Abstract
Numerous brain regions are believed to be involved in the neuropathology of panic disorder (PD) including fronto-limbic regions, thalamus, brain stem, and cerebellum. However, while several previous studies have demonstrated volumetric gray matter reductions in these brain regions, there have been no studies evaluating volumetric white matter changes in the fiber bundles connecting these regions. In addition, although patients with PD typically exhibit social, interpersonal and occupational dysfunction, the neuropathologies underlying these dysfunctions remain unclear. A voxel-based morphometry study was conducted to evaluate differences in regional white matter volume between 40 patients with PD and 40 healthy control subjects (HC). Correlation analyses were performed between the regional white matter volumes and patients' scores on the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients with PD demonstrated significant volumetric reductions in widespread white matter regions including fronto-limbic, thalamo-cortical and cerebellar pathways (p<0.05, FDR corrected). Furthermore, there was a significant negative relationship between right orbitofrontal gyrus (OFG) white matter volume and the severity of patients' clinical symptoms, as assessed with the PDSS. A significant positive relationship was also observed between patients' right OFG volumes and their scores on the GAF. Our results suggest that volumetric reductions in widespread white matter regions may play an important role in the pathology of PD. In particular, our results suggest that structural white matter abnormalities in the right OFG may contribute to the social, personal and occupational dysfunction typically experienced by patients with PD.
Highlights
Multiple brain regions are thought to be affected in panic disorder (PD), including the limbic, frontal, and subcortical regions of the brain, as well as the brain stem [1,2,3]
The self socio-economic status (SES) was lower, but not significant, in patients with PD compared to healthy control subjects (HC)
Voxel-Based Morphometry The voxel-based morphometry (VBM) analysis revealed that the PD group had significant volume reductions in 14 distinct white matter regions compared with the HC group (p,.05, False Discovery Rate (FDR)-corrected) (Figure 1 and Table 2)
Summary
Multiple brain regions are thought to be affected in panic disorder (PD), including the limbic, frontal, and subcortical regions of the brain, as well as the brain stem [1,2,3]. Gorman et al (2000) have presented a neuroanatomical hypothesis of PD based on previous researches about human panic attacks and preclinical fear conditioning Their hypothesis postulates that neurocognitive disturbances relating to viscerosensory information in cerebral regions (e.g., medial frontal region, cingulate gyrus, insula, thalamus, and hippocampus) could hyperactivate the amygdala [1]. Dresler et al (2013) have suggested that Gorman’s hypothesis depends on animal studies largely so that it might not sufficiently explain the neuropathology of PD They have described that pathophysiological model of PD might be more intricate and more widely considering brain regions amygdala and other brain regions such as insula and anterior cingulate gyrus (ACG). It has been suggested that pathophysiology of PD is related with abnormality of certain ‘network’ rather than that of a local brain region
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