Clinical trial NCT00026559: Effects of Arousal and Stress in Anxiety
Official title: Effects of Arousal and Stress on Classical Conditioning
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Volunteers
Keywords: Classical Conditioning
Fear Conditioning
Stress
Learning
Normal Volunteers
Healthy Volunteer
Normal Control
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2001-11-12
Enrollment: 1418
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: * 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.

Primary outcomes:
measure: Go Correct Hits Followed by Button Press
timeFrame: 250 ms at a rate of one every 2000 ms
measure: Nogo Trials Followed by no Button Press
timeFrame: 250 ms at a rate of one every 2000 ms
measure: Correct-go Reaction Time (RT)
timeFrame: 2000 ms during trial
measure: Response to Startle Reflex
timeFrame: 20-100 ms window following the onset of the startle stimulus
measure: Subjective Measures of Level of Anxiety
timeFrame: Every 100 sec repeated 8 times
Secondary outcomes:
measure: Measure of Attention Control
timeFrame: 1-3 weeks before start of study
measure: Measure of Level of Anxiety
timeFrame: 1-3 weeks before start of study
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Institute of Mental Health (NIMH)
name: Maryland Pao, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.