Associations Among Suicidal Ideation, White Matter Integrity and Cognitive Deficit in First-Episode Schizophrenia

Abstract Background Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. Methods Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. Results Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)–left inferior temporal gyrus (ITG), right IFG–left ITG, right IFG–left middle frontal gyrus (MFG), and right IFG–right MFG in the FES group. Conclusion Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.

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Reduced white matter integrity and facial emotion perception in never-medicated patients with first-episode schizophrenia: A diffusion tensor imaging study

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2017.03.025 ◽

2017 ◽

Vol 77 ◽

pp. 57-64 ◽

Cited By ~ 1

Author(s):

Xiaoxin Zhao ◽

Yuxiu Sui ◽

Jingjing Yao ◽

Yiding Lv ◽

Xinyue Zhang ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Imaging Study ◽

Facial Emotion ◽

White Matter Integrity ◽

First Episode ◽

First Episode Schizophrenia ◽

Diffusion Tensor Imaging Study ◽

Facial Emotion Perception

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White matter integrity of the whole brain is disrupted in first-episode schizophrenia

Neuroreport ◽

10.1097/01.wnr.0000195664.15090.46 ◽

2006 ◽

Vol 17 (1) ◽

pp. 23-26 ◽

Cited By ~ 99

Author(s):

Yihui Hao ◽

Zhening Liu ◽

Tianzi Jiang ◽

Gaolang Gong ◽

Haihong Liu ◽

...

Keyword(s):

White Matter ◽

White Matter Integrity ◽

First Episode ◽

Whole Brain ◽

First Episode Schizophrenia

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

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.237 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S102-S102

Author(s):

Wenjun Su ◽

Tianyuan Zhu ◽

Lihua Xu ◽

Yanyan Wei ◽

Botao Zeng ◽

...

Keyword(s):

Working Memory ◽

Genetic Variation ◽

Cognitive Function ◽

White Matter ◽

Corpus Callosum ◽

White Matter Integrity ◽

First Episode ◽

Healthy Controls ◽

Corona Radiata ◽

First Episode Schizophrenia

Abstract 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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Combined analyses of thalamic volume, shape and white matter integrity in first-episode schizophrenia

NeuroImage ◽

10.1016/j.neuroimage.2009.04.027 ◽

2009 ◽

Vol 47 (4) ◽

pp. 1163-1171 ◽

Cited By ~ 36

Author(s):

Anqi Qiu ◽

Jidan Zhong ◽

Steven Graham ◽

Ming Ying Chia ◽

Kang Sim

Keyword(s):

White Matter ◽

White Matter Integrity ◽

First Episode ◽

First Episode Schizophrenia

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DNA Methylation Basis in the Effect of White Matter Integrity Deficits on Cognitive Impairments and Psychopathological Symptoms in Drug-Naive First-Episode Schizophrenia

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.777407 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaofen Zong ◽

Qinran Zhang ◽

Changchun He ◽

Xinyue Huang ◽

Jiangbo Zhang ◽

...

Keyword(s):

Dna Methylation ◽

White Matter ◽

Cognitive Impairments ◽

Digit Span ◽

Critical Role ◽

Anterior Cingulate ◽

White Matter Integrity ◽

First Episode ◽

Brain White Matter ◽

First Episode Schizophrenia

Background: Mounting evidence from diffusion tensor imaging (DTI) and epigenetic studies, respectively, confirmed the abnormal alterations of brain white matter integrity and DNA methylation (DNAm) in schizophrenia. However, few studies have been carried out in the same sample to simultaneously explore the WM pathology relating to clinical behaviors, as well as the DNA methylation basis underlying the WM deficits.Methods: We performed DTI scans in 42 treatment-naïve first-episode schizophrenia patients and 38 healthy controls. Voxel-based method of fractional anisotropy (FA) derived from DTI was used to assess WM integrity. Participants' peripheral blood genomic DNAm status, quantified by using Infinium® Human Methylation 450K BeadChip, was examined in parallel with DTI scanning. Participants completed Digit Span test and Trail Making test, as well as Positive and Negative Syndrome Scale measurement. We acquired genes that are differentially expressed in the brain regions with abnormal FA values according to the Allen anatomically comprehensive atlas, obtained DNAm levels of the corresponding genes, and then performed Z-test to compare the differential epigenetic-imaging associations (DEIAs) between the two groups.Results: Significant decreases of FA values in the patient group were in the right middle temporal lobe WM, right cuneus WM, right anterior cingulate WM, and right inferior parietal lobe WM, while the significant increases were in the bilateral middle cingulate WM (Ps < 0.01, GRF correction). Abnormal FA values were correlated with patients' clinical symptoms and cognitive impairments. In the DEIAs, patients showed abnormal couple patterns between altered FA and DNAm components, for which the enriched biological processes and pathways could be largely grouped into three biological procedures: the neurocognition, immune, and nervous system.Conclusion: Schizophrenia may not cause widespread neuropathological changes, but subtle alterations affecting local cingulum WM, which may play a critical role in positive symptoms and cognitive impairments. This imaging-epigenetics study revealed for the first time that DNAm of genes enriched in neuronal, immunologic, and cognitive processes may serve as the basis in the effect of WM deficits on clinical behaviors in schizophrenia.

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