Expectation of Unpleasant Events in Anxiety Disorders

NCT00055224 | Completed Results FDA Device

• 2 other identifiers: 03009303-M-0093
• Study Type: interventional
• Target: 921
• Locations: 1 country
• Sites: 1

Brief Summary

Fear and anxiety are normal responses to a threat. However, anxiety is considered abnormal when the response to the threat is excessive or inappropriate. This study will examine changes in the body and brain that occur during unpleasant learning experiences in healthy volunteers with high, moderate, and low levels of anxiety. A high degree of generalized anxiety is a component of many anxiety disorders and is regarded as a marker of vulnerability for these disorders. People with anxiety disorders and individuals with high degrees of anxiety have inappropriate expectations of unpleasant events. This study will investigate the development of expecting unpleasant events in healthy volunteers with varying degrees of anxiety using aversive conditioning models. A later phase of the study will enroll participants with anxiety disorders and compare their responses to those of healthy volunteers. Patients who meet criteria for an anxiety disorder, and healthy volunteers who have no history of psychiatric or major medical illness will be enrolled in this study. Volunteers will come to the NIH Clinical Center three times for outpatient testing....

Conditions

Anxiety Disorders

Keywords

Anxiety Disorder; Psychophysiology; Shock Threat; Context Conditioning; Agoraphobia; Panic Disorder; Generalized Anxiety Disorder; GAD; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (24)

• Change in Percent of Correct Button Presses During Threat Compared to the Safe Condition (AAST)

  Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct responses by the total number of each trial type. Improvement in accuracy was measured as a higher percent of correct button presses during threat compared to safety.

  2000 ms during trial

• Change in Percent of Correct no Button Presses During Threat Compared to the Safe Condition

  Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct responses by the total number of each trial type. Improvement in accuracy was measured as a higher percent of correct button presses during threat compared to safety.

  2000 ms during trial

• Correct-go Reaction Time (RT) - Safe Condition

  Correct go responses were go trials followed by button press. Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe). Mean reaction time (RT) was calculated for correct-go to evaluate speed-accuracy trade-off.

  2000 ms during trial

• Correct-go Reaction Time (RT) - Threat Condition

  Correct go responses were go trials followed by button press. Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe). Mean reaction time (RT) was calculated for correct-go to evaluate speed-accuracy trade-off.

  2000 ms during trial

• Go Correct Hits Followed by Button Press - Safe Condition

  Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.

  2000 ms during trial

• Go Correct Hits Followed by Button Press - Threat Condition

  Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent (91%) 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent (9%) 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.

  2000 ms during trial

• Nogo Trials Followed by no Button Press - Safe Condition

  Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.

  2000 ms during trial

• Nogo Trials Followed by no Button Press - Threat Condition

  Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 ms to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.

  2000 ms during trial

• Stroop Effect on Accuracy During Congruent Task Viewing Positive Images: Safe Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Congruent Task Viewing Positive Images: Threat Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Congruent Task Viewing Negative Images: Safe Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Congruent Task Viewing Negative Images: Threat Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Congruent Task Viewing Neutral Images: Safe Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Congruent Task Viewing Neutral Images: Threat Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Incongruent Task Viewing Positive Images: Safe Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Incongruent Task Viewing Positive Images: Threat Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Incongruent Task Viewing Negative Images: Safe Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Incongruent Task Viewing Negative Images: Threat Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Incongruent Task Viewing Neutral Images: Safe Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Stroop Effect on Accuracy During Incongruent Task Viewing Neutral Images: Threat Condition

  Participants watched as six trial types differing by congruence and emotion (negative, neutral, positive) were presented during condition blocks (safe, threat) on a computer screen. Each trial began with a fixation point which was then immediately followed by a picture stimulus, followed by a numerical display, followed by a repeat of the picture stimulus, and followed by a blank screen. During threat, a participant could receive a shock. During safe, a participant could not receive a shock. The effect of accuracy on congruence across negative, positive, and neutral images in threat and safe conditions was assessed by participants accurate identification of facial expression.

  11.2 minutes per run for a total of 22.4 minutes

• Subjective Rating of Difficulty With Attention During Safe Condition

  Following tasks completion, participants provided retrospective ratings of: anxiety and attention during safe and threat conditions using an analog scale ranging from 1 (not at all) to 10 (extremely). Participants rated overall subjective difficulty with attention ('How difficult was it to pay attention during threat/safe?') and level of anxiety ('How anxious were you during threat/safe?'). Retrospective ratings of anxiety and difficulty with attention were analyzed with two way Diagnosis x Condition (safe, threat) ANOVA.

  Assessed immediately after completing the affective Stroop task

• Subjective Rating of Difficulty With Attention During Threat Condition

  Following tasks completion, participants provided retrospective ratings of: anxiety and attention during safe and threat conditions using an analog scale ranging from 1 (not at all) to 10 (extremely). Participants rated overall subjective difficulty with attention ('How difficult was it to pay attention during threat/safe?') and level of anxiety ('How anxious were you during threat/safe?'). Retrospective ratings of anxiety and difficulty with attention were analyzed with two way Diagnosis x Condition (safe, threat) ANOVA.

  Assessed immediately after completing the affective Stroop task

• Subjective Rating of Level of Anxiety During Safe Condition

  Following tasks completion, participants provided retrospective ratings of: anxiety and attention during safe and threat conditions using an analog scale ranging from 1 (not at all) to 10 (extremely). Participants rated overall subjective difficulty with attention ('How difficult was it to pay attention during threat/safe?') and level of anxiety ('How anxious were you during threat/safe?'). Retrospective ratings of anxiety and difficulty with attention were analyzed with two way Diagnosis x Condition (safe, threat) ANOVA.

  Assessed immediately after completing the affective Stroop task

• Subjective Rating of Level of Anxiety During Threat Condition

  Following tasks completion, participants provided retrospective ratings of: anxiety and attention during safe and threat conditions using an analog scale ranging from 1 (not at all) to 10 (extremely). Participants rated overall subjective difficulty with attention ('How difficult was it to pay attention during threat/safe?') and level of anxiety ('How anxious were you during threat/safe?'). Retrospective ratings of anxiety and difficulty with attention were analyzed with two way Diagnosis x Condition (safe, threat) ANOVA.

  Assessed immediately after completing the affective Stroop task

Study Arms (2)

Healthy Participants

EXPERIMENTAL

Substudy 1/ Neutral, Predictable, and Unpredictable Responses (NPU): physiological responses to different threat of shock conditions - no shock, unpredictable shock, and predictable-cued shock. Substudy 2/ Working Memory Task: Subjects performed a working memory task under threat of shock and in safety. Substudy 5 /Face Stroop Task: Stimuli were pictures of faces exhibiting anger, disgust, fear, happiness, sadness, and surprise intermixed with pleasant, unpleasant, and neutral pictures. Substudy 7/ Active Avoidance Signal Task (AAST) and Sustained Attention Response Task (SART): In AAST, participants performed paradigms which tested whether threats impact the initiation and the inhibition of behavioral responses. In SART, participants were presented with stimuli and either initiated a go or nogo response. Pilot Tasks: Participants completed one/more tasks: nerve stimulation, short speech, air burst, saliva samples, squeezer task, virtual reality task, or computer-based task.

Device: Threat of shock

Anxiety subjects

EXPERIMENTAL

Substudy 1/ Neutral, Predictable, and Unpredictable Responses (NPU): physiological responses to different threat of shock conditions - no shock, unpredictable shock, and predictable-cued shock. Substudy 2/ Working Memory Task: Subjects performed a working memory task under threat of shock and in safety. Substudy 5 /Face Stroop Task: Stimuli were pictures of faces exhibiting anger, disgust, fear, happiness, sadness, and surprise intermixed with pleasant, unpleasant, and neutral pictures. Substudy 7/ Active Avoidance Signal Task (AAST) and Sustained Attention Response Task (SART): In AAST, participants performed paradigms which tested whether threats impact the initiation and the inhibition of behavioral responses. In SART, participants were presented with stimuli and either initiated a go or nogo response. Pilot Tasks: Participants completed one/more tasks: nerve stimulation, short speech, air burst, saliva samples, squeezer task, virtual reality task, or computer-based task.

Device: Threat of shock

Interventions

Threat of shock DEVICE

During threat, a participant could receive a shock. During safe, a participant could not receive as shock. Participants selected their highest tolerable level of shock.

Anxiety subjects; Healthy Participants

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All subjects must be able to give written informed consent prior to participation in this study.
• PATIENTS ONLY: May have DSM-IV-TR diagnoses of an anxiety disorder (GAD; SAD; Panic disorder; specific phobia) or mood disorder (MDD; BP).
• PATIENTS ONLY: May be taking the mood stabilizers, Depakote or Lithium Carbonate.
• Speaks English fluently

You may not qualify if:

• Female subjects who are currently pregnant
• Subjects who meet DSM-IV criteria for current alcohol or substance abuse
• Subjects with a history of alcohol or substance dependence within 6 months prior to screening
• Current Axis I psychiatric disorders as identified with the Structured Clinical Interview for DSM-IV-TR axis disorders, non-patient edition (SCID-np). Past history of any psychotic disorder or bipolar disorder.
• intelligence quotient (I-Q)\<80
• Medical illnesses (such as diabetes or hypertension) or neurological illnesses (such as carpal tunnel syndrome for shocks to be delivered on affected arm; organic brain impairment; seizure disorder) likely to interfere with the study.
• Subjects who are on a medication that may interfere with the study.
• Employee of National Institute of Mental Health (NIMH) or an immediate family member who is a NIMH employee.
• Patients who would be unable to comply with study procedures or assessments;
• Female patients who are currently pregnant;
• Patients who meet DSM-IV criteria for current alcohol or substance abuse
• Subjects with a history of alcohol or substance dependence within 6 months prior to screening;
• Patients who are on a medication (other than mood stabilizers lithium carbonate or Depakote) that may interfere with the study
• Medical illnesses (such as diabetes or hypertension) or neurological illnesses (such as carpal tunnel syndrome; organic brain impairment; seizure disorder) likely to interfere with the study.
• Patients will be excluded if they have a current or past history of, delirium, dementia, amnestic disorder, any of the pervasive developmental disorders; or cognitive impairment.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 8018793 BACKGROUND

• Grillon C, Morgan CA 3rd, Davis M, Southwick SM. Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder. Biol Psychiatry. 1998 Nov 15;44(10):1027-36. doi: 10.1016/s0006-3223(98)00034-1.

  PMID: 9821567 BACKGROUND

• 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.

  PMID: 10066999 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anxiety Disorders; Agoraphobia; Panic Disorder; Generalized Anxiety Disorder

Condition Hierarchy (Ancestors)

Mental Disorders; Phobic Disorders

Limitations and Caveats

This protocol was a series of sub-studies using sample subjects which explains the low numbers of participants per study.

Results Point of Contact

• Title: Dr Maryland Pao
• Organization: National Institute of Mental Health

paom@mail.nih.gov

(301) 435 5770

Study Officials

• Monique Ernst, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2003
• First Posted: February 21, 2003
• Study Start: March 24, 2003
• Primary Completion: March 11, 2020
• Study Completion: July 28, 2022
• Last Updated: January 9, 2024
• Results First Posted: January 9, 2024

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: The data will be placed into a repository indefinitely. We plan to start uploading data in the next few months and continue until project completion.
• Access Criteria: Questionnaire and biophysiological data will be shared into the DSP and repository.

Locations

US (1)