Effects of  BDNF  Val66Met Polymorphism on White Matter Microalterations of the Corpus Callosum in Patients with Panic Disorder in Korean Populations

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Abstract

Objective

The brain-derived neurotrophic factor ( BDNF) Val66Met (rs6265) polymorphism is suggested to be associated with the pathophysiology of anxiety disorders, including panic disorder (PD). Although the fronto-limbic white matter (WM) microstructures have been investigated, the corpus callosum (CC) has not yet been studied regarding its relationship with BDNF Val66Met polymorphism in PD.

Methods

Ninety-five PD patients were enrolled. The Neuroticism, the Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, and Beck Depression Inventory-II (BDI-II) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the CC regions using Tract-Based Spatial Statistics.

Results

The GG genotype in BDNF Val66Met polymorphism has significantly higher fractional anisotropy (FA) values of the body and splenium of the CC, neuroticism and depressive symptom scale scores than the non-GG genotype in PD. The FA values of the body of the CC in the two groups were significantly different independent of age, sex, neuroticism, and BDI-II.

Conclusion

Our findings demonstrate that the BDNF Val66Met polymorphism is associated with WM connectivity of the body and splenium of the CC, and may be related to neuroticism and depressive symptoms in PD. Additionally, the CC connectivity according to BDNF polymorphism may play a role in the pathophysiology of PD.

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Most cited references 51

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Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data.

Stephen Smith, Mark Jenkinson, Heidi Johansen-Berg … (2006)

There has been much recent interest in using magnetic resonance diffusion imaging to provide information about anatomical connectivity in the brain, by measuring the anisotropic diffusion of water in white matter tracts. One of the measures most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies how strongly directional the local tract structure is. Many imaging studies are starting to use FA images in voxelwise statistical analyses, in order to localise brain changes related to development, degeneration and disease. However, optimal analysis is compromised by the use of standard registration algorithms; there has not to date been a satisfactory solution to the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the arbitrariness of the choice of spatial smoothing extent has not yet been resolved. In this paper, we present a new method that aims to solve these issues via (a) carefully tuned non-linear registration, followed by (b) projection onto an alignment-invariant tract representation (the "mean FA skeleton"). We refer to this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies. We describe TBSS in detail and present example TBSS results from several diffusion imaging studies.

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An inventory for measuring clinical anxiety: psychometric properties.

A. Beck, N. Epstein, G. Brown … (1988)

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Topography of the human corpus callosum revisited--comprehensive fiber tractography using diffusion tensor magnetic resonance imaging.

Sabine Hofer, Jens Frahm (2006)

Several tracing studies have established a topographical distribution of fiber connections to the cortex in midsagittal cross-sections of the corpus callosum (CC). The most prominent example is Witelson's scheme, which defines five vertical partitions mainly based on primate data. Conventional MRI of the human CC does not reveal morphologically discernable structures, although microscopy techniques identified myelinated axons with a relatively small diameter in the anterior and posterior third of the CC as opposed to thick fibers in the midbody and posterior splenium. Here, we applied diffusion tensor imaging (DTI) in conjunction with a tract-tracing algorithm to gain cortical connectivity information of the CC in individual subjects. With DTI-based tractography, we distinguished five vertical segments of the CC, containing fibers projecting into prefrontal, premotor (and supplementary motor), primary motor, and primary sensory areas as well as into parietal, temporal, and occipital cortical areas. Striking differences to Witelson's classification were recognized in the midbody and anterior third of the CC. In particular, callosal motor fiber bundles were found to cross the CC in a much more posterior location than previously indicated. Differences in water mobility were found to be in qualitative agreement with differences in the microstructure of transcallosal fibers yielding the highest anisotropy in posterior regions of the CC. The lowest anisotropy was observed in compartments assigned to motor and sensory cortical areas. In conclusion, DTI-based fiber tractography of healthy human subjects suggests a modification of the widely accepted Witelson scheme and a new classification of vertical CC partitions.

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Author and article information

Journal

Journal ID (nlm-ta): Psychiatry Investig

Journal ID (iso-abbrev): Psychiatry Investig

Journal ID (publisher-id): PI

Title: Psychiatry Investigation

Publisher: Korean Neuropsychiatric Association

ISSN (Print): 1738-3684

ISSN (Electronic): 1976-3026

Publication date (Print): October 2020

Publication date (Electronic): 7 October 2020

Volume: 17

Issue: 10

Pages: 967-975

Affiliations

[1 ]Department of Psychiatry, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea

[2 ]Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea

Author notes

Correspondence: Sang-Hyuk Lee, MD, PhD Department of Psychiatry, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Republic of Korea Tel: +82-31-780-5694, Fax: +82-31-780-5862, E-mail: drshlee@ 123456cha.ac.kr

Correspondence: Chun Il Park, MD Department of Psychiatry, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Republic of Korea Tel: +82-31-780-5694, Fax: +82-31-780-5862, E-mail: chunil1001@ 123456cha.ac.kr

Author information

Hyun-Ju Kim http://orcid.org/0000-0002-8093-3366

Minji Bang http://orcid.org/0000-0002-1669-4014

Kang Soo Lee http://orcid.org/0000-0001-6587-5623

Tai Kiu Choi http://orcid.org/0000-0003-0896-1925

Chun Il Park http://orcid.org/0000-0003-0119-0443

Sang-Hyuk Lee http://orcid.org/0000-0001-7939-3000

Article

Publisher ID: pi-2020-0186

DOI: 10.30773/pi.2020.0186

PMC ID: 7596279

PubMed ID: 33017888

SO-VID: 0b3034e8-dbc3-4f6a-a4ea-ee71c5b58943

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 18 May 2020

Date revision received : 6 July 2020

Date accepted : 5 August 2020

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Effects of BDNF Val66Met Polymorphism on White Matter Microalterations of the Corpus Callosum in Patients with Panic Disorder in Korean Populations

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Abstract

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Methods

Results

Conclusion

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Measurement of Glucocorticoid Receptor Signaling in Major Depression

Most cited references 51

Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data.

An inventory for measuring clinical anxiety: psychometric properties.

Topography of the human corpus callosum revisited--comprehensive fiber tractography using diffusion tensor magnetic resonance imaging.

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