Effects of Arousal and Stress in Anxiety

NCT ID: NCT00026559

Last Updated: 2024-01-09

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1418 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-01-10

Study Completion Date

2022-07-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study has several parts. One part will examine the influence of factors such as personality and past experience on reactions to unpleasant stimuli. Others will examine the effect of personality and emotional and attentional states on learning and memory.

When confronted with fearful or unpleasant events, people can develop fear of specific cues that were associated with these events as well as to the environmental context in which the events occurred via a process called classical conditioning. Classical conditioning has been used to model anxiety disorders, but the relationship between stress and anxiety and conditioned responses remains unclear. This study will examine the relationship between cued conditioning and context conditioning . This study will also explore the acquisition and retention of different types of motor, emotional, and cognitive associative processes during various tasks that range from mildly arousing to stressful.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Objective: Fear and anxiety are adaptive responses to different types of threats. Fear is a short-duration response evoked by explicit threat cues and anxiety a more sustained state of apprehension evoked by unpredictable threat. This protocol studied fear using Pavlovian fear conditioning in two studies. Studies 1 and 3. Study 2 focused on anxiety. Studies 1 and 3 will be discontinued to focus uniquely on the study of anxiety. Specifically, we will examine the interactions between anxiety induced experimentally using verbal threat and cognitive processes. We will seek to 1) characterize the effect of anxiety on key cognitive processes including working memory and attention control and 2) examine the extent to which performance of cognitive tasks distract from anxiety.

Study population: This more-than-minimal-risk protocol will test medically and psychiatrically healthy volunteers aged 18-50. Pregnant or nursing women will be excluded.

Method: Fear and anxiety will be measured using the startle reflex to brief and loud sounds. Fear conditioning will be assessed using shock as unconditioned stimulus. Cognitive performance will be examined during periods of unpredictable shock anticipation.

Outcome measures: The study will include cognitive performance and measure of aversive states, primarily the startle reflex.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy Volunteers

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Healthy volunteers

Sub-study A: Working memory task / Participant performed a working memory task in two conditions, under threat of shock and in safety and asked to remember verbal and nonverbal stimuli from the current stimulus on the screen (N-back task) Sub-study C: Sustained attention to response task (SART) / participant was presented with stimuli and either initiated a response (i.e. "go") or inhibited their response (i.e. "stop") based on what stimuli were presented Sub-study D: Stroop task/ In the classic Stroop test, the name of a color is printed in a color that conflicts or does not conflict with the word. In the emotional Stroop, the words emotional words. The participant's task was to name the color of the word Pilot studies / (1) Shocks were delivered via electrodes located on the forearm or fingers while participant performed a working memory or vigilance task or (2) Subject performed cognitive tasks during alternating safe and threat periods

Group Type EXPERIMENTAL

Shock Device

Intervention Type DEVICE

Shock Device

Auditory Startle Device

Intervention Type DEVICE

Auditory Startle Device

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Shock Device

Shock Device

Intervention Type DEVICE

Auditory Startle Device

Auditory Startle Device

Intervention Type DEVICE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Males and females
* Age 18-50

Exclusion Criteria

* Pregnancy
* Any current ongoing medical illness
* Current Axis I disorders
* Past significant psychiatric disorders (e.g., psychotic disorders) according to Diagnostic and Statistical Manual (DSM)-IV
* Current alcohol or substance abuse according to DSM-IV criteria
* History of alcohol or substance dependence based on DSM-IV criteria within 6 months prior to screening
* Current psychotropic medication use
* Current or past organic central nervous system disorders, including but not limited to seizure disorder or neurological symptoms of the wrist and arms (e.g., carpal tunnel syndrome). The latter exclusion is for shock studies only.
* Positive urine toxicology screen
* Employees of National Institute of Mental Health (NIMH) or an immediate family member of a NIMH employee.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute of Mental Health (NIMH)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Maryland Pao, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Mental Health (NIMH)

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Grillon C, Morgan CA 3rd. Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder. J Abnorm Psychol. 1999 Feb;108(1):134-42. doi: 10.1037//0021-843x.108.1.134.

Reference Type BACKGROUND
PMID: 10066999 (View on PubMed)

Grillon C, Ameli R, Goddard A, Woods SW, Davis M. Baseline and fear-potentiated startle in panic disorder patients. Biol Psychiatry. 1994 Apr 1;35(7):431-9. doi: 10.1016/0006-3223(94)90040-x.

Reference Type BACKGROUND
PMID: 8018793 (View on PubMed)

Phillips RG, LeDoux JE. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci. 1992 Apr;106(2):274-85. doi: 10.1037//0735-7044.106.2.274.

Reference Type BACKGROUND
PMID: 1590953 (View on PubMed)

Balderston NL, Liu J, Roberson-Nay R, Ernst M, Grillon C. The relationship between dlPFC activity during unpredictable threat and CO2-induced panic symptoms. Transl Psychiatry. 2017 Nov 30;7(12):1266. doi: 10.1038/s41398-017-0006-5.

Reference Type RESULT
PMID: 29213110 (View on PubMed)

Grillon C, Robinson OJ, Krimsky M, O'Connell K, Alvarez G, Ernst M. Anxiety-mediated facilitation of behavioral inhibition: Threat processing and defensive reactivity during a go/no-go task. Emotion. 2017 Mar;17(2):259-266. doi: 10.1037/emo0000214. Epub 2016 Sep 19.

Reference Type RESULT
PMID: 27642657 (View on PubMed)

Grillon C, Robinson OJ, Mathur A, Ernst M. Effect of attention control on sustained attention during induced anxiety. Cogn Emot. 2016;30(4):700-12. doi: 10.1080/02699931.2015.1024614. Epub 2015 Apr 22.

Reference Type RESULT
PMID: 25899613 (View on PubMed)

Lago TR, Hsiung A, Leitner BP, Duckworth CJ, Balderston NL, Chen KY, Grillon C, Ernst M. Exercise modulates the interaction between cognition and anxiety in humans. Cogn Emot. 2019 Jun;33(4):863-870. doi: 10.1080/02699931.2018.1500445. Epub 2018 Jul 23.

Reference Type RESULT
PMID: 30032703 (View on PubMed)

Roxburgh AD, White DJ, Grillon C, Cornwell BR. A neural oscillatory signature of sustained anxiety. Cogn Affect Behav Neurosci. 2023 Dec;23(6):1534-1544. doi: 10.3758/s13415-023-01132-1. Epub 2023 Oct 25.

Reference Type DERIVED
PMID: 37880568 (View on PubMed)

Grillon C, Ernst M. A way forward for anxiolytic drug development: Testing candidate anxiolytics with anxiety-potentiated startle in healthy humans. Neurosci Biobehav Rev. 2020 Dec;119:348-354. doi: 10.1016/j.neubiorev.2020.09.024. Epub 2020 Oct 7.

Reference Type DERIVED
PMID: 33038346 (View on PubMed)

Grillon C, Lago T, Stahl S, Beale A, Balderston N, Ernst M. Better cognitive efficiency is associated with increased experimental anxiety. Psychophysiology. 2020 Aug;57(8):e13559. doi: 10.1111/psyp.13559. Epub 2020 Mar 17.

Reference Type DERIVED
PMID: 32180239 (View on PubMed)

Sarigiannidis I, Grillon C, Ernst M, Roiser JP, Robinson OJ. Anxiety makes time pass quicker while fear has no effect. Cognition. 2020 Apr;197:104116. doi: 10.1016/j.cognition.2019.104116. Epub 2019 Dec 26.

Reference Type DERIVED
PMID: 31883966 (View on PubMed)

Robinson OJ, Pike AC, Cornwell B, Grillon C. The translational neural circuitry of anxiety. J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1353-1360. doi: 10.1136/jnnp-2019-321400. Epub 2019 Jun 29.

Reference Type DERIVED
PMID: 31256001 (View on PubMed)

Balderston NL, Hsiung A, Liu J, Ernst M, Grillon C. Reducing State Anxiety Using Working Memory Maintenance. J Vis Exp. 2017 Jul 19;(125):55727. doi: 10.3791/55727.

Reference Type DERIVED
PMID: 28745646 (View on PubMed)

Lago T, Davis A, Grillon C, Ernst M. Striatum on the anxiety map: Small detours into adolescence. Brain Res. 2017 Jan 1;1654(Pt B):177-184. doi: 10.1016/j.brainres.2016.06.006. Epub 2016 Jun 6.

Reference Type DERIVED
PMID: 27276526 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

01-M-0185

Identifier Type: -

Identifier Source: secondary_id

010185

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Fear and Avoidance in PTSD Patients
NCT04770584 RECRUITING NA
Cognitive Training for PTSD
NCT03316196 COMPLETED NA