Frontal White Matter Alterations in Short-Term Medicated Panic Disorder Patients without Comorbid Conditions: A Diffusion Tensor Imaging Study

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Abstract

The frontal cortex might play an important role in the fear network, and white matter (WM) integrity could be related to the pathophysiology of panic disorder (PD). A few studies have investigated alterations of WM integrity in PD. The aim of this study was to determine frontal WM integrity differences between patients with PD without comorbid conditions and healthy control (HC) subjects by using diffusion tensor imaging. Thirty-six patients with PD who had used medication within 1 week and 27 age- and sex-matched HC subjects participated in this study. Structural brain magnetic resonance imaging was performed on all participants. Panic Disorder Severity Scale and Beck Anxiety Inventory (BAI) scores were assessed. Tract-based spatial statistics (TBSS) was used for image analysis. TBSS analysis showed decreased fractional anisotropy (FA) in frontal WM and WM around the frontal lobe, including the corpus callosum of both hemispheres, in patients with PD compared to HC subjects. Moreover, voxel-wise correlation analysis revealed that the BAI scores for patients with PD were positively correlated with their FA values for regions showing group differences in the FA of frontal WM of both hemispheres. Altered integrity in frontal WM of patients with PD without comorbid conditions might represent the structural pathophysiology in these patients, and these changes could be related to clinical symptoms of PD.

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Most cited references 38

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Prefrontal cortical function and anxiety: controlling attention to threat-related stimuli.

Sonia Bishop, John Duncan, Matthew Brett … (2004)

Threat-related stimuli are strong competitors for attention, particularly in anxious individuals. We used functional magnetic resonance imaging (fMRI) with healthy human volunteers to study how the processing of threat-related distractors is controlled and whether this alters as anxiety levels increase. Our work builds upon prior analyses of the cognitive control functions of lateral prefrontal cortex (lateral PFC) and anterior cingulate cortex (ACC). We found that rostral ACC was strongly activated by infrequent threat-related distractors, consistent with a role for this area in responding to unexpected processing conflict caused by salient emotional stimuli. Participants with higher anxiety levels showed both less rostral ACC activity overall and reduced recruitment of lateral PFC as expectancy of threat-related distractors was established. This supports the proposal that anxiety is associated with reduced top-down control over threat-related distractors. Our results suggest distinct roles for rostral ACC and lateral PFC in governing the processing of task-irrelevant, threat-related stimuli, and indicate reduced recruitment of this circuitry in anxiety.

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Human Fear Conditioning and Extinction in Neuroimaging: A Systematic Review

Christina Sehlmeyer, Sonja Schöning, Pienie Zwitserlood … (2009)

Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm. A Pubmed search, as of December 2008, was performed and supplemented by manual searches of bibliographies of key articles. Two independent reviewers made the final study selection and data extraction. A total of 46 studies on cued fear conditioning and/or extinction on healthy volunteers using positron emission tomography or functional magnetic resonance imaging were reviewed. The influence of specific experimental factors, such as contingency and timing parameters, assessment of conditioned responses, and characteristics of conditioned and unconditioned stimuli, on cerebral activation patterns was examined. Results were summarized descriptively. A network consisting of fear-related brain areas, such as amygdala, insula, and anterior cingulate cortex, is activated independently of design parameters. However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities. Furthermore, other brain areas are differentially activated, depending on specific design parameters. These include stronger hippocampal activation in trace conditioning and tactile stimulation. Furthermore, tactile unconditioned stimuli enhance activation of pain related, motor, and somatosensory areas. Differences concerning experimental factors may partly explain the variance between neuroimaging investigations on human fear conditioning and extinction and should, therefore, be taken into serious consideration in the planning and the interpretation of research projects.

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The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication.

Ronald C Kessler, Wai Tat Chiu, Robert Jin … (2006)

Only limited information exists about the epidemiology of DSM-IV panic attacks (PAs) and panic disorder (PD). To present nationally representative data about the epidemiology of PAs and PD with or without agoraphobia (AG) on the basis of the US National Comorbidity Survey Replication findings. Nationally representative face-to-face household survey conducted using the fully structured World Health Organization Composite International Diagnostic Interview. English-speaking respondents (N=9282) 18 years or older. Respondents who met DSM-IV lifetime criteria for PAs and PD with and without AG. Lifetime prevalence estimates are 22.7% for isolated panic without AG (PA only), 0.8% for PA with AG without PD (PA-AG), 3.7% for PD without AG (PD only), and 1.1% for PD with AG (PD-AG). Persistence, lifetime number of attacks, and number of years with attacks increase monotonically across these 4 subgroups. All 4 subgroups are significantly comorbid with other lifetime DSM-IV disorders, with the highest odds for PD-AG and the lowest for PA only. Scores on the Panic Disorder Severity Scale are also highest for PD-AG (86.3% moderate or severe) and lowest for PA only (6.7% moderate or severe). Agoraphobia is associated with substantial severity, impairment, and comorbidity. Lifetime treatment is high (from 96.1% for PD-AG to 61.1% for PA only), but 12-month treatment meeting published treatment guidelines is low (from 54.9% for PD-AG to 18.2% for PA only). Although the major societal burden of panic is caused by PD and PA-AG, isolated PAs also have high prevalence and meaningful role impairment.

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Author and article information

Contributors

Wang Zhan: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 30 April 2014

Volume: 9

Issue: 4

Electronic Location Identifier: e95279

Affiliations

[1 ]Department of Psychiatry, CHA Bundang Medical Center, CHA University, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea

[2 ]Department of Psychiatry, Bundang Jaesaeng Hospital, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea

[3 ]Department of Psychiatry, CHA Gangnam Medical Center, CHA University, Gangnam-gu, Seoul, Republic of Korea

[4 ]Sujiyonsei Psychiatric Clinic, Suji-gu, Yongin-si, Gyeonggi-do, Republic of Korea

[5 ]Department of Applied Bioscience, College of Life Science, CHA University, Pocheon-si, Gyeonggi-do, Republic of Korea

University of Maryland, College Park, United States of America

Author notes

* E-mail: leesanghyuk@ 123456yahoo.com (S-HL); ytkim@ 123456cha.ac.kr (YTK)

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

Conceived and designed the experiments: BK SHL. Performed the experiments: BK SHL JHK. Analyzed the data: BK SHL YK YTK MKK. Contributed reagents/materials/analysis tools: BK SHL YTK KSL TKC. Wrote the paper: BK SHL.

Article

Publisher ID: PONE-D-13-40134

DOI: 10.1371/journal.pone.0095279

PMC ID: 4005735

PubMed ID: 24788587

SO-VID: 033be81e-5cc6-496c-a0a8-fa5ad30cd0e3

License:

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.

History

Date received : 26 September 2013

Date accepted : 25 March 2014

Page count

Pages: 8

Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2011-0023359) to S.H. Lee. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Frontal White Matter Alterations in Short-Term Medicated Panic Disorder Patients without Comorbid Conditions: A Diffusion Tensor Imaging Study

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Most cited references 38

Prefrontal cortical function and anxiety: controlling attention to threat-related stimuli.

Human Fear Conditioning and Extinction in Neuroimaging: A Systematic Review

The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication.

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