: Sham control 30 minutes before learning in males
Stress, immediate, females
Experimental group
Description:
Stress immediately before learning in females
Treatment:
Behavioral: Stress immediately before learning in females
Stress, delayed, females
Experimental group
Description:
Stress 30 minutes before learning in females
Treatment:
Behavioral: Stress 30 minutes before learning in females
Sham control, immediate, females
Sham Comparator group
Description:
Sham control immediately before learning in females
Treatment:
Behavioral: Sham control immediately before learning in females
Sham control, delayed, females
Sham Comparator group
Description:
Sham control 30 minutes before learning in females
Treatment:
Behavioral: Sham control 30 minutes before learning in females

Trial documents
1

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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