Neurobiological Mechanisms in Panic Disorder
|First Received Date ICMJE||February 17, 2005|
|Last Updated Date||November 13, 2010|
|Start Date ICMJE||February 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00103987 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Neurobiological Mechanisms in Panic Disorder|
|Official Title ICMJE||Neurobiological Mechanisms in Panic Disorder: Behavioral, Genetic, & Neural Correlates of Noradrenergic Function|
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:
A considerable body of preclinical and clinical evidence suggests that dysregulated activity of noradrenergic systems in the brain is involved in the development of mood disturbance, anxiety, and fear. Neuroanatomical and neurophysiological studies of the noradrenergic system provide a basis for relating increased activity of this system to the behavioral expression of fear and anxiety and the somatic symptoms and cardiovascular changes that accompany severe anxiety states. Previously, extensive research has been done on the role of noradrenergic mechanisms in panic disorder (PD), and it has been suggested that in at least a subgroup of PD patients an abnormality of noradrenergic mechanisms may exist. Studies in patients with PD using the alpha2-adrenoreceptor (AR) antagonist yohimbine showed that a subgroup of PD patients exhibit abnormalities in the regulation of noradrenergic function. Yohimbine, which activates noradrenergic neurons, has been shown to produce greater increases in anxiety, somatic symptoms, blood pressure and plasma levels of the noradrenergic metabolite MHPG in some patients with PD relative to healthy controls. The effect of yohimbine on brain regions hypothesized to be involved in the pathogenesis of PD has not been determined in PD patients using modern neuroimaging techniques. The anxiogenic effects of yohimbine do not occur in all PD patients, although the neurobiological basis for this differential response to yohimbine has not been identified.
This research project proposes to address these two unresolved questions. The effects of yohimbine on regional cerebral glucose metabolism will be determined in PD patients and healthy controls. In addition, preliminary data will be obtained as to whether the behavioral and cerebral metabolic responses to yohimbine relate to functional polymorphisms of the COMT gene which affect catecholamine metabolism.
It is predicted that yohimbine will produce decreases in cerebral metabolism in the prefrontal cortex, orbitofrontal cortex, and anterior cingulate. Healthy controls will exhibit an inverse direction of change in these brain regions. These findings would be similar to those we have previously observed in PTSD patients and may reflect an altered dose-response effect of yohimbine in PD and PTSD relative to controls since preclinical pharmacological studies of stress have shown that high levels of norepinephrine release in the brain decrease brain metabolism whereas lower levels increase brain metabolism. In terms of polymorphisms of the COMT and other catecholamine systems-related gene polymorphisms, it is predicted that the low-activity COMT (met allele) alleles will be associated with greater behavioral and cerebral metabolic responses to yohimbine.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||Panic Disorder|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||November 2010|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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.
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:
Subjects beyond age 60 are excluded.
|Ages||18 Years to 60 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00103987|
|Other Study ID Numbers ICMJE||050102, 05-M-0102|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Mental Health (NIMH)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||November 2010|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP