Psychiatry and Clinical Neurosciences最新文献

{"title":"Development of disease-modifying therapies against Alzheimer's disease.","authors":"Takeshi Iwatsubo","doi":"10.1111/pcn.13681","DOIUrl":"10.1111/pcn.13681","url":null,"abstract":"<p><p>To successfully develop disease-modifying therapies (DMT) against Alzheimer's disease (AD), it is important to target the mild stage of the disease, before the pathological changes progress and dementia symptoms are fully manifested. To this end, the AD Neuroimaging Initiative (ADNI), a large-scale observational study, was initiated in the U.S. with the goal of development of DMT that are effective in the early stages of mild cognitive impairment (MCI) by utilizing imaging and biomarkers. In Japan, J-ADNI enrolled and followed up 537 patients, mainly with MCI, and established a platform for evaluation including amyloid PET, and demonstrated a high similarity in the clinical course of amyloid-positive MCI (prodromal AD) in Japan and the U.S. In 2023, the anti-Aβ antibody lecanemab successfully completed a Phase III clinical trial for early AD (prodromal AD + mild AD dementia) and was granted regulatory approval and made available both in the US and Japan. Also, phase III trial of donanemab was completed successful. The J-TRC study was initiated in Japan as a \"trial ready cohort (TRC)\" consisting of participants who met the eligibility criteria for participation in preclinical and prodromal AD trials. Based on such a platform, the development of DMT for AD will progress more rapidly in the future.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"491-494"},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergism of ApoE4 and systemic infectious burden is mediated by the APOE-NLRP3 axis in Alzheimer's disease.","authors":"Xue-Ting Liu, Xiu Chen, Na Zhao, Fan Geng, Meng-Meng Zhu, Qing-Guo Ren","doi":"10.1111/pcn.13704","DOIUrl":"10.1111/pcn.13704","url":null,"abstract":"<p><strong>Background: </strong>Systemic infections are associated with the development of AD, especially in individuals carrying the APOE4 genotype. However, the detailed mechanism through which APOE4 affects microglia inflammatory response remains unclear.</p><p><strong>Methods: </strong>We obtained human snRNA-seq data from the Synapse AD Knowledge Portal and assessed the DEGs between APOE3 and APOE4 isoforms in microglia. To verify the interaction between ApoE and infectious products, we used ApoE to stimulate in vitro and in vivo models in the presence or absence of LPS (or ATP). The NLRP3 gene knockout experiment was performed to demonstrate whether the APOE-NLRP3 axis was indispensable for microglia to regulate inflammation and mitochondrial autophagy. Results were evaluated by biochemical analyses and fluorescence imaging.</p><p><strong>Results: </strong>Compared with APOE3, up-regulated genes in APOE4 gene carriers were involved in pro-inflammatory responses. ApoE4-stimulation significantly increased the levels of NLRP3 inflammasomes and ROS in microglia. Moreover, compared with ApoE4 alone, the co-incubation of ApoE4 with LPS (or ATP) markedly promoted pyroptosis. Both NF-κB activation and mitochondrial autophagy dysfunction were contributed by the increased level of NLRP3 inflammasomes induced by ApoE4. Furthermore, the pathological impairment induced by ApoE4 could be reversed by NLRP3 KO.</p><p><strong>Conclusions: </strong>Our study highlights the importance of NLRP3 inflammasomes in linking ApoE4 with microglia innate immune function. These findings not only provide a molecular basis for APOE4-mediated neuroinflammatory but also reveal the potential reason for the increased risk of AD in APOE4 gene carriers after contracting infectious diseases.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"517-526"},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial.","authors":"Yohei Ohtani, Hideaki Tani, Kie Nomoto-Takahashi, Taisuke Yatomi, Kengo Yonezawa, Sota Tomiyama, Nobuhiro Nagai, Keisuke Kusudo, Shiori Honda, Sotaro Moriyama, Shinichiro Nakajima, Takashige Yamada, Hiroshi Morisaki, Yu Iwabuchi, Masahiro Jinzaki, Kimio Yoshimura, Tsuyoshi Eiro, Sakiko Tsugawa, Sadamitsu Ichijo, Yu Fujimoto, Tomoyuki Miyazaki, Takuya Takahashi, Hiroyuki Uchida","doi":"10.1111/pcn.13734","DOIUrl":"https://doi.org/10.1111/pcn.13734","url":null,"abstract":"<p><strong>Aim: </strong>Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD.</p><p><strong>Methods: </strong>In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score.</p><p><strong>Results: </strong>Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score.</p><p><strong>Conclusion: </strong>Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular disease, and major depression: Study on both diseases and serum brain-derived neurotrophic factor (BDNF).","authors":"Reiji Yoshimura","doi":"10.1111/pcn.13678","DOIUrl":"10.1111/pcn.13678","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"429"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Habenular volume changes after venlafaxine treatment in patients with major depression.","authors":"Josselin Etienne, Alexandre Boutigny, Denis J David, Eric Deflesselle, Florence Gressier, Laurent Becquemont, Emmanuelle Corruble, Romain Colle","doi":"10.1111/pcn.13684","DOIUrl":"10.1111/pcn.13684","url":null,"abstract":"<p><strong>Background: </strong>Habenula, a hub brain region controlling monoaminergic brain center, has been implicated in major depressive disorder (MDD) and as a possible target of antidepressant response. Nevertheless, the effect of antidepressant drug treatment on habenular volumes remains unknown. The objective of the present research was to study habenular volume change after antidepressant treatment in patients with MDD, and assess whether it is associated with clinical improvement.</p><p><strong>Methods: </strong>Fifty patients with a current major depressive episode (MDE) in the context of MDD, and antidepressant-free for at least 1 month, were assessed for habenula volume (3T MRI with manual segmentation) before and after a 3 months sequence of venlafaxine antidepressant treatment.</p><p><strong>Results: </strong>A 2.3% significant increase in total habenular volume (absolute volume: P = 0.0013; relative volume: P = 0.0055) and a 3.3% significant increase in left habenular volume (absolute volume: P = 0.00080; relative volume: P = 0.0028) were observed. A significant greater variation was observed in male patients (4.8%) compared to female patients. No association was observed between habenular volume changes and response and remission. Some habenula volume changes were associated with improvement of olfactory pleasantness.</p><p><strong>Conclusion: </strong>Habenular volumes increased after 3 months of venlafaxine treatment in depressed patients. Further studies should assess whether cell proliferation and density or dendritic structure variations are implied in these volume changes.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"468-472"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metacognition as a window into subjective affective experience.","authors":"Cody A Cushing, Hakwan Lau, Stefan G Hofmann, Joseph E LeDoux, Vincent Taschereau-Dumouchel","doi":"10.1111/pcn.13683","DOIUrl":"10.1111/pcn.13683","url":null,"abstract":"<p><p>When patients seek professional help for mental disorders, they often do so because of troubling subjective affective experiences. While these subjective states are at the center of the patient's symptomatology, scientific tools for studying them and their cognitive antecedents are limited. Here, we explore the use of concepts and analytic tools from the science of consciousness, a field of research that has faced similar challenges in having to develop robust empirical methods for addressing a phenomenon that has been considered difficult to pin down experimentally. One important strand is the operationalization of some relevant processes in terms of metacognition and confidence ratings, which can be rigorously studied in both humans and animals. By assessing subjective experience with similar approaches, we hope to develop new scientific approaches for studying affective processes and promoting psychological resilience in the face of debilitating emotional experiences.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"430-437"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of synaptic density and cognitive performance in temporal lobe epilepsy: Humans and animals PET imaging study with [¹⁸F]SynVesT-1.","authors":"Ling Xiao, Shijun Xiang, Chen Chen, Haoyue Zhu, Ming Zhou, Yongxiang Tang, Li Feng, Shuo Hu","doi":"10.1111/pcn.13682","DOIUrl":"10.1111/pcn.13682","url":null,"abstract":"<p><strong>Aim: </strong>Cognitive impairment is a common comorbidity in individuals with temporal lobe epilepsy (TLE), yet the underlying mechanisms remain unknown. This study explored the putative association between in vivo synaptic loss and cognitive outcomes in TLE patients by PET imaging of synaptic vesicle glycoprotein 2A (SV2A).</p><p><strong>Methods: </strong>We enrolled 16 TLE patients and 10 cognitively normal controls. All participants underwent SV2A PET imaging using [¹⁸F]SynVesT-1 and cognitive assessment. Lithium chloride-pilocarpine-induced rats with status epilepticus (n = 20) and controls (n = 6) rats received levetiracetam (LEV, specifically binds to SV2A), valproic acid (VPA), or saline for 14 days. Then, synaptic density was quantified by [¹⁸F]SynVesT-1 micro-PET/CT. The novel object recognition and Morris water maze tests evaluated TLE-related cognitive function. SV2A expression was examined and confirmed by immunohistochemistry.</p><p><strong>Results: </strong>Temporal lobe epilepsy patients showed significantly reduced synaptic density in hippocampus, which was associated with cognitive performance. In the rat model of TLE, the expression of SV2A and synaptic density decreased consistently in a wider range of brain regions, including the entorhinal cortex, insula, hippocampus, amygdala, thalamus, and cortex. We treated TLE animal models with LEV or VPA to explore whether synaptic loss contributes to cognitive deficits. It was found that LEV significantly exerted protective effects against brain synaptic deficits and cognitive impairment.</p><p><strong>Conclusion: </strong>This is the first study to link synaptic loss to cognitive deficits in TLE, suggesting [¹⁸F]SynVesT-1 PET could be a promising biomarker for monitoring synaptic loss and cognitive dysfunction. LEV might help reverse synaptic deficits and ameliorate learning and memory impairments in TLE patients.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"456-467"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct biological property of tau in tau-first cognitive proteinopathy: Evidence by longitudinal clinical neuroimaging profiles and compared with late-onset Alzheimer disease.","authors":"Hsin-I Chang, Chi-Wei Huang, Shu-Hua Huang, Shih-Wei Hsu, Kun-Ju Lin, Tsung-Ying Ho, Hsiu-Chuan Wu, Chiung-Chih Chang","doi":"10.1111/pcn.13680","DOIUrl":"10.1111/pcn.13680","url":null,"abstract":"<p><strong>Background: </strong>Tau-first cognitive proteinopathy (TCP) denotes a clinical phenotype of Alzheimer disease (AD) showing Florzolotau(18F) positron emission tomography (PET) positivity but a negative amyloid status.</p><p><strong>Aim: </strong>We explored the biological property of tau using longitudinal cognitive and neuroimaging data in TCP and compared with late-onset AD (LOAD).</p><p><strong>Method: </strong>We enrolled 56 patients with LOAD, 34 patients with TCP, and 26 cognitive unimpaired controls. All of the participants had historical data of 2 to 4 three-dimensional T1 images and 2 to 6 annual cognitive evaluations over a follow-up period of 7 years. Tau topography was measured using Florzolotau(18F) PET. In the LOAD and TCP groups, we constructed tau or gray matter clusters covarying with the cognitive measurements. We used mediator analysis to explore the regional tau load as predictor, gray matter partitions as mediators, and significant cognitive test scores as outcomes. Longitudinal cognitive decline and cortical thickness degeneration pattern were analyzed using a linear mixed-effects model.</p><p><strong>Results: </strong>The TCP group had longitudinal declines in nonexecutive domains. The deterministic factor predicting the short-term memory score in TCP was the hippocampal volume and not directly via the medial and lateral temporal tau load. These features formed the conceptual differences with LOAD.</p><p><strong>Discussion: </strong>The biological properties of tau and the longitudinal cognitive-imaging trajectory support the conceptual distinction between TCP and LOAD. TCP represents one specific entity featuring salient short-term memory impairment, declines in nonexecutive domains, a slower gray matter degenerative pattern, and a restricted impact of tau.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"446-455"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCN Art Brut Series No. 40, Artwork Description.","authors":"Kenjiro Hosaka","doi":"10.1111/pcn.13719","DOIUrl":"https://doi.org/10.1111/pcn.13719","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":"78 8","pages":"482"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol profiling reveals 7β-hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.","authors":"Junghee Ha, Go Eun Kwon, Yumi Son, Soo Ah Jang, So Yeon Cho, Soo Jin Park, Hyunjeong Kim, Jimin Lee, Juseok Lee, Dongryul Seo, Myeongjee Lee, Do Yup Lee, Man Ho Choi, Eosu Kim","doi":"10.1111/pcn.13706","DOIUrl":"10.1111/pcn.13706","url":null,"abstract":"<p><strong>Aim: </strong>Cholesterol homeostasis is associated with Alzheimer's disease (AD). Despite the multitude of cholesterol metabolites, little is known about which metabolites are directly involved in AD pathogenesis and can serve as its potential biomarkers.</p><p><strong>Methods: </strong>To identify \"hit\" metabolites, steroid profiling was conducted in mice with different age, diet, and genotype and also in humans with normal cognition, mild cognitive impairment, and AD using gas chromatography-mass spectrometry. Then, using one of the \"hit\" molecules (7β-hydroxycholesterol; OHC), molecular and histopathological experiment and behavioral testing were conducted in normal mice following its intracranial stereotaxic injection to see whether this molecule drives AD pathogenesis and causes cognitive impairment.</p><p><strong>Results: </strong>The serum levels of several metabolites, including 7β-OHC, were increased by aging in the 3xTg-AD unlike normal mice. Consistently, the levels of 7β-OHC were increased in the hairs of patients with AD and were correlated with clinical severity. We found that 7β-OHC directly affects AD-related pathophysiology; intrahippocampal injection of 7β-OHC induced astrocyte and microglial cell activation, increased the levels of pro-inflammatory cytokines (TNF-alpha, IL-1β, IL-6), and enhanced amyloidogenic pathway. Mice treated with 7β-OHC also exhibited deficits in memory and frontal/executive functions assessed by object recognition and 5-choice serial reaction time task, respectively.</p><p><strong>Conclusions: </strong>Our results suggest that 7β-OHC could serve as a convenient, peripheral biomarker of AD. As directly involved in AD pathogenesis, 7β-OHC assay may help actualize personalized medicine in a way to identify an at-risk subgroup as a candidate population for statin-based AD treatment.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"473-481"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}