Publications by authors named "Huaning Wang"

59 Publications

Improved Pre-attentive Processing With Occipital rTMS Treatment in Major Depressive Disorder Patients Revealed by MMN.

Front Hum Neurosci 2021 8;15:648816. Epub 2021 Jun 8.

Department of Psychiatry, Xijing Hospital, Air Force Medical University, Xi'an, China.

Objectives: To investigate the improvement effect of occipital repetitive transcranial magnetic stimulation (rTMS) combined with escitalopram oxalate tablets on pre-attentive processing in patients with first-episode, medication-naive depression.

Methods: Patients who were hospitalized between January and December 2019 were selected. They were randomly allocated to real occipital rTMS stimulation group with 27 cases receiving intermittent theta-burst (iTBS) and sham stimulation group with 24 cases over 20 days. The rTMS treatment target is located at the Oz point of the occipital region. Both groups took escitalopram oxalate tablets, and the average daily drug dose was 15.294 ± 5.041 mg. Hamilton Depression Rating Scale (HAMD) was used to assess the symptoms of depression before and after treatment, and mismatch negativity (MMN) was used to assess the improvement of pre-attentive processing before and after treatment.

Results: After 20 days of treatment, the total score of HAMD (13.495 ± 3.700) in both groups was significantly lower than that before treatment [21.910 ± 3.841, (1, 49) = 46, 3.690, < 0.001]. After treatment, the latency of MMN in the real stimulation group (182.204 ± 31.878 ms) was significantly lower than that in the sham stimulation group (219.896 ± 42.634 ms, < 0.001), and the amplitude of MMN in the real stimulation group (-7.107 ± 3.374 ms) was significantly higher than that in the sham stimulation group (-2.773 ± 3.7 32 ms, < 0.001).

Conclusion: Occipital rTMS treatment can enhance the early therapeutic effect and effectively improve the pre-attentive processing of patients with depression and provide a scientific basis for the new target of rTMS therapy in clinical patients with depression.
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http://dx.doi.org/10.3389/fnhum.2021.648816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256852PMC
June 2021

Distinct basal brain functional activity and connectivity in the emotional-arousal network and thalamus in patients with functional constipation associated with anxiety and/or depressive disorders.

Psychosom Med 2021 Jun 11. Epub 2021 Jun 11.

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China Department of Radiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710038, China Department of Psychiatry, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

Objective: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood.

Methods: Sixty-five FC patients and forty-two healthy controls (HC) were recruited, and hierarchical-clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional Magnetic Resonance Imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were employed to investigate brain functional differences.

Results: 37 patients were classified as FCAD and 28 patients were classified as FCNAD; both groups showed decreased activity (fALFF) than HC in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC) and precuneus; enhanced precentral gyrus (PreCen)-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (PFWE < .05). FCAD also had decreased fALFF than FCNAD/HC in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/PreCen-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD.

Conclusions: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD. It might help portray important clues for improving new treatment strategies.
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http://dx.doi.org/10.1097/PSY.0000000000000958DOI Listing
June 2021

Early-Stage Repetitive Transcranial Magnetic Stimulation Altered Posterior-Anterior Cerebrum Effective Connectivity in Methylazoxymethanol Acetate Rats.

Front Neurosci 2021 21;15:652715. Epub 2021 May 21.

Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.

The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to investigate the potential mechanism of schizophrenia through the posterior-anterior cerebrum imbalance in methylazoxymethanol acetate (MAM) rats and to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an early-stage intervention. The rats were divided into four groups: the MAM-sham group, vehicle-sham group, MAM-rTMS group, and vehicle-rTMS group. The rTMS treatment was targeted in the visual cortex (VC) in adolescent rats. Granger Causality Analysis (GCA) was used to evaluate the effective connectivity between regions of interest. Results demonstrated a critical right VC-nucleus accumbens (Acb)-orbitofrontal cortex (OFC) pathway in MAM rats; significant differences of effective connectivity (EC) were found between MAM-sham and vehicle-sham groups (from Acb shell to OFC: = -2.553, = 0.021), MAM-rTMS and MAM-sham groups (from VC to Acb core: = -2.206, = 0.043; from Acb core to OFC: = 4.861, < 0.001; from Acb shell to OFC: = 4.025, = 0.001), and MAM-rTMS and vehicle-rTMS groups (from VC to Acb core: = -2.482, = 0.025; from VC to Acb shell: = -2.872, = 0.012; from Acb core to OFC: = 4.066, = 0.001; from Acb shell to OFC: = 3.458, = 0.004) in the right hemisphere. Results of the early-stage rTMS intervention revealed that right nucleus accumbens played the role as a central hub, and VC was a potentially novel rTMS target region during adolescent schizophrenia. Moreover, the EC of right nucleus accumbens shell and orbitofrontal cortex was demonstrated to be a potential biomarker. To our knowledge, this was the first resting-state fMRI study using GCA to assess the deficits of a visual-reward neural pathway and the effectiveness of rTMS treatment in MAM rats. More randomized controlled trials in both animal models and schizophrenia patients are needed to further elucidate the disease characteristics.
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http://dx.doi.org/10.3389/fnins.2021.652715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176023PMC
May 2021

Functional Connectivity Combined With a Machine Learning Algorithm Can Classify High-Risk First-Degree Relatives of Patients With Schizophrenia and Identify Correlates of Cognitive Impairments.

Front Neurosci 2020 23;14:577568. Epub 2020 Nov 23.

Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Schizophrenia (SCZ) is an inherited disease, with the familial risk being among the most important factors when evaluating an individual's risk for SCZ. However, robust imaging biomarkers for the disease that can be used for diagnosis and determination of the prognosis are lacking. Here, we explore the potential of functional connectivity (FC) for use as a biomarker for the early detection of high-risk first-degree relatives (FDRs). Thirty-eight first-episode SCZ patients, 38 healthy controls (HCs), and 33 FDRs were scanned using resting-state functional magnetic resonance imaging. The subjects' brains were parcellated into 200 regions using the Craddock atlas, and the FC between each pair of regions was used as a classification feature. Multivariate pattern analysis using leave-one-out cross-validation achieved a correct classification rate of 88.15% [sensitivity 84.06%, specificity 92.18%, and area under the receiver operating characteristic curve (AUC) 0.93] for differentiating SCZ patients from HCs. FC located within the default mode, frontal-parietal, auditory, and sensorimotor networks contributed mostly to the accurate classification. The FC patterns of each FDR were input into each classification model as test data to obtain a corresponding prediction label (a total of 76 individual classification scores), and the averaged individual classification score was then used as a robust measure to characterize whether each FDR showed an SCZ-type or HC-type FC pattern. A significant negative correlation was found between the average classification scores of the FDRs and their semantic fluency scores. These findings suggest that FC combined with a machine learning algorithm could help to predict whether FDRs are likely to show an SCZ-specific or HC-specific FC pattern.
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http://dx.doi.org/10.3389/fnins.2020.577568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725002PMC
November 2020

Disrupted structural covariance network in first episode schizophrenia patients: Evidence from a large sample MRI-based morphometric study.

Schizophr Res 2020 10 14;224:24-32. Epub 2020 Nov 14.

Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address:

Background: Recent progress in neuroscience research has provided evidence that schizophrenia is a disease that involves dysconnectivity of brain networks. Widespread gray matter loss was commonly observed but how these gray matter abnormalities are characterized at the large-scale network-level in schizophrenia, especially patients with first-episode (FE-SCZ) remains unclear.

Methods: In this study, gray matter structural network aberrations were investigated by applying structural covariance network analysis to 193 first episode schizophrenia patients and 178 age and gender-matched healthy controls (HCs). The mean gray matter volume in seed regions relating to eight specific networks (visual, auditory, sensorimotor, speech, semantic, default-mode, executive control, and salience) were extracted, and voxel-wise analyses of covariance were conducted to compare the association between whole-brain gray matter volume and each seed region for FE-SCZ and HCs.

Results: The auditory network was less extended in FE-SCZ compared with HCs, with a significant decrease in the structural association between the Hesch's gyrus and the middle frontal gyrus and the superior frontal gyrus. Hyperconnectivity was observed in executive control network with a significant increase in the structural association between the dorsal lateral prefrontal cortex and the superior frontal gyrus and supplementary motor area.

Conclusion: Our research shows that seed based structural covariance analysis can well characterize multiple large-scale networks, the observed changes might underly the hallucinations and cognitive impairments observed in FE-SCZ. Given that these patients were experiencing their first episode of schizophrenia, our findings suggest that such structural network deficits are present at an early stage in this disorder.
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http://dx.doi.org/10.1016/j.schres.2020.11.004DOI Listing
October 2020

Codonopis bulleynana Forest ex Diels (cbFeD) effectively attenuates hepatic fibrosis in CCl-induced fibrotic mice model.

Biomed Pharmacother 2021 Jan 13;133:110960. Epub 2020 Nov 13.

Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 650224, China; Southwest China Eco-development Academy, Southwest Forestry University, Kunming 650224, China. Electronic address:

The root of Codonopis bulleynana Forest ex Diels (cbFeD), a tonic food widely used in Yunnan Province of China, was found to have a wide range of pharmacological effects. The present study was designed to investigate the anti-fibrotic effect of water extracts of cbFeD in chronic liver injury mice model induced by carbon tetrachloride (CCl) and to explore its underlying mechanisms. Phytochemical analysis revealed multiple components were present in the water extract of cbFeD and the compounds were mostly enriched in organic acid and its derivatives, flavone, amino acid derivatives, nucleotide and its derivatives, carbohydrates etc. Treatment with cbFeD significantly attenuated liver injury and fibrosis in CCl-administered mice evidenced by improved liver histology, ameliorated apoptosis of hepatocytes, and decreased transaminase levels in the serum. Decreased activities of superoxide dismutase (SOD) and catalase (CAT) were markedly reversed upon treatment with cbFeD while levels of malondialdehyde (MDA) and glutathione (GSH) were significantly restored towards normal values. cbFeD also suppressed intrahepatic inflammatory cell infiltration and Kupffer cell activation. Furthermore, our study revealed an inhibitory effect of cbFeD on hepatic stellate cells (HSCs) activation both in vitro and in vivo. In conclusion, cbFeD could exert a protective role against liver fibrosis in mice model induced by CCl that is comparable to the positive control silymarin and might be developed into a promising anti-fibrotic drug.
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http://dx.doi.org/10.1016/j.biopha.2020.110960DOI Listing
January 2021

Functional constipation is associated with alterations in thalamo-limbic/parietal structural connectivity.

Neurogastroenterol Motil 2020 Oct 19:e13992. Epub 2020 Oct 19.

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China.

Background: Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID) with a high prevalence in clinical practice. Previous studies have identified that FCon is associated with functional and structural alterations in the primary brain regions involved in emotional arousal processing, sensory processing, somatic/motor-control, and self-referential processing. However, whether FCon is associated with abnormal structural connectivity (SC) among these brain regions remains unclear.

Methods: We selected the brain regions with functional and structural abnormalities as seed regions and employed diffusion tensor imaging (DTI) with probabilistic tractography to investigate SC changes in 29 patients with FCon and 31 healthy controls (HC).

Key Results: Results showed lower fractional anisotropy (FA) in the fibers connecting the thalamus, a region involved in sensory processing, with the amygdala (AMY), hippocampal gyrus (HIPP), precentral (PreCen) and postcentral gyrus (PostCen), supplementary motor area (SMA) and precuneus in patients with FCon compared with HC. FCon had higher mean diffusivity (MD) and radial diffusivity (RD) in the thalamus connected to the AMY and HIPP. In addition, FCon had significantly increased RD of the thalamus-SMA tract. Sensation of incomplete evacuation was negatively correlated with FA of the thalamus-PostCen and thalamus-HIPP tracts, and there was a negative correlation between difficulty of defecation and FA of the thalamus-SMA tract.

Conclusions And Inferences: These findings reflected that FCon is associated with alterations in SC between the thalamus and limbic/parietal cortex, highlighting the integrative role of the thalamus in brain structural network.
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http://dx.doi.org/10.1111/nmo.13992DOI Listing
October 2020

Brain Connectivity, and Hormonal and Behavioral Correlates of Sustained Weight Loss in Obese Patients after Laparoscopic Sleeve Gastrectomy.

Cereb Cortex 2021 Jan;31(2):1284-1295

Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA.

The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery.
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http://dx.doi.org/10.1093/cercor/bhaa294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179510PMC
January 2021

Abnormalities in the thalamo-cortical network in patients with functional constipation.

Brain Imaging Behav 2021 Apr;15(2):630-642

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, 710126, Shaanxi, China.

Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID); neuroimaging studies have shown brain functional abnormalities in thalamo-cortical regions in patients with FGID. However, association between FCon and topological characteristics of brain networks remains largely unknown. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory approach to investigate functional brain topological organization in 42 patients with FCon and 41 healthy controls (HC) from perspectives of global, regional and modular levels. Results showed patients with FCon had a significantly lower normalized clustering coefficient and small-worldness, implying decreased brain functional connectivity. Regions showed altered nodal degree and efficiency mainly located in the thalamus, rostral anterior cingulate cortex (rACC), and supplementary motor area (SMA), which are involved in somatic/sensory, emotional processing and motor-control. For the modular analysis, thalamus, rACC and SMA had an aberrant within-module nodal degree and nodal efficiency, and thalamus-related network exhibited abnormal interaction with the limbic network (amygdala and hippocampal gyrus). Nodal degree in the thalamus was negatively correlated with difficulty of defecation, and nodal degree in the rACC was negatively correlated with sensation of incomplete evacuation. These findings indicated that FCon was associated with abnormalities in the thalamo-cortical network.
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http://dx.doi.org/10.1007/s11682-020-00273-yDOI Listing
April 2021

A neuroimaging biomarker for striatal dysfunction in schizophrenia.

Nat Med 2020 04 23;26(4):558-565. Epub 2020 Mar 23.

Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

Mounting evidence suggests that function and connectivity of the striatum is disrupted in schizophrenia. We have developed a new hypothesis-driven neuroimaging biomarker for schizophrenia identification, prognosis and subtyping based on functional striatal abnormalities (FSA). FSA scores provide a personalized index of striatal dysfunction, ranging from normal to highly pathological. Using inter-site cross-validation on functional magnetic resonance images acquired from seven independent scanners (n = 1,100), FSA distinguished individuals with schizophrenia from healthy controls with an accuracy exceeding 80% (sensitivity, 79.3%; specificity, 81.5%). In two longitudinal cohorts, inter-individual variation in baseline FSA scores was significantly associated with antipsychotic treatment response. FSA revealed a spectrum of severity in striatal dysfunction across neuropsychiatric disorders, where dysfunction was most severe in schizophrenia, milder in bipolar disorder, and indistinguishable from healthy individuals in depression, obsessive-compulsive disorder and attention-deficit hyperactivity disorder. Loci of striatal hyperactivity recapitulated the spatial distribution of dopaminergic function and the expression profiles of polygenic risk for schizophrenia. In conclusion, we have developed a new biomarker to index striatal dysfunction and established its utility in predicting antipsychotic treatment response, clinical stratification and elucidating striatal dysfunction in neuropsychiatric disorders.
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http://dx.doi.org/10.1038/s41591-020-0793-8DOI Listing
April 2020

Laparoscopic sleeve gastrectomy improves brain connectivity in obese patients.

J Neurol 2020 Jul 13;267(7):1931-1940. Epub 2020 Mar 13.

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, 710071, Shaanxi, China.

Objective: Obese individuals have shown functional abnormalities in frontal-limbic regions, and bariatric surgery is an effective treatment for morbid obesity. The aim of the study was to investigate how bariatric surgery modulates brain regional activation and functional connectivity (FC) to food cues, and whether the underlying structural connectivity (SC) alterations contribute to these functional changes as well as behavioral changes.

Methods: A functional magnetic resonance imaging cue-reactivity task with high- (HiCal) and low-calorie (LoCal) food pictures and diffusion tensor imaging (DTI) with deterministic tractography were used to investigate brain reactivity, FC and SC in 28 obese participants tested before and 1 month after laparoscopic sleeve gastrectomy (LSG). Twenty-two obese controls (Ctr) without surgery were also tested at baseline and 1 month later.

Results: LSG significantly decreased right dorsolateral prefrontal cortex (DLPFC) activation to HiCal versus LoCal cues and increased FC between DLPFC and ventral anterior cingulate cortex (vACC), which are regions involved in self-regulation of feeding behaviors. LSG also increased SC between DLPFC and ACC as quantified by fractional anisotropy. Increases in SC and FC between DLPFC and ACC were associated with greater reductions in BMI, and SC changes were positively correlated with FC changes. Increased SC between right DLPFC and ACC mediated the relationship between reduced BMI and increased right DLPFC-vACC FC; likewise, increases in right DLPFC-vACC FC mediated the relationship between increased right DLPFC-ACC SC and reduced BMI.

Conclusion: LSG might induce weight loss in part by increasing SC and FC between DLPFC and ACC, and thus strengthening top-down control over food intake.
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http://dx.doi.org/10.1007/s00415-020-09780-wDOI Listing
July 2020

Altered Interactions Among Resting-State Networks in Individuals with Obesity.

Obesity (Silver Spring) 2020 03;28(3):601-608

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China.

Objective: The aim of this study was to investigate alterations in functional connectivity (FC) within and interactions between resting-state networks involved in salience, executive control, and interoception in participants with obesity (OB).

Methods: Using resting-state functional magnetic resonance imaging with independent component analysis and FC, alterations within and interactions between resting-state networks in 35 OB and 35 normal-weight controls (NW) were investigated.

Results: Compared with NW, OB showed reduced FC strength in the ventromedial prefrontal cortex and posterior cingulate cortex/precuneus within the default-mode network, dorsal anterior cingulate cortex within the salience network (SN), bilateral dorsolateral prefrontal cortex-angular gyrus within the frontoparietal network (FPN), and increased FC strength in the insula (INS) (P  < 0.0125). The dorsal anterior cingulate cortex FC strength was negatively correlated with craving for food cues, left dorsolateral prefrontal cortex FC strength was negatively correlated with Yale Food Addiction Scale scores, and right INS FC strength was positively correlated with craving for high-calorie food cues. Compared with NW, OB also showed increased FC between the SN and FPN driven by altered FC of bilateral INS and anterior cingulate cortex-angular gyrus.

Conclusions: Alterations in FC within and interactions between the SN, default-mode network, and FPN might contribute to the high incentive value of food (craving), lack of control of overeating (compulsive overeating), and increased awareness of hunger (impaired interoception) in OB.
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http://dx.doi.org/10.1002/oby.22731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098432PMC
March 2020

Potential Anti-Depressive Treatment Maneuvers from Bench to Bedside.

Adv Exp Med Biol 2019 ;1180:277-295

Departments of Psychiatry and Cellular and Molecular Medicine, University of Ottawa, Institute of Mental Health Research at the Royal, Ottawa, ON, Canada.

Numerous antidepressants are available for the treatment of the major depressive disorder (MDD). Unfortunately, the disadvantages of these antidepressive medications, including inadequate treatment response, the therapeutic lag between drug administration and the onset of symptoms alleviation, and the safety consideration limit their clinical use and accelerate the exploration of advanced antidepressants with novel action mechanisms/newer targets, with fewer side effects. In this chapter, a series of compounds showing clinical potent in the treatment of MDD has been reviewed based on their reported results from different phase clinical trials. Although the majority of these strategies currently only lead to a systematic approach in the aspects of treatment resistant depression, some of them would be a routine clinical practice which is usable in the treatment of MDD, such as ketamine. Additionally, beyond the mechanism of action for novel therapeutic molecules involving glutamatergic, opiate, cholinergic receptors, and neuroplasticity, some supplemental procedures such as polyunsaturated fatty acids were also included in this chapter due to their solid property against MDD.
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http://dx.doi.org/10.1007/978-981-32-9271-0_15DOI Listing
December 2019

Distinct hemispheric specialization of functional connectivity in schizophrenia with and without auditory verbal hallucinations.

Neuroreport 2019 12;30(18):1294-1298

College of Intelligence Science and Technology, National University of Defense Technology, Changsha (P.T., L.P., H.S., D.H., L.-L.Z.).

As a basic organizing principle of the human brain, hemispheric specialization is an important perspective to explore the pathology of schizophrenia. However, it remains unclearly whether the hemispheric specialization of functional connectivity plays a role in mediating auditory verbal hallucinations in schizophrenia. In this study, 18 schizophrenic patients with auditory verbal hallucinations, 18 patients without auditory verbal hallucinations, and 18 matched healthy controls underwent resting-state functional MRI scans, and seed-based voxel-wise functional connectivity was calculated to quantify the degree of hemispheric specialization. The results revealed that both the auditory verbal hallucinations and non-auditory verbal hallucinations groups exhibited significantly increased specialization in the left middle temporal gyrus and left precuneus, and significantly reduced specialization in the right precuneus relative to healthy controls, and that the auditory verbal hallucinations severity was significantly correlated with the hemispheric specialization of the right precuneus in the auditory verbal hallucinations group. Moreover, the left frontal lobe exhibited reduced hemispheric specialization in the auditory verbal hallucinations group compared with non-auditory verbal hallucinations group, and the patients with and without auditory verbal hallucinations could be clustered into two groups with an accuracy of 80.6% based on the brain regions exhibiting significant specialization changes. The findings indicate that the hemispheric specialization of the aforementioned regions may play a role in mediating auditory verbal hallucinations in schizophrenia, and the distinct hemispheric specialization patterns of functional connectivity may provide a potential biomarker to differentiate schizophrenic patients with and without auditory verbal hallucinations.
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http://dx.doi.org/10.1097/WNR.0000000000001364DOI Listing
December 2019

Laparoscopic sleeve gastrectomy induces sustained changes in gray and white matter brain volumes and resting functional connectivity in obese patients.

Surg Obes Relat Dis 2020 Jan 11;16(1):1-9. Epub 2019 Oct 11.

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China. Electronic address:

Background: Obesity is associated with decreased brain gray- (GM) and white-matter (WM) volumes in regions. Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery associated with neuroplastic changes in patients with obesity at 1 month postLSG.

Objective: To investigate whether LSG can induce sustained neuroplastic recovery of brain structural abnormalities, and whether structural changes are accompanied by functional alterations.

Setting: University hospital, longitudinal study.

Methods: Structural magnetic resonance imaging and voxel-based morphometry analysis were employed to assess GM/WM volumes in 30 obese participants at preLSG and 1 and 3 months postLSG. One-way analysis of variance modeled time effects on GM/WM volumes, and then alterations in resting-state functional connectivity (RSFC) were assessed.

Results: Significant time effects on GM volumes were in caudate (F = 11.20), insula (INS; F = 10.11), posterior cingulate cortex (PCC; F = 13.32), and inferior frontal gyrus (F = 12.18), and on WM volumes in anterior cingulate cortex (F = 15.70), PCC (F = 15.56), and parahippocampus (F = 17.96, P < .05). Post hoc tests showed significantly increased GM volumes in caudate (mean change ± SEM .018 ± .005 and P = .001, .031 ± .007 and P < .001), INS (.027 ± .008 and P = .003, .043 ± .009 and P < .001), and PCC (.008 ± .004 and P = .042, .026 ± .006 and P < .001), and increased WM volumes in anterior cingulate cortex (.029 ± .006 and P < .001, .041 ± .008 and P < .001), PCC (.017 ± .004 and P < .001, .032 ± .006 and P < .001), and parahippocampus (.031 ± .008 and P =.001, .075 ± .013 and P < .001) at 1 and 3 months postLSG compared with preLSG. Significant increases in GM volumes were in caudate (.013 ± .006 and P = .036), PCC (.019 ± .006 and P = .006), and inferior frontal gyrus (.019 ± .005 and P = .001), and in WM volumes in anterior cingulate cortex (.012 ± .005 and P = .028), PCC (.014 ± .006 and P = .017), and parahippocampus (.044 ± .014 and P = .003) at 3 relative to 1 month postLSG. GM volumes in INS and PCC showed a positive correlation at 1 (r = .57, P = .001) and 3 months postLSG (r = .55, P = .001). GM volume in INS and PCC were positively correlated with RSFC of INS-PCC (r = .40 and P = .03, r = .55 and P = .001) and PCC-INS (r = .37 and P = .046, r = .57 and P < .001) at 1 month postLSG. GM volume in INS was also positively correlated with RSFC of INS-PCC (r = .44, P = .014) and PCC-INS (r = .38, P = .037) at 3 months postLSG.

Conclusion: LSG induces sustained structural brain changes, which might mediate long-term benefits of bariatric surgery in weight reduction. Associations between regional GM volume and RSFC suggest that LSG-induced structural changes contribute to RSFC changes.
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http://dx.doi.org/10.1016/j.soard.2019.09.074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994381PMC
January 2020

Fluoxetine ameliorates dysbiosis in a depression model induced by chronic unpredicted mild stress in mice.

Int J Med Sci 2019 7;16(9):1260-1270. Epub 2019 Sep 7.

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China.

: Accumulating evidence has shown that neuropsychiatric disorders are associated with gut microbiota through the gut-brain axis. However, the effects of antidepressant treatment on gut microbiota are rarely studied. Here, we investigated whether stress led to gut microbiota changes and whether fluoxetine plays a role in microbiota alteration. : We investigated changes in gut microbiota in a depression model induced by chronic unpredicted mild stress (CUMS) and a restoration model by applying the classic antidepressant drug fluoxetine. : We found that stress led to low bacterial diversity, simpler bacterial network, and increased abundance of pathogens, such as , and conditional pathogens, such as , , and However, these changes were attenuated by fluoxetine directly and indirectly. Furthermore, the correlation analysis indicated strong correlations between gut microbiota and anxiety- and depression-like behaviors. : This study revealed that fluoxetine led to restoration of dysbiosis induced by stress stimulation, which may imply a possible pathway through which one CNS target drug plays its role in reshaping the gut microbiota.
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http://dx.doi.org/10.7150/ijms.37322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775263PMC
April 2020

Multifunctional REDV-G-TAT-G-NLS-Cys peptide sequence conjugated gene carriers to enhance gene transfection efficiency in endothelial cells.

Colloids Surf B Biointerfaces 2019 Dec 17;184:110510. Epub 2019 Sep 17.

School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Tianjin 300350, China; Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin 300350, China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China. Electronic address:

Rapid endothelialization on small diameter artificial blood vessels is an effective strategy to facilitate long-term patency and inhibit thrombosis. The gene delivery can enhance the proliferation and migration of endothelial cells (ECs), which is beneficial for rapid endothelialization. REDV-G-TAT-G-NLS-Cys (abbreviated as TP-G) peptide could weakly condense pEGFP-ZNF580 (pZNF580) and transfect ECs, but its transfection efficiency was still very low because of its low positive charge, low stability and weak endosome escape ability. In order to develop more stable and efficient gene carriers with low cytotoxicity, in the present study, we conjugated different amounts of TP-G peptide onto poly(lactide-co-glycolide)-g-polyethylenimine (PLGA-g-PEI) amphiphilic copolymers via a hetero-poly(ethylene glycol) spacer (OPSS-PEG-NHS). The TP-G peptide and PEI could cooperatively and strongly condense pZNF580. The carrier's cytotoxicity was reduced by the introduction of poly(ethylene glycol) spacer. They condensed pZNF580 to form gene complexes (PPP-TP-G/pZNF580) with suitable size and positive zeta potential for gene delivery. The transfected ECs promoted their migration ability as demonstrated by cell migration assay. The results of cellular uptake and confocal laser scanning microscopy showed significantly high internalization efficiency, endosomal/lysosomal escape and nucleus location of pZNF580 by this multifunctional TP-G peptide sequence conjugated gene delivery system. Furthermore, several inhibitors were used to study the cellular uptake pathways of PPP-TP-G/pZNF580 complexes. The results showed that PPP-TP-G2/Cy5-oligonucleotide complexes exhibited the optimized endocytosis pathways which facilitated for cellular uptake. In conclusion, the multifunctional TP-G peptide conjugated gene carriers could promote the transfection efficiency due to the multifunction of REDV, cell-penetrating peptide and nuclear localization signal in the peptide sequence, which could be a suitable gene carrier for endothelialization.
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http://dx.doi.org/10.1016/j.colsurfb.2019.110510DOI Listing
December 2019

Discriminating schizophrenia using recurrent neural network applied on time courses of multi-site FMRI data.

EBioMedicine 2019 Sep 13;47:543-552. Epub 2019 Aug 13.

National Laboratory of Pattern Recognition and Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China. Electronic address:

Background: Current fMRI-based classification approaches mostly use functional connectivity or spatial maps as input, instead of exploring the dynamic time courses directly, which does not leverage the full temporal information.

Methods: Motivated by the ability of recurrent neural networks (RNN) in capturing dynamic information of time sequences, we propose a multi-scale RNN model, which enables classification between 558 schizophrenia and 542 healthy controls by using time courses of fMRI independent components (ICs) directly. To increase interpretability, we also propose a leave-one-IC-out looping strategy for estimating the top contributing ICs.

Findings: Accuracies of 83·2% and 80·2% were obtained respectively for the multi-site pooling and leave-one-site-out transfer classification. Subsequently, dorsal striatum and cerebellum components contribute the top two group-discriminative time courses, which is true even when adopting different brain atlases to extract time series.

Interpretation: This is the first attempt to apply a multi-scale RNN model directly on fMRI time courses for classification of mental disorders, and shows the potential for multi-scale RNN-based neuroimaging classifications. FUND: Natural Science Foundation of China, the Strategic Priority Research Program of the Chinese Academy of Sciences, National Institutes of Health Grants, National Science Foundation.
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http://dx.doi.org/10.1016/j.ebiom.2019.08.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796503PMC
September 2019

Voxel-based morphometry results in first-episode schizophrenia: a comparison of publicly available software packages.

Brain Imaging Behav 2020 Dec;14(6):2224-2231

Department of Radiology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi'an, 710032, China.

Investigations of brain structure in schizophrenia using magnetic resonance imaging (MRI) have identified variations in regional grey matter (GM) volume throughout the brain but the results are mixed. This study aims to investigate whether the inconsistent voxel-based morphometry (VBM) findings in schizophrenia are due to the use of different software packages. T1 MRI images were obtained from 86 first-episode schizophrenia (FESZ) patients and 86 age- and gender-matched Healthy controls (HCs). VBM analysis was carried out using FMRIB software library (FSL) 5.0 and statistical parametric mapping 8 (SPM8). All images were processed using the default parameter settings as provided by these software packages. FSL-VBM revealed widespread GM volume reductions in FESZ patients compared with HCs, however, for SPM-VBM, only increased and circumscribed GM volume changes were found, both software revealed increased GM volume within cerebellum. Significant correlations between Positive and Negative Syndrome Scale (PANSS) and GM volume were mainly found in frontal regions. Algorithms of GM tissue segmentation, image registration and statistical strategies might contribute to these disparate results.
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http://dx.doi.org/10.1007/s11682-019-00172-xDOI Listing
December 2020

A glutamatergic insular-striatal projection regulates the reinstatement of cue-associated morphine-seeking behavior in mice.

Brain Res Bull 2019 10 24;152:257-264. Epub 2019 Jul 24.

Department of Psychosomatic, Xijing Hospital, Air Force Medical University, China. Electronic address:

Recently, the insular cortex (IC) was identified as part of the neuronal circuit responsible for the reward expectations in cue-triggered behaviours. Moreover, there are evidences that connections between the IC and the ventral striatum, particularly with the nucleus accumbens (NAc), may mediate the retrieval and performance of actions based on incentive memory. However, the precise role of the IC-NAc connections in cue-related drug-seeking behaviour remains unclear. We used the morphine-induced conditioned place preference (CPP) paradigm to assess the formation and relapse of cue-related drug-seeking. cFos immunostaining was used to determine the activation of the brain regions. Chemogenetic and optogenetic methods were used to manipulate the activity of IC-to-NAc projection neurons. The result showed that neurons in IC and NAc core but not NAc shell were activated following cue-induced morphine-seeking behaviour. Negligible effect of inhibition of IC-to-NAc core projection (IC) on morphine CPP expression, whereas chemogenetic inactivation of this projection potently blocked the reinstatement of expressed morphine CPP. Furthermore, optogenetic inhibition of glutamatergic IC inputs significant suppressed the CPP reinstatement without significant effect on CPP expression. We demonstrated here, for the first time, that IC glutamatergic projection is required for the reinstatement of cue-associated drug seeking behaviour in mice. The present study provide insights into modulations of relapse of cue-associated drug-seeking behaviour following repeated overexposure to opioids in humans.
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http://dx.doi.org/10.1016/j.brainresbull.2019.07.023DOI Listing
October 2019

Cortical morphometry alterations in brain regions involved in emotional, motor-control and self-referential processing in patients with functional constipation.

Brain Imaging Behav 2020 Oct;14(5):1899-1907

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, 710126, Shaanxi, China.

Functional constipation (FC) is a common functional gastrointestinal disorder (FGID). Neuroimaging studies on patients with FC showed brain functional abnormalities in regions involved in emotional process modulation, somatic and sensory processing and motor control. Brain structural imaging studies in patients with FGID have also shown disease-related alterations in cortical morphometry, but whether and how FC affects brain structure remains unclear. Structural Magnetic Resonance Imaging and surface-based morphometry analysis were used to investigate the impact of FC on cortical morphometry in 29 patients with FC and 29 healthy controls (HC). Results showed that patients with FC compared to HC had significantly decreased cortical thickness in the left middle frontal gyrus (MFG), dorsomedial (DMPFC) and ventromedial prefrontal gyrus (VMPFC), right dorsal anterior cingulate cortex (dACC), left orbitofrontal cortex (OFC), posterior cingulate cortex (PCC)/precuneus, middle temporal gyrus (MTG), and supplementary motor area (SMA) (P < 0.01). Correlation analysis showed that sensation of incomplete evacuation was negatively correlated with cortical thickness in the SMA (P < 0.0001). In addition, patients with FC also had decreased cortical volume than HC in the MTG, precentral gyrus (PreCen) and precuneus/cuneus (P < 0.01), as well as decreased cortical surface area in the PreCen (P < 0.01). No correlation was found between cortical volume/surface area and behavioral measures. These findings suggest that patients with FC are associated with cortical morphometric abnormalities in brain regions implicated in somatic/motor-control, emotional processing and self-referential processing.
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http://dx.doi.org/10.1007/s11682-019-00133-4DOI Listing
October 2020

Polygenic effects of schizophrenia on hippocampal grey matter volume and hippocampus-medial prefrontal cortex functional connectivity.

Br J Psychiatry 2020 05;216(5):267-274

School of Artificial Intelligence, University of Chinese Academy of Sciences, China.

Background: Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.

Aims: To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.

Method: Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.

Results: The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus-medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.

Conclusions: These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
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http://dx.doi.org/10.1192/bjp.2019.127DOI Listing
May 2020

Sex-related differences in resting-state brain activity and connectivity in the orbital frontal cortex and insula in patients with functional constipation.

Neurogastroenterol Motil 2019 05 6;31(5):e13566. Epub 2019 Feb 6.

Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, China.

Functional magnetic resonance imaging (fMRI) has been used to investigate sex-related differences in brain abnormalities in patients with irritable bowel syndrome (IBS). Like IBS, women with functional constipation (FC) are 2.1 times as many as men. No study has been performed yet to examine sex-related differences in brain activity and connectivity in patients with FC. Here, we employed resting-state fMRI with amplitude of low-frequency fluctuation (ALFF) to investigate brain functional differences in 51 patients with FC (34 females) and 52 healthy controls (34 females). Results showed abdominal pain and abdominal distension correlated with trait (TAI) and state (SAI) anxiety ratings in the female FC group, and abdominal distension correlated with sensation of incomplete evacuation in the male FC group. Two-way ANOVA revealed sex effects on ALFF in precentral gyrus, thalamus, insula (INS), and orbital frontal cortex (OFC, P  < 0.05). Post hoc test showed that the female FC group had lower ALFF than males in these brain regions (P < 0.01), and ALFF in INS and OFC was correlated with abdominal pain and difficulty of defecation, respectively. Seed voxel correlation analysis showed that the female FC group had weaker connectivity than males between INS and lateral OFC (lOFC). INS-lOFC connectivity was negatively correlated with the anxiety score in the female FC group and was negatively correlated with abdominal distension in the male FC group. These findings provide the first insight into sex-related differences in patients with FC and highlight that INS and OFC play an important role in modulating the intrinsic functional connectivity of the resting brain network showing that this role is influenced by sex.
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http://dx.doi.org/10.1111/nmo.13566DOI Listing
May 2019

Probing prefrontal cortex hemodynamic alterations during facial emotion recognition for major depression disorder through functional near-infrared spectroscopy.

J Neural Eng 2019 04 22;16(2):026026. Epub 2019 Jan 22.

State Key Laboratory of Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, Shaanxi, People's Republic of China. School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an, 710049, Shaanxi, People's Republic of China.

Objective: A serious issue in psychiatric practice is a lack of specific, objective biomarker to assist clinicians in establishing differential diagnosis and improving individualized treatment. Major depression disorder (MDD) is characterized by poorer ability in processing of facial emotional expressions.

Approach: Applying a portable neuroimaging system using near-infrared spectroscopy, we investigated the prefrontal cortex hemodynamic activation changes during facial emotion recognition and rest periods for 27 MDD patients compared with 24 healthy controls (HC).

Main Results: The hemodynamic changes in the left prefrontal cortex for the MDD group showed significant differences in the median values and the Mayer wave power ratios of the oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) during the emotional face recognition compared with the HC subjects, indicating the abnormal oxidative metabolism and weaker local hemodynamic oscillations for the MDD. The mean cross wavelet coefficients and the average wavelet coherence coefficient between oxy-Hb and deoxy-Hb over the left prefrontal cortex, and also between the bilateral oxy-Hb in the MDD patients were significantly lower than the HC group, demonstrating abnormal locally functional connectivity over the left prefrontal cortex, and the inter-hemispheric connection between the bilateral prefrontal cortices.

Significance: These results suggested that the hemodynamic changes over the left prefrontal cortex and between the bilateral prefrontal cortices detected by fNIRS could provide reliable predictors for the diagnosis of the depression in clinic, and also supported the rationale for use of transcranial magnetic stimulation over the left dorsolateral prefrontal cortex to restore excitability of prefrontal cortex that exhibits diminished regulation of emotion-generative systems in the MDD patients.
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http://dx.doi.org/10.1088/1741-2552/ab0093DOI Listing
April 2019

Hyperconnectivity in perisylvian language pathways in schizophrenia with auditory verbal hallucinations: A multi-site diffusion MRI study.

Schizophr Res 2019 08 23;210:262-269. Epub 2018 Dec 23.

Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100190, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address:

Auditory verbal hallucinations (AVH) are one of the cardinal symptoms of schizophrenia, and are proposed to be associated with altered integrity of the left perisylvian language pathways. There is considerable heterogeneity in the pattern of white matter abnormalities across previous studies. We investigated the white matter integrity of the perisylvian language pathways in schizophrenia patients with AVH based on a relatively large sample dataset from four different sites. 113 schizophrenia patients with AVH, 96 patients without AVH (nAVH), and 269 healthy controls (HC) underwent diffusion-weighted imaging. Between-group comparisons were performed on the fractional anisotropy (FA) values of the anterior, posterior, and long segment fasciculi within the perisylvian language network. Analysis of covariance among the 3 groups revealed the long segment of the left perisylvian language pathways was significantly different in FA value. Post hoc analysis showed that compared with the HC group, the AVH group had significantly higher FA measurements in the left long segment. The nAVH group showed intermediate FA values for this segment compared to the AVH and HC group but did not differ significantly from either group. Furthermore, the prospective meta-analyses also revealed that FA value of the left long segment was significantly higher in the AVH group compared to the HC group. Our findings suggest the hyperconnectivity pattern of the left perisylvian language pathways in the presence of AVH in schizophrenia and support the self-monitoring of inner speech model.
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http://dx.doi.org/10.1016/j.schres.2018.12.024DOI Listing
August 2019

Structural networks analysis for depression combined with graph theory and the properties of fiber tracts via diffusion tensor imaging.

Neurosci Lett 2019 02 19;694:34-40. Epub 2018 Nov 19.

School of Biomedical Engineering, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address:

Previous studies have suggested that major depressive disorder was associated with topological properties of impaired white matter. However, most related studies only use one property of nerve fibers to construct whole-brain structural brain network. Considering white matter changes variously, We hypothesized whether the alternations of white matter topological properties could reflect different impairment of white matter integrity. In addition, it is still unknown whether impaired integrity of the white matter fiber tracts has relationship with abnormal topological properties in MDD. This study investigated the impaired white matter by using graph theoretic analyses in a cohort of 37 MDD patients and 38 matched control subjects. In addition, we further investigated fiber tracts differences in three interregional connectivity matrixes of significant different topological regions in MDD. Our graph theoretic analyses demonstrated that 7 different regions were observed for the local measures in patients with MDD compared with control groups. These regions were the central nodes of cortical-limbic network, frontal-cingulate network, default mode network (DMN), cognitive control network(CCN)and affective network (AN). In addition, two impaired white matter pathways which included inferior longitudinal fasciculus (ILF) and cingulum were observed in MDD using fiber tracts analysis. We speculate impaired integrity of ILF is due to the alternations in the number of axons or myelination. The results further demonstrated that the number of fiber tracts of anterior cingulum was associated with the depression scores in MDD.
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http://dx.doi.org/10.1016/j.neulet.2018.11.025DOI Listing
February 2019

Reduced plasma ghrelin concentrations are associated with decreased brain reactivity to food cues after laparoscopic sleeve gastrectomy.

Psychoneuroendocrinology 2019 02 25;100:229-236. Epub 2018 Oct 25.

Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA. Electronic address:

The "hunger" hormone ghrelin regulates food-intake and preference for high-calorie (HC) food through modulation of the mesocortico-limbic dopaminergic pathway. Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery to treat morbid obesity. We tested the hypothesis that LSG-induced reductions in appetite and total ghrelin levels in blood are associated with reduced prefrontal brain reactivity to food cues. A functional magnetic resonance imaging (fMRI) cue-reactivity task with HC and low-calorie (LC) food pictures was used to investigate brain reactivity in 22 obese participants tested before and one month after bariatric surgery (BS). Nineteen obese controls (Ctr) without surgery were also tested at baseline and one-month later. LSG significantly decreased (1) fasting plasma concentrations of total ghrelin, leptin and insulin, (2) craving for HC food, and (3) brain activation in the right dorsolateral prefrontal cortex (DLPFC) in response to HC vs. LC food cues (P < 0.05). LSG-induced reduction in DLPFC activation to food cues were positively correlated with reduction in ghrelin levels and reduction in craving ratings for food. Psychophysiological interaction (PPI) connectivity analyses showed that the right DLPFC had stronger connectivity with the ventral anterior cingulate cortex (vACC) after LSG, and changes in BMI were negatively correlated with changes in connectivity between the right DLPFC and vACC in the LSG group only. These findings suggest that LSG-induced weight-loss may be related to reductions in ghrelin, possibly leading to decreased food craving and hypothetically reducing DLPFC response to the HC food cues.
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http://dx.doi.org/10.1016/j.psyneuen.2018.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802281PMC
February 2019

A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population.

EBioMedicine 2018 Nov 16;37:471-482. Epub 2018 Oct 16.

Institute of Mental Health, Peking University Sixth Hospital, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China.

Background: In the past decades, substantial effort has been made to explore the genetic influence on brain structural/functional abnormalities in schizophrenia, as well as cognitive impairments. In this work, we aimed to extend previous studies to explore the internal mediation pathway among genetic factor, brain features and cognitive scores in a large Chinese dataset.

Methods: Gray matter (GM) volume, fractional amplitude of low-frequency fluctuations (fALFF), and 4522 schizophrenia-susceptible single nucleotide polymorphisms (SNP) from 905 Chinese subjects were jointly analyzed, to investigate the multimodal association. Based on the identified imaging-genetic pattern, correlations with cognition and mediation analysis were then conducted to reveal the potential mediation pathways.

Findings: One linked imaging-genetic pattern was identified to be group discriminative, which was also associated with working memory performance. Particularly, GM reduction in thalamus, putamen and bilateral temporal gyrus in schizophrenia was associated with fALFF decrease in medial prefrontal cortex, both were also associated with genetic factors enriched in neuron development, synapse organization and axon pathways, highlighting genes including CSMD1, CNTNAP2, DCC, GABBR2 etc. This linked pattern was also replicated in an independent cohort (166 subjects), which although showed certain age and clinical differences with the discovery cohort. A further mediation analysis suggested that GM alterations significantly mediated the association from SNP to fALFF, while fALFF mediated the association from SNP and GM to working memory performance.

Interpretation: This study has not only verified the impaired imaging-genetic association in schizophrenia, but also initially revealed a potential genetic-brain-cognition mediation pathway, indicating that polygenic risk factors could exert impact on phenotypic measures from brain structure to function, thus could further affect cognition in schizophrenia.
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http://dx.doi.org/10.1016/j.ebiom.2018.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284414PMC
November 2018

Antipsychotic polypharmacy in the treatment of schizophrenia in China and Japan.

Aust N Z J Psychiatry 2018 Dec 12;52(12):1202-1212. Epub 2018 Oct 12.

Peking University Sixth Hospital (Institute of Mental Health), Beijing, China.

Background: Although antipsychotic monotherapy is recommended as the main treatment for schizophrenia, antipsychotic polypharmacy is not rare in practice. However, longitudinal data on antipsychotic polypharmacy in schizophrenia treatment are limited.

Methods: This longitudinal database study described antipsychotic polypharmacy in the treatment of schizophrenia in real-world settings in China and Japan. We retrieved information about antipsychotic treatment for schizophrenia from January 2010 to December 2014 from two hospital Electronic Medical Records databases in China and one claims database, Japan Medical Data Centre in Japan. Eligible patients had a diagnosis of schizophrenia (International Classification of Diseases, Tenth Revision F20.x) and at least one prescription for first or second generation antipsychotics. Antipsychotic polypharmacy was defined as having more than one antipsychotic medication overlapping for ⩾60 days. The Japan Medical Data Centre study cohort was further stratified by employees (insurance beneficiaries) and their dependents.

Results: The study cohorts comprised 11,961 patients from China and 25,034 (10,661 employee sub-cohort and 14,373 dependent sub-cohort) from 14 days Japan Medical Data Centre in Japan. Most patients were prescribed monotherapy (87.3% in China and 80.1% in Japan), of which oral second-generation antipsychotics were the majority (78.9% in China and 65.8% in Japan). The prevalence rate of antipsychotic polypharmacy was 12.7% in China and 19.9% in Japan (13.7% in employees vs 24.5% in dependents). The most common combinations were two oral antipsychotics. Combinations of more than two drugs were uncommon in China (0.3%) but were prescribed for 5.3% of patients in Japan. Among patients treated with monotherapy, 12.6/100 person-years (11.8%) in China and 9.6/100 person-years (11.0%) in Japan switched to antipsychotic polypharmacy during follow-up. Younger patients were more likely to switch to antipsychotic polypharmacy than older patents in all study cohorts.

Conclusion: The observed rates of antipsychotic polypharmacy ranged from 12.7% in China to 19.9% in Japan. Switching from monotherapy to antipsychotic polypharmacy was most likely to occur in younger patients with schizophrenia.
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http://dx.doi.org/10.1177/0004867418805559DOI Listing
December 2018
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