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

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.

Effects of polygenic risk of schizophrenia on interhemispheric callosal white matter integrity and frontotemporal functional connectivity in first-episode schizophrenia

2022 ◽  
pp. 1-10
Author(s):  
Wenjun Su ◽  
Aihua Yuan ◽  
Yingying Tang ◽  
Lihua Xu ◽  
Yanyan Wei ◽  
...  
Keyword(s):  
White Matter ◽  
Functional Connectivity ◽  
White Matter Integrity ◽  
First Episode ◽  
Polygenic Risk Score ◽  
Polygenic Inheritance ◽  
Polygenic Risk ◽  
Corona Radiata ◽  
Brain White Matter ◽  
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.

Pretreatment abnormalities in white matter integrity predict one-year clinical outcome in first episode schizophrenia

2021 ◽  
Vol 228 ◽  
pp. 241-248
Author(s):  
Jiaxin Zeng ◽  
Wenjing Zhang ◽  
Yuan Xiao ◽  
Gui Fu ◽  
Lu Liu ◽  
...  
Keyword(s):  
White Matter ◽  
Clinical Outcome ◽  
White Matter Integrity ◽  
First Episode ◽  
One Year ◽  
First Episode Schizophrenia

scholarly journals Genes in immune pathways associated with abnormal white matter integrity in first-episode and treatment-naïve patients with schizophrenia

2019 ◽  
Vol 214 (5) ◽  
pp. 281-287
Author(s):  
Bo Xiang ◽  
Qiang Wang ◽  
Wei Lei ◽  
Mingli Li ◽  
Yinfei Li ◽  
...  
Keyword(s):  
White Matter ◽  
Anterior Cingulate Cortex ◽  
Genetic Variants ◽  
Rare Variants ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
White Matter Integrity ◽  
First Episode ◽  
Treatment Naïve ◽  
Left And Right

BackgroundPrevious studies have inferred a strong genetic component in schizophrenia. However, the genetic variants involved in the susceptibility to schizophrenia remain unclear.AimsTo detect potential gene pathways and networks associated with schizophrenia, and to explore the relationship between common and rare variants in these pathways and abnormal white matter integrity in schizophrenia.MethodThe analysis included 100 first-episode treatment-naïve patients with schizophrenia and 140 healthy controls. A network-based analysis was carried out on the data collected from the Psychiatric Genomics Consortium Phase I (PGC-I). Based on our genome-wide association study and whole-exome sequencing data-sets, we performed a gene-set analysis to detect associations between the combining effects of common and rare genetic variants and abnormal white matter integrity in schizophrenia.ResultsPatients had significantly reduced functional anisotropy in the left and right anterior cingulate cortex, left and right precuneus and extra-nuclear (t = 4.61–5.10, PFDR < 0.01), compared with controls. Generated from co-expression network analysis of the PGC-1 summary statistics of schizophrenia, a subnetwork of 207 genes associated with schizophrenia was identified (P < 0.01), and 176 genes were co-expressed in four gene modules. Functional enrichment analysis for genes in each module revealed that the yellow module was enriched with highly co-expressed, innate immune response genes. Furthermore, rare variants of enriched genes in the yellow module were associated with reduced functional anisotropy in the left anterior cingulate cortex (P = 0.006; Padjusted = 0.024) in patients only.ConclusionsThe pathogenesis of schizophrenia may be substantially influenced by genes involved in the immune system, via both pathway and network.Declaration of interestsNone.

White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment

2013 ◽  
Vol 43 (11) ◽  
pp. 2301-2309 ◽  
Author(s):  
Q. Wang ◽  
C. Cheung ◽  
W. Deng ◽  
M. Li ◽  
C. Huang ◽  
...  
Keyword(s):  
White Matter ◽  
Early Phase ◽  
Clinical Symptoms ◽  
Diffusion Tensor ◽  
Disease Process ◽  
Anterior Cingulate ◽  
First Episode ◽  
Drug Naïve ◽  
The Right ◽  
First Episode Schizophrenia

BackgroundIt is not clear whether the progressive changes in brain microstructural deficits documented in previous longitudinal magnetic resonance imaging (MRI) studies might be due to the disease process or to other factors such as medication. It is important to explore the longitudinal alterations in white-matter (WM) microstructure in antipsychotic-naive patients with first-episode schizophrenia during the very early phase of treatment when relatively ‘free’ from chronicity.MethodThirty-five patients with first-episode schizophrenia and 22 healthy volunteers were recruited. High-resolution diffusion tensor imaging (DTI) was obtained from participants at baseline and after 6 weeks of treatment. A ‘difference map’ for each individual was calculated from the 6-week follow-up fractional anisotropy (FA) of DTI minus the baseline FA. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Global Assessment of Functioning (GAF) scores between baseline and 6 weeks were also evaluated and expressed as a 6-week/baseline ratio.ResultsCompared to healthy controls, there was a significant decrease in absolute FA of WM around the bilateral anterior cingulate gyrus and the right anterior corona radiata of the frontal lobe in first-episode drug-naive patients with schizophrenia following 6 weeks of treatment. Clinical symptoms improved during this period but the change in FA did not correlate with the changes in clinical symptoms or the dose of antipsychotic medication.ConclusionsDuring the early phase of treatment, there is an acute reduction in WM FA that may be due to the effects of antipsychotic medications. However, it is not possible to entirely exclude the effects of underlying progression of illness.

scholarly journals Anterior cingulate grey-matter deficits and cannabis use in first-episode schizophrenia

2007 ◽  
Vol 190 (3) ◽  
pp. 230-236 ◽  
Author(s):  
Philip R. Szeszko ◽  
Delbert G. Robinson ◽  
Serge Sevy ◽  
Sanjiv Kumra ◽  
Claudia I. Rupp ◽  
...  
Keyword(s):  
White Matter ◽  
Healthy Volunteers ◽  
Grey Matter ◽  
Magnetic Resonance Images ◽  
Cannabis Use ◽  
Anterior Cingulate ◽  
First Episode ◽  
History Of ◽  
First Episode Schizophrenia ◽  
First Episode Of Schizophrenia

BackgroundDespite the high prevalence of cannabis use in schizophrenia, few studies have examined the potential relationship between cannabis exposure and brain structural abnormalities in schizophrenia.AimsTo investigate prefrontal grey and white matter regions in patients experiencing a first episode of schizophrenia with an additional diagnosis of cannabis use or dependence (n=20) compared with similar patients with no cannabis use (n=31) and healthy volunteers (n=56).MethodVolumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous magnetic resonance images and automatically segmented into grey and white matter.ResultsPatients who used cannabis had less anterior cingulate grey matter compared with both patients who did not use cannabis and healthy volunteers.ConclusionsA defect in the anterior cingulate is associated with a history of cannabis use among patients experiencing a first episode of schizophrenia and could have a role in poor decision-making and in choosing more risky outcomes.

scholarly journals Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia

2010 ◽  
Vol 41 (8) ◽  
pp. 1709-1719 ◽  
Author(s):  
V. Cheung ◽  
C. P. Y. Chiu ◽  
C. W. Law ◽  
C. Cheung ◽  
C. L. M. Hui ◽  
...  
Keyword(s):  
White Matter ◽  
Negative Symptoms ◽  
Diffusion Tensor ◽  
Structural Connectivity ◽  
Anterior Cingulate ◽  
Middle Temporal Gyrus ◽  
First Episode ◽  
Positive Symptoms ◽  
Cingulate Gyrus ◽  
First Episode Schizophrenia

BackgroundWe investigated cerebral structural connectivity and its relationship to symptoms in never-medicated individuals with first-onset schizophrenia using diffusion tensor imaging (DTI).MethodWe recruited subjects with first episode DSM-IV schizophrenia who had never been exposed to antipsychotic medication (n=34) and age-matched healthy volunteers (n=32). All subjects received DTI and structural magnetic resonance imaging scans. Patients' symptoms were assessed on the Positive and Negative Syndrome Scale. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values significantly correlated with symptom scores.ResultsIn patients with first-episode schizophrenia, positive symptoms correlated positively with FA scores in white matter associated with the right frontal lobe, left anterior cingulate gyrus, left superior temporal gyrus, right middle temporal gyrus, right middle cingulate gyrus, and left cuneus. Importantly, FA in each of these regions was lower in patients than controls, but patients with more positive symptoms had FA values closer to controls. We found no significant correlations between FA and negative symptoms.ConclusionsThe newly-diagnosed, neuroleptic-naive patients had lower FA scores in the brain compared with controls. There was positive correlation between FA scores and positive symptoms scores in frontotemporal tracts, including left fronto-occipital fasciculus and left inferior longitudinal fasciculus. This implies that white matter dysintegrity is already present in the pre-treatment phase and that FA is likely to decrease after clinical treatment or symptom remission.

scholarly journals M160. INVESTIGATING STRUCTURAL CONNECTIVITY CORRELATES OF VERBAL MEMORY DEFICITS AMONG FIRST-EPISODE PSYCHOSIS PATIENTS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S196-S197
Author(s):  
Charlie Henri-Bellemare ◽  
Raihaan Patel ◽  
Katie Lavigne ◽  
M Mallar Chakravarty ◽  
Martin Lepage
Keyword(s):  
White Matter ◽  
Verbal Memory ◽  
Multiple Comparisons ◽  
Anterior Cingulate ◽  
First Episode ◽  
Healthy Controls ◽  
White Matter Tract ◽  
Whole Brain ◽  
Brain White Matter ◽  
Main Effect

Abstract Background Verbal memory is one of the most affected cognitive domains in patients with schizophrenia and related psychoses. Several studies have found associations between cognitive abilities and white matter fractional anisotropy (FA) in schizophrenia; however, only a few tractography studies have investigated FA relative to verbal memory in patients with a first episode of psychosis (FEP) compared with healthy controls (HC). Although white matter tractography differences have been well established between chronic patients and HC, the direction of findings from FEP studies has been inconsistent. Thus, the present study aims to examine whole-brain white matter differences and its association with verbal memory in individuals with a FEP relative to HC using tractography. Methods Diffusion-weighted images were acquired on a 1.5T scanner for patients (n=65) and controls (n=54) at baseline. The Wechsler Memory Scale was used as a measure of verbal memory. Pre-processing was performed on a subject-by-subject basis using MRtrix. Diffusion tractography was generated using a probabilistic anatomically-constrained tractography algorithm, which constrains the reconstruction to specific biological priors. Furthermore, the spherical-deconvolution informed filtering of tractograms (SIFT) tool will be used to ensure the tractogram is biologically meaningful. This results in subject-specific connectomes defining the mean FA between two regions of interest that were defined using the Desikan- Killiany atlas. A linear model was used to test for main effect of group and main effect of verbal memory on white matter tract FA, covarying for age and sex. For both sets of analyses, results were corrected for multiple comparisons using false discovery rate (FDR). Results A significant main effect of group on whole-brain average FA was observed, with patients displaying lower average FA compared to healthy controls (Patients=0.291, controls=0.300, p&lt;0.05). Whole-brain white matter tract FA analysis revealed that there are widespread differences between controls and individuals with a FEP. Group most strongly predicted white matter tract FA differences between left caudal anterior cingulate and left lateral orbitofrontal (patients mean FA=0.302, controls mean FA=0.342), left hippocampus and right isthmus cingulate (patient mean FA= 0.217 controls mean FA= 0.318), and finally left lingual and left rostral anterior cingulate (patients mean FA=0.162, controls mean FA= 0.249. However, none survived correction for multiple comparisons. Further, there was no significant association between verbal memory and white matter tract FA in FEP or HC. Discussion Findings from this study suggest there are some significant differences in whole-brain average FA between individuals experiencing a FEP and healthy controls. However, when analyzing whole-brain tract FA, none of the connections survived corrections for multiple comparisons. These findings might be limited by the scanner resolution included in this study, which may not capture more subtle differences. Nonetheless, these results are consistent with a cross-sectional study comparing healthy individuals to chronic and first-episode patients suggesting that modest differences are present early in the disease and increase as the disease progresses. We suggest that future studies analyze white matter tract using a longitudinal design to identify disease progression.

Classification of first-episode schizophrenia spectrum disorders and controls from whole brain white matter fractional anisotropy using machine learning

2017 ◽  
Vol 41 (S1) ◽  
pp. S191-S191 ◽  
Author(s):  
P. Mikolas ◽  
J. Hlinka ◽  
Z. Pitra ◽  
A. Skoch ◽  
T. Frodl ◽  
...  
Keyword(s):  
Machine Learning ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Classification Performance ◽  
Classification Model ◽  
First Episode ◽  
Support Vector ◽  
Brain White Matter ◽  
First Episode Schizophrenia

BackgroundSchizophrenia is a chronic disorder with an early onset and high disease burden in terms of life disability. Its early recognition may delay the resulting brain structural/functional alterations and improve treatment outcomes. Unlike conventional group-statistics, machine-learning techniques made it possible to classify patients and controls based on the disease patterns on an individual level. Diagnostic classification in first-episode schizophrenia to date was mostly performed on sMRI or fMRI data. DTI modalities have not gained comparable attention.MethodsWe performed the classification of 77 FES patients and 77 healthy controls matched by age and sex from fractional anisotropy data from using linear support-vector machine (SVM). We further analyzed the effect of medication and symptoms on the classification performance using standard statistical measures (t-test, linear regression) and machine learning (Kernel–Ridge regression).ResultsThe SVM distinguished between patients and controls with significant accuracy of 62.34% (P = 0.005). There was no association between the classification performance and medication nor symptoms. Group level statistical analysis yielded brain-wide significant differences in FA.ConclusionThe SVM in combination with brain white-matter fractional anisotropy might help differentiate FES from HC. The performance of our classification model was not associated with symptoms or medications and therefore reflects trait markers in the early course of the disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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

Neuroreport ◽  
2006 ◽  
Vol 17 (1) ◽  
pp. 23-26 ◽  
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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