Key brain regions in patients with panic disorder have a reduction of nearly one third in a certain type of serotonin receptor, a finding that may in part explain genetic vulnerability to the disorder, according to an article in the January 21^st issue of the Journal of Neuroscience.

Each year, panic attacks abruptly strike about 2.4 million American adults. Unchecked, the disorder often sets in motion a debilitating psychological sequel syndrome of agoraphobia. 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.

Work with a strain of genetically altered knockout mice that lack the receptor during a critical period of early development showed that adult mice exhibit a variety of anxiety traits such as reluctance to eat in an unfamiliar environment. More recent work with the same mice has shown that a serotonin selective reuptake inhibitor stimulates formation of new neurons in the hippocampus via activity of the serotonin 5-HT1A receptor.

In the current study, American researchers used positron-emission tomography (PET) scans to visualize 5-HT1A receptors in brain areas of interest in 16 patients with panic disorder, 7 of whom also had major depression, and in 15 matched healthy controls. A new radioactive tracer (FCWAY), developed at the National Institutes of Health, binds to the receptors to reveal their locations and numerical count by brain region. Subjects also underwent structural magnetic resonance imaging (MRI) scans, which were overlaid with the PET scan data to precisely match receptor maps with brain structures.

In the panic disorder patients (including those with depression), receptors were reduced by an average of nearly one third in the anterior cingulate, the posterior cingulate, and in the raphe. 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 that used a different tracer, the same research team found less dramatic receptor reductions in the anterior and posterior cingulate, but a 41 percent reduction in the raphe. The current findings add to evidence for an overlap between depression and anxiety disorders.

Although animal experiments have shown that cortisol secretion triggered by repeated stress reduces expression of the gene for the 5-HT1A receptor, such stress hormone elevations are usually not found in panic disorder. Noting the recent discovery of a variant of the 5-HT1A receptor gene linked to major depression and suicide, the researchers suggest that reduced expression of the receptor "may be a source of vulnerability in humans, and that abnormal function of these receptors appears to specifically impact the cortical circuitry involved in the regulation of anxiety."