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Effects of VRK2 (rs2312147) on white matter connectivity in patients with schizophrenia.

Sohn H, Kim B, Kim KH, Kim MK, Choi TK, Lee SH - PLoS ONE (2014)

Bottom Line: However, its effect on the brain structure in schizophrenia is little known.The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part), the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM.Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.

ABSTRACT
Recent genome-wide association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2), in multiple Asian and European samples. However, its effect on the brain structure in schizophrenia is little known. We analyzed the brain structure of 36 schizophrenia patients and 18 healthy subjects with regard to rs2312147 genotype groups. Brain magnetic resonance scans for gray matter (GM) and white matter (WM) analysis, and genotype analysis for VRK2 rs2312147, were conducted. The Positive and Negative Syndrome Scale and the Digit Symbol Test were assessed for schizophrenia patients. There was no significant difference in either GM volume or WM connectivity with regard to rs2312147 genotype in healthy subjects. In contrast, we found significant differences in the WM connectivity between rs2312147 CC and CT/TT genotype groups of schizophrenia patients. The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part), the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM. Voxelwise correlation analysis revealed that the Digit Symbol Test scores (age corrected) correlated with the fractional anisotropy in WM tracts that previously showed significant group differences between the CT/TT and CC genotypes in the rs2312147 CT/TT genotype group, while no significant correlation was found in the CC genotype group. Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.

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Tract-Based Spatial Statistics (TBSS) analysis showing significant differences in fractional anisotropy (FA) values between the rs2312147 CC genotype group and the CT/TT genotype group in patients with schizophrenia.Voxels demonstrating significant increases in FA values for the CC genotype group compared with the CT/TT genotype group are shown in red-yellow (TFCE-corrected p<0.05). Results are overlaid on the Montreal Neurologic Institute 1 mm template (Z = −20 to Z = 46) and the mean FA skeleton (green). A threshold-free cluster enhancement method was applied using a permutation-based inference tool for nonparametric statistics. The number of permutations was 10,000. Left-right orientation is according to radiological convention.
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pone-0103519-g001: Tract-Based Spatial Statistics (TBSS) analysis showing significant differences in fractional anisotropy (FA) values between the rs2312147 CC genotype group and the CT/TT genotype group in patients with schizophrenia.Voxels demonstrating significant increases in FA values for the CC genotype group compared with the CT/TT genotype group are shown in red-yellow (TFCE-corrected p<0.05). Results are overlaid on the Montreal Neurologic Institute 1 mm template (Z = −20 to Z = 46) and the mean FA skeleton (green). A threshold-free cluster enhancement method was applied using a permutation-based inference tool for nonparametric statistics. The number of permutations was 10,000. Left-right orientation is according to radiological convention.

Mentions: There was no significant difference between schizophrenia and HC with regard to FA value. Results of TBSS analysis between the CC and CT/TT genotype groups in schizophrenia patients yielded four clusters of significant (TFCE-corrected p<0.05) voxels on the WM skeleton. However, no regions of significantly different FA values between the two genotype groups were found within HC subjects, and there was no significant diagnosis-by-genotype interaction according to two-way ANOVA with age and sex as covariates. According to the group comparison of FA between the CC and CT/TT genotype groups in schizophrenia patients, the FA value was significantly higher (TFCE-corrected p<0.05) in the rs2312147 CC genotype group than in the CT/TT genotype group in four clusters of significant voxels on the WM skeleton (Figure 1). For each cluster, the total number of voxels, the Z-value, peak coordinates, and the anatomic locations are listed in Table 3. The largest cluster (6967 voxels) was located in the splenium of corpus callosum, the left occipital lobe WM, the left anterior limb of the internal capsule, the left temporal lobe WM, and the left fornix/stria terminalis. The second cluster (1565 voxels) was located in the right retrolenticular part of the internal capsule. And the third (181 voxels) and the fourth (163 voxels) clusters were located in the left cingulate gyrus, the left parietal lobe WM, and the right temporal lobe WM. Including age and sex as covariates in the analysis did not influence the obtained results.


Effects of VRK2 (rs2312147) on white matter connectivity in patients with schizophrenia.

Sohn H, Kim B, Kim KH, Kim MK, Choi TK, Lee SH - PLoS ONE (2014)

Tract-Based Spatial Statistics (TBSS) analysis showing significant differences in fractional anisotropy (FA) values between the rs2312147 CC genotype group and the CT/TT genotype group in patients with schizophrenia.Voxels demonstrating significant increases in FA values for the CC genotype group compared with the CT/TT genotype group are shown in red-yellow (TFCE-corrected p<0.05). Results are overlaid on the Montreal Neurologic Institute 1 mm template (Z = −20 to Z = 46) and the mean FA skeleton (green). A threshold-free cluster enhancement method was applied using a permutation-based inference tool for nonparametric statistics. The number of permutations was 10,000. Left-right orientation is according to radiological convention.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4117506&req=5

pone-0103519-g001: Tract-Based Spatial Statistics (TBSS) analysis showing significant differences in fractional anisotropy (FA) values between the rs2312147 CC genotype group and the CT/TT genotype group in patients with schizophrenia.Voxels demonstrating significant increases in FA values for the CC genotype group compared with the CT/TT genotype group are shown in red-yellow (TFCE-corrected p<0.05). Results are overlaid on the Montreal Neurologic Institute 1 mm template (Z = −20 to Z = 46) and the mean FA skeleton (green). A threshold-free cluster enhancement method was applied using a permutation-based inference tool for nonparametric statistics. The number of permutations was 10,000. Left-right orientation is according to radiological convention.
Mentions: There was no significant difference between schizophrenia and HC with regard to FA value. Results of TBSS analysis between the CC and CT/TT genotype groups in schizophrenia patients yielded four clusters of significant (TFCE-corrected p<0.05) voxels on the WM skeleton. However, no regions of significantly different FA values between the two genotype groups were found within HC subjects, and there was no significant diagnosis-by-genotype interaction according to two-way ANOVA with age and sex as covariates. According to the group comparison of FA between the CC and CT/TT genotype groups in schizophrenia patients, the FA value was significantly higher (TFCE-corrected p<0.05) in the rs2312147 CC genotype group than in the CT/TT genotype group in four clusters of significant voxels on the WM skeleton (Figure 1). For each cluster, the total number of voxels, the Z-value, peak coordinates, and the anatomic locations are listed in Table 3. The largest cluster (6967 voxels) was located in the splenium of corpus callosum, the left occipital lobe WM, the left anterior limb of the internal capsule, the left temporal lobe WM, and the left fornix/stria terminalis. The second cluster (1565 voxels) was located in the right retrolenticular part of the internal capsule. And the third (181 voxels) and the fourth (163 voxels) clusters were located in the left cingulate gyrus, the left parietal lobe WM, and the right temporal lobe WM. Including age and sex as covariates in the analysis did not influence the obtained results.

Bottom Line: However, its effect on the brain structure in schizophrenia is little known.The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part), the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM.Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.

ABSTRACT
Recent genome-wide association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2), in multiple Asian and European samples. However, its effect on the brain structure in schizophrenia is little known. We analyzed the brain structure of 36 schizophrenia patients and 18 healthy subjects with regard to rs2312147 genotype groups. Brain magnetic resonance scans for gray matter (GM) and white matter (WM) analysis, and genotype analysis for VRK2 rs2312147, were conducted. The Positive and Negative Syndrome Scale and the Digit Symbol Test were assessed for schizophrenia patients. There was no significant difference in either GM volume or WM connectivity with regard to rs2312147 genotype in healthy subjects. In contrast, we found significant differences in the WM connectivity between rs2312147 CC and CT/TT genotype groups of schizophrenia patients. The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part), the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM. Voxelwise correlation analysis revealed that the Digit Symbol Test scores (age corrected) correlated with the fractional anisotropy in WM tracts that previously showed significant group differences between the CT/TT and CC genotypes in the rs2312147 CT/TT genotype group, while no significant correlation was found in the CC genotype group. Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.

Show MeSH
Related in: MedlinePlus