Serotonin 5-HT_1A receptor binding in people with panic disorder: positron emission tomography study

Abstract

The monoamine neurotransmitter serotonin (5-HT) has an important role in both the pathophysiology and treatment of anxiety and panic attacks.1,2 The strongest evidence that a specific abnormality of the serotonin system predisposes or contributes to anxiety comes from studies of the 5-HT 1A receptor. 'Knockout' mice bred without 5-HT 1A receptors in the cerebral cortex and limbic system show increased anxiety behaviours 3 and patients with panic disorder have been shown by challenge testing to have subsensitivity of these receptors. 4 Furthermore, the azapirone 5-HT 1A agonist buspirone is licensed for the treatment of generalised anxiety disorder in the UK. In a systematic review of 36 trials of patients treated for generalised anxiety disorder azapirones, including buspirone, were found to be superior to placebo in short-term studies (4-9 weeks). 5The development of select radiotracers for the 5-HT 1A receptor now allows a direct examination of this receptor system in living patients with panic disorder. Neumeister et al 6 reported the first full positron emission tomography (PET) study of 5-HT 1A binding in 16 unmedicated patients with panic disorder and 15 healthy controls. Regions of interest examined were limited to the anterior cingulate cortex, posterior cingulate cortex, anterior insula, mesiotemporal cortex, anterior temporopolar cortex and midbrain raphe -all areas of high 5-HT 1A binding. Lower 5-HT 1A binding occurred in anterior cingulate, posterior cingulate and raphe only in patients with panic disorder. Seven of the 16 patients with panic disorder had comorbid depression, although there was no difference in 5-HT 1A binding between the patients with panic disorder with comorbid depression and those without. The radiotracer used for Neumeister et al's study [18 F]-FCWAY, gives a reliable signal subcortically, but quantification in cortical areas is limited because of retained fluoride signal in bone. 7A further recent PET study using [11 C]WAY-100635 found reduced 5-HT 1A binding in social anxiety disorder. 8 That study compared 12 unmedicated male patients with social anxiety disorder with 18 healthy controls. Six of these patients had comorbid agoraphobia. Six regions of interest were examined a priorireduction of 5-HT 1A binding was found in the amygdala, anterior cingulate, insula, medial orbitofrontal cortex and raphe. After Bonferroni correction only the differences in the amygdala and anterior cingulate cortex remained significant. There was no significant correlation between state or trait anxiety scores and regional 5-HT 1A binding potential in both groups.In this study, we used the PET tracer [ 11 C]WAY-100635 which allows in vivo quantification of 5-HT 1A receptors with exquisite delineation and precision.9,10 Specifically, we wished to confirm the findings of Neumeister et al, 6 extend the findings to look at more regions of interest and finally examine the effect of SSRI treatment. Our specific hypothesis was that patients with panic disorder would have reductions in 5-HT 1A receptor ...

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“…Thus, additional work is required to evaluate associations of 5-HT 1A binding specifically in panic disorder. However, the inclusion of these patients improved the regression model, and considering consistent deficiencies in regional 5-HT 1A binding within social anxiety and panic disorder (Nash et al, 2008), we would expect similar changes on a network level.…”

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The Potential Role of Serotonin1A Receptors in Post-weaning Social Isolation–Induced Abnormal Behaviors in Rodents

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Escitalopram Response in Panic Disorder is Not Associated with Three 5-HT1A Receptor Gene Polymorphisms (Rs6295, Rs10042486, or Rs1364043) in Chinese-Han Patients

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