Search

Introduction: Gut microbial disturbance has been established as potential pathogenesis of mental disorders. However, the signatures and differences regarding patients with schizophrenia (SCH) or bipolar disorder (BD) in emerging adulthood as well as their subtypes have been poorly addressed., Methods: In the present study, stool samples obtained from 63 emerging adult patients with schizophrenia (SCH), 50 with bipolar disorder (BD), and 40 healthy controls (HC) were analyzed by 16 S rRNA gene sequencing; psychiatric symptoms and psychological, social, and professional functioning were also assessed., Results: We found that gut microbiota composition was remarkably changed in the patients with SCH and BD. Moreover, the distinct gut microbiome signatures and their potential function in bipolar depression (BP-D) and SCH with predominantly negative symptoms (SCH-N) as well as bipolar mania (BP-M) and SCH with predominantly positive symptoms (SCH-P) were also observed. Furthermore, we identified diagnostic potential biomarkers that can distinguish BD from HC (38 genera, AUC = 0.961), SCH from HC (32 genera, AUC = 0.962), and BD from Scheme (13 genera, AUC = 0.823). Potential diagnostic biomarkers that can distinguish BD-D from SCH-N (16 genera, AUC = 0.969) and BD-M from SCH-P (31 genera, AUC = 0.938) were also identified., Conclusion: This study provides further understanding of abnormal gut microbiome in emerging adulthood patients with SCH and BD and lay the potential foundation for the development of microbe-based clinical diagnosis for BD and SCH., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Previous sleep electroencephalography studies have detected abnormalities in sleep architecture and sleep spindle deficits in schizophrenia (SCZ), but the consistency of these results was not robust, which might be due to the small sample size and the influence of clinical factors such as the various medication therapies and symptom heterogeneity. This study aimed to regard auditory verbal hallucinations (AVHs) as a pointcut to downscale the heterogeneity of SCZ and explore whether some sleep architecture and spindle parameters were more severely impaired in SCZ patients with AVHs compared with those without AVHs., Methods: A total of 90 SCZ patients with AVHs, 92 SCZ patients without AVHs, and 91 healthy control subjects were recruited, and parameters of sleep architecture and spindle activities were compared between groups. The correlation between significant sleep parameters and clinical indicators was analyzed., Results: Deficits of sleep spindle activities at prefrontal electrodes and intrahemispheric spindle coherence were observed in both AVH and non-AVH groups, several of which were more serious in the AVH group. In addition, deficits of spindle activities at central and occipital electrodes and interhemispheric spindle coherence mainly manifested accompanying AVH symptoms, most of which were retained in the medication-naive first-episode patients, and were associated with Auditory Hallucination Rating Scale scores., Conclusions: Our results suggest that the underlying mechanism of spindle deficits might be different between SCZ patients with and without AVHs. In the future, the sleep feature of SCZ patients with different symptoms and the influence of clinical factors, such as medication therapy, should be further illustrated., (Copyright © 2021. Published by Elsevier Inc.)

Objective: The symptom-related neurobiology characteristic of schizophrenia in the brain from a network perspective is still poorly understood, leading to a lack of potential biologically-based markers and difficulty identifying therapeutic targets. We aim to test the dysregulated cross-network interactions among the Salience Network (SN), Central Executive Network (CEN) and Default Mode Network (DMN) and how they contributed to different symptoms in schizophrenia patients., Methods: We examined network interactions among the SN, CEN and DMN in 76 patients with schizophrenia vs. 80 well-matched controls using dynamic causal modeling (DCM). We further analyzed the relation between network dynamics and Positive and Negative Syndrome Scale (PANSS)., Results: We observed that the DMN, CEN and SN across healthy controls and schizophrenia patients showed several similarities within or between-network pattern in the resting state. Comparing schizophrenia to controls, SN-centered cross-network interactions were most significantly reduced. Crucially, the strength of connections from CEN subnetwork 1 to DMN subnetwork 1 was positively correlated with the Positive Score of PANSS. The connection from the DMN subnetwork 2 to CEN subnetwork 2 was negatively correlated with the Negative Score of PANSS., Conclusions: Our study provides strong evidence for the dysregulation among SN, CEN and DMN in a triple-network perspective in schizophrenia. The connection between DMN and CEN could be clinically-relevant neurobiological signature of schizophrenia symptoms. Our study indicated that the description of brain triple network hypothesis could be a novel and possible bio-marker for schizophrenia., (Copyright © 2021. Published by Elsevier B.V.)

Multimodal neuroimaging features provide opportunities for accurate classification and personalized treatment options in the psychiatric domain. This study aimed to investigate whether brain features predict responses to the overall treatment of schizophrenia at the end of the first or a single hospitalization. Structural and functional magnetic resonance imaging (MRI) data from two independent samples (N = 85 and 63, separately) of schizophrenia patients at baseline were included. After treatment, patients were classified as responders and non-responders. Radiomics features of gray matter morphology and functional connectivity were extracted using Least Absolute Shrinkage and Selection Operator. Support vector machine was used to explore the predictive performance. Prediction models were based on structural features (cortical thickness, surface area, gray matter regional volume, mean curvature, metric distortion, and sulcal depth), functional features (functional connectivity), and combined features. There were 12 features after dimensionality reduction. The structural features involved the right precuneus, cuneus, and inferior parietal lobule. The functional features predominately included inter-hemispheric connectivity. We observed a prediction accuracy of 80.38% (sensitivity: 87.28%; specificity 82.47%) for the model using functional features, and 69.68% (sensitivity: 83.96%; specificity: 72.41%) for the one using structural features. Our model combining both structural and functional features achieved a higher accuracy of 85.03%, with 92.04% responder and 80.23% non-responders to the overall treatment to be correctly predicted. These results highlight the power of structural and functional MRI-derived radiomics features to predict early response to treatment in schizophrenia. Prediction models of the very early treatment response in schizophrenia could augment effective therapeutic strategies., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The antipsychotic effect of Quetiapine (Que) has been extensively studied and growing evidence suggests that Que has a beneficial effect, improving cognitive functions and promoting myelin repair. However, the effects of Que on the brain lipidome and the association between Que-associated cognitive improvement and changes in lipids remain elusive. In the present study, we assessed the cognitive protective effects of Que treatment and used a mass spectrometry-based lipidomic approach to evaluated changes in lipid composition in the hippocampus, prefrontal cortex (PFC), and striatum in a mouse model of cuprizone (CPZ)-induced demyelination. CPZ induces cognitive impairment and remarkable lipid changes in the brain, specifically in lipid species of glycerophospholipids and sphingolipids. Moreover, the changes in lipid classes of the PFC were more extensive than those observed in the hippocampus and striatum. Notably, Que treatment ameliorated cuprizone-induced cognitive impairment and partly normalized CPZ-induced lipid changes. Taken together, our data suggest that Que may rescue cognitive behavioral changes from CPZ-induced demyelination through modulation of the brain lipidome, providing new insights into the pharmacological mechanism of Que for schizophrenia., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Despite evidence of structural brain abnormalities in schizophrenia, the current study aimed to explore the effects of antipsychotic treatment on gray matter (GM) volume using structural magnetic resonance imaging (MRI) and investigate the relationship between brain structure and treatment response. The GM volumes of 33 patients with first-episode schizophrenia were calculated with voxel-based morphometry (VBM), with 33 matched healthy controls. Longitudinal volume changes within subjects after 4-month antipsychotic treatment were also evaluated. Correlation between volumetric changes and clinical symptoms derived from the Positive and Negative Syndrome Scale (PANSS) were further investigated. Compared with healthy controls, decreased GM volumes in the frontal gyrus were observed in schizophrenia patients. After 4-month treatment, patients showed significantly decreased GM volume primarily in the bilateral frontal, temporal and left parietal brain regions. In addition, the GM volume changes of the left postcentral gyrus was positively correlated with negative symptoms improvement, and the correlation analysis revealed the total PANSS scores changes were associated with GM volume changes in the right inferior frontal gyrus and the right superior temporal gyrus. Besides, non-responders had reduced GM volume in the bilateral middle frontal gyrus and the right superior frontal gyrus compared with responders and healthy controls. Our results suggest that the abnormality in the right frontal gyrus exists in the early stage of schizophrenia. Moreover, the relationship between antipsychotics and structural changes was identified. The GM volume might have the potential to reflect the symptom improvement in schizophrenia patients. And MRI may assist in predicting the antipsychotic treatment response in first-episode schizophrenia patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: We aimed to evaluate the functional network properties in first-episode schizophrenia (SZ) patients at baseline and after 4-months treatment with second-generation antipsychotic drugs., Methods: Resting-state functional magnetic resonance imaging and graph theory approaches were utilized to evaluate the functional integration and segregation of brain networks in 36 first-episode patients (20 male/16 female) with SZ and 36 age and sex matched healthy controls (20 male/16 female)., Results: Compared with healthy controls, SZ at baseline showed lower clustering coefficient (C p ) and local network efficiency (E loc ), and this abnormal pattern was modulated with treatment of antipsychotic drugs at follow-up. Longitudinally, the increase of C p was associated with the improvement of negative symptom. We found that the strength of functional connectivity between brain regions were significantly increased in three connections after treatment, mainly involving the frontal, parietal and occipital lobes., Conclusion: The current study suggested that antipsychotic drugs could modulate the faulty local clustering of the functional connectome in SZ. Furthermore, C p , the parameter that reflects local clustering of topological organization, demonstrated the potential to be a connectome-based biomarker of treatment response to second-generation antipsychotics in patients with SZ., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Treatment response at an early stage of schizophrenia is of considerable value with regard to future management of the disorder; however, there are currently no biomarkers that can inform physicians about the likelihood of response., Objects: We aim to develop and validate regional brain activity derived from functional magnetic resonance imaging (fMRI) as a potential signature to predict early treatment response in schizophrenia., Methods: Amplitude of low-frequency fluctuation (ALFF) was measured at the start of the first/single episode resulting in hospitalization. Inpatients were included in a principal dataset (n = 79) and a replication dataset (n = 44). Two groups of healthy controls (n = 87; n = 106) were also recruited for each dataset. The clinical response was assessed at discharge from the hospital. The predictive capacity of normalized ALFF in patients by healthy controls, ALFF ratio , was evaluated based on diagnostic tests and clinical correlates., Results: In the principal dataset, responders exhibited increased baseline ALFF in the left postcentral gyrus/inferior parietal lobule relative to non-responders. ALFF ratio of responders before treatment was significantly higher than that of non-responders (p < 0.001). The area under the receiver operating characteristic curve was 0.746 for baseline ALFF ratio to distinguish responders from non-responders, and the sensitivity, specificity, and accuracy were 72.7%, 68.6%, and 70.9%, respectively. Similar results were found in the independent replication dataset., Conclusions: Baseline regional activity of the brain seems to be predictive of early response to treatment for schizophrenia. This study shows that psycho-neuroimaging holds promise for influencing the clinical treatment and management of schizophrenia., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Specific biomarker reflecting neurobiological substrates of schizophrenia (SZ) is required for its diagnosis and treatment selection of SZ. Evidence from neuroimaging has implicated disrupted functional connectivity in the pathophysiology. We aimed to develop and validate a method of disease definition for SZ by resting-state functional connectivity using radiomics strategy. This study included 2 data sets collected with different scanners. A total of 108 first-episode SZ patients and 121 healthy controls (HCs) participated in the current study, among which 80% patients and HCs (n = 183) and 20% (n = 46) were selected for training and testing in intra-data set validation and 1 of the 2 data sets was selected for training and the other for testing in inter-data set validation, respectively. Functional connectivity was calculated for both groups, features were selected by Least Absolute Shrinkage and Selection Operator (LASSO) method, and the clinical utility of its features and the generalizability of effects across samples were assessed using machine learning by training and validating multivariate classifiers in the independent samples. We found that the accuracy of intra-data set training was 87.09% for diagnosing SZ patients by applying functional connectivity features, with a validation in the independent replication data set (accuracy = 82.61%). The inter-data set validation further confirmed the disease definition by functional connectivity features (accuracy = 83.15% for training and 80.07% for testing). Our findings demonstrate a valid radiomics approach by functional connectivity to diagnose SZ, which is helpful to facilitate objective SZ individualized diagnosis using quantitative and specific functional connectivity biomarker.

Antipsychotic agents have been reported to promote hippocampal neurogenesis and improve cognitive deficits; yet, the molecular mechanisms underlying these actions remain unclear. In the present study, we used a murine model of schizophrenia induced by 5-day intraperitoneal injection with the non-competitive N-methyl-d-aspartate receptor antagonist MK801 (0.3mg/kg/day) to assess cognitive behavioral deficits, changes in Notch signaling, and cellular proliferation in the hippocampus of adult male C57BL/6 mice after 2-week administration of risperidone (Rip, 0.2mg/kg/day) or vehicle. We then utilized in vivo stereotaxic injections of a lentivirus expressing a short hairpin RNA (shRNA) for Notch1 into the dentate gyrus to examine the role of Notch1 in the observed actions of Rip. We found that Rip ameliorated cognitive deficits and restored cell proliferation in MK801-treated mice in a manner associated with the up-regulation of Notch signaling molecules, including Notch1, Hes1, and Hes5. Moreover, these effects were abolished by pretreatment with Notch1 shRNA. Our results suggest that the ability of Rip to improve cognitive function in schizophrenia is mediated in part by Notch signaling., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Neural substrates behind schizophrenia (SZ) and its heritability mediated by brain function are largely unknown. Cerebral blood flow (CBF), as a biomarker of activation in the brain, reflects the neuronal metabolism, and is promisingly used to detect cerebral alteration thereby shedding light on the features of individuals at high genetic risk. We performed a cross-sectional functional magnetic resonance imaging (MRI) study enrolling 45 first-episode drug-naïve patients with SZ, 32 unaffected first-degree relatives of these patients, and 51 healthy controls (HCs). We examined CBF, CBF connectivity, and CBF topological properties. SZ patients showed increased CBF in the left medial superior frontal gyrus and right precuneus compared with HCs, and decreased CBF in the left middle temporal gyrus compared with their relatives. Furthermore, unaffected relatives revealed higher level of CBF pronounced in regions within default mode network (DMN). Both SZ patients and their relatives exhibited dysconnectivity patterns. Notably, as for the network properties, unaffected relatives were with an intermediate level between SZ patients and HCs in the local efficiency and global efficiency. Our findings demonstrate the aberrant CBF of areas within DMN and the CBF connectivity pattern might be a familial feature in the brain of first-episode SZ patients and their relatives.

Purpose To investigate auditory verbal hallucination (AVH)-specific patterns of brain activity within the resting-state networks (RSNs) that have been proposed to underpin the neural mechanisms of schizophrenia (SZ). Materials and Methods This cross-sectional study was approved by the local ethics committee, and written informed consent was obtained from all participants prospectively recruited. Independent component analysis was used to investigate RSNs in 17 patients with first-episode untreated SZ with AVHs, 15 patients with SZ without AVHs, and 19 healthy control subjects who underwent resting-state functional magnetic resonance imaging. Dual regression was implemented to perform between-group analysis. Regional brain function was then explored within RSNs by using the amplitude of low-frequency fluctuation. Two-sample t tests were used to compare regional brain function between the two patient groups, and Pearson correlation analysis was used to characterize the relationship between imaging findings and severity of AVHs. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of these brain function measures. Results Independent component analysis demonstrated symptom-specific abnormal disrupted coactivation within the auditory, default mode, executive, motor, and frontoparietal networks and was pronounced in the auditory cortex, supramarginal gyrus, insula, putamen, dorsolateral prefrontal cortex, angular gyrus, precuneus, and thalamus (P < .05 with false discovery rate correction). Amplitude of low-frequency fluctuation analysis demonstrated similar patterns within these RSNs (P < .05 with false discovery rate correction). Furthermore, a positive correlation between the degree of coactivation within the motor network and the severity of AVHs was observed in patients with SZ with AVHs (r = 0.67, P = .003). The area under the receiver operating characteristic curve was 0.76-0.90 for all RSNs. Conclusion These findings indicate that dysfunctional brain regions are involved in auditory processing, language production and monitoring, and sensory information filtering in patients with SZ with AVHs, which may be helpful in furthering the understanding of pathophysiological correlates of AVHs in SZ. Online supplemental material is available for this article.

Information flow among auditory and language processing-related regions implicated in the pathophysiology of auditory verbal hallucinations (AVHs) in schizophrenia (SZ) remains unclear. In this study, we used stochastic dynamic causal modeling (sDCM) to quantify connections among the left dorsolateral prefrontal cortex (inner speech monitoring), auditory cortex (auditory processing), hippocampus (memory retrieval), thalamus (information filtering), and Broca's area (language production) in 17 first-episode drug-naïve SZ patients with AVHs, 15 without AVHs, and 19 healthy controls using resting-state functional magnetic resonance imaging. Finally, we performed receiver operating characteristic (ROC) analysis and correlation analysis between image measures and symptoms. sDCM revealed an increased sensitivity of auditory cortex to its thalamic afferents and a decrease in hippocampal sensitivity to auditory inputs in SZ patients with AVHs. The area under the ROC curve showed the diagnostic value of these two connections to distinguish SZ patients with AVHs from those without AVHs. Furthermore, we found a positive correlation between the strength of the connectivity from Broca's area to the auditory cortex and the severity of AVHs. These findings demonstrate, for the first time, augmented AVH-specific excitatory afferents from the thalamus to the auditory cortex in SZ patients, resulting in auditory perception without external auditory stimuli. Our results provide insights into the neural mechanisms underlying AVHs in SZ. This thalamic-auditory cortical-hippocampal dysconnectivity may also serve as a diagnostic biomarker of AVHs in SZ and a therapeutic target based on direct in vivo evidence.

The goal of the study was to investigate cerebral blood flow (CBF) and its connectivity (an across-subject covariance measure) patterns of schizophrenia (SZ) patients with auditory verbal hallucinations (AVHs). A total of demographically matched 25 SZ patients with AVHs, 25 without AVHs, and 25 healthy controls (HCs) underwent resting state perfusion imaging using a pulsed arterial spin labeling sequence. CBF and its connectivity were analyzed and then CBF topological properties were calculated. AVHs patients exhibited decreased CBF in the bilateral superior and middle frontal gyri and postcentral gyri, and right supplementary motor area compared with SZ patients without AVHs. SZ patients without AVHs showed reduced CBF in the left middle frontal gyrus relative to HCs. Moreover, AVHs groups showed distinct connectivity pattern, an intermediate level between HCs and patients without AVHs in the global efficiency. Our study demonstrates aberrant CBF in the brain regions associated with inner speech monitoring and language processing in SZ patients with AVHs. The complex network measures showed by CBF-derived functional connectivity indicate dysconnectivity between different functional units within the network of AVHs in SZ. Our findings might shed light on the neural underpinnings behind AVHs in this devastating disease at the level of CBF and its connectivity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Ziprasidone (ZIP) is often used with olanzapine (OLZ) in 'switch' and combination therapy but empirical evidence to support these strategies is limited., Objective: This study was therefore designed to compare the efficacy and tolerability of switching from OLZ to ZIP, the combination of both medications, and OLZ and ZIP monotherapy, in patients with schizophrenia spectrum disorders (SSD)., Methods: In this 12 week open-label, assessor-blinded randomized trial, 148 patients with SSD who had not used antipsychotics for at least 3 months were assigned to ZIP (n = 49) or OLZ monotherapy (n = 31); OLZ for 4 weeks then a switch to ZIP (OLZ/ZIP, n = 35); or combination therapy (OLZ + ZIP, n = 33). The severity of psychosis and abnormal involuntary movements was evaluated at baseline, 1, 2, 4, 8, and 12 weeks using standard instruments. Baseline-to-endpoint changes in weight gain and metabolic measures were compared., Results: The efficacy of both OLZ/ZIP and OLZ + ZIP was comparable OLZ monotherapy and better than ZIP monotherapy in reducing overall psychotic and negative symptoms at most 8 and 12 week measurement points. Changes in weight gain, glucose, and lipid measures did not differ between OLZ/ZIP and OLZ + ZIP, but were markedly higher following OLZ monotherapy. The OLZ + ZIP group had the lowest overall incidence of adverse events and extrapyramidal symptoms of all the treatment regimens., Conclusions: We conclude that combining ZIP and OLZ at the outset of treatment is superior to switching from OLZ to ZIP in terms of improving psychotic symptoms and limiting movement side effects without increasing the risk of metabolic syndrome., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: An herbal preparation called peony-glycyrrhiza decoction (PGD) may have the potential in reducing antipsychotic-related hyperprolactinemia (hyperPRL). This double-blind, randomized placebo-controlled study aimed to reevaluate the efficacy of PGD against antipsychotic-related hyperPRL., Methods: Ninety-nine schizophrenic women who were under antipsychotic therapy and had symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/d) for 16 weeks. The severity of hyperPRL, psychosis, and abnormal involuntary movements was assessed at baseline and weeks 8 and 16 using standard instruments including the Prolactin Related Adverse Event Questionnaire. Blood levels of prolactin (PRL) and related pituitary and sex hormones were measured at the same time points., Results: Peony-glycyrrhiza decoction treatment produced a significantly greater reduction of the Prolactin Related Adverse Event Questionnaire score at weeks 8 and 16 and a greater improvement on abnormal involuntary movements at end point compared with placebo, without altering the severity of psychosis. The group treated with PGD showed significantly higher proportion of having overall improvement on hyperPRL symptoms (χ = 4.010, P = 0.045) and menstrual resumption (χ = 4.549, P = 0.033) at week 8 than placebo. Serum PRL levels were similar in the 2 groups., Conclusions: Peony-glycyrrhiza decoction is effective in reducing antipsychotic-related hyperPRL and abnormal involuntary movement symptoms, but no reduction in blood PRL concentrations was observed. The underlying mechanisms of PGD's effects need further investigation (trial registration of NCT01852331 at www.clinicaltrials.gov).

Heterogeneous findings across studies of structural abnormality in schizophrenia (SZ) have impeded the development a unified theory of white matter pathology. As a cardinal symptom of SZ, auditory verbal hallucination (AVH) has been suspected to be associated with improper communication among several brain regions, which might indicated white matter pathology. Participants comprised 25 first-episode (FE) patients with AVH, 25 patients without AVH and 25 healthy subjects. Diffusion tensor imaging (DTI) measures were calculated using the TBSS of FSL. Voxel-based ANOVA tests were performed among the three groups and threshold-free cluster enhancement (TFCE) method correction was used for multiple comparisons. Voxel-based one-way ANOVA showed significant group effects for fractional anisotropy (FA) and radial diffusivity (RD) values. Post-hoc t-tests indicated that schizophrenia patients had lower FA and higher RD values in the internal capsule and anterior corona radiata than control subjects. Post-hoc analyses exhibited more widespread fiber disruptions in AVH patients than non-AVH patients. These results hinted on the important role of projection fiber disruption in schizophrenia patients. In addition, the current study also suggested that direct comparison between studies using patients with different symptom profiles should be interpreted with caution., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Objective: Auditory verbal hallucinations (AVHs) are one of the cardinal symptoms of schizophrenia (SZ). Cerebral dysfunction may represent pathophysiological underpinnings behind AVHs in SZ. However, regional and network functional deficits for AVHs in SZ remain to be identified., Methods: Seventeen medication-naïve first-episode SZ patients with AVHs, 15 without AVHs, and 19 healthy controls (HCs) were studied using resting-state functional magnetic resonance imaging. We compared the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) among these subjects. Areas with both ALFF and ReHo alterations were used as seeds in functional connectivity (FC) analysis. Then we performed correlation analysis between image measures and symptoms and receiver operating characteristic analysis., Results: One-way analysis of variance showed significant differences of ALFF and ReHo in the bilateral putamen, thereby being used as seeds. SZ patients with AVHs showed decreased ALFF in the left putamen, increased ReHo in the right dorsolateral prefrontal cortex (DLPFC), and increased right putamen-seeded FC with the left DLPFC and Broca's area relative to those without AVHs. Furthermore, the increased strength of the connectivity between the right putamen and left Broca's area correlated with the severity of SZ symptoms. Both patient groups demonstrated hypoconnectivity within frontal/parietal/temporal cortico-striatal-cerebellar networks compared with HCs., Conclusion: AVHs in SZ may be caused by abnormal regional function in the putamen and prefrontal cortex, as well as hyperconnectivity between them. The putamen-related regional and network functional deficits may reflect imbalance in neuromodulation of AVHs in SZ. Furthermore, dysconnectivity within cortico-striatal-cerebellar networks might subserve the pathogenesis of SZ., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: White matter disturbances and myelin impairment are key features of schizophrenia. The antipsychotic drug quetiapine can promote the maturation of oligodendrocytes, but the molecular mechanisms remain largely unknown., Methods: The schizophrenia-like behaviors, degrees of demyelination, and levels of Notch signaling molecules in forebrains of adult male C57BL/6 mice were examined after fed with cuprizone (0.2% wt/wt) in the presence or absence of 10mg/kg/d quetiapine for 6 weeks. These parameters were also observed after the transcranial injection of Notch signaling inhibitor MW167 (1mM) daily during the last week of the treatment period., Results: Quetiapine ameliorated the schizophrenia-like behaviors and decreased expression of myelin basic protein and inhibition of Notch signaling molecules, such as Notch1, Hes1, and Hes5, in the forebrain that induced by cuprizone. These beneficial effects of quetiapine were abolished by MW167., Conclusions: The antipsychotic and myelin protective effects of quetiapine are mediated by Notch signaling in a mouse model of cuprizone-induced demyelination associated with schizophrenia-like behaviors. The Notch pathway might therefore be a novel target for the development of antipsychotic drugs., (© The Author 2015. Published by Oxford University Press on behalf of CINP.)

Evidence from behavioral, electrophysiological and diffusion-weighted imaging studies suggest that schizophrenia patients suffer from deficiencies in bilateral brain communication, and this disruption may be related to the occurrence of auditory verbal hallucinations (AVH). To increase our understanding of aberrant inter-hemispheric communication in relation to AVH, we recruited two groups of first-episode schizophrenia patients: one group with AVH (N = 18 AVH patients) and one without hallucinations (N = 18 Non-AVH patients), and 20 healthy controls. All participants received T1 structural imaging and resting-state fMRI scanning. We adopted a newly developed index, voxel-mirrored homotopic connectivity (VMHC), to quantitatively describe bilateral functional connectivity. The whole-brain VMHC measure was compared among the three groups and correlation analyses were conducted between symptomology scores and neurological measures. Our findings suggest all patients shared abnormalities in parahippocampus and striatum. Aberrant bilateral connectivity of default mode network (DMN), inferior frontal gyrus and cerebellum only showed in AVH patients, whereas aberrances in superior temporal gyrus and precentral gyrus were specific to Non-AVH patients. Meanwhile, inter-hemispheric connectivity of DMN correlated with patients' symptomatology scores. This study corroborates that schizophrenia is characterized by inter-hemispheric dysconnectivity, and suggests the localization of such abnormalities may be crucial to whether auditory verbal hallucinations develop.

Electroacupuncture (EA) and electroconvulsive therapy (ECT) are often used in the management of schizophrenia. This study sought to determine whether additional EA and ECT could augment antipsychotic response and reduce related side effects. In this retrospective controlled study, 287 hospitalized schizophrenic patients who received antipsychotics (controls, n = 50) alone or combined with EA (n = 101), ECT (n = 55) or both (EA + ECT, n = 81) were identified. EA and ECT were conducted for 5 and 3 sessions per week, respectively, with a maximum of 12 sessions for ECT during hospitalization. The Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were used to assess the severity of psychotic symptoms. Clinical response on SAPS and SANS, weight gain, and adverse events were compared. Survival analysis revealed that the ECT and EA + ECT groups had markedly greater clinical response rate than controls on SAPS [72.7 and 90.1% vs. 64.0%; relative risk (RR), 1.974 and 2.628, respectively, P ≤ 0.004] and on SANS (67.3 and 70.4% vs. 42.0%; RR, 1.951 and 2.009, respectively, P ≤ 0.015). A significantly greater response rate on SANS than controls was also observed in the EA group (64.4% vs. 42.0%; RR = 1.938, P = 0.008). EA-containing regimens remarkably reduced weight gain and incidences of headache, insomnia, dry mouth, and electrocardiographic abnormalities. These results suggest that EA and ECT can serve as additional treatment for enhancing antipsychotic response and reduce the side effects in hospitalized patients with schizophrenia. Clinical Trial Registration: http://www.chictr.org.cn/showprojen.aspx?proj=38901, identifier ChiCTR1900023563. [ABSTRACT FROM AUTHOR]

Background: Hippocampal dysconnectivity has been detected in schizophrenia patients with auditory verbal hallucinations (AVHs). Neuroanatomical evidence has indicated distinct sub-regions in the hippocampus, but which sub-regions within the hippocampus may emerge dysfunction in the brain network, and the relationship between connection strength and the severity of this debilitating disorder have yet to be revealed. Masked independent component analysis (mICA), i.e., ICA restricted to a defined region of interest, can provide insight into observing local functional connectivity in a particular brain region. We aim to map out the sub-regions in the hippocampus with dysconnectivity linked to AVHs in schizophrenia. Methods: In this functional magnetic resonance imaging study of schizophrenia patients with (n = 57) and without (n = 83) AVHs, and 71 healthy controls, we first examined hippocampal connectivity using mICA, and then the correlation between connection metric and clinical severity was generated. Results: As compared with patients without AVHs, mICA showed a group of hyper-connections for the left middle part, as well as another group of hypo-connections for the bilateral antero-lateral and right antero-medial parts in patients with AVHs. Connectivity was linked to the clinical symptoms scores in the sample of patients with AVHs. Conclusion: These findings demonstrate that the left middle part is more densely connected, but the bilateral antero-lateral and right antero-medial parts are more sparsely connected in schizophrenia patients with AVHs. The findings in the present study show proof of precious location in the hippocampus mediating the neural mechanism behind AVHs in schizophrenia. [ABSTRACT FROM AUTHOR]