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.

Condition
Anxiety Disorder

Further Study Details: 

Expected Total Enrollment:  570

Classical conditioning theories have long played a role in models and treatment of anxiety disorders, but important questions about the relationship between stress/anxiety and conditioned responses remain. This project has two main objectives: 1) To examine whether failure or delay in learning explicit cue conditioning increases contextual fear, and whether this effect is greater in vulnerable individuals; and 2) to explore the impact of arousal and stress on various components of classical conditioning. To accomplish our first objective, we will develop a procedure to increase contextual fear, characterize the psychological and psychophysiological concomitants of contextual fear, and assess the susceptibility of high trait anxious and anhedonic individuals to contextual fear. To accomplish our second objective, we will explore the acquisition and retention of different types on motor (cerebellum-dependent), emotional (amygdala-dependent), and cognitive (hippocampus-dependent) associative processes during various tasks that range from mildly arousing to stressful.

During fear conditioning, the organism develops fear to the phasic explicit cue (e.g., a light) that was associated with the aversive unconditioned stimulus during conditioning as well as to the environmental context. Explicit cue conditioning and context conditioning are separate processes mediated by distinct brain structures. Whereas explicit cue conditioning is only dependent on the amygdala, context conditioning involves the hippocampus and the bed nucleus of the stria terminalis (BNST). Context conditioning varies as a function of explicit cue conditioning. Poor explicit cue conditioning increases context conditioning. Human studies indicate enhanced contextual fear in patients with anxiety disorders and in anxious nonpatients. Pre-clinical investigations suggest an association between CRH activity in the BNST and anhedonia. We hypothesize that pre-exposure to the aversive/unconditioned stimulus before conditioning will delay acquisition of fear to an explicit cue and will increase contextual fear, especially in anxious and anhedonic individuals.

Stressful life events have been shown to increase vulnerability to mood and anxiety disorders. The mechanisms of this vulnerability remain uncertain. Stress affects limbic regions that are implicated in both learning and memory, and mood and anxiety disorders, suggesting that stress impairs limbic-mediated components of associative learning. We hypothesize that arousal will have little impact on implicit motor learning, but will affect associative learning that are dependent on the hippocampus.

A total of 570 healthy adult volunteers will be recruited. The anxious and anhedonic subjects will be identified with questionnaires.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
Healthy volunteers ages 18-65.
Subjects will be free of current or past psychopathology and organic central nervous system disorders.
EXCLUSION CRITERIA:
IQ less than than 70;
Ongoing medical illness;
Psychiatric or neurological disorder (including seizure);
Past or present substance abuse;
Current psychotropic medication;
Impaired hearing.
In addition, subjects will be excluded from CO2 studies if they suffer from current or a history of cerebral aneurysm, hypertension, angina, asthma, or cardiovascular problems. Pregnancy will also be an exclusion factor.
Female participants in the stress/learning study will be excluded if they suffer from premenstrual syndrome or irregular menses
Exclusion criteria for studies using virtual reality include, sensitivity to motion sickness as determined with Motion History Questionnaires, visual acuity of less than 20/40, color blind.

Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  010185; 01-M-0185
Record last reviewed:  June 24, 2004
Last Updated:  February 3, 2005
Record first received:  November 10, 2001
ClinicalTrials.gov Identifier:  NCT00026559
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08