Clinical trial NCT00055224: Expectation of Unpleasant Events in Anxiety Disorders
Official title: Predictability and Aversive Expectancies in Anxiety and Depressive Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anxiety Disorders
Keywords: Anxiety Disorder
Psychophysiology
Shock Threat
Context Conditioning
Agoraphobia
Panic Disorder
Generalized Anxiety Disorder
GAD
Healthy Volunteer
HV
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2003-02-21
Enrollment: 921
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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....

Detailed description: High-generalized anxiety is a concomitant of many anxiety disorders and is often regarded as a vulnerability marker for these disorders. One characteristic of patients with anxiety disorders and high trait-anxious individuals is inappropriate expectancies of aversive events. The overall aim of the present protocol is to investigate mechanisms that may promote the development of these aversive expectancies using expectancy-based, associative-learning models.

During aversive conditioning in which a phasic explicit-cue (e.g., a light) is repeatedly associated with an aversive unconditioned-stimulus (e.g., a shock), the organism develops fear to the explicit cue as well as to the environmental context in which the experiment took place. We have obtained preliminary evidence suggesting that contextual fear represents aspects of aversive states that are central to anxiety disorders. In this protocol, we seek further evidence for the relevance of contextual fear to mood anxiety disorders.

One important determinant of contextual fear in both humans and animals is predictability: contextual fear increases when aversive events (e.g., electric shock) are unpredictable, as opposed to when they are predictable. The present protocol will examine the role of predictability of aversive states and of conditioning on threat appraisal in individuals with mood and anxiety disorders.

A second aim is to examine the interaction between experimentally-induced anxiety and cognitive processes, more specifically working memory, in mood and anxiety disorders.

Eligibility criteria: * INCLUSION CRITERIA:
* Inclusion criteria for both patients and healthy controls

  * 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

EXCLUSION CRITERIA:

* Exclusion criteria for healthy subjects

  * 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.
* Exclusion criteria for patients

  * 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.
  * Current Axis I psychiatric disorders as identified with the Structured Clinical Interview for DSM-IV-TR axis disorders, non-patient edition (SCID) with the exception of the mood and anxiety disorders. Past history of any psychotic disorder or bipolar disorder..
  * IQ\<80
  * Employee of NIMH or an immediate family member who is an NIMH employee.
* Additional exclusion criteria for the active avoidance task

  * Color blindness

Primary outcomes:
measure: Change in Percent of Correct Button Presses During Threat Compared to the Safe Condition (AAST)
timeFrame: 2000 ms during trial
measure: Change in Percent of Correct no Button Presses During Threat Compared to the Safe Condition
timeFrame: 2000 ms during trial
measure: Correct-go Reaction Time (RT) - Safe Condition
timeFrame: 2000 ms during trial
measure: Correct-go Reaction Time (RT) - Threat Condition
timeFrame: 2000 ms during trial
measure: Go Correct Hits Followed by Button Press - Safe Condition
timeFrame: 2000 ms during trial
measure: Go Correct Hits Followed by Button Press - Threat Condition
timeFrame: 2000 ms during trial
measure: Nogo Trials Followed by no Button Press - Safe Condition
timeFrame: 2000 ms during trial
measure: Nogo Trials Followed by no Button Press - Threat Condition
timeFrame: 2000 ms during trial
measure: Stroop Effect on Accuracy During Congruent Task Viewing Positive Images: Safe Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Congruent Task Viewing Positive Images: Threat Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Congruent Task Viewing Negative Images: Safe Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Congruent Task Viewing Negative Images: Threat Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Congruent Task Viewing Neutral Images: Safe Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Congruent Task Viewing Neutral Images: Threat Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Incongruent Task Viewing Positive Images: Safe Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Incongruent Task Viewing Positive Images: Threat Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Incongruent Task Viewing Negative Images: Safe Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Incongruent Task Viewing Negative Images: Threat Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Incongruent Task Viewing Neutral Images: Safe Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Stroop Effect on Accuracy During Incongruent Task Viewing Neutral Images: Threat Condition
timeFrame: 11.2 minutes per run for a total of 22.4 minutes
measure: Subjective Rating of Difficulty With Attention During Safe Condition
timeFrame: Assessed immediately after completing the affective Stroop task
measure: Subjective Rating of Difficulty With Attention During Threat Condition
timeFrame: Assessed immediately after completing the affective Stroop task
measure: Subjective Rating of Level of Anxiety During Safe Condition
timeFrame: Assessed immediately after completing the affective Stroop task
measure: Subjective Rating of Level of Anxiety During Threat Condition
timeFrame: Assessed immediately after completing the affective Stroop task
Secondary outcomes:
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: Monique Ernst, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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: 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.
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.