Clinical trial NCT03786952: Stress, Sex, and the Generalization of Fear
Official title: Stress, Sex, and the Generalization of Fear
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Psychological Stress
Keywords: stress
sex
fear
generalization
cortisol
alpha-amylase
estradiol
progesterone
Lead sponsor: Ohio Northern University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2018-12-26
Enrollment: 606
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition
timeFrame: Average of the responses from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1
measure: EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing
timeFrame: Average of responses from all trials on Day 2
measure: Skin Conductance Responses to CS+ and CS- During Acquisition
timeFrame: Average of the responses from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1
measure: Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing
timeFrame: Average of responses from all trials on Day 2
measure: US Expectancy Ratings to CS+ and CS- During Acquisition
timeFrame: Average of the ratings from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1
measure: US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing
timeFrame: Average of ratings from all trials on Day 2
Secondary outcomes:
measure: Change in Baseline Salivary Cortisol (Nmol/l)
timeFrame: Day 1 (change from baseline to 25 min post-stress)
measure: Change in Baseline Salivary Alpha-amylase (U/ml)
timeFrame: Day 1 (change from baseline to immediately after stress)
measure: Average Subjective Pain, as Assessed by Verbal Self Report
timeFrame: Stress or sham control condition on Day 1
measure: Average Subjective Stress, as Assessed by Verbal Self Report
timeFrame: Stress or sham control condition on Day 1
measure: Change in Heart Rate (Bpm)
timeFrame: Day 1 (change from baseline to during stress or sham control manipulation)
measure: Change in Salivary Progesterone (pg/ml)
timeFrame: Day 1 (change from baseline to 25 min post-stress)
Other outcomes:
measure: Salivary Estradiol (pg/ml)
timeFrame: Average across Day 1 (baseline) and Day 2 (baseline)
measure: State Anxiety
timeFrame: Day 2 - following generalization testing
measure: Childhood Trauma Questionnaire (CTQ)
timeFrame: Day 2 - following generalization testing
measure: Anxiety Sensitivity Index
timeFrame: Day 2 - following generalization testing
measure: Center for Epidemiological Studies Depression Scale (CES-D)
timeFrame: Day 2 - following generalization testing
measure: PTSD Checklist - Civilian Version
timeFrame: Day 2 - following generalization testing
Locations:
city: Ada
country: United States
facility: Ohio Northern University
state: Ohio
Study officials:
affiliation: Ohio Northern University
name: Phillip Zoladz, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: