Regular articleAmygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging
Introduction
The biological basis of panic disorder (PD) remains unknown, despite the fact that a large number of hypotheses have been proposed. In the puzzling task of identifying the exact mechanisms underlying its pathophysiology, one of the main current lines of research focuses on brain circuitry.
Multiple preclinical studies with animals have provided detailed descriptions of the brain pathways involved in conditioned fear responses (for a review, see LeDoux, 1996 and Davis, 1992), and recent review articles have suggested that abnormalities in similar circuits may be involved in the pathophysiology of human anxiety disorders, and more specifically of PD Coplan and Lydiard 1998, Gorman et al 2000. According to these authors, the amygdalar region, near-by structures, its projections, and the medial prefrontal cortex may be abnormally sensitive in PD. It is suggested that that there may be a deficit in the relay and coordination of “upstream” (cortical) and “downstream” (brain stem) sensory information, which results in heightened amygdalar activity with resultant behavioral, autonomic, and neuroendocrine activation.
To date, although few papers have focused on the possible abnormalities of the amygdala in PD, structural and functional neuroimaging techniques have provided indirect evidence of abnormalities in the mesial areas of the temporal lobe. Qualitative magnetic resonance imaging (MRI) studies in PD have identified structural temporal lobe lesions, mainly located in the mesiotemporal area Ontiveros et al 1989, Fontaine et al 1990. In addition, a high frequency of structural septohippocampal abnormalities has been reported in PD associated with nonepileptic EEG abnormalities (Dantendorfer et al., 1996). The only study using quantitative MRI (Vythilingam et al., 2000) found a bilateral decrease in temporal lobe volume in PD patients. Functional neuroimaging studies have also been used to study patients with PD. Reiman et al. (1986) found an abnormal hemispheric asymmetry of parahippocampal blood flow and oxygen metabolism in PD patients in the resting, nonpanic states. Although the study presented important methodological limitations, this asymmetry was interpreted by the authors as an abnormal increase in right parahippocampal measurements. An asymmetry in the glucose metabolism of both the hippocampal and parahippocampal structures has since been reported (Nordahl et al., 1990), also suggesting an increase in glucose metabolic rates on the right side. Similar results were found by Nordahl et al. (1998) in a study of asymptomatic, imipramine-treated PD patients, suggesting that this abnormality could reflect a trait marker for the illness. De Cristofaro et al. (1993) found lower perfusion indices in both right and left hippocampal regions, and Bisaga et al. (1998) found a significant increase in glucose metabolism in the left hippocampus and parahippocampal area in women. Using proton magnetic resonance spectroscopy, our group (Massana et al., 2002) found decreased levels of creatine plus phosphocreatine in the right medial temporal lobe region of PD patients compared to healthy matched controls. Moreover, a decrease in measures of benzodiazepine receptor binding has recently been found in the left hippocampus and precuneus in PD patients relative to controls (Bremner et al., 2000a).
The aim of our study was to examine possible alterations in the brain amygdalar anatomy in PD by means of quantitative MRI. As part of the study, the temporal lobes and the hippocampi were also assessed. To our knowledge, amygdalar volume in PD has not been examined to date.
Section snippets
Subjects
The study was carried out at the Hospital Clínic i Provincial de Barcelona (Catalonia, Spain), and was approved by the Local Research Ethics Committee. All patients and comparison subjects signed written informed consent agreements following detailed explanation of the study and procedure.
Twelve individuals with PD (six male, six female), aged 26 to 43 years, were included in the study. Screening visit included a detailed medical history, physical, and neurological examination, and the
Results
Volumetric measurements did not reveal group differences in the brain measurements, i.e., intracranial volume, cerebrospinal fluid, cerebral gray matter, and cerebral white matter (Table 2). However, the PD group had significantly lower absolute and normalized mean amygdalar volumes, with reductions, for normalized volumes, of 31.85% (right hemisphere, t = 4.807, df = 11, P = .001) and 23.44% (left hemisphere, t = 4.107, df = 11, P = .002) compared to the healthy comparison group (Table 3 and
Discussion
Patients with PD had smaller right and left amygdalar volumes than healthy matched comparison subjects. To our knowledge, this is the first study to examine the amygdalar volume in PD patients, and our results are the first MRI evidence of reduced amygdalar volume in this disorder. No differences were found for the right and left hippocampi nor for the right and left temporal lobes between PD patients and healthy matched subjects. Of particular note is the fact that these findings were obtained
Acknowledgements
This study has been possible thanks to two research grants (99/0191, 01/1503) from the Fondo de Investigaciones Sanitarias, Instituto Carlos III, Spain.
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