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Neural substrates underlying delusions in schizophrenia

Jiajia Zhu, Chuanjun Zhuo, Feng Liu, Lixue Xu, Chunshui Yu
2016 Scientific Reports  
Delusions are cardinal positive symptoms in schizophrenia; however, the neural substrates of delusions remain unknown. In the present study, we investigated the neural correlates of delusions in schizophrenia using multi-modal magnetic resonance imaging (MRI) techniques. Diffusion, structural and perfusion MRIs were performed in 19 schizophrenia patients with severe delusions, 30 patients without delusions and 30 healthy controls. Fractional anisotropy (FA), gray matter volume (GMV) and
more » ... blood flow (CBF) were voxel-wisely compared among the three groups. Although patients without delusions exhibited decreased FA in white matter regions and decreased GMV in gray matter regions relative to controls, patients with severe delusions demonstrated comparable FA in all of these white matter regions and similar GMV in most of these gray matter regions. Both patient subgroups had less GMV in the amygdala and anterior cingulate cortex than controls. Although two patient subgroups showed consistent CBF changes relative to controls, only CBF in the anterior cingulate cortex was lower in patients with severe delusions than in patients without delusions. These findings suggest that schizophrenia patients with severe delusions have relatively normal structural integrity. Importantly, the excessively reduced perfusion in the anterior cingulate cortex may be associated with the development of delusions in schizophrenia. Schizophrenia manifests as a complex composition of many symptoms, including delusions, hallucinations, disorganization, avolition, apathy, and cognitive decline 1,2 . Each symptom shows variable degrees of expression in individual patients and possibly has unique neuropathology and etiology in schizophrenia. It has been suggested that clinical subtypes of schizophrenia have distinct genetic antecedents 3 and are associated with different brain imaging changes 4 . The inconsistencies across studies may arise from all-inclusive, unpartitioned clinical phenotypes. Identification of the relevant features specific to a certain schizophrenic symptom is important for precision clinical diagnosis, treatment, and research. Delusions are one of the cardinal positive symptoms of schizophrenia 5 and affects more than 70% of schizophrenia patients 6 . It has been shown that delusions are associated with specific behavioral deficits, such as defective verbal self-monitoring 7,8 and low cognitive insight 9 . However, the neural mechanisms of delusions in schizophrenia remain largely unknown. Delusions probably arise from the brain's attempts to integrate erroneous perceptions and disorganized neural processes 10 . To identify neural substrates of delusions, multiple diffusion tensor imaging (DTI) and structural magnetic resonance imaging (MRI) studies have attempted to identify correlations between structural impairments and delusions in schizophrenia (Supplementary Table S1 and S2). However, both positive 11-20 and negative 21-33 correlations have been reported. As a measure of cerebral perfusion, both positive and negative correlations between regional cerebral blood flow (CBF) and delusions have been found in schizophrenia 34 . These discrepant findings prevent us from drawing a conclusion about the association between structural/functional impairments and delusions in schizophrenia. Most of the previous studies on the neural substrates of delusions in schizophrenia have been based on a single imaging modality, which has prevented us from establishing a comprehensive understanding on the question. However, the developments of MRI imaging and processing techniques now provide us an opportunity to better characterize brain structural and functional changes in brain disorders. The DTI theory assumes that the diffusion of water molecules occurs in a free and unrestricted environment with a perfect Gaussian probability distribution 35 , which is not valid in biological tissues where water molecules often display non-Gaussian diffusion due to the presence of barriers such as cell membranes and organelles 36 . Diffusion kurtosis imaging (DKI) has been proposed to simultaneously characterize Gaussian and non-Gaussian diffusion 37-41 , which can make a more
doi:10.1038/srep33857 pmid:27651212 pmcid:PMC5030611 fatcat:2hgzrosxibhy3geje7hhicqen4

Altered Cerebral Blood Flow Covariance Network in Schizophrenia

Feng Liu, Chuanjun Zhuo, Chunshui Yu
2016 Frontiers in Neuroscience  
Copyright © 2016 Liu, Zhuo and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).  ... 
doi:10.3389/fnins.2016.00308 pmid:27445677 pmcid:PMC4927570 fatcat:4h3fi6j24reehfopino4vklcla

Association of Schizophrenia With the Risk of Breast Cancer Incidence

Chuanjun Zhuo, Patrick Todd Triplett
2018 JAMA psychiatry  
IMPORTANCE Patients with schizophrenia are considered to have many risk factors for the development of cancer. However, the incidence of breast cancer in women with schizophrenia compared with the general population remains uncertain. OBJECTIVE To perform an updated meta-analysis to evaluate the association between schizophrenia and the risk of breast cancer. DATA SOURCES A systematic search of the PubMed and EMBASE databases was conducted using the search terms schizophrenia, schizophrenic,
more » ... chosis, combined with breast and cancer, tumor, neoplasm, or carcinoma. The final literature search was performed on August 15, 2017. STUDY SELECTION Cohort studies reporting the standardized incidence ratio (SIR) for the risk of breast cancer in women with schizophrenia compared with the general population. DATA EXTRACTION AND SYNTHESIS The meta-analysis adhered to Meta-analysis of Observational Studies in Epidemiology and the Cochrane Handbook for Systematic Reviews of Interventions. Data extraction was performed independently. A random-effects model was used to pool the results, and a recently proposed prediction interval was calculated to describe the heterogeneity. MAIN OUTCOMES AND MEASURES The SIR for the risk of breast cancer in women with schizophrenia compared with the general population or those without schizophrenia. RESULTS Twelve cohorts including 125 760 women were included in this meta-analysis. The results of the meta-analysis showed that schizophrenia was associated with a significantly increased risk of breast cancer incidence in women (SIR, 1.31; 95% CI, 1.14-1.50; P < .001), with significant heterogeneity (P < .001; I 2 = 89%). Substantial between-study variance was also suggested by the wide prediction interval (0.81-2.10), which indicated that it is possible that a future study will show a decreased breast cancer risk in women with schizophrenia compared with the general population. The subgroup analysis results showed that the association was not significantly affected by whether breast cancer cases were excluded at baseline or the sample size of the included studies. CONCLUSIONS AND RELEVANCE The incidence of breast cancer in women with schizophrenia is higher than that of the general female population. However, significant heterogeneity exists among the included studies. Women with schizophrenia deserve intensive prevention and treatment of breast cancer.
doi:10.1001/jamapsychiatry.2017.4748 pmid:29516094 pmcid:PMC5875321 fatcat:4mf7vv7r55bklk33fa7kyfxit4

LncRNA H19 inhibits autophagy by epigenetically silencing of DIRAS3 in diabetic cardiomyopathy

Chuanjun Zhuo, Ronghuan Jiang, Xiaodong Lin, Mingjing Shao
2016 OncoTarget  
We previously generated a rat model of diabetic cardiomyopathy and found that the expression of long non-coding RNA H19 was downregulated. The present study was aimed to explore the pathogenic role of H19 in the development of diabetic cardiomyopathy. Overexpression of H19 in diabetic rats attenuated cardiomyocyte autophagy and improved left ventricular function. High glucose was found to reduce H19 expression and increase autophagy in cultured neonatal cardiomyocytes. The results of
more » ... protein immunoprecipitation showed that H19 could directly bind with EZH2 in cardiomyocytes. The chromatin immunoprecipitation assays indicated that H19 knockdown could reduce EZH2 occupancy and H3K27me3 binding in the promoter of DIRAS3. In addition, overexpression of H19 was found to downregulate DIRAS3 expression, promote mTOR phosphorylation and inhibit autophagy activation in cardiomyocytes exposed to high glucose. Furthermore, we also found that high glucose increased DIRAS3 expression in cardiomyocytes and DIRAS3 induced autophagy by inhibiting mTOR signaling. In conclusion, our study suggested that H19 could inhibit autophagy in cardiomyocytes by epigenetically silencing of DIRAS3, which might provide novel insights into understanding the molecular mechanisms of diabetic cardiomyopathy.
doi:10.18632/oncotarget.13637 pmid:27903964 pmcid:PMC5352066 fatcat:looew7zgajef7jn6efmg2zdxdq

Functional connectivity density alterations in schizophrenia

Chuanjun Zhuo, Jiajia Zhu, Wen Qin, Hongru Qu, Xiaolei Ma, Hongjun Tian, Qingying Xu, Chunshui Yu
2014 Frontiers in Behavioral Neuroscience  
cn † These authors have contributed equally to this work. Background: Schizophrenia is characterized by altered resting-state functional connectivity. Most previous studies have focused on changes in connectivity strengths; however, the alterations in connectivity density in schizophrenia remain largely unknown. Here, we aimed to investigate changes in resting-state functional connectivity density (rsFCD) in schizophrenia. Methods: A total of 95 schizophrenia patients and 93 sex-and age-matched
more » ... healthy controls (HCs) underwent resting-state functional MRI examinations. The rsFCD, which reflects the total number of functional connections between a given brain voxel and all other voxels in the entire brain, was calculated for each voxel of each subject. Voxel-based comparisons were performed to identify brain regions with significant rsFCD differences between patients and controls (P < 0.05, corrected). Results: Compared with HCs, patients with schizophrenia showed significantly increased rsFCD in the bilateral striatum and hippocampus and significantly decreased rsFCD in the bilateral sensorimotor cortices and right occipital cortex. However, the rsFCD values of these brain regions were not correlated with antipsychotic dosage, illness duration, or clinical symptom severity. Conclusions: The striatal and hippocampal regions and parietal-occipital regions exhibited completely different changes in rsFCD in schizophrenia, which roughly correspond to dopamine activity in these regions in schizophrenia. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia.
doi:10.3389/fnbeh.2014.00404 pmid:25477799 pmcid:PMC4237131 fatcat:qsehkc6dvbekvo43dwsbr6qyea

Potential Value of Genomic Copy Number Variations in Schizophrenia

Chuanjun Zhuo, Weihong Hou, Chongguang Lin, Lirong Hu, Jie Li
2017 Frontiers in Molecular Neuroscience  
Copyright © 2017 Zhuo, Hou, Lin, Hu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).  ... 
doi:10.3389/fnmol.2017.00204 pmid:28680393 pmcid:PMC5478687 fatcat:wr2sbxuej5fjhccdsmuwi6th24

Lung cancer incidence in patients with schizophrenia: meta-analysis

Chuanjun Zhuo, Hongqing Zhuang, Xiangyang Gao, Patrick Todd Triplett
2019 British Journal of Psychiatry  
BackgroundLung cancer risk factors, like tobacco smoking, are highly prevalent in patients with schizophrenia. Whether these patients have a higher risk of lung cancer remains unknown.AimsWe aimed to investigate whether patients with schizophrenia have a higher incidence of lung cancer compared with general population, in a meta-analysis.MethodEligible studies were searched from PubMed and EMBASE databases to identify cases of lung cancer in patients with schizophrenia and the general
more » ... . This meta-analysis utilised the random-effects model and prediction interval was used to calculate the heterogeneity of these eligible studies. We assessed the quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsThere were 12 studies, totalling 496 265 patients, included in this meta-analysis. The data showed that the baseline schizophrenia diagnosis was not associated with any changes in lung cancer incidence in the overall population, with a standardised incidence ratio of 1.11 (95% CI 0.90–1.37; P = 0.31), although there was a significant heterogeneity among these studies (I2 = 94%). Moreover, there was also a substantial between-study variance with wide prediction interval values (0.47–2.64). The data were consistent for both males and females.ConclusionsUp-to-date evidence from epidemiological studies indicates the lack of certainty about the association between schizophrenia diagnosis and lung cancer incidence.Declaration of interestNone.
doi:10.1192/bjp.2019.23 pmid:30806345 pmcid:PMC7557637 fatcat:arsyro5xibdshaeqrqca563phu

Brain structural and functional dissociated patterns in schizophrenia

Chuanjun Zhuo, Jiajia Zhu, Chunli Wang, Hongru Qu, Xiaolei Ma, Hongjun Tian, Mei Liu, Wen Qin
2017 BMC Psychiatry  
Although previous studies found that aberrations in gray matter volume (GMV) and global functional connectivity density (gFCD) are important characteristics of schizophrenia, to the best of our knowledge no study to date has investigated the associations between the spatial distribution patterns of GMV and gFCD alterations. We investigated pattern changes in gFCD and GMV among patients with schizophrenia and their associated spatial distributions. Methods: Ninety-five patients with
more » ... and 93 matched healthy controls underwent structural and resting-state functional MRI scanning to assess gFCD and GMV. Results: We found that gFCD increased in the subcortical regions (caudate, pallidum, putamen, and thalami) and limbic system (left hippocampus and parahippocampus), and decreased in the posterior parieto-occipito-temporal cortices (postcentral gyri, occipital cortex, temporo-occipital conjunction, and inferior parietal lobule), in patients with schizophrenia. By contrast, we found decreased GMV in brain regions including the frontal, parietal, temporal, occipital, cingulate cortices, and the insular, striatum, thalamus in these patients. Increased gFCD primarily occurred in subcortical regions including the basal ganglia and some regions of the limbic system. Decreased gFCD appeared primarily in the cortical regions. There were no statistically significant correlations between changes in gFCD and GMV, and their spatial distribution patterns, in different regions. Conclusions: Our findings indicate that gFCD and GMV are both perturbed in multiple brain regions in schizophrenia. gFCD and GMV consistently decreased in the cortical regions, with the exception of the Supplementary Motor Area (SMA). However, in the sub-cortical regions, the alterations of gFCD and GMV showed the opposite pattern, with increased gFCD and decreased GMV simultaneously observed in these regions. Overall, our findings suggest that structural and functional alterations appear to contribute independently to the neurobiology of schizophrenia.
doi:10.1186/s12888-017-1194-5 pmid:28143464 pmcid:PMC5282790 fatcat:d63see7o7vhn7eqs7igqzuyprq

LncRNA TINCR attenuates cardiac hypertrophy by epigenetically silencing CaMKII

Mingjing Shao, Guangdong Chen, Fengli Lv, Yanyan Liu, Hongjun Tian, Ran Tao, Ronghuan Jiang, Wei Zhang, Chuanjun Zhuo
2017 OncoTarget  
In the previous study, we established a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC) and found that the expression of long non-coding RNAs TINCR was downregulated in myocardial tissue. The present study was designed to determine the potential role of TINCR in the pathogenesis of cardiac hypertrophy. Our results showed that enforced expression of TINCR could attenuate cardiac hypertrophy in TAC mice. Angiotensin II (Ang-II) was found to be associated with reduced
more » ... TINCR expression and increased hypertrophy in cultured neonatal cardiomyocytes. RNAbinding protein immunoprecipitation assay confirmed that TINCR could directly bind with EZH2 in cardiomyocytes. The results of chromatin immunoprecipitation assay revealed that EZH2 could directly bind to CaMKII promoter region and mediate H3K27me3 modification. Knockdown of TINCR was found to reduce EZH2 occupancy and H3K27me3 binding in the promoter of CaMKII in cardiomyocytes. In addition, enforced expression of TINCR was found to decrease CaMKII expression and attenuate Ang-II-induced cardiomyocyte hypertrophy. Furthermore, our results also showed that Ang-II could increase CaMKII expression in cardiomyocytes, which consequently contributed to cellular hypertrophy. In conclusion, our findings demonstrated that TINCR could attenuate myocardial hypertrophy by epigenetically silencing of CaMKII, which may provide a novel therapeutic strategy for cardiac hypertrophy.
doi:10.18632/oncotarget.17735 pmid:28548932 pmcid:PMC5564587 fatcat:4plgq3ypofcdbefbzgxjy62axa

Efficacy of antidepressive medication for depression in Parkinson disease

Chuanjun Zhuo, Rong Xue, Lanlan Luo, Feng Ji, Hongjun Tian, Hongru Qu, Xiaodong Lin, Ronghuan Jiang, Ran Tao
2017 Medicine  
Zhuo et al. Medicine (2017) 96:22 effects compared with placebo (OR = 2.29, 95% CrI: [1.67, 3.17]; OR = 2.58, 95% CrI: [1.00, 6.77], respectively).  ... 
doi:10.1097/md.0000000000006698 pmid:28562526 pmcid:PMC5459691 fatcat:pebeemats5hbnityxkquzryc6m

The rise and fall of MRI studies in major depressive disorder

Chuanjun Zhuo, Gongying Li, Xiaodong Lin, Deguo Jiang, Yong Xu, Hongjun Tian, Wenqiang Wang, Xueqin Song
2019 Translational Psychiatry  
Structural and functional brain alterations are common in patients with major depressive disorder (MDD). In this review, we assessed the recent literature (1995-2018) on the structural and functional magnetic resonance imaging (MRI) studies of MDD. Despite the growing number of MRI studies on MDD, reverse inference is not possible as MRI scans cannot be used to aid in the diagnosis or treatment planning of patients with MDD. Hence, researchers must develop "bridges" to overcome the reverse
more » ... ence fallacy in order to build effective tools for MDD diagnostics. From our findings, we proposed that the "bridges" may be built using multidisciplinary technologies, such as artificial intelligence, multimodality imaging, and nanotheranostics, allowing for the further study of MDD at the biological level. In return, the "bridges" will aid in the development of future diagnostics for MDD and other mental disorders.
doi:10.1038/s41398-019-0680-6 pmid:31819044 pmcid:PMC6901449 fatcat:zmkbis54ivgrtkx7bdlsmnxz3m

Protective effect of hydrogen sulphide against myocardial hypertrophy in mice

Mingjing Shao, Chuanjun Zhuo, Ronghuan Jiang, Guangdong Chen, Jianmin Shan, Jing Ping, Hongjun Tian, Lina Wang, Chongguang Lin, Lirong Hu
2017 OncoTarget  
Cardiac hypertrophy is a critical component of phenotype in the failing heart. Recently, increasing evidence has demonstrated that oxidative stress plays an important role in the pathogenesis of myocardial hypertrophy. In the present study, we generated a mouse model of transverse aortic constriction (TAC) to investigate whether hydrogen sulfide (H 2 S) has protective effects against cardiac hypertrophy. Left ventricular structure was analyzed by two-dimensional echocardiography. Oxidative
more » ... s was evaluated by measuring malondialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen specie in the myocardium. Angiotensin II (Ang-II) was used to induce cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes pretreated with H 2 S donor sodium hydrosulfide prior to Ang-II exposure were used to determine the involvement of Nrf2 and PI3K/Akt pathway in the antioxidant effects of H 2 S. Our findings showed that H 2 S could protect against cardiac hypertrophy by attenuating oxidative stress. The antioxidant roles of H 2 S in myocardial hypertrophy probably depend on the activation of PI3K/Akt signaling, which consequently increases Nrf2 activity and HO-1 and GCLM expression. In summary, H 2 S may exert antioxidant effect on cardiac hypertrophy via PI3K/Akt-dependent activation of Nrf2 pathway.
doi:10.18632/oncotarget.15765 pmid:28423592 pmcid:PMC5410227 fatcat:df2t5skh2ncgfi56xbyjqpbfoq

Distinct disruptions of resting-state functional brain networks in familial and sporadic schizophrenia

Jiajia Zhu, Chuanjun Zhuo, Feng Liu, Wen Qin, Lixue Xu, Chunshui Yu
2016 Scientific Reports  
Clinical and brain structural differences have been reported between patients with familial and sporadic schizophrenia; however, little is known about the brain functional differences between the two subtypes of schizophrenia. Twenty-six patients with familial schizophrenia (PFS), 26 patients with sporadic schizophrenia (PSS) and 26 healthy controls (HC) underwent a resting-state functional magnetic resonance imaging. The whole-brain functional network was constructed and analyzed using graph
more » ... eoretical approaches. Topological properties (including global, nodal and edge measures) were compared among the three groups. We found that PFS, PSS and HC exhibited common smallworld architecture of the functional brain networks. However, at a global level, only PFS showed significantly lower normalized clustering coefficient, small-worldness, and local efficiency, indicating a randomization shift of their brain networks. At a regional level, PFS and PSS disrupted different neural circuits, consisting of abnormal nodes (increased or decreased nodal centrality) and edges (decreased functional connectivity strength), which were widely distributed throughout the entire brain. Furthermore, some of these altered network measures were significantly correlated with severity of psychotic symptoms. These results suggest that familial and sporadic schizophrenia had segregated disruptions in the topological organization of the intrinsic functional brain network, which may be due to different etiological contributions.
doi:10.1038/srep23577 pmid:27032817 pmcid:PMC4817042 fatcat:m5baxngzsrefxjs25ylbzpoaxe

Cancer mortality in patients with schizophrenia: systematic review and meta-analysis

Chuanjun Zhuo, Ran Tao, Ronghuan Jiang, Xiaodong Lin, Mingjing Shao
2017 British Journal of Psychiatry  
Previous studies have reported conflicting results on the association between schizophrenia and cancer mortality. Aims To summarise available evidence and quantify the association between schizophrenia and cancer mortality using meta-analysis. Method We systematically searched literature in the PubMed and Embase databases. Risk estimates and 95% confidence intervals reported in individual studies were pooled using the DerSimonian–Laird random-effects model. Results We included 19 studies in the
more » ... meta-analysis. Among them, 15 studies reported standardised mortality ratios (SMRs) comparing patients with schizophrenia with the general population, and the pooled SMR was 1.40 (95% CI 1.29–1.52, P&lt;0.001). The other four studies reported hazard ratios (HRs) comparing individuals with schizophrenia with those without schizophrenia; the pooled HR was 1.51 (95% CI 1.13–2.03, P = 0.006). Conclusions Patients with schizophrenia are at a significantly increased risk of cancer mortality compared with the general population or individuals without schizophrenia.
doi:10.1192/bjp.bp.116.195776 pmid:28596246 fatcat:466fn2o2knedlghwyv45jkkfgi

Cerebral blood flow alterations specific to auditory verbal hallucinations in schizophrenia

Chuanjun Zhuo, Jiajia Zhu, Wen Qin, Hongru Qu, Xiaolei Ma, Chunshui Yu
2017 British Journal of Psychiatry  
Zhuo,* Jiajia Zhu,* Wen Qin, Hongru Qu, Xiaolei Ma and Chunshui Yu Background Auditory verbal hallucinations (AVHs) have been associated with deficits in auditory and speech-related networks.  ...  physical illness such as cardiovascular disease or neurological disorders, as diagnosed by an interview 209 Cerebral blood flow alterations specific to auditory verbal hallucinations in schizophrenia Chuanjun  ... 
doi:10.1192/bjp.bp.115.174961 pmid:28104737 fatcat:tpb4u3ifenhlngu274bbd4aehq
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