Protocol Number: 02-M-0002

Title:

Serotonin 1A Receptor Imaging and Benzodiazepine Receptor Imaging in Panic Disorder and Posttraumatic Stress Disorder

Number:

02-M-0002

Summary:

The purpose of this study is to examine how certain brain chemicals work in patients with Panic Disorder (PD) and Post-Traumatic Stress Disorder (PTSD) with and without major depressive disorder (MDD).

Brain chemicals that regulate emotion, anxiety, sleep, stress hormones, and other body functions bind to serotonin (5-HT1A) and benzodiazepine (BZD) receptors. Evidence suggests that 5-HT1A and BZD receptor function is abnormal in patients with PD, PTSD, and depression. This study will use positron emission tomography (PET) scans to examine BZD and 5-HT1A receptor binding potential in patients with PD and patients with PTSD with and without co-morbid MDD, as well as in healthy volunteers. This study will also determine the effects of the stress hormone cortisol on 5-HT1A and BZD receptors.

The current emotional state and psychiatric, medical, and family history of potential participants will be evaluated during an initial telephone interview. After entering the study, participants will be asked questions about general mood, degree of nervousness, and behavior. A physical examination, an electrocardiogram (EKG), and tests of intelligence and cognition will be given. Urine, blood, and saliva samples will be taken. Women will be given pregnancy tests and tests to determine menstrual phase and time of ovulation. All volunteers will undergo magnetic resonance imaging (MRI) and PET scans of the brain.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

ANXIETY DISORDERS SAMPLES:

Sixty subjects (ages 18-60) with anxiety disorders (PD and PTSD) will be selected who additionally meet criteria for one of 4 subgroups:

A) PD, Currently Depressed:

As defined by DSM-IV criteria for PD, and still symptomatic as defined by at least 1 panic attack/week or a CGI score of at least 4, and current HDRS score in the mild-moderately-to-severely depressed range (greater than 15).

Patients are requested to meet the DSM-IV criteria for a single or recurrent episode of major depressive disorder.

In case of comorbid depression it will be ensured that PD had an earlier onset than the depressive disorder.

B) PD, Currently Not Depressed:

Defined as having symptomatic PD with at least 1 panic attack/week or a CGI score of at least 4 and never having had experienced a depressive episode meeting DSM-IV criteria for major depressive disorder or dysthymia, OR a period of at least six months with no more than one clinically significant symptom, and during which time subjects were not taking an AD agent, with Hamilton Depression Rating Scale (HDRS; 25 item) scores in the non-depressed range (less than or equal to 7) will be selected.

C) PTSD, Currently Depressed:

As defined by DSM-IV with a duration of illness at least three months.

Patients must score greater than or equal to 50 on Clinician-Administered PTSD Scale (CAPS-2) as a measure of PTSD symptom severity.

Patients are requested to meet the DSM-IV criteria for a single or recurrent episode of major depressive disorder.

Current HDRS score is in the mild-moderately-to-severely depressed range (greater than or equal to 15).

In case of comorbid depression it will be ensured that PTSD had an earlier onset than the depressive disorder.

D) PTSD, Currently Not Depressed:

Defined as having PTSD and never having had experienced a depressive episode meeting DSM-IV criteria for major depressive disorder or dysthymia which time subjects were not taking an AD agent, with Hamilton Depression Rating Scale (HDRS; 25 item) scores in the non-depressed range (less than or equal to 7) will be selected.

HEALTHY CONTROL SAMPLE:

Thirty subjects (ages 18-65) who have not met criteria for any major psychiatric disorder.

The control subjects will have no known first-degree relatives with PD or PTSD.

PSYCHIATRIC CONTROL SAMPLE:

Subjects with Major Depressive Disorder (MDD), currently depressed, as defined by DSM-IV criteria for recurrent MDD and current HDRS score in the moderately-to-severely depressed range (greater than or equal to 18).

These subjects must not have a history of PTSD and/or serious trauma.

EXCLUSION CRITERIA:

Subjects will be recruited who are drug-naive or who are not currently receiving psychotropic drugs at least 3 weeks (8 weeks for fluoxetine). In case a patient is on psychotropic medications and this treatment is not successful (as defined by meeting the inclusion criteria as noted above), the medication will be tapered off to ensure that the subject is drug-free for at least 3 weeks prior to PET scanning.

Subjects will be also be excluded if they have: a) serious suicidal ideation or behavior, b) psychosis to the extent that the ability to provide informed consent is in doubt, c) medical or neurological illnesses likely to affect physiology or anatomy, d) a history of drug (including BZDs) or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria), e) current pregnancy (as documented by pregnancy testing prior to scanning), f) current breast feeding, g) general MRI exclusion criteria, h) patients who are currently taking fluoxetine.

Patients and controls must exhibit no or only moderate alcohol use.

Subjects with current or previous regular (greater than 4 weeks) of BZDs and excessive use of alcohol (greater than 8 ounce/day for men and greater than six ounces /day for women) in the past or present are ineligible to participate, as they may produce a downregulation of the BZD receptor that may confound the results.

Postmenopausal female subjects.

Subjects beyond age 60 are excluded to reduce the biological heterogeneity encompassed by the MDD and anxiety disorders criteria.

Subjects whose first anxiety disorder episode arose temporally after other major medical or psychiatric conditions will also be excluded.

Special Instructions: Currently Not Provided

Keywords:

PET

5-HT1A Receptors

Benzodiazepine Receptors

Panic Disorder

PTSD

Serotonin Type 1A Receptors

Post-Traumatic Stress Disorder

Depression

Recruitment Keywords:

Post-Traumatic Stress Disorder

PTSD

Anxiety

Panic Disorder

Depression

Healthy Volunteer

HV

Normal Control

Conditions:

Panic Disorder

Posttraumatic Stress Disorder

Major Depressive Disorder

Investigational Drug(s):

O15 Water

FCWAY

flumazenil

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system

Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons

Effects of the 5-hydroxytryptamine receptor antagonist, BMY 7378, on 5-hydroxytryptamine neurotransmission electrophysiological studies in the rat central nervous system

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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