Panic Disorder Patients Deficient In Emotion-Regulating Receptor
January 22, 2004

BETHESDA, MD (NIH) -- Three brain areas of panic disorder patients are lacking in a key component of a chemical messenger system that regulates emotion, researchers at the NIH's National Institute of Mental Health (NIMH) have discovered.

Brain scans revealed that a type of serotonin receptor is reduced by nearly a third in three structures straddling the center of the brain. The finding is the first in living humans to show that the receptor, which is pivotal to the action of widely prescribed anti-anxiety medications, may be abnormal in the disorder, and may help to explain how genes might influence vulnerability. Drs. Alexander Neumeister and Wayne Drevets, NIMH Mood and Anxiety Disorders Program, and colleagues, report on their findings in the January 21, 2004 "Journal of Neuroscience".

Each year, panic attacks strike about 2.4 million American adults "out of the blue," with feelings of intense fear and physical symptoms sometimes confused with a heart attack. Unchecked, the disorder often sets in motion a debilitating psychological sequel syndrome of agoraphobia, avoiding public places. Panic disorder runs in families and researchers have long suspected that it has a genetic component. The new finding, combined with evidence from recent animal studies, suggests that genes might increase risk for the disorder by coding for decreased expression of the receptors, say the researchers....

In the current study, Neumeister and Drevets used PET scans... to visualize 5- HT1A receptors in brain areas of interest in 16 panic disorder patients -- seven of whom also suffered from major depression -- and 15 matched healthy controls... Subjects also underwent structural MRI (magnetic resonance imaging) scans, which were overlaid with their PET scan data to precisely match it with brain structures.

In the panic disorder patients, including those who also had depression, receptors were reduced by an average of nearly a third in the anterior cingulate in the front middle part of the brain, the posterior cingulate, in the rear middle part of the brain, and in the raphe, in the midbrain. Previous functional brain imaging studies have implicated both the anterior and posterior cingulate in the regulation of anxiety. Stimulation of 5-HT1A receptors in the raphe regulates serotonin synthesis and release. In an earlier PET study of depressed patients, using a different tracer, Drevets and colleagues found less dramatic reductions of the receptor in the anterior and posterior cingulate, but a 41 percent reduction in the raphe. These findings add to evidence for overlap between depression and anxiety disorders.