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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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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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Molecular biomarkers for vascular cognitive impairment and dementia:the current status and directions for the future

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Neural Regeneration Research 2024年第12期19卷 2579-2580页

作者： Satoshi Hosoki Perminder SSachdev Centre for Healthy Brain Ageing Discipline of Psychiatry and Mental HealthSchool of Clinical MedicineFaculty of Medicine and HealthUniversity of New South WalesSydneyAustralia Department of Neurology National Cerebral and Cardiovascular CenterOsakaJapan

Dementia is a syndrome with various underlying pathologies acting independently or in concert to cause cognitive *** development of disease-specific treatments and targeted prevention strategies requires precise clinical sub-typing via etiology and pathophysiological ***,recent research advances in biomarkers,especially for Alzheimer's disease(AD)diagnosis,have improved diagnostic precision for dementia.

关键词： prevention diagnosis impairment

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Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

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Journal of Integrative medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold Jenifer Murphy-Smith Chee H.Ng David Mischoulon Gerard J.Byrne Chad A.Bousman Con Stough Michael Berk Jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression Clinical and Research Program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of psychiatry the University of MelbourneMelbourne 3052Australia Centre for Human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical Health and Clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The Centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health Research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo Depression Nutraceutical psychiatry

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Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie Department of Emergency medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA Department of psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA Department of Emergency medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

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Lactate:a prospective target for therapeutic intervention in psychiatric disease

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Neural Regeneration Research 2024年第7期19卷 1473-1479页

作者： Yanhui Cai Haiyun Guo Tianle Han Huaning Wang Department of psychiatry Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Department of Anesthesiology and Perioperative medicine Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina

Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde *** may be attributed to the limited range of neurotransmitters that are regulated by psychotropic *** findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte *** these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent *** studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant *** this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling *** addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.

关键词： antidepressant anxiety bipolar disorder depression lactate psychiatric disease psychopharmacology schizophrenia signal molecular therapeutics

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Event segmentation in ADHD:neglect of social information and deviant theta activity point to a mechanism underlying ADHD

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General psychiatry 2024年第3期37卷 431-439页

作者： Astrid Prochnow Xianzhen Zhou Foroogh Ghorbani Veit Roessner Bernhard Hommel Christian Beste Cognitive Neurophysiology Department of Child and Adolescent PsychiatryFaculty of MedicineTU DresdenDresdenGermany Faculty of Psychology Shandong Normal UniversityJinanShandongChina

Background Attention-deficit/hyperactivity disorder(ADHD)is one of the most frequently diagnosed psychiatric conditions in children and *** the symptoms appear to be well described,no coherent conceptual mechanistic framework integrates their occurrence and variance and the associated problems that people with ADHD *** The current study proposes that altered event segmentation processes provide a novel mechanistic framework for understanding deficits in *** Adolescents with ADHD and neurotypically developing(NT)peers watched a short movie and were then asked to indicate the boundaries between meaningful segments of the *** recorded electroencephalography(EEG)data were analysed for differences in frequency band activity and effective connectivity between brain *** Compared with their NT peers,the ADHD group showed less dependence of their segmentation behaviour on social information,indicating that they did not consider social information to the same extent as their unaffected *** divergence was accompanied by differences in EEG theta band activity and a different effective connectivity network architecture at the source ***,NT adolescents primarily showed error signalling in and between the left and right fusiform gyri related to social information processing,which was not the case in the ADHD *** the ADHD group,the inferior frontal cortex associated with attentional sampling served as a hub instead,indicating problems in the deployment of attentional *** This study shows that adolescents with ADHD perceive events differently from their NT peers,in association with a different brain network architecture that reflects less adaptation to the situation and problems in attentional sampling of environmental *** results call for a novel conceptual view of ADHD,based on event segmentation theory.

关键词： instead meaningful primarily

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Fentanyl and xylazine crisis:Crafting coherent strategies for opioid overdose prevention

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World Journal of psychiatry 2024年第6期14卷 760-766页

作者： Lakshit Jain Jasleen Kaur Shahana Ayub Danya Ansari Rizwan Ahmed Abdul Qadir Dada Saeed Ahmed Department of psychiatry University of ConnecticutFarmingtonCT 06032United States Addiction Services Division Connecticut Valley HospitalMiddletownCT 06457United States Department of psychiatry Institute of LivingHartfordCT 06102United States Department of medicine Islamabad Medical and Dental CollegeIslamabad 44000Pakistan Department of medicine Liaquat College of Medicine and DentistryKarachi 75290Pakistan Department of medicine Trinity School of MedicineRoswellGA 30075United States Addiction Services and Dual Diagnosis Unit Saint Francis Hospital and Medical CenterHartfordCT 06105United States

The United States is in the throes of a severe opioid overdose epidemic,primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine,a veterinary sedative often mixed with *** high potency and long duration of fentanyl is compounded by the added risks from xylazine,heightening the lethal danger faced by opioid *** such as enhanced surveillance,public awareness campaigns,and the distribution of fentanylxylazine test kits,and naloxone have been undertaken to mitigate this ***-related overdose deaths persist despite these efforts,partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies.A multifaceted approach is imperative in effectively combating the opioid overdose *** approach should include expansion of treatment access,broadening the availability of medications for opioid use disorder,implementation of harm reduction strategies,and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.

关键词： Fentanyl Xylazine Opioid overdose Epidemic Opioid use disorder Buprenorphine Medications for opioid use disorder

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Need for education of psychiatric evaluation of offenders with mental disorders:A questionnaire survey for Japanese designated psychiatrists

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World Journal of psychiatry 2024年第5期14卷 726-734页

作者： Akihiro Shiina Tomihisa Niitsu Masaomi Iyo Chiyo Fujii Division of Medical Treatment and Rehabilitation Chiba University Center for Forensic Mental HealthChiba-shi 2608670Japan Department of psychiatry Chiba University Graduate School of MedicineChiba-shi 2608670Japan Department of Community Mental Health&Law National Center of Neurology and PsychiatryKodaira-shi 1878553Japan

BACKGROUND The management of offenders with mental disorders has been a significant concern in forensic *** Japan,the introduction of the Medical Treatment and Supervision Act in 2005 addressed the ***,numerous psychiatric patients at risk of violence still find themselves subject to the administrative involuntary hospitalization(AIH)scheme,which lacks clarity and updated *** To explore current as well as optimized learning strategies for risk assessment in AIH decision *** We conducted a questionnaire survey among designated psychiatrists to explore their experiences and expectations regarding training methods for psychiatric assessments of offenders with mental *** The findings of this study’s survey suggest a prevalent reliance on traditional learning approaches such as oral education and on-the-job *** This underscores the pressing need for structured training protocols in AIH ***,feedback derived from inpatient treatment experiences is identified as a crucial element for enhancing risk assessment skills.

关键词： Forensic psychiatry Administrative involuntary hospitalization Psychiatric assessment Risk assessment Mental disorders Training protocols Clinical practice Structured learning Feedback mechanisms Program development

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