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Arch Gen Psychiatry. 2008 Oct;65(10):1166-75. doi: 10.1001/archpsyc.65.10.1166.

Altered cerebral gamma-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by [11C]flumazenil positron emission tomography.

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  • 1Department of Psychiatry, University Hospital, Culmannstrasse 8, 8091 Zurich, Switzerland. g.hasler@bluewin.ch

Abstract

CONTEXT:

The benzodiazepine (BZD) receptor system has been implicated in the pathophysiologic mechanism of panic disorder (PD) by indirect evidence from pharmacological challenge studies and by direct evidence from single-photon emission computed tomography and positron emission tomography neuroimaging studies. However, the results of previous neuroimaging studies are in disagreement, possibly because of experimental design limitations related to sample size, matching between patients and controls, and confounding medication effects.

OBJECTIVE:

To compare BZD receptor binding between subjects with PD and healthy control subjects.

DESIGN:

Cross-sectional study for association.

SETTING:

Psychiatric outpatient clinic of the National Institute of Mental Health.

PARTICIPANTS:

Fifteen subjects with PD who were naïve to BZD drug exposure and were not receiving other drug treatment, and 18 healthy controls.

INTERVENTION:

Images of BZD receptor binding were acquired using positron emission tomography and flumazenil tagged with carbon 11.

MAIN OUTCOME MEASURES:

The BZD receptor binding potential was assessed by a simplified reference tissue-tracer kinetic model.

RESULTS:

The BZD receptor binding potential was decreased in multiple areas of the frontal, temporal, and parietal cortices and was increased in the hippocampus/parahippocampal region in subjects with PD vs controls. The most significant decrease was located in the dorsal anterolateral prefrontal cortex (DALPFC); the most significant increase, in the hippocampus/parahippocampal gyrus. These abnormalities were not accounted for by comorbid depression. In subjects with PD, the severity of panic and anxiety symptoms correlated positively with BZD receptor binding in the DALPFC but negatively with binding in the hippocampus/parahippocampal gyrus.

CONCLUSIONS:

These data provide evidence of abnormal BZD-gamma-aminobutyric acid type A receptor binding in PD, suggesting that basal and/or compensatory changes in inhibitory neurotransmission play roles in the pathophysiologic mechanism of PD. They also provide evidence of an impairment of frontal-limbic interaction in the modulation of anxiety responses, consistent with previous functional and structural neuroimaging studies in PD.

PMID:
18838633
[PubMed - indexed for MEDLINE]
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