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S171. EFFECT OF DAOA GENETIC VARIATION ON WHITE MATTER ALTERATION IN CORPUS CALLOSUM IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA

BACKGROUND: D-amino acid oxidase activator (DAOA) gene, which plays a key role in glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. In this study, we aimed to investigate whether the variation of DAOA rs2391191 could be associated with...

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Autores principales: Su, Wenjun, Zhu, Tianyuan, Xu, Lihua, Wei, Yanyan, Zeng, Botao, Zhang, Tianhong, Cui, Huiru, Wang, Junjie, Jia, Yuping, Wang, Jinhong, Goff, Donald C, Tang, Yingying, Wang, Jijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234743/
http://dx.doi.org/10.1093/schbul/sbaa031.237
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author Su, Wenjun
Zhu, Tianyuan
Xu, Lihua
Wei, Yanyan
Zeng, Botao
Zhang, Tianhong
Cui, Huiru
Wang, Junjie
Jia, Yuping
Wang, Jinhong
Goff, Donald C
Tang, Yingying
Wang, Jijun
author_facet Su, Wenjun
Zhu, Tianyuan
Xu, Lihua
Wei, Yanyan
Zeng, Botao
Zhang, Tianhong
Cui, Huiru
Wang, Junjie
Jia, Yuping
Wang, Jinhong
Goff, Donald C
Tang, Yingying
Wang, Jijun
author_sort Su, Wenjun
collection PubMed
description BACKGROUND: D-amino acid oxidase activator (DAOA) gene, which plays a key role in glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. In this study, we aimed to investigate whether the variation of DAOA rs2391191 could be associated with alterations in white matter integrity in first episode schizophrenia patients, and whether it influences the association between white matter integrity, cognitive function and clinical symptoms of schizophrenia. METHODS: Forty-six patients with first-episode schizophrenia and forty-nine sex, age and education-matched healthy controls underwent diffusion tensor imaging (DTI) and were genotyped for SNP DAOA rs2391191. Tract-based spatial statistics (TBSS) was used to delineate the major fiber tracts that showed significant group difference. Patients underwent pathophysiological assessments using Brief Psychiatric Rating Scale (BPRS) and Scale for Assessment of Negative Symptoms (SANS). Cognitive function assessments were performed by Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Schizophrenia patients presented lower fractional anisotropy (FA) and higher radial diffusivity (RD) mainly spreading over corpus callosum and corona radiata compared with healthy controls (FWE-corrected p<0.05). Compared with patients carrying G allele, patients with AA genotype showed lower FA in body of corpus callosum, and higher RD in genu of corpus callosum, right superior and anterior corona radiata, and left posterior corona radiata. But there were no significant FA or RD differences between two genotype groups in healthy controls. In patients carrying G allele, mean FA values in body of corpus callosum were positively correlated with working memory, mean RD values in genu of corpus callosum were negatively associated with speed of processing, working memory and composite score of MATRICS Consensus Cognitive Battery (MCCB), whilst there were no significant correlations found in AA homozygotes. DISCUSSION: Abnormal white matter integrity in corpus callosum and corona radiata were replicated among our sample of first episode schizophrenia. Genetic variation of DAOA rs2391191 was associated with this abnormality, with AA homozygotes showing less white matter integrity in corpus callosum. Our findings also suggested that rs2391191influenced the association between white matter integrity and cognitive function of schizophrenia patients. Such results might be due to the process of glutamatergic neurotransmission and mitochondrial function DAOA involves in as pinpointed by previous in vitro studies.
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spelling pubmed-72347432020-05-23 S171. EFFECT OF DAOA GENETIC VARIATION ON WHITE MATTER ALTERATION IN CORPUS CALLOSUM IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA Su, Wenjun Zhu, Tianyuan Xu, Lihua Wei, Yanyan Zeng, Botao Zhang, Tianhong Cui, Huiru Wang, Junjie Jia, Yuping Wang, Jinhong Goff, Donald C Tang, Yingying Wang, Jijun Schizophr Bull Poster Session I BACKGROUND: D-amino acid oxidase activator (DAOA) gene, which plays a key role in glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. In this study, we aimed to investigate whether the variation of DAOA rs2391191 could be associated with alterations in white matter integrity in first episode schizophrenia patients, and whether it influences the association between white matter integrity, cognitive function and clinical symptoms of schizophrenia. METHODS: Forty-six patients with first-episode schizophrenia and forty-nine sex, age and education-matched healthy controls underwent diffusion tensor imaging (DTI) and were genotyped for SNP DAOA rs2391191. Tract-based spatial statistics (TBSS) was used to delineate the major fiber tracts that showed significant group difference. Patients underwent pathophysiological assessments using Brief Psychiatric Rating Scale (BPRS) and Scale for Assessment of Negative Symptoms (SANS). Cognitive function assessments were performed by Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Schizophrenia patients presented lower fractional anisotropy (FA) and higher radial diffusivity (RD) mainly spreading over corpus callosum and corona radiata compared with healthy controls (FWE-corrected p<0.05). Compared with patients carrying G allele, patients with AA genotype showed lower FA in body of corpus callosum, and higher RD in genu of corpus callosum, right superior and anterior corona radiata, and left posterior corona radiata. But there were no significant FA or RD differences between two genotype groups in healthy controls. In patients carrying G allele, mean FA values in body of corpus callosum were positively correlated with working memory, mean RD values in genu of corpus callosum were negatively associated with speed of processing, working memory and composite score of MATRICS Consensus Cognitive Battery (MCCB), whilst there were no significant correlations found in AA homozygotes. DISCUSSION: Abnormal white matter integrity in corpus callosum and corona radiata were replicated among our sample of first episode schizophrenia. Genetic variation of DAOA rs2391191 was associated with this abnormality, with AA homozygotes showing less white matter integrity in corpus callosum. Our findings also suggested that rs2391191influenced the association between white matter integrity and cognitive function of schizophrenia patients. Such results might be due to the process of glutamatergic neurotransmission and mitochondrial function DAOA involves in as pinpointed by previous in vitro studies. Oxford University Press 2020-05 2020-05-18 /pmc/articles/PMC7234743/ http://dx.doi.org/10.1093/schbul/sbaa031.237 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. http://creativecommons.org/licenses/by-nc/4.0/ 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 non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Poster Session I
Su, Wenjun
Zhu, Tianyuan
Xu, Lihua
Wei, Yanyan
Zeng, Botao
Zhang, Tianhong
Cui, Huiru
Wang, Junjie
Jia, Yuping
Wang, Jinhong
Goff, Donald C
Tang, Yingying
Wang, Jijun
S171. EFFECT OF DAOA GENETIC VARIATION ON WHITE MATTER ALTERATION IN CORPUS CALLOSUM IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA
title S171. EFFECT OF DAOA GENETIC VARIATION ON WHITE MATTER ALTERATION IN CORPUS CALLOSUM IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA
title_full S171. EFFECT OF DAOA GENETIC VARIATION ON WHITE MATTER ALTERATION IN CORPUS CALLOSUM IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA
title_fullStr S171. EFFECT OF DAOA GENETIC VARIATION ON WHITE MATTER ALTERATION IN CORPUS CALLOSUM IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA
title_full_unstemmed S171. EFFECT OF DAOA GENETIC VARIATION ON WHITE MATTER ALTERATION IN CORPUS CALLOSUM IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA
title_short S171. EFFECT OF DAOA GENETIC VARIATION ON WHITE MATTER ALTERATION IN CORPUS CALLOSUM IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA
title_sort s171. effect of daoa genetic variation on white matter alteration in corpus callosum in patients with first-episode schizophrenia
topic Poster Session I
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234743/
http://dx.doi.org/10.1093/schbul/sbaa031.237
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