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      Multiple White Matter Volume Reductions in Patients with Panic Disorder: Relationships between Orbitofrontal Gyrus Volume and Symptom Severity and Social Dysfunction

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          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.

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                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                24 March 2014
                : 9
                : 3
                [1 ]Department of Psychiatry, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
                [2 ]School of Psychology, University of New South Wales, Sydney, New South Wales, Australia
                [3 ]Department of Radiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
                Hangzhou Normal University, China
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JK TA YH. Performed the experiments: JK TA FH AY SH HF. Analyzed the data: JK TA. Contributed reagents/materials/analysis tools: TJW TI. Wrote the paper: JK TA YH.


                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 8
                This study was supported by grants from the Ministry of Health, Labor and Welfare (Kokoro 200400762A, 200500806A, and 200632005A, B) (Dr. Hirayasu), and from the Grant-in-Aid for Young Scientists (B) of the Japan Society for the Promotion of Science (13 25861023) (Dr. Asami) of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Biology and Life Sciences
                Nervous System
                Sensory Perception
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Mental Health and Psychiatry
                Anxiety Disorders
                Radiology and Imaging
                Physical Sciences
                Statistics (Mathematics)
                Statistical Methods
                Research and Analysis Methods
                Research Design
                Clinical Research Design



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