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• Analytical solution is developed for deeply tunnelling in viscoelastic-plastic geomaterials, considering actual loading path. • The solutions are compared with the previous ones without considering stress path, and the difference is identified. • The influence of supporting time etc. on the time-dependent responses of surrounding rock is investigated. The rock rheology and time process of tunnel construction make the mechanical responses of rock a function of time and are closely related to the loading path, however, these factors are not properly or correctly considered in analytical studies. The analytical study for deep tunnels in rheological rock is performed in this study, strictly taking into account the viscoelastic‒plastic characteristic of surrounding rocks and the actual loading path during excavation and supporting stages. The plane-strain problem of a circular tunnel in infinite plane under hydraulic far-field stress is simplified, with the time-dependent supporting pressure exerted at a specific time to consider the effect of delay installation of yielding support. The solving procedure as well as the time-dependent analytical solution of displacement, stress, and plastic radius in the excavation and supporting stages are presented in detail when the rocks satisfy the Unified strength theory and perfect plasticity. The analytical solutions agree very well with the numerical results, where the time procedure of tunnel excavation and support is simulated in the numerical model. Furthermore, the proposed solution can predict well the long-term deformation of the Shangxinzhai tunnel, which validates its applicability in real engineering. It is found that the tunnel deformation is underestimated if the unloading stage is not correctly considered. Based on the analytical solution, the influence of the supporting time, start time of the yielding stage and viscosity coefficient on the time dependence of tunnel convergence and stresses is investigated. [ABSTRACT FROM AUTHOR]

In this paper, we study analytically the three-dimensional (3D) stress–strain relationships at the elastic stage with regard to the anisotropic granular materials composed of regularly arranged bonded ellipsoidal particles by the micro-structural mechanics approach, where the macroscopic elastic constants are expressed in closed form with respect to the microscopic parameters. The bonded ellipsoidal particle assembly is first equivalent to a 3D lattice network composed of lattice beams with different contact properties. Based on the principle of energy balance, the macroscopic elastic stress–strain relationships for the equivalent micropolar continuum are obtained by analysing the unit cells of the lattice beam system. Using the proposed closed-form expressions of the anisotropic elastic constants, the elastic moduli, Poisson's ratios, Cauchy and Cosserat shear moduli and bending moduli can be expressed as functions of the microscopic parameters pertaining to the particle shape, size and contact properties. The elastic moduli and Poisson's ratios from closed-form expressions for regular particle arrangement and modified expressions for irregular particle arrangement are noted to be in agreement with the results obtained using distinct element method (DEM). The results suggest that the regularly arranged ellipsoid particle assembly shows a typical 3D orthotropic feature, and the elastic constants change significantly as the anisotropy of particle increases. [ABSTRACT FROM AUTHOR]

Summary: Background: Disturbances in emotion regulation are the hallmarks of major depressive disorder (MDD). The incapacity to control negative emotion in patients has been associated with abnormal hyperactivation of the limbic system and hypoactivation of the frontal cortex. The amygdala and orbital frontal cortex (OFC) are two critical regions of the emotion regulation neural systems. Methods: This study investigated the anatomical basis of abnormal emotion regulation by tracking the fiber tracts connecting the amygdala and OFC. In addition, using dynamic casual modeling on resting‐state fMRI data of 20 MDD patients and equivalent controls, we investigated the exact neural mechanism through which abnormal communications between these two nodes were mediated in MDD. Key Results: The results revealed disrupted white matter integrity of fiber tracts in MDD, suggesting that functional abnormalities were accompanied by underlying anatomical basis. We also detected a failure of inhibition of the OFC on the activity of the amygdala in MDD, suggesting dysconnectivity was mediated through "top‐down" influences from the frontal cortex to the amygdala. Following 8 weeks of antidepressant treatment, the patients showed significant clinical improvement and normalization of the abnormal OFC‐amygdala structural and effective connectivity in the left hemisphere. Conclusions & Inferences: Our findings suggest that pathways connecting these two nodes may be core targets of the antidepressant treatment. In particular, it raised the intriguing question: Does the reversal of structural markers of connectivity reflect a response to antidepressant medication or activity‐dependent myelination following a therapeutic restoration of effective connectivity? [ABSTRACT FROM AUTHOR]

• A cross-sectional study was conducted on 1289 young Chinese outpatients with first-episode medication-naïve major depressive disorder. • The prevalence of abnormal glucose metabolism was 12.57%. • Higher TSH levels and more severe anxiety symptoms were associated with fasting glucose levels in young patients with first-episode medication-naïve major depressive disorder. • TSH could distinguish patients with abnormal glucose metabolism from those without. The high co-morbidity of abnormal glucose metabolism in depressed patients has been extensively studied, but few studies have explored abnormal glucose metabolism in young patients with major depressive disorder (MDD). This study aimed to examine the prevalence and clinical correlates of abnormal glucose metabolism in young patients with first-episode medication-naïve (FEMN) MDD. A cross-sectional study was conducted on 1289 young Chinese outpatients with FEMN MDD. All subjects were assessed on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale, and their sociodemographic information was collected, and blood pressure, blood glucose, lipid and thyroid hormone levels were measured. The prevalence of abnormal glucose metabolism was 12.57% in young FEMN MDD outpatients. Thyroid stimulating hormone (TSH) levels and HAMA scale scores were associated with fasting blood glucose levels in patients with FEMN MDD (P <0.05), and TSH could differentiate patients with abnormal normal glucose metabolism from those without abnormal glucose metabolism (Area Under Curve of 0.774). Our study showed a high prevalence of comorbid glucose metabolism abnormalities in young FEMN MDD outpatients. TSH may be a promising biomarker of abnormal glucose metabolism in young patients with FEMN MDD. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a safe, tolerable, and evidence‐based intervention for major depressive disorder (MDD). However, even after decades of research, nearly half of the patients with MDD fail to respond to conventional TMS, with responding slowly and requiring daily attendance at the treatment site for 4–6 weeks. To intensify antidepressant efficacy and shorten treatment duration, accelerated TMS protocols, which involve multiple sessions per day over a few days, have been proposed and evaluated for safety and viability. We reviewed and summarized the current knowledge in accelerated TMS, including stimulation parameters, antidepressant efficacy, anti‐suicidal efficacy, safety, and adverse effects. Limitations and suggestions for future directions are also addressed, along with a brief discussion on the application of accelerated TMS during the COVID‐19 pandemic. This article is categorized under:Neuroscience > Clinical Neuroscience [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) has been employed for decades as a non-pharmacologic treatment for post-traumatic stress disorder (PTSD). Although a link has been suggested between PTSD and impaired sensorimotor gating (SG), studies assessing the effects of rTMS against PTSD or PTSD with impaired SG are scarce. Aim: To assess the benefit of rTMS in a rat model of PTSD. Methods: Using a modified single prolonged stress (SPS&S) rat model of PTSD, behavioral parameters were acquired using open field test (OFT), elevated plus maze test (EPMT), and prepulse inhibition trial (PPI), with or without 7 days of high frequency (10Hz) rTMS treatment of SPS&S rats. Results: Anxiety-like behavior, impaired SG and increased plasma level of cortisol were observed in SPS&S animals after stress for a prolonged time. Interestingly, rTMS administered immediately after stress prevented those impairment. Conclusion: Stress-induced anxiety-like behavior, increased plasma level of cortisol and impaired PPI occur after stress and high-frequency rTMS has the potential to ameliorate this behavior, suggesting that high frequency rTMS should be further evaluated for its use as a method for preventing PTSD. [ABSTRACT FROM AUTHOR]

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established. Methods: Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive‐like behaviors, the composition of gut microbiota of stool samples, as well as medium‐ and long‐chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated. Results: CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive‐like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC. Conclusion: These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS. [ABSTRACT FROM AUTHOR]

Neural oscillations play a role in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, the effects of high-frequency rTMS on the neural oscillations of the medial prefrontal cortex (mPFC) and hippocampus (HPC) and its molecular mechanism have not been fully clarified. The depressive-like behaviours, local field potentials (LFPs) of the ventral HPC (vHPC)-mPFC, and alternations of endocannabinoid system (ECS) in the HPC and mPFC were observed after rTMS treatment. Meanwhile, depressive-like behaviours and LFPs were also observed after cannabinoid type-1 receptor (CB1R) antagonist AM281 or monoacylglycerol lipase inhibitor JZL184 injection. Moreover, the antidepressant effect of rTMS was further assessed in glutamatergic-CB1R and gamma-amino butyric acid (GABA)-ergic -CB1R knockout mice. Alternations of endocannabinoids and energy value and synchronisation of mPFC-vHPC, especially the decrease of theta oscillation induced by CUMS, were alleviated by rTMS. JZL184 has similar effects to rTMS and AM281 blocked the effects of rTMS. GABAergic-CB1R deletion inhibited CUMS-induced depressive-like behaviours whereas Glutaminergic-CB1R deletion dampened the antidepressant effects of rTMS. The immediate effect of rTMS on field-potential regulation was not observed. Moreover, the role of region-specific regulation of the ECS in the antidepressant effect of rTMS was unclear and the effects of cell-specific CB1R knockout on neuronal oscillations of the mPFC and vHPC should be further investigated. Endocannabinoid system mediated the antidepressant effects and was involved in the regulation of LFP in the vHPC-mPFC of high-frequency rTMS. [Display omitted] • CUMS induces neural oscillation and ECS dysfunction in mPFC and HPC • These dysfunctions are restored after rTMS • JZL184 has similar effects to rTMS and AM281 blocked the effects of rTMS • GABAergic-CB1R deletion inhibits CUMS-induced depressive-like behaviours • Glutaminergic-CB1R deletion inhibits the antidepressant effects of rTMS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Notice on strengthening the treatment and management of patients with severe mental disorders during the outbreak of novel coronavirus pneumonia. Expert consensus on managing pathway and coping strategies for patients with mental disorders during prevention and control of serious and outbreak infectious diseases (novel coronavirus pneumonia). [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The association between abnormal gut microbiome composition and depression is well established. However, the composition and functional capacity of the gut microbiota regarding depressed women has been poorly addressed.Methods: Stool samples from 62 female patients with major depressive disorder (MDD) and 46 healthy controls (Con) were analyzed by 16S rRNA gene sequencing; Twenty fecal samples from the patient group and 21 fecal samples from the Con group were further analyzed by shotgun metagenomic sequencing. Psychiatric symptoms and psychological, social, and professional functioning was also assessed.Results: Phylum Bacteroidetes, proteobaeteria, and Fusobacteria were greatly enriched in patients with MDD, while the Firmicutes and Actinobacteria phyla were consistently higher in Con. Notably, 18 microbial markers were identified on a random forest model and achieve an area under the curve of 0.92 between patients with MDD and the Con group. Forty-five species and their associated function were identified with statistically significant differences between patients with MDD and the Con group.Limitations: The number of recruited samples, especially samples enrolled for shotgun metagenomic sequencing was relatively small, and the stool samples were collected only at baseline, making it difficult to establish a causal association between changes in gut microbiota compositions and disease remission.Conclusions: This study characterizes the gut microbiota and their related function in female MDD. The gut microbiota-based biomarkers may be helpful in diagnosis and the altered gut microbial metabolites may contribute to the pathogenesis of MDD in women, representing potential microbial targets. [ABSTRACT FROM AUTHOR]

Background: Associations between abnormal gut microbiome compositions and anxiety-like behaviors are well established. However, it is unknown whether the gut microbiome composition is associated with the severity of generalized anxiety disorder (GAD) and relief from clinical symptoms in patients.Methods: Stool samples from 36 patients with active GAD (A-GAD group) and 24 matched healthy control subjects (HC group) were analyzed by 16S rRNA gene sequencing. Anxiety was assessed with the Hamilton Anxiety Rating Scale and the Self-rating Anxiety Scale, and global assessments of functioning were performed at baseline and 1 month after drug treatment.Results: Gut microbiome compositions were altered in A-GAD patients, with fewer operational taxonomic units and lower fecal bacterial α-diversity. Specifically, Firmicutes and Tenericutes abundances were lower in A-GAD patients, and several genera were differentially represented in the A-GAD and HC groups. The abundances of Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-014, and Prevotella_9 correlated negatively with the anxiety severity and positively with anxiety reduction, whereas the abundances of Bacteroides and Escherichia-Shigella were positively associated with anxiety severity. Sex, smoking, and alcohol intake influenced the gut microbiome composition.Limitations: The sample sizes were small and the stool samples were collected only at baseline; therefore, a causal association between changes in intestinal flora and disease remission was not established. Moreover, the effects of different drugs on gut microbiome composition were not investigated.Conclusions: Altered gut microbiome composition may contribute to GAD pathogenesis and remission. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lily bulb is often used as a dietary supplement for menopause. This study was aimed to investigate the ameliorative effects of aqueous extract of lily bulb (AELB) on the menopause-associated psychiatric disorders and the underlying mechanisms in comparison with estrogen therapy. Ovariectomized (OVX) mice were treated with 1.8 g/kg AELB or 0.3 mg/kg estradiol for 5 weeks. Animals were tested in multiple behavioral paradigms. Serum, uterus, and brain tissues were collected for the measurement of neurotransmitters and their related biomarkers, neurotrophins, and estrogen receptor α (ERα) and β (ERβ). AELB and estradiol had similar anxiolytic, antidepressant, and cognition-improving effects. While estradiol limited OVX-induced weight gains and prevented uterine shrinkage and the drop of serum estrogen level, AELB had minor and even no effects on these indices. AELB, but not estradiol, reversed OVX-induced decreases in the expression levels of hippocampal nerve growth factor (NGF) and prefrontal glial cell-derived neurotrophic factor (GDNF). In addition to hypothalamic and prefrontal ERα, AELB enhanced uterine and brain regional ERβ expression levels without affecting uterine ERα, NGF, and GDNF. Conversely, estradiol completely restored the expression levels of estrogen receptors and neurotrophins in uterus. While AELB is comparable to estradiol in alleviating menopause-like behavior, it has distinct brain-uterus mechanisms in association with the predominant protection of catecholamine synthesis, neurotrophins, and ERβ receptors in brain, but with minor effects on uterus. AELB and its constituents may be novel treatments for menopause. [ABSTRACT FROM AUTHOR]

Electroacupuncture (EA) is a clinically useful physiological therapy that has been recently adopted to treat several brain disorders. However, the potential role of early EA intervention in the prevention of posttraumatic stress disorder (PTSD) as well as its potential cellular and molecular mechanism has never been investigated previously. In the present study, we used an enhanced single prolonged stress (ESPS) model to access the effects of early EA intervention on the prevention of anxiety-like and fear learning behaviors, as well as the influence of the expression of post-synaptic density protein 95 (PSD95), synaptophysin (Syn), brain derived neurotrophic factor (BDNF), diacylglycerol lipase alpha (DAGLα) and cannabinoid type 1 receptor (CB1R) in the hippocampus with or without DAGLα or CB1R knockdown by a short hairpin RNA (shRNA) in the hippocampus. Moreover, the effects of electrical stimulation with different parameters on the expression of DAGLα and CB1R in the hippocampal astrocytes were also observed. The results showed that Early EA intervention improved hippocampal synaptic plasticity and ameliorated PTSD-like behaviors and also increased expression of BDNF, DAGLα and CB1R. However, either DAGLα or CB1R knockdown by a short hairpin RNA (shRNA) eliminated the neuroprotective effects of early EA intervention. Furthermore, electrical stimulation with 2/15 Hz 1 mA elevated the expression of DAGLα and CB1R. Altogether, our findings provide new insights regarding the possibility of using early EA intervention in the prevention of PTSD, and the protective effects of EA is involving the activation of DAGLα and CB1R. • Early EA intervention protects against PTSD-like behaviors. • Early EA intervention prevents hippocampal synaptic plasticity damage. • EA preventive effects in PTSD may involve the activation of DAGLα and CB1R. [ABSTRACT FROM AUTHOR]

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 (Cp) and local network efficiency (Eloc), and this abnormal pattern was modulated with treatment of antipsychotic drugs at follow-up. Longitudinally, the increase of Cp 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, Cp, 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. [ABSTRACT FROM AUTHOR]

Aim: Transcutaneous electrical acupoint stimulation (TEAS) has the potential to alleviate post‐traumatic stress disorder (PTSD). The purpose of this study was to determine whether adding TEAS to sertraline or cognitive behavioral therapy (CBT) could improve the anti‐PTSD efficacy. Methods: In this randomized controlled trial, 240 PTSD patients (60 in each group) were assigned to receive simulated TEAS combined with sertraline (group A) or with CBT (group B), active TEAS combined with CBT (group C), or active TEAS combined with CBT plus sertraline (group D) for 12 weeks. The outcomes were measured using the Clinician‐Administered PTSD Scale, PTSD Check List‐Civilian Version, and 17‐item Hamilton Rating Scale for Depression. Results: While PTSD symptoms reduced over time in all patients, groups C and D had markedly greater improvement in both PTSD and depressive measures than groups A and B in all post‐baseline measurement points, with moderate to very large effect sizes of 0.484–2.244. Groups C and D also had a significantly higher rate than groups A and B on clinical response (85.0% and 95.0% vs 63.3% and 60.0%, P < 0.001) and on remission (15.0% and 25.0% vs 3.3% and 1.7%, P < 0.001). The incidence of adverse events was similar between groups A and D and between groups B and C. Conclusions: Additional TEAS augments the anti‐PTSD and antidepressant efficacy of antidepressants or CBT, without increasing the incidence of adverse effects. TEAS could serve as an effective intervention for PTSD and comorbid depression. This trial was registered with www.chictr.org (no.: ChiCTR1800017255). [ABSTRACT FROM AUTHOR]

Understanding the neural substrates of depression is crucial for diagnosis and treatment. Here, we review recent studies of functional and effective connectivity in depression, in terms of functional integration in the brain. Findings from these studies, including our own, point to the involvement of at least four networks in patients with depression. Elevated connectivity of a ventral limbic affective network appears to be associated with excessive negative mood (dysphoria) in the patients; decreased connectivity of a frontal‐striatal reward network has been suggested to account for loss of interest, motivation, and pleasure (anhedonia); enhanced default mode network connectivity seems to be associated with depressive rumination; and diminished connectivity of a dorsal cognitive control network is thought to underlie cognitive deficits especially ineffective top‐down control of negative thoughts and emotions in depressed patients. Moreover, the restoration of connectivity of these networks—and corresponding symptom improvement—following antidepressant treatment (including medication, psychotherapy, and brain stimulation techniques) serves as evidence for the crucial role of these networks in the pathophysiology of depression. [ABSTRACT FROM AUTHOR]

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 (0.3 mg/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, 0.2 mg/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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Quetiapine (QUE) and repetitive transcranial magnetic stimulation (rTMS) have been considered to be possible monotherapies for depression or adjunctive therapies for the treatment of the resistant depression, but the underlying mechanisms remain unclear. The present study aimed to assess the effects of combined QUE and rTMS treatment on depressive-like behaviors, hippocampal proliferation, and the in vivo and in vitro expressions of phosphorylated extracellular signal-regulated protein kinase (pERK1/2) and brain-derived neurotrophic factor (BDNF) in male Sprague–Dawley rats. The administration of QUE and rTMS was determined not only to reverse the depressive-like behaviors of rats exposed to chronic unpredictable stress (CUS) but also to restore the protein expressions of pERK1/2 and BDNF and cell proliferation in the hippocampus. Additionally, QUE and rTMS promoted the proliferation and increased the expression of pERK1/2 and BDNF in hippocampal-derived neural stem cells (NSCs), and these effects were abolished by U0126. Taken together, these results suggest that the antidepressive-like effects of QUE and rTMS might be related to the activation of the BDNF/ERK signaling pathway and the up-regulation of cell proliferation in the hippocampus. [ABSTRACT FROM AUTHOR]

• This parallel-group study assessed the efficacy of Near-infrared spectroscopy (NIRS) based neurofeedback (NF) compared to atomoxetine(AT) on patients with ADHD. • Up to now, our trial is one of the few trials performed to evaluate its efficacy relative to medication. In this trial, NIRS-NF was an effective intervention for ADHD patients. • During the observation of 8 weeks, Patients in NIRS group showed significant efficacy in inattention, compared to AT group at week 3 and week 6. • At the same time, NIRS group had faster reaction time (RT) during Go/No-Go task and less errors during N-back than AT group. • The findings of this study reveal that NIRS-NF improves the behavioral performance more compared to AT, highlighting its potential role in treating patients with ADHD. The present study aimed to assess the efficacy of Near-infrared spectroscopy (NIRS) real-time neurofeedback (NF) vs. atomoxetine (AT) in children with attention deficit hyperactivity disorder (ADHD). A parallel-group study was conducted to enroll children with ADHD between 8 and 12 years of age. Participants were assigned into the NIRS group and AT group as their wish. Subjects in the NIRS group received 12 sessions of NF training within 6 weeks, and subjects in the AT group were given oral medication. Changes in Swanson, Nolan, and Pelham-V rating scales (SNAP-IV), and performance of Go/No-Go and N-back working memory tasks at week 3, 6 and 8 were evaluated. Forty-nine patients completed the study, including 18 ADHD in the NIRS group and 31 in the AT group. Total scores of SNAP-IV significantly decreased from baseline to week 3, week 6, and week 8 in both groups. Patients in the NIRS group showed significant lower scores on the inattention subscale of SNAP-IV at week 3 and week 6, compared to the AT group. NIRS group had a shorter reaction time during the Go/No-Go task at week 6 and fewer errors during 2-back than the AT group at week 3. The findings revealed that NIRS real-time NF is more efficacious relative to AT in improving behavioral performance, highlighting its potential role and advantages in treating patients with ADHD. [ABSTRACT FROM AUTHOR]

CPZ induces cognitive impairment and remarkable lipid changes in the brain, Que treatment ameliorated cuprizone-induced cognitive impairment and partly normalized CPZ-induced lipid changes, suggest that Que may rescue cognitive behavioral changes from CPZ-induced demyelination through modulation of the brain lipidome. • CPZ induces cognitive impairment and remarkable lipid changes in the brain. • Que treatment ameliorated CPZ-induced cognitive impairment. • Que partly normalized CPZ-induced lipid changes in the brain. 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. [ABSTRACT FROM AUTHOR]

Background: Improving the psychotherapies for generalized anxiety disorder (GAD) is dependent on a deeper understanding of the relations between GAD and its associated cognitive factors. In the present study, we investigate how the core feature of GAD (i.e., worry) and its associated cognitive factors, such as meta-worry, intolerance of uncertainty, and attention bias towards threat, relate to each other in men at high risk for GAD. Methods: We used network analysis to explore the relations among these variables in a cross-sectional sample of 122 men at high risk for generalized anxiety disorder. Specifically, we computed the expected influence and predictability of each variable. Results: In the final network, we found that worry and meta-worry had the highest expected influence and predictability. In contrast, attention bias towards threat showed the lowest expected influence and predictability. The estimates of the expected influence of the nodes were stable (correlation stability coefficient = 0.52). Conclusions: The present study is the first to investigate the relations among worry, meta-worry, intolerance of uncertainty, and attention bias towards threat in men at high risk for generalized anxiety disorder. These findings indicate that worry and meta-worry may play important roles in the present network. The implications for clinical interventions and future studies are discussed. [ABSTRACT FROM AUTHOR]

The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) has been extensively studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of depression and may be a targeted mechanism for treatment. However, the influence of rTMS on lipid composition and the differences between these effects compared to antidepressants like fluoxetine (Flx) have never been investigated. Using a chronic unpredictable stress (CUS) model in rats, we assessed the antidepressive effects of rTMS and Flx treatments and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. Both rTMS and Flx treatments ameliorated depressive-like behaviors induced by CUS. Moreover, changes in lipid composition, especially glycerophospholipids, sphingolipids, and glycerolipids induced by CUS in the hippocampus were more robust than those observed in the PFC. CUS led to decreased levels of 20 carbon-containing fatty acyls and polyunsaturated fatty acyls in the PFC, and decreased levels of acyl carnitines (AcCa) in both the hippocampus and PFC. Notably, rTMS treatment had higher impact than Flx on composition of glycerophospholipids and sphingolipids in the hippocampus that were altered by CUS, while Flx attenuated CUS-induced changes in the PFC to a greater extent than rTMS. However, neither was able to restore fatty acyls and AcCa to baseline levels. Altogether, modulation of the brain lipidome may be involved in the antidepressant action of rTMS and Flx, and the degree to which these treatments induce changes in lipid composition within the hippocampus and PFC might explain their differential antidepressant effects. • rTMS and fluoxetine ameliorates depressive-like behaviours. • CUS induces robust changes of lipid composition in hippocampus than PFC. • rTMS completely restored the changes in lipid species in the hippocampus. • Flx attenuated changes in lipid species in the PFC to a greater extent than rTMS. [ABSTRACT FROM AUTHOR]

The anti-depressant effect of repetitive transcranial magnetic stimulation (rTMS), a clinically-useful treatment for depression, is associated with changes to the endocannabinoid system (ECS). However, it is currently unknown whether different frequencies of rTMS alter the ECS differently. To test this, rats exposed to chronic unpredictable stress (CUS) were treated with rTMS at two different frequencies (5 (high) or 1 Hz (low), 1.26 Tesla) for 7 consecutive days. Twenty-four hours after the final rTMS treatment, we evaluated depressive-like behaviors and the expression of several synaptic proteins and ECS-related proteins in the hippocampus. In addition, we knocked-down diacylglycerol lipase alpha (DAGLα) and cannabinoid type 1 receptor (CB1R), two important components of the ECS, and measured depressive-like behaviors and synaptic protein expression following rTMS. Furthermore, we measured the expression levels of several components of the ECS system in hippocampal-derived astrocytes and neurons exposed to repetitive magnetic stimulation (rMS) with different parameters (5 or 1 Hz, 0.84 or 1.26 Tesla). Interestingly, we found that only high-frequency rTMS ameliorated depressive-like behaviors and normalized the expression of hippocampal synaptic proteins in CUS-treated rats; this effect was eliminated by knockdown of DAGLα or CB1R. Moreover, we found that rMS at 5 Hz increased the expression of DAGLα and CB1R in hippocampal astrocytes and neurons. Collectively, our results suggest that high-frequency rTMS exerts its anti-depressant effect by up-regulating DAGLα and CB1R. [ABSTRACT FROM AUTHOR]

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, ALFFratio, 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. ALFFratio 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 ALFFratio 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. The amplitude of low‐frequency fluctuation (ALFF) was measured at the beginning of hospitalization. Baseline regional activity of the brain seems to be able to predict early response to treatment for schizophrenia. [ABSTRACT FROM AUTHOR]

Front cover: The cover image, by Bao‐Juan Li et al., is based on the Review Article A brain network model for depression: From symptom understanding to disease intervention. DOI: https://doi.org/10.1111/cns.12998. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]