The GABA neuronal system, the major inhibitory system in the brain, has been implicated in animal and human models of stress. Compounds that enhance GABA function, e.g. benzodiazepine (BZD) receptor agonists, are anxiolytic in animals and man, while those that decrease GABA function (e.g. beta carbolines) are pro-convulsant and anxiogenic. Medications that augment GABA function such as the BZDs and valproic acid, are known to be effective clinical treatments for panic disorder (PD). In addition, other effective antipanic medications, imipramine and phenelzine, increase brain GABA. Recently, animal models PD have been created by causing specific defects in GABA function. In contrast to these data, peripheral measurements (plasma and CSF) of GABA concentrations appear to be normal in PD patients. These measures, however, may be confounded with sampling artifacts or GABA contributions from spinal cord, and thus may be insensitive to regional changes in brain GABA. Advances in 1H-magnetic resonance spectroscopy (MRS), now permit direct in vivo determination of cortical GABA levels in neuropsychiatric disease. The MRS pilot data we have gathered in PD patients thus far suggests that brain GABA levels are abnormally reduced in occipital cortex in this disorder. The goal of this research proposal is to test the hypothesis that deficits in brain GABA function contribute to the pathophysiology of PD. We have designed one study to test this hypothesis. In the study we plan to perform baseline MRS determinations of cortical GABA levels (frontal and occipital regions) in a group of unmedicated PD patients (n=30), and in a comparison group of matched healthy control subjects (n=30). A positive finding (i.e. detection of abnormally low GABA levels in frontal and/or occipital cortex in patients) would implicate regional cortical deficits in GABA function in the pathophysiology of PD.
|Effective start/end date||8/15/99 → 7/31/01|
- National Institutes of Health: $171,709.00
- National Institutes of Health
Magnetic Resonance Spectroscopy