Stress, Sex, and the Generalization of Fear

NCT03786952 | Completed Results DMC

• 2 other identifiers: 1R15MH116337-01A1R15MH116337
• Study Type: interventional
• Target: 606
• Locations: 1 country
• Sites: 1

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.

Conditions

Psychological Stress

Keywords

stress; sex; fear; generalization; cortisol; alpha-amylase; estradiol; progesterone

Outcome Measures

Primary Outcomes (6)

• Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition

  Peak eyeblink startle responses 20-200 ms following presentation of a startle probe were measured. Startle responses were assessed for each of 3 trial types: (1) following the startle probe alone \[noise alone (NA) trials\], (2) following the CS+ and startle probe (CS+ trials), and (3) following the CS- and startle probe (CS- trials). Participants were exposed to 16 blocks of trials, and each block included 1 presentation of each trial type. During the last 12 blocks, CS+ trials also included the presentation of an aversive US. For each block, startle responses to NA trials were subtracted from startle responses to CS+ trials and from startle responses to CS- trials to create 2 separate fear-potentiated startle response measures: 1 for the CS+ and 1 for the CS-. Average fear-potentiated startle responses to the CS+ and CS- during the last 4 blocks of trials were used as an indicator of fear learning (greater responses to the CS+, relative to the CS-, indicated greater learning).

  Average of the responses from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1

• EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing

  Peak eyeblink startle responses 20-200 ms following the presentation of a startle probe were measured. Startle responses were assessed for each of 10 trial types: (1) following the startle probe alone \[noise alone (NA) trials\], (2) following the CS+ and startle probe (CS+ trials), (3) following each of 7 generalization stimuli and startle probe (GS trials), and (4) following the CS- and startle probe (CS- trials). Participants were exposed to 3 blocks of trials, and each block included 1 presentation of each trial type. For each block, startle responses to the NA trials were subtracted from startle responses to the CS+, GSs, and CS- trials to create separate fear-potentiated startle response measures for each of the 9 different stimuli. Average fear-potentiated startle responses to each stimulus across all 3 blocks were used as an indicator of fear expression. Greater scores for the generalization stimuli (GS) indicated a greater generalization of fear.

  Average of responses from all trials on Day 2

• Skin Conductance Responses to CS+ and CS- During Acquisition

  Electrodermal activity was measured following presentation of the CS+ and CS- during acquisition on Day 1. Participants were exposed to 16 blocks of trials, with each block including a single presentation of each stimulus. During the last 12 blocks, CS+ trials included the presentation of an aversive US. For each block, skin conductance responses were quantified by calculating the average increase in electrodermal activity (from a 1 s pre-stimulus baseline) 3-6 s after CS+ or CS- onset. Average skin conductance responses to the CS+ and CS- during the last 4 blocks of trials were used as an indicator of fear learning (greater responses to the CS+, relative to the CS-, indicated greater learning).

  Average of the responses from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1

• Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing

  Electrodermal activity was measured following presentation of the CS+, 7 generalization stimuli (GSs), and CS- during generalization testing on Day 2. Participants were exposed to 3 blocks of trials, with each block including a single presentation of each stimulus. For each block, skin conductance responses were quantified by calculating the average increase in electrodermal activity (from a 1 s pre-stimulus baseline) 3-6 s after onset of the CS+, 7 GSs, or CS- onset.. Average skin conductance responses to each stimulus across all 3 blocks were used as an indicator of fear expression. Greater scores for the generalization stimuli (GS) indicated a greater generalization of fear.

  Average of responses from all trials on Day 2

• US Expectancy Ratings to CS+ and CS- During Acquisition

  Participants were exposed to 16 blocks of trials, and each block included 1 presentation of the CS+ and one presentation of the CS-. During the last 12 blocks, CS+ trials included the presentation of an aversive US. During each trial, participants pressed, within 3 seconds of stimulus onset, a button marked "+" if they expected the stimulus to be followed by the US, a button marked "-" if they did not expect the stimulus to be followed by the US, or a button marked "0" if they were uncertain. For the purpose of data analysis, + was scored as +1, - were scored as -1, and 0 was scored as 0. Average expectancy ratings during the last 4 blocks of trials were used as an indicator of fear learning (greater responses to the CS+, relative to the CS-, indicated greater learning).

  Average of the ratings from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1

• US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing

  Participants were exposed to 3 blocks of trials, and each block included 1 presentation of the CS+, one presentation of each of 7 generalization stimuli (GSs), and one presentation of the CS-. Participants were instructed to press, within 3 seconds of stimulus onset, a button marked "+" if they expected the stimulus to be followed by the US, a button marked "-" if they did not expect the stimulus to be followed by the US, or a button marked "0" if they were uncertain. For the purpose of data analysis, + was scored as +1, - was scored as -1, and 0 was scored as 0. Average expectancy ratings for each stimulus across all 3 blocks were used as an indicator of fear. Greater scores for the generalization stimuli (GS) indicated a greater generalization of fear.

  Average of ratings from all trials on Day 2

Secondary Outcomes (6)

• Change in Baseline Salivary Cortisol (Nmol/l)

  Day 1 (change from baseline to 25 min post-stress)

• Change in Baseline Salivary Alpha-amylase (U/ml)

  Day 1 (change from baseline to immediately after stress)

• Average Subjective Pain, as Assessed by Verbal Self Report

  Stress or sham control condition on Day 1

• Average Subjective Stress, as Assessed by Verbal Self Report

  Stress or sham control condition on Day 1

• Change in Heart Rate (Bpm)

  Day 1 (change from baseline to during stress or sham control manipulation)

Other Outcomes (6)

• Salivary Estradiol (pg/ml)

  Average across Day 1 (baseline) and Day 2 (baseline)

• State Anxiety

  Day 2 - following generalization testing

• Childhood Trauma Questionnaire (CTQ)

  Day 2 - following generalization testing

Study Arms (8)

Stress, immediate, males

EXPERIMENTAL

Stress immediately before learning in males

Behavioral: Stress immediately before learning in males

Stress, delayed, males

EXPERIMENTAL

Stress 30 minutes before learning in males

Behavioral: Stress 30 minutes before learning in males

Sham control, immediate, males

SHAM COMPARATOR

Sham control immediately before learning in males

Behavioral: Sham control immediately before learning in males

Sham control, delayed, males

SHAM COMPARATOR

Sham control 30 minutes before learning in males

Behavioral: Sham control 30 minutes before learning in males

Stress, immediate, females

EXPERIMENTAL

Stress immediately before learning in females

Behavioral: Stress immediately before learning in females

Stress, delayed, females

EXPERIMENTAL

Stress 30 minutes before learning in females

Behavioral: Stress 30 minutes before learning in females

Sham control, immediate, females

SHAM COMPARATOR

Sham control immediately before learning in females

Behavioral: Sham control immediately before learning in females

Sham control, delayed, females

SHAM COMPARATOR

Sham control 30 minutes before learning in females

Behavioral: Sham control 30 minutes before learning in females

Interventions

Stress immediately before learning in males 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, immediate, males

Sham control immediately before learning in males 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, immediate, males

Stress 30 minutes before learning in males 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.

Stress, delayed, males

Sham control 30 minutes before learning in males 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.

Sham control, delayed, males

Stress immediately before learning in females 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, immediate, females

Sham control immediately before learning in females 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, immediate, females

Stress 30 minutes before learning in females 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.

Stress, delayed, females

Sham control 30 minutes before learning in females 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.

Sham control, delayed, females

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ohio Northern University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Ohio Northern University

Ada, Ohio, 45810, United States

Location

MeSH Terms

Conditions

Stress, Psychological; Coitus

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Sexual Behavior

Results Point of Contact

• Title: Phillip Zoladz
• Organization: Ohio Northern University

p-zoladz@onu.edu

419-772-2142

Study Officials

• Phillip Zoladz, Ph.D.

  Ohio Northern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 26, 2018
• Study Start: January 25, 2019
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: March 23, 2023
• Results First Posted: March 23, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data were shared on a semi-annual basis, beginning in January 2020.
• Access Criteria: NIMH Data Archive

Locations

US (1)