Panic disorder (PD) is characterized by recurrent panic attacks and severe, progressive disability. Preclinical work and neuroimaging studies suggest that pathological dysregulation of fear neurocircuitry may be fundamental to the etiology. Panic responses in PD are hypothetically mediated by overactivity in subcortical and paleocortical fear circuits and underactivity in frontal cortical processing that would otherwise serve to moderate anxiety. Efficacy of serotonergic (5-HT) therapies, reactivity to 5-HT compounds in PD and in 3reclinical anxiety models, and work in the 5-HT1A knockout mouse all point to a role for the 5-HT system in modulating pathological anxiety. The Candidate has developed a program of training and research aimed at elucidating the neural circuitry involved in the panic response in PD and defining a neurochemical deficiency that may be involved, if not etiological. Utilizing prior training in both the neuroscience of fear and the psychophysiology of PD, he plans to: 1) characterize the regional 5-HT1A binding potential in PD, an anxiety disorder control group, and a healthy volunteer group using quantitative positron emission tomography (PET) and [11C]-WAY 100635; and 2) measure change in regional cerebral blood flow (rCBF) in response to a panicogen using [150]-H20 PET in these same groups. Generalized social phobia will serve as the anxiety disorder control group due to overlapping phenomenology suggestive of commonalities in the pathological neural substrates. Defining key neurocircuitry by rCBF is considered the 1st step in a research career aimed at characterizing the chemical mediators of pathological anxiety circuits using PET. The Candidate will require intensive mentoring and didactics in PET rCBF and ligand methodologies. He has designed a 5-year program of mentorship and training by experts in the fields of neuroscience, anxiety disorders, and PET methodologies. Through such work, he seeks to contribute to the understanding of the pathophysiology of PD in order to suggest improved therapeutics for this devastating and underrecognized brain disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08MH067015-04
Application #
7272005
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Wynne, Debra K
Project Start
2004-09-01
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
4
Fiscal Year
2007
Total Cost
$177,444
Indirect Cost
Name
Columbia University (N.Y.)
Department
Psychiatry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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