Official Title: “The Effects of Cortisol and Norepinephrine Modulation on Emotional and Nonemotional Processing”

The purpose of this study is to examine how hormonal changes that occur during stressful situations affect thought and emotions. Results from this study may lead to treatments that can alleviate the psychological effects of trauma.

Levels of cortisol and norepinephrine increase in response to stress; these hormones also influence thought processes. This study will give hydrocortisone and/or yohimbine (a stimulator of central norepinephrine) to healthy adults in order to model the stress response and to better understand the way people process information during traumatic events.

This study comprises two experiments in which the stress response is pharmacologically modeled. Participants in the study will have two study visits. During Visit 1, participants will undergo a psychiatric assessment, complete neuropsychological tasks, and have their IQ measured. During Visit 2, participants will be given hydrocortisone and/or yohimbine. Blood will be collected before and during this. Participants will then perform two experiments. In one experiment, participants will hear a story with emotional and non-emotional segments; in a second experiment, participants will view both emotional and non-emotional stimuli.

Study Type: Observational

Study Design: N/A

Memories for traumatic events are fundamentally different from typical memories. Individuals who witness or are involved in an extremely stressful event, such as a robbery or a violent act, retain highly accurate memories for the information directly related to the trauma (e.g., a gun or verbal threat), while surrounding details are poorly remembered. This so-called weapon focus phenomenon has been found in both naturalistic and laboratory studies with humans. However, difficulties with the control of naturalistic studies and approximating trauma in the lab limit the validity of these findings.

Neurophysiologically, cortisol and norepinephrine are principal mediators of the stress response, and both influence memory function. In particular, cortisol improves memory at low levels but impairs memory at higher doses. Similarly, some evidence indicates that norepinephrine also enhances memory in low doses and either impairs or does not influence memory at high doses. Much of the experimental work in this area has been conducted with animals. Studies have recently begun to extend these paradigms to humans.

To better understand memory processing during trauma, hydrocortisone and/or yohimbine (a stimulator of central norepinephrine) will be administered to healthy adults in two experiments in order to pharmacologically model the stress response. Following infusion, participants will hear a story with emotional and nonemotional segments in one experiment (N = 80) and emotional as well as nonemotional stimuli (faces and scenes) in another experiment (N = 80). It is predicted that relative to the placebo, hydrocortisone will impair memory for both emotional and nonemotional information, yohimbine will improve memory for both types of information, and the combination of hydrocortisone and yohimbine will enhance memory for emotional aspects and impair memory for the nonemotional segments of the story. Results from this study will permit a better understanding of how emotionally charged memories are encoded and will potentially lead to treatments to mitigate the psychological effects of traumatic exposure.

Intervention(s) in this Clinical Trial

• Drug: Yohimbine

INCLUSION CRITERIA:

• Age: 18-36
• IQ: all subjects will have IQ greater than 85
• Follicular cycle: Women will participate in the encoding task between days 3-10.

EXCLUSION CRITERIA:

• Pregnancy/Nursing
• Only healthy individuals will participate; special attention will be taken to ensure that no subject has: hypertension, glaucoma, cataracts, ulcers, renal insufficiency, osteoporosis, hypothyroidism, cirrhosis, ocular herpes simplex and myocardial infarction.
• Use of hormonal contraception
• Use of glucocorticoids within past 3 years
• Use of any psychoactive substance; current or past psychiatric diagnosis.
• Irregular sleep pattern as defined as getting less than 6 hours of sleep per night, going to sleep after 2:00 AM; waking up before 5:00 AM or after 11:00 AM
• Weight that is 15% more or less than ideal body weight for sex and height
• History of panic attacks or first degree relative with history of panic attacks

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: National Institute of Mental Health (NIMH)

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00032838

Study ID Number: 020155

ClinicalTrials.gov Identifier: NCT00032838

Health Authority: United States: Federal Government