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Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

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Neural Regeneration Research 2024年第10期19卷 2202-2211页

作者： Chika Fujii Charles F.Zorumski Yukitoshi Izumi department of psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative psychiatric Research Washington University School of MedicineSt.LouisMOUSA

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

关键词： allopregnanolone fluvoxamine ketamine neurosteroids postpartum depression quercetin

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Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

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Neural Regeneration Research 2024年第10期19卷 2212-2218页

作者： Yukitoshi Izumi Kazuko A.O'Dell Charles F.Zorumski department of psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative psychiatric Research Washington University School of MedicineSt.LouisMOUSA

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

关键词： cognitive impairment glyphosate microglia neuroinflammation roundup toll-like receptor 4 zinc chelation

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Abnormalities of electroencephalography microstates in patients with depression and their association with cognitive function

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World Journal of psychiatry 2024年第1期14卷 128-140页

作者： Rui-Jie Peng Yu Fan Jin Li Feng Zhu Qing Tian Xiao-Bin Zhang Suzhou Medical College Soochow UniversitySuzhou 215123Jiangsu ProvinceChina department of psychiatry Suzhou Psychiatric HospitalThe Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina

BACKGROUND A growing number of recent studies have explored underlying activity in the brain by measuring electroencephalography(EEG)in people with ***,the consistency of findings on EEG microstates in patients with depression is poor,and few studies have reported the relationship between EEG microstates,cognitive scales,and depression severity *** To investigate the EEG microstate characteristics of patients with depression and their association with cognitive *** A total of 24 patients diagnosed with depression and 32 healthy controls were included in this study using the Structured Clinical Interview for Disease for The Diagnostic and Statistical Manual of Mental Disorders,Fifth *** collected information relating to demographic and clinical characteristics,as well as data from the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS;Chinese version)and *** Compared with the controls,the duration,occurrence,and contribution of microstate C were significantly higher[depression(DEP):Duration 84.58±24.35,occurrence 3.72±0.56,contribution 30.39±8.59;CON:Duration 72.77±10.23,occurrence 3.41±0.36,contribution 24.46±4.66;Duration F=6.02,P=0.049;Occurrence F=6.19,P=0.049;Contribution F=10.82,P=0.011]while the duration,occurrence,and contribution of microstate D were significantly lower(DEP:Duration 70.00±15.92,occurrence 3.18±0.71,contribution 22.48±8.12;CON:Duration 85.46±10.23,occurrence 3.54±0.41,contribution 28.25±5.85;Duration F=19.18,P<0.001;Occurrence F=5.79,P=0.050;Contribution F=9.41,P=0.013)in patients with depression.A positive correlation was observed between the visuospatial/constructional scores of the RBANS scale and the transition probability of microstate class C to B(r=0.405,P=0.049).CONCLUSION EEG microstate,especially C and D,is a possible biomarker in *** with depression had a more frequent transition from microstate C to B,which may relate to more negative ruminati

关键词： Depression Electroencephalography Microstates Cognitive functions

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Dopamine Switches Affective States Under Acute Sleep Deprivation

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Neuroscience Bulletin 2024年第8期40卷 1205-1208页

作者： Zhou-Cai Luo Tian-Ming Gao State Key laboratory of Organ Failure Research Key Laboratory of Mental Health of the Ministry of EducationGuangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired IntelligenceGuangdong-Hong Kong Joint Laboratory for Psychiatric DisordersGuangdong Province Key Laboratory of Psychiatric DisordersGuangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi DiseasesDepartment of NeurobiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

The transition of affective states manifests affective regulation,wherein individuals adaptively adjust their emotional states to cope with changes in the external environment,reflecting their sensitivity and adaptability to environmental *** process of affective state transition is complex,involving both instantaneous and persistent changes influenced by environmental,behavioral,and pharmacological *** underlying neural mechanisms encompass alterations in neurotransmitter release,neural circuit activity,and the plasticity of brain structures[1].

关键词： alterations Dopamine neural

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First 150 years of catatonia:Looking back at its complicated history and forward to the road ahead

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World Journal of psychiatry 2024年第5期14卷 600-606页

作者： Levente Csihi Gabor S Ungvari Stanley N Caroff Gábor Gazdag department of psychiatry and psychiatric Rehabilitation Jahn Ferenc South Pest HospitalBudapest 1204Hungary Division of psychiatry School of MedicineUniversity of Western AustraliaCrawley 6009Western AustraliaAustralia Section of psychiatry University of Notre DameFremantle 6160Western AustraliaAustralia Behavioral Health Service Corporal Michael J CresenczVeterans Affairs Medical CenterPhiladelphiaPA 19104United States department of psychiatry University of PennsylvaniaPerelman School of MedicinePhiladelphiaPA 19104United States department of psychiatry and Psychotherapy Faculty of MedicineSemmelweis UniversityBudapest 1083Hungary

Karl Ludwig Kahlbaum(1828-1899)was the first to conceptualize and describe the main clinical features of a novel psychiatric illness,which he termed catatonia in his groundbreaking monograph published 150 years *** Kahlbaum postulated catatonia as a separate disease entity characterized by psychomotor symptoms and a cyclical course,a close examination of his 26 cases reveals that most of them presented with motor symptom complexes or syndromes associated with various psychiatric and medical *** his classification system,Kraepelin categorized catatonic motor symptoms that occur in combination with psychotic symptoms and typically have a poor prognosis within his dementia praecox(schizophrenia)disease *** of the substantial influence of Kraepelin’s classification,catatonia was predominantly perceived as a component of schizophrenia for most of the 20th ***,with the advent of the psychopharmacotherapy era starting from the early 1950s,interest in catatonia in both clinical practice and research subsided until the early *** past two decades have witnessed a resurgence of interest in *** Diagnostic and Statistical Manual of Mental Disorders Fifth Edition,marked a paradigmatic shift by acknowledging that catatonia can occur secondary to various psychiatric and medical *** introduction of an independent diagnostic category termed“Catatonia Not Otherwise Specified”significantly stimulated research in this *** authors briefly review the history and findings of recent catatonia research and highlight promising directions for future exploration.

关键词： Catatonia Historical overview Psychopharmacology Diagnostic and Statistical Manual of Mental Disorders-5 Wernicke-Kleist-Leonhard school

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Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia

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World Journal of psychiatry 2024年第6期14卷 794-803页

作者： Peng Chen Hai-Dong Yang Jun-Jie Wang Zhen-Hua Zhu Hui-Min Zhao Xu-Yuan Yin Yuan Cai Hong-LiangZhu Jia-Lin Fu Xin-Zhu Zhang Wen-Xi Sun Li Hui Xiao-Bin Zhang Suzhou Medical College of Soochow University Suzhou 215123Jiangsu ProvinceChina department of psychiatry Suzhou Psychiatric HospitalInstitute of Mental HealthThe Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina department of psychiatry The Fourth People’s Hospital of LianyungangThe Affiliated Kangda College of Nanjing Medical UniversityLianyungang 222003Jiangsu ProvinceChina Research Center of Biological psychiatry Suzhou Psychiatric HospitalInstitute of Mental HealthThe Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina department of Neurology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215002Jiangsu ProvinceChina

BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6(IL-6)contributes to the pathophysiology of psychiatric ***,there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia(EOS).AIM To investigate the relationship between serum IL-6 concentration and the clinical features of *** We measured serum IL-6 Levels from 74 patients with chronic schizophrenia,including 33 with age at onset0.05)after controlling for age,body mass index,and other *** symptom scores were higher in the EOS group than the AOS group(F=6.199,P=0.015).Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score(r=-0.389,P=0.032)and avolition/asociality subscore(r=-0.387,P=0.026).CONCLUSION Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the ***-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

关键词： Early-onset schizophrenia Interleukin 6 Negative symptoms Avolition Asociality

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Cognitive dysfunction in schizophrenia patients caused by downregulation of γ-aminobutyric acid receptor subunits

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World Journal of psychiatry 2024年第6期14卷 784-793页

作者： Xi Chen Ya-Nan Zhou Xiao-Zi Lu Ren-Jiao Li Yi-Fan Xiong Xia Sheng Wei-Wei Zhu department of Child and Adolescent psychiatric Brain Hospital of Hunan ProvinceThe Second People’s Hospital of Hunan ProvinceChangsha 410007Hunan ProvinceChina department of psychiatry Qingdao Mental Health CenterQingdao 266034Shandong ProvinceChina department of psychiatry Brain Hospital of Hunan ProvinceThe Second People’s Hospital of Hunan ProvinceChangsha 410007Hunan ProvinceChina department of Sleep Disorders and Neurosis Brain Hospital of Hunan ProvinceThe Second People’s Hospital of Hunan ProvinceChangsha 410007Hunan ProvinceChina

BACKGROUND The expression pattern of gamma aminobutyric acid(GABA)receptor subunits are commonly altered in patients with schizophrenia,which may lead to nerve excitation/inhibition problems,affecting cognition,emotion,and *** To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective *** This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same *** expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance *** recognized cognitive battery tool,the MATRICS Consensus Cognitive Battery,was used to evaluate the scores for various dimensions of cognitive *** correlation between GABA receptor subunit downregulation and schizophrenia was also *** Significant differences in GABA receptor subunit levels were found between the case and control groups(P0.05).CONCLUSION Downregulation of the GABA receptor subunits is positively correlated with *** other words,when GABA receptor subunits are downregulated in patients,cognitive impairment becomes more severe.

关键词： Cognitive function Schizophrenia Downregulation Gamma-aminobutyric acid receptor subunits Correlation

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Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons

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Neural Regeneration Research 2024年第4期19卷 908-914页

作者： Yalan Chen Junxin Kuang Yimei Niu Hongyao Zhu Xiaoxia Chen Kwok-Fai So Anding Xu Lingling Shi Guangdong-Hong Kong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan University department of Neurology and Stroke Center The First Affiliated HospitalJinan University department of psychiatry The First Affiliated HospitalJinan University Co-innovation Center of Neuroregeneration Nantong University

Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative *** also represent a potential source of transplanted cells for therapeutic *** vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal *** evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons *** SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic *** obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of *** increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing *** further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 ***,we have established three induction protocols for dopaminergic *** on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.

关键词： dopaminergic neurons FGF signal induced pluripotent stem cells midbrain neural differentiation SHH signal SMAD signal WNT signal

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Digital psychiatry in low-and-middle-income countries:New developments and the way forward

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World Journal of psychiatry 2024年第3期14卷 350-361页

作者： Subho Chakrabarti department of psychiatry Postgraduate Institute of Medical Education and ResearchChandigarh 160012UTIndia

Low-and middle-income countries(LMICs)bear the greater share of the global mental health burden but are ill-equipped to deal with it because of severe resource constraints leading to a large treatment *** remote provision of mental health services by digital means can effectively augment conventional services in LMICs to reduce the treatment *** psychiatry in LMICs has always lagged behind high-income countries,but there have been encouraging developments in the last *** is increasing research on the efficacy of digital psychiatric ***,the evidence is not adequate to conclude that digital psychiatric interventions are invariably effective in LMICs.A striking development has been the rise in mobile and smartphone ownership in LMICs,which has driven the increasing use of mobile technologies to deliver mental health *** innovative use of mobile technologies has been to optimize task-shifting,which involves delivering mental healthcare services in community settings using non-specialist health *** evidence from LMICs shows that it is possible to use digital tools to train non-specialist workers effectively and ensure that the psychosocial interventions they deliver are *** these promising developments,many barriers such as service costs,underdeveloped infrastructure,lack of trained professionals,and significant disparities in access to digital services impede the progress of digital psychiatry in *** overcome these barriers,digital psychiatric services in LMICs should address contextual factors influencing the delivery of digital services,ensure collaboration between different stakeholders,and focus on reducing the digital divide.

关键词： Digital psychiatry Low-and middle-income countries Developments Mental health

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Network analysis of suicide ideation and depression-anxiety symptoms among Chinese adolescents

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General psychiatry 2024年第2期37卷 216-223页

作者： Shuyin Xu Yumeng Ju Xiyu Wei Wenwen Ou Mohan Ma Guanyi Lv Xiaotian Zhao Yaqi Qin Yunjing Li Liang Li Mei Huang Siqi Yang Yimei Lu Yafei Chen Junwu Liu Jin Liu Bangshan Liu Yan Zhang department of psychiatry National Clinical Research Center for Mental Disordersand National Center for Mental DisordersThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina Mental Health Institute of Central South University China National Technology Institute on Mental DisordersHunan Technology Institute of PsychiatryHunan Key Laboratory of Psychiatry and Mental HealthHunan Medical Center for Mental HealthChangshaHunanChina

Background The co-occurrence of depression and anxiety among adolescents is typically associated with suicide *** The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and *** 1501 adolescents aged 12-19 years were assessed using the Patient Health Questionnaire(PHQ-9)and the Generalized Anxiety Disorder Scale,and 716 adolescents who scored≥5 on both scales were selected as *** analysis was used to identify the network structure of depressive symptoms and anxiety *** were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9.A comparison was made between the depression-anxiety symptom networks of the two ***‘Restlessness’,‘sad mood’and‘trouble relaxing’were the most prominent central symptoms in the depression-anxiety symptom network,and‘restlessness’,‘nervousness’and‘reduced movement’were the bridge symptoms in this network.‘Sad mood’was found to be directly related to‘suicide ideation’with the highest *** network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group,with‘restlessness’and‘sad mood’exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation *** Restlessness and sad mood could be targeted for the intervention of depression-anxiety symptoms among adolescents with suicide ideation.

关键词： symptoms adolescent assessed

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