Protocol Number: 05-M-0102

Title:

Neurobiological Mechanisms in Panic Disorder: Behavioral, Genetic, & Neural Correlates of Noradrenergic Function

Number:

05-M-0102

Summary:

This study will examine brain and noradrenaline function in panic disorder. Noradrenaline is a brain chemical that is involved in the regulation of emotion, anxiety, sleep, stress hormones such as cortisol, and other body functions that are disturbed in panic disorder.

Healthy normal volunteers and patients with panic disorder between 18 and 60 years of age may be eligible for this study. Candidates are screened with psychiatric and medical histories, a physical examination, blood and urine tests, and an electrocardiogram.

Participants undergo the following tests and procedures:

- Blood draw to obtain DNA for genetic studies of panic disorder - particularly of a gene that helps control noradrenaline activity - and to grow cell lines that can be frozen and used for future research on the disorder.

- Magnetic resonance imaging: MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the subject lies on a table that is moved into the scanner (a narrow cylinder), and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. The procedure lasts about 60 minutes, during which the patient is asked to lie still for 10 to 15 minutes at a time.

- Yohimbine injection with PET scanning: Catheters (plastic tubes) are placed in two veins, one to administer yohimbine, a drug that increases noradrenaline activity in the body for about 60 minutes, and one to draw blood samples. Yohimbine often causes temporary trembling, goosebumps, and clammy palms, and may cause emotions such as elation, anxiety, panic attacks, or depression. During yohimbine administration, subjects undergo positron emission tomography (PET) scanning. PET uses small amounts of a radioactive chemical called [fluoro-18]-fluorodeoxyglucose that "labels" active areas of the brain, showing patterns of glucose (sugar) metabolism. For the procedure, the subject lies on the scanner bed, with a special mask fitted to his or her head and attached to the bed to help keep the head still. A brief "transmission" scan is done just before the radioactive tracer is injected in order to calibrate the scanner. After the tracer is injected through the catheter, pictures are taken for about an hour, while the subject lies still on the scanner bed.

- Saline injection with PET scanning: The procedure is the same as that described above, except a saline solution is administered as placebo instead of yohimbine.

After the yohimbine and saline PET sessions, patients are asked about their mood and general well being. When the study is completed, patients with panic disorder are offered participation in treatment studies if available or standard treatment free of charge at NIMH for up to three months.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Up to 120 drug-free subjects (ages 18-60) will be selected who additionally meet criteria for one of 3 subgroups:

I. PD, current (n=30), 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. In case of co-morbid depression it will be ensured that PD is the primary diagnosis. This means that PD preceded the onset of MDD. These patients will be drug-free for at least 2 weeks prior to being enrolled in the study.

II. PD, remitted (n=30), as defined by DSM-IV criteria for PD, and asymptomatic as no longer meeting criteria for PD while being drug-free during the past 6 months.

III. Healthy Control Sample. Sixty subjects (ages 18-60) who have not met criteria for any major psychiatric disorder (axis I diagnosis according to DSM-IV). A control subject will be matched to each PD subject for age, gender, menopausal and estrogen replacement status, and handedness. The control subjects will have no known first-degree relatives with any axis I disorder.

EXCLUSION CRITERIA:

Symptomatic PD patients must not have taken any antidepressant or other medications likely to alter monoamine neurochemistry or cerebrovascular and cardiovascular function for at least 2 weeks prior to the challenge studies.

Remitted PD patients will be drug-free for at least 6 months prior to enrollment.

Subjects will also be excluded if they have:

a) evidence for an axis I psychiatric disorder (DSM-IV criteria) other than panic disorder with/without agoraphobia with/without comorbid depression,

b) medical or neurological illnesses likely to affect physiology or anatomy, i.e. hypertension, cardiovascular disorders, seizures,

c) a history of drug (including BZDs) or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria),

d) current pregnancy (as documented by pregnancy testing at screening or on the days of the challenge studies),

e) current breast feeding,

f) are smokers,

g) presence of an axis II personality disorder,

h) current treatment with fluoxetine, or

i) history of an adverse reaction associated with the administration of yohimbine.

Subjects beyond age 60 are excluded.

Special Instructions:

Currently Not Provided

Keywords:

Panic Disorder

Norepinephrine

Yohimbine

Genes

Pathophysiology

Noradrenergic Mechanisms

PET Imaging

Recruitment Keyword(s):

Panic Disorder

PD

Healthy Volunteer

HV

Condition(s):

Panic Disorder

Investigational Drug(s):

Yohimbine

FDG

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Mental Health

Contact(s):

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

Citation(s):

Bisaga A, Katz JL, Antonini A, Wright CE, Margouleff C, Gorman JM, Eidelberg D. Cerebral glucose metabolism in women with panic disorder. Am J Psychiatry. 1998 Sep;155(9):1178-83.

Cameron OG, Zubieta JK, Grunhaus L, Minoshima S. Effects of yohimbine on cerebral blood flow, symptoms, and physiological functions in humans. Psychosom Med. 2000 Jul-Aug;62(4):549-59.

Schmidt ME, Oshinsky RJ, Kim HG, Schouten JL, Folley BS, Potter WZ. Cerebral glucose metabolic and plasma catecholamine responses to the alpha(2) adrenoceptor antagonist ethoxyidazoxan given to healthy volunteers. Psychopharmacology (Berl). 1999 Sep;146(2):119-27.

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