首页 > 最新文献

International Journal of Neuropsychopharmacology最新文献

英文 中文
Risk of cognitive decline among patients with dengue virus infection: A systematic review. 登革热病毒感染者认知能力下降的风险:系统综述。
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-02 DOI: 10.1093/ijnp/pyae053
Lakshmi Thangavelu, Siddig Ibrahim Abdelwahab, Abdullah Farasani, Suhas Ballal, Pooja Bansal, Deepak Nathiya, Kiranjeet Kaur, M Ravi Kumar, Aashna Sinha, Hayam A Alrasheed, Maha F Al-Subaie, Nawal A Al Kaabi, Ali Al Bshabshe, Mona A Al Fares, Hawra Albayat, Ali A Rabaan, Kumud Pant, Quazi Syed Zahiruddin, Arathi P Rao, Mahalaqua Nazli Khatib, Hassan Ahmad Alfaifi, Syam Mohan, Sanjit Sah, Prakasini Satapathy

Background: Dengue fever, caused by the dengue virus and transmitted through Aedes mosquitoes, is a growing public health concern, particularly in tropical and subtropical regions. Traditionally associated with febrile and hemorrhagic symptoms, recent research suggests a potential link between dengue and cognitive impairments. This systematic review assessed existing research to understand the association between dengue virus infection and cognitive impairments, including dementia, Alzheimer's disease, memory loss, and confusion.

Methods: This systematic review followed PRISMA guidelines. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science up to January 18, 2024. Studies examining the prevalence and association of cognitive impairments in dengue patients were included. Data extraction and quality assessment were performed using Nested Knowledge software and the Newcastle-Ottawa Scale.

Results: Of the 1,129 articles identified, five were included in the review, covering a total of 200,873 participants from Taiwan, Brazil, and France. Evidence from population-based cohort studies indicated short-term cognitive impairments, including confusion and memory loss, in some dengue patients. Additionally, long-term risks of dementia, including Alzheimer's disease and vascular dementia, were observed, particularly among older adults. Although the findings suggest there might be an association between dengue infection and cognitive decline, the mechanisms underlying this link remain unclear.

Conclusion: This systematic review suggests that dengue virus infection may affect cognitive function in both acute and long-term contexts. However, the current evidence is not strong enough to establish a conclusive link. Further research with larger sample sizes and longitudinal studies is essential to confirm the impact of dengue virus on cognitive health.

背景:登革热由登革病毒引起,通过伊蚊传播,是一个日益严重的公共卫生问题,尤其是在热带和亚热带地区。登革热传统上与发热和出血性症状有关,最近的研究表明登革热与认知障碍之间存在潜在联系。本系统综述对现有研究进行了评估,以了解登革热病毒感染与认知障碍(包括痴呆症、阿尔茨海默病、记忆力减退和意识模糊)之间的关系:本系统性综述遵循 PRISMA 指南。截至 2024 年 1 月 18 日,在 PubMed、EMBASE 和 Web of Science 上进行了全面的文献检索。纳入了研究登革热患者认知障碍发生率和相关性的研究。采用 Nested Knowledge 软件和纽卡斯尔-渥太华量表进行数据提取和质量评估:在确定的 1,129 篇文章中,有 5 篇被纳入综述,涉及来自台湾、巴西和法国的 200,873 名参与者。来自人群队列研究的证据表明,一些登革热患者会出现短期认知障碍,包括意识模糊和记忆力减退。此外,还观察到痴呆症(包括阿尔茨海默病和血管性痴呆症)的长期风险,尤其是在老年人中。尽管研究结果表明,登革热感染与认知能力下降之间可能存在关联,但这种关联的机制仍不清楚:本系统综述表明,登革热病毒感染可能会在急性和长期情况下影响认知功能。然而,目前的证据还不足以确定两者之间的联系。要确认登革热病毒对认知健康的影响,必须开展样本量更大的进一步研究和纵向研究。
{"title":"Risk of cognitive decline among patients with dengue virus infection: A systematic review.","authors":"Lakshmi Thangavelu, Siddig Ibrahim Abdelwahab, Abdullah Farasani, Suhas Ballal, Pooja Bansal, Deepak Nathiya, Kiranjeet Kaur, M Ravi Kumar, Aashna Sinha, Hayam A Alrasheed, Maha F Al-Subaie, Nawal A Al Kaabi, Ali Al Bshabshe, Mona A Al Fares, Hawra Albayat, Ali A Rabaan, Kumud Pant, Quazi Syed Zahiruddin, Arathi P Rao, Mahalaqua Nazli Khatib, Hassan Ahmad Alfaifi, Syam Mohan, Sanjit Sah, Prakasini Satapathy","doi":"10.1093/ijnp/pyae053","DOIUrl":"https://doi.org/10.1093/ijnp/pyae053","url":null,"abstract":"<p><strong>Background: </strong>Dengue fever, caused by the dengue virus and transmitted through Aedes mosquitoes, is a growing public health concern, particularly in tropical and subtropical regions. Traditionally associated with febrile and hemorrhagic symptoms, recent research suggests a potential link between dengue and cognitive impairments. This systematic review assessed existing research to understand the association between dengue virus infection and cognitive impairments, including dementia, Alzheimer's disease, memory loss, and confusion.</p><p><strong>Methods: </strong>This systematic review followed PRISMA guidelines. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science up to January 18, 2024. Studies examining the prevalence and association of cognitive impairments in dengue patients were included. Data extraction and quality assessment were performed using Nested Knowledge software and the Newcastle-Ottawa Scale.</p><p><strong>Results: </strong>Of the 1,129 articles identified, five were included in the review, covering a total of 200,873 participants from Taiwan, Brazil, and France. Evidence from population-based cohort studies indicated short-term cognitive impairments, including confusion and memory loss, in some dengue patients. Additionally, long-term risks of dementia, including Alzheimer's disease and vascular dementia, were observed, particularly among older adults. Although the findings suggest there might be an association between dengue infection and cognitive decline, the mechanisms underlying this link remain unclear.</p><p><strong>Conclusion: </strong>This systematic review suggests that dengue virus infection may affect cognitive function in both acute and long-term contexts. However, the current evidence is not strong enough to establish a conclusive link. Further research with larger sample sizes and longitudinal studies is essential to confirm the impact of dengue virus on cognitive health.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and Safety of Lumateperone for Bipolar Depression and Schizophrenia: A Systematic Review and Meta-Analysis. 鲁马培龙治疗双相抑郁症和精神分裂症的疗效和安全性:系统回顾与元分析》。
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-02 DOI: 10.1093/ijnp/pyae052
Hanrui Peng, Kewen Yan, Shouhuan Liu, Xin Li, Xin Wang, Pu Peng, Xueyi Li, Min Wu, Huixue Xu, Qiuxia Wu, Tieqiao Liu, Zejun Li

Objective: This study aimed to evaluate the efficacy and safety of lumateperone in treating bipolar disorder and schizophrenia.

Methods: A comprehensive literature search was conducted across multiple databases and websites from inception to July 16, 2024, to identify both published and unpublished randomized controlled trials (RCTs). Meta-analyses were performed using random-effects or fixed-effects models depending on statistical heterogeneity. Relative risks (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to summarize the effects.

Results: Out of 931 records screened, seven RCTs (four focusing on bipolar depression and three on schizophrenia) were eligible for inclusion. Lumateperone was efficacious in reducing depressive symptoms in bipolar depression (SMDs = -0.36, 95% CI: -0.59 to -0.13). In treating schizophrenia, lumateperone exhibited a lower combined SMD of -0.14 (95% CI: -0.27 to 0, P = 0.051, I² = 49.6%), showing no significant difference from the placebo group, although the p-value approached significance. The lumateperone group showed significantly higher response rates compared to placebo in both bipolar depression (RRs = 1.27, 95% CI: 1.07 to 1.51) and schizophrenia (RRs = 1.44, 95% CI: 1.12 to 1.86). Common treatment-emergent adverse events included somnolence, dry mouth, dizziness, nausea, and headache (RRs = 1.30 to 3.29). Importantly, lumateperone did not significantly increase extrapyramidal symptoms (EPS, RRs = 1.46, 95% CI: 0.84 to 2.53).

Conclusions: Lumateperone is effective in treating bipolar depression but does not significantly reduce symptom severity in schizophrenia. It has a favorable safety and tolerability profile. However, caution is warranted in interpreting these findings due to the limited number of studies included.

研究目的本研究旨在评估鲁米培酮治疗双相情感障碍和精神分裂症的疗效和安全性:方法:我们在多个数据库和网站上进行了全面的文献检索,检索时间从开始到2024年7月16日,以确定已发表和未发表的随机对照试验(RCT)。根据统计异质性,采用随机效应或固定效应模型进行元分析。采用相对风险(RRs)或标准化平均差(SMDs)及 95% 置信区间(CIs)来总结疗效:在筛选出的 931 条记录中,有 7 项研究符合纳入条件(其中 4 项针对双相抑郁症,3 项针对精神分裂症)。鲁马培龙对减少双相抑郁症患者的抑郁症状有疗效(SMD = -0.36,95% CI:-0.59 至 -0.13)。在治疗精神分裂症方面,鲁马培龙的综合SMD较低,为-0.14(95% CI:-0.27至0,P = 0.051,I² = 49.6%),与安慰剂组无显著差异,但P值接近显著。在双相抑郁症(RRs = 1.27,95% CI:1.07 至 1.51)和精神分裂症(RRs = 1.44,95% CI:1.12 至 1.86)方面,鲁马培龙组的应答率明显高于安慰剂组。常见的治疗突发不良事件包括嗜睡、口干、头晕、恶心和头痛(RRs = 1.30 至 3.29)。重要的是,鲁马培龙不会明显增加锥体外系症状(EPS,RRs = 1.46,95% CI:0.84 至 2.53):结论:鲁马培龙能有效治疗双相抑郁症,但不能明显减轻精神分裂症的症状严重程度。它具有良好的安全性和耐受性。然而,由于纳入的研究数量有限,在解释这些研究结果时需要谨慎。
{"title":"Efficacy and Safety of Lumateperone for Bipolar Depression and Schizophrenia: A Systematic Review and Meta-Analysis.","authors":"Hanrui Peng, Kewen Yan, Shouhuan Liu, Xin Li, Xin Wang, Pu Peng, Xueyi Li, Min Wu, Huixue Xu, Qiuxia Wu, Tieqiao Liu, Zejun Li","doi":"10.1093/ijnp/pyae052","DOIUrl":"https://doi.org/10.1093/ijnp/pyae052","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the efficacy and safety of lumateperone in treating bipolar disorder and schizophrenia.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted across multiple databases and websites from inception to July 16, 2024, to identify both published and unpublished randomized controlled trials (RCTs). Meta-analyses were performed using random-effects or fixed-effects models depending on statistical heterogeneity. Relative risks (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to summarize the effects.</p><p><strong>Results: </strong>Out of 931 records screened, seven RCTs (four focusing on bipolar depression and three on schizophrenia) were eligible for inclusion. Lumateperone was efficacious in reducing depressive symptoms in bipolar depression (SMDs = -0.36, 95% CI: -0.59 to -0.13). In treating schizophrenia, lumateperone exhibited a lower combined SMD of -0.14 (95% CI: -0.27 to 0, P = 0.051, I² = 49.6%), showing no significant difference from the placebo group, although the p-value approached significance. The lumateperone group showed significantly higher response rates compared to placebo in both bipolar depression (RRs = 1.27, 95% CI: 1.07 to 1.51) and schizophrenia (RRs = 1.44, 95% CI: 1.12 to 1.86). Common treatment-emergent adverse events included somnolence, dry mouth, dizziness, nausea, and headache (RRs = 1.30 to 3.29). Importantly, lumateperone did not significantly increase extrapyramidal symptoms (EPS, RRs = 1.46, 95% CI: 0.84 to 2.53).</p><p><strong>Conclusions: </strong>Lumateperone is effective in treating bipolar depression but does not significantly reduce symptom severity in schizophrenia. It has a favorable safety and tolerability profile. However, caution is warranted in interpreting these findings due to the limited number of studies included.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Identification of Phosphodiesterase-7A (PDE7A) as a Novel Target for Reducing Ethanol Consumption in Mice. 更正:鉴定磷酸二酯酶-7A (PDE7A) 作为降低小鼠乙醇消耗量的新靶点。
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-01 DOI: 10.1093/ijnp/pyae049
{"title":"Correction to: Identification of Phosphodiesterase-7A (PDE7A) as a Novel Target for Reducing Ethanol Consumption in Mice.","authors":"","doi":"10.1093/ijnp/pyae049","DOIUrl":"10.1093/ijnp/pyae049","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Behavioral and neurophysiological signatures of cognitive control in humans and rats. 人类和大鼠认知控制的行为和神经生理学特征
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-01 DOI: 10.1093/ijnp/pyae050
Samantha R Linton, Ty Lees, Ann Iturra-Mena, Brian D Kangas, Genevieve Nowicki, Rachel Lobien, Gordana Vitaliano, Jack Bergman, William A Carlezon, Diego A Pizzagalli

Background: Deficits in cognitive control are implicated in numerous neuropsychiatric disorders. However, relevant pharmacological treatments are limited, likely due to weak translational validity of applicable preclinical models used. Neural indices derived from electroencephalography may prove useful in comparing and translating the effects of cognition-enhancing drugs between species. In the current study, we aimed to extend our previous cross-species results by examining if methylphenidate (MPH) modulates behavioral and neural indices of cognitive control in independent cohorts of humans and rats.

Methods: We measured continuous electroencephalography data from healthy adults (n = 25; 14 female) and Long Evans rats (n = 22; 8 female) and compared both stimulus- and response-locked event-related potentials and spectral power measures across species, and their MPH-related moderation following treatment with vehicle (placebo) or 1 of 2 doses of MPH.

Results: Across both species, linear mixed effects modeling confirmed the expected Flanker interference effect on behavior (eg, accuracy) and response-related event-related potentials. Unexpectedly, in contrast to past work, we did not observe any task-related effects on the spectral power of rodents. Moreover, MPH generally did not modulate cognitive control of either species, although some species-specific patterns offer insight for future research.

Conclusions: Collectively, these findings in independent human and rodent subjects replicate some of our previously reported behavioral and neurophysiological patterns partly consistent with the notion that similar neural mechanisms may regulate cognitive control in both species. Nonetheless, these results showcase an approach to accelerate translation using a coordinated between-species platform to evaluate pro-cognitive treatments.

背景:许多神经精神疾病都与认知控制缺陷有关。然而,相关的药物治疗却很有限,这可能是由于适用的临床前模型的转化有效性较弱。脑电图(EEG)得出的神经指数可能有助于比较和转化不同物种间认知增强药物的效果。在目前的研究中,我们旨在通过研究哌醋甲酯(MPH)是否会调节人类和大鼠独立群体的认知控制行为和神经指数,从而扩展我们之前的跨物种研究结果:我们测量了健康成年人(n=25;14只雌性)和Long Evans大鼠(n=22;8只雌性)的连续脑电图数据,并比较了不同物种的刺激和反应锁定事件相关电位(ERPs)和频谱功率测量,以及它们在接受药物(安慰剂)或两种剂量之一的MPH治疗后与MPH相关的调节作用:在两个物种中,线性混合效应模型证实了预期的Flanker干扰对行为(如准确性)和反应相关ERPs的影响。出乎意料的是,与过去的研究不同,我们没有观察到啮齿动物的频谱功率受到任何任务相关的影响。此外,虽然某些物种的特定模式为未来研究提供了启示,但 MPH 一般不会调节这两种动物的认知控制:总之,这些在独立的人类和啮齿动物受试者身上得到的研究结果复制了我们之前报道的一些行为和神经生理学模式,部分符合两种动物中类似的神经机制可能调节认知控制的观点。尽管如此,这些结果展示了一种利用物种间协调平台加速转化的方法,以评估有利于认知的治疗方法。
{"title":"Behavioral and neurophysiological signatures of cognitive control in humans and rats.","authors":"Samantha R Linton, Ty Lees, Ann Iturra-Mena, Brian D Kangas, Genevieve Nowicki, Rachel Lobien, Gordana Vitaliano, Jack Bergman, William A Carlezon, Diego A Pizzagalli","doi":"10.1093/ijnp/pyae050","DOIUrl":"10.1093/ijnp/pyae050","url":null,"abstract":"<p><strong>Background: </strong>Deficits in cognitive control are implicated in numerous neuropsychiatric disorders. However, relevant pharmacological treatments are limited, likely due to weak translational validity of applicable preclinical models used. Neural indices derived from electroencephalography may prove useful in comparing and translating the effects of cognition-enhancing drugs between species. In the current study, we aimed to extend our previous cross-species results by examining if methylphenidate (MPH) modulates behavioral and neural indices of cognitive control in independent cohorts of humans and rats.</p><p><strong>Methods: </strong>We measured continuous electroencephalography data from healthy adults (n = 25; 14 female) and Long Evans rats (n = 22; 8 female) and compared both stimulus- and response-locked event-related potentials and spectral power measures across species, and their MPH-related moderation following treatment with vehicle (placebo) or 1 of 2 doses of MPH.</p><p><strong>Results: </strong>Across both species, linear mixed effects modeling confirmed the expected Flanker interference effect on behavior (eg, accuracy) and response-related event-related potentials. Unexpectedly, in contrast to past work, we did not observe any task-related effects on the spectral power of rodents. Moreover, MPH generally did not modulate cognitive control of either species, although some species-specific patterns offer insight for future research.</p><p><strong>Conclusions: </strong>Collectively, these findings in independent human and rodent subjects replicate some of our previously reported behavioral and neurophysiological patterns partly consistent with the notion that similar neural mechanisms may regulate cognitive control in both species. Nonetheless, these results showcase an approach to accelerate translation using a coordinated between-species platform to evaluate pro-cognitive treatments.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epigenome-Wide DNA Methylation in Unipolar Depression - Predictive Biomarker of Antidepressant Treatment Response? 单相抑郁症的表观基因组DNA甲基化--抗抑郁治疗反应的预测性生物标志物?
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-05 DOI: 10.1093/ijnp/pyae045
Miriam A Schiele, Oscar Crespo Salvador, Jan Lipovsek, Kathrin Schwarte, Pascal Schlosser, Peter Zwanzger, Volker Arolt, Bernhard T Baune, Anna Köttgen, Katharina Domschke

Background: Despite the well-documented efficacy of antidepressant agents for the treatment of major depressive disorder (MDD), initial treatment non-response rates are high. Recent years have seen an increase in research into predictive biomarkers towards improving diagnosis and individualized treatment. Among those, epigenetic mechanisms such as DNA methylation constitute promising candidate markers in predicting antidepressant treatment response in MDD. The present study sought to address epigenome-wide DNA methylation as a predictor of antidepressant treatment response in the so far largest sample of patients with MDD.

Methods: Epigenome-wide DNA methylation was analyzed using the Infinium MethylationEPIC BeadChip in peripheral blood of N=230 Caucasian patients with MDD receiving six-week antidepressant treatment in a naturalistic in-patient setting as well as in a subsample of N=107 patients primarily receiving continuous treatment with SSRIs or SNRIs. Treatment response was assessed by means of the Hamilton Depression Scale (HAM-D).

Results: No genome-wide significant hits were observed. Suggestive (p<1E-5) epigenome-wide evidence was discerned for altered DNA methylation at six CpG sites (LOC102724467, LOC100506023, RSPO2, SAG, IL16, PRKCI) to predict response to naturalistic antidepressant treatment. In patients treated with SSRIs or SNRIs, differential DNA methylation at 11 CpGs, e.g. mapping to the TIMP2, VDAC1 or SORL1 genes, was suggestively associated with treatment response.

Conclusions: The present results provide preliminary evidence for altered DNA methylation patterns to be associated with antidepressant treatment response in MDD. Provided significant replication in independent and larger samples, the present findings might in the future aid in clinical decision making towards more individualized and thus more efficacious treatments of MDD.

背景:尽管抗抑郁药物治疗重度抑郁障碍(MDD)的疗效已得到充分证实,但初始治疗的无应答率却很高。近年来,为改进诊断和个体化治疗,对预测性生物标志物的研究不断增加。其中,DNA 甲基化等表观遗传机制是预测 MDD 抗抑郁治疗反应的有希望的候选标志物。本研究试图将整个表观基因组的DNA甲基化作为迄今为止最大样本的MDD患者抗抑郁治疗反应的预测指标:采用Infinium MethylationEPIC BeadChip分析了在自然住院环境中接受六周抗抑郁治疗的230名白种MDD患者外周血中的表观基因组DNA甲基化,以及主要接受SSRIs或SNRIs持续治疗的107名患者的子样本。治疗反应通过汉密尔顿抑郁量表(HAM-D)进行评估:结果:未观察到全基因组范围内的重大突变。提示性(pConclusions:本研究结果提供了 DNA 甲基化模式改变与 MDD 抗抑郁治疗反应相关的初步证据。如果能在独立的、更大的样本中进行重要的复制,本研究结果将来可能有助于临床决策,从而对 MDD 进行更个体化、更有效的治疗。
{"title":"Epigenome-Wide DNA Methylation in Unipolar Depression - Predictive Biomarker of Antidepressant Treatment Response?","authors":"Miriam A Schiele, Oscar Crespo Salvador, Jan Lipovsek, Kathrin Schwarte, Pascal Schlosser, Peter Zwanzger, Volker Arolt, Bernhard T Baune, Anna Köttgen, Katharina Domschke","doi":"10.1093/ijnp/pyae045","DOIUrl":"10.1093/ijnp/pyae045","url":null,"abstract":"<p><strong>Background: </strong>Despite the well-documented efficacy of antidepressant agents for the treatment of major depressive disorder (MDD), initial treatment non-response rates are high. Recent years have seen an increase in research into predictive biomarkers towards improving diagnosis and individualized treatment. Among those, epigenetic mechanisms such as DNA methylation constitute promising candidate markers in predicting antidepressant treatment response in MDD. The present study sought to address epigenome-wide DNA methylation as a predictor of antidepressant treatment response in the so far largest sample of patients with MDD.</p><p><strong>Methods: </strong>Epigenome-wide DNA methylation was analyzed using the Infinium MethylationEPIC BeadChip in peripheral blood of N=230 Caucasian patients with MDD receiving six-week antidepressant treatment in a naturalistic in-patient setting as well as in a subsample of N=107 patients primarily receiving continuous treatment with SSRIs or SNRIs. Treatment response was assessed by means of the Hamilton Depression Scale (HAM-D).</p><p><strong>Results: </strong>No genome-wide significant hits were observed. Suggestive (p<1E-5) epigenome-wide evidence was discerned for altered DNA methylation at six CpG sites (LOC102724467, LOC100506023, RSPO2, SAG, IL16, PRKCI) to predict response to naturalistic antidepressant treatment. In patients treated with SSRIs or SNRIs, differential DNA methylation at 11 CpGs, e.g. mapping to the TIMP2, VDAC1 or SORL1 genes, was suggestively associated with treatment response.</p><p><strong>Conclusions: </strong>The present results provide preliminary evidence for altered DNA methylation patterns to be associated with antidepressant treatment response in MDD. Provided significant replication in independent and larger samples, the present findings might in the future aid in clinical decision making towards more individualized and thus more efficacious treatments of MDD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Upregulation of Phosphodiesterase 7A Contributes to Concurrent Pain and Depression via Inhibition of cAMP-PKA-CREB-BDNF Signaling and Neuroinflammation in the Hippocampus of Mice. 磷酸二酯酶7A的上调会导致海马中cAMP-PKA-CREB-BDNF信号传导和神经炎症的下调,并导致两种小鼠模型中同时出现慢性疼痛和抑郁。
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-01 DOI: 10.1093/ijnp/pyae040
Shi-Cai Chen, Yan-Han Chen, Yan Song, Shu-Hua Zong, Ming-Xia Wu, Wei Wang, Hao Wang, Feng Zhang, Yan-Meng Zhou, Hai-Yang Yu, Han-Ting Zhang, Fang-Fang Zhang

Background: Phosphodiesterases (PDEs) are enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate AMP (cAMP) and/or cyclic guanosine monophosphate (cGMP). PDE inhibitors can mitigate chronic pain and depression when these disorders occur individually; however, there is limited understanding of their role in concurrent chronic pain and depression. We aimed to evaluate the mechanisms of action of PDE using 2 mouse models of concurrent chronic pain and depression.

Methods: C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) to induce chronic neuropathic pain or injected with complete Freund's adjuvant (CFA) to induce inflammatory pain, and both animals showed depression-like behavior. First, we determined the change in PDE expression in both animal models. Next, we determined the effect of PDE7 inhibitor BRL50481 or hippocampal PDE7A knockdown on PSNL- or CFA-induced chronic pain and depression-like behavior. We also investigated the role of cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling and neuroinflammation in the effect of PDE7A inhibition on PSNL- or CFA-induced chronic pain and depression-like behavior.

Results: This induction of chronic pain and depression in the 2 animal models upregulated hippocampal PDE7A. Oral administration of PDE7 inhibitor, BRL50481, or hippocampal PDE7A knockdown significantly reduced mechanical hypersensitivity and depression-like behavior. Hippocampal PDE7 inhibition reversed PSNL- or CFA-induced downregulation of cAMP and BDNF and the phosphorylation of PKA, CREB, and p65. cAMP agonist forskolin reversed these changes and caused milder behavioral symptoms of pain and depression. BRL50481 reversed neuroinflammation in the hippocampus in PSNL mice.

Conclusions: Hippocampal PDE7A mediated concurrent chronic pain and depression in both mouse models by inhibiting cAMP-PKA-CREB-BDNF signaling. Inhibiting PDE7A or activating cAMP-PKA-CREB-BDNF signaling are potential strategies to treat concurrent chronic pain and depression.

背景:磷酸二酯酶(PDE)是催化环磷酸腺苷 AMP(cAMP)和/或环磷酸鸟苷(cGMP)水解的酶。当慢性疼痛和抑郁症单独发生时,PDE 抑制剂可减轻这两种疾病;然而,人们对其在同时发生的慢性疼痛和抑郁症中的作用了解有限。我们的目的是利用两种并发慢性疼痛和抑郁的小鼠模型来评估 PDE 的作用机制:方法:对 C57BL/6J 小鼠进行坐骨神经部分结扎(PSNL)以诱导慢性神经病理性疼痛,或注射完全弗氏佐剂(CFA)以诱导炎症性疼痛,两种动物均表现出抑郁样行为。首先,我们测定了两种动物模型中 PDE 表达的变化。接着,我们测定了 PDE7 抑制剂 BRL50481 或海马 PDE7A 敲除对 PSNL 或 CFA 诱导的慢性疼痛和抑郁样行为的影响。我们还研究了cAMP-蛋白激酶A(PKA)-cAMP反应元件结合蛋白(CREB)-脑源性神经营养因子(BDNF)信号传导和神经炎症在PDE7A抑制对PSNL或CFA诱导的慢性疼痛和抑郁样行为的影响中的作用:结果:在两种动物模型中诱导慢性疼痛和抑郁会上调海马 PDE7A。口服 PDE7 抑制剂 BRL50481 或敲除海马 PDE7A 能显著降低机械过敏性和抑郁样行为。抑制海马 PDE7 可逆转 PSNL 或 CFA 诱导的 cAMP 和 BDNF 下调以及 PKA、CREB 和 p65 的磷酸化。BRL50481 逆转了 PSNL 小鼠海马的神经炎症:抑制 PDE7A 或激活 cAMP-PKA-CREB-BDNF 信号是治疗并发慢性疼痛和抑郁症的潜在策略。
{"title":"Upregulation of Phosphodiesterase 7A Contributes to Concurrent Pain and Depression via Inhibition of cAMP-PKA-CREB-BDNF Signaling and Neuroinflammation in the Hippocampus of Mice.","authors":"Shi-Cai Chen, Yan-Han Chen, Yan Song, Shu-Hua Zong, Ming-Xia Wu, Wei Wang, Hao Wang, Feng Zhang, Yan-Meng Zhou, Hai-Yang Yu, Han-Ting Zhang, Fang-Fang Zhang","doi":"10.1093/ijnp/pyae040","DOIUrl":"10.1093/ijnp/pyae040","url":null,"abstract":"<p><strong>Background: </strong>Phosphodiesterases (PDEs) are enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate AMP (cAMP) and/or cyclic guanosine monophosphate (cGMP). PDE inhibitors can mitigate chronic pain and depression when these disorders occur individually; however, there is limited understanding of their role in concurrent chronic pain and depression. We aimed to evaluate the mechanisms of action of PDE using 2 mouse models of concurrent chronic pain and depression.</p><p><strong>Methods: </strong>C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) to induce chronic neuropathic pain or injected with complete Freund's adjuvant (CFA) to induce inflammatory pain, and both animals showed depression-like behavior. First, we determined the change in PDE expression in both animal models. Next, we determined the effect of PDE7 inhibitor BRL50481 or hippocampal PDE7A knockdown on PSNL- or CFA-induced chronic pain and depression-like behavior. We also investigated the role of cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling and neuroinflammation in the effect of PDE7A inhibition on PSNL- or CFA-induced chronic pain and depression-like behavior.</p><p><strong>Results: </strong>This induction of chronic pain and depression in the 2 animal models upregulated hippocampal PDE7A. Oral administration of PDE7 inhibitor, BRL50481, or hippocampal PDE7A knockdown significantly reduced mechanical hypersensitivity and depression-like behavior. Hippocampal PDE7 inhibition reversed PSNL- or CFA-induced downregulation of cAMP and BDNF and the phosphorylation of PKA, CREB, and p65. cAMP agonist forskolin reversed these changes and caused milder behavioral symptoms of pain and depression. BRL50481 reversed neuroinflammation in the hippocampus in PSNL mice.</p><p><strong>Conclusions: </strong>Hippocampal PDE7A mediated concurrent chronic pain and depression in both mouse models by inhibiting cAMP-PKA-CREB-BDNF signaling. Inhibiting PDE7A or activating cAMP-PKA-CREB-BDNF signaling are potential strategies to treat concurrent chronic pain and depression.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Working Memory Performance Predicts, but Does Not Reduce, Cocaine and Cannabinoid Seeking in Adult Male Rats. 成年雄性大鼠的工作记忆能力可预测可卡因和大麻素的觅药行为,但不会减少这种行为。
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-01 DOI: 10.1093/ijnp/pyae048
Sierra J Stringfield, Erin K Kirschmann, Mary M Torregrossa

Background: Cognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking.

Methods: Adult male rats were trained to perform a "simple" or "complex" version of a delayed-match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression.

Results: Training on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence.

Conclusions: These results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance before drug exposure may predict vulnerability to future drug use.

背景:认知缺陷反映出执行功能受损,通常与精神疾病(包括药物使用)有关。认知训练可促进前额叶皮层的神经可塑性,增强执行控制能力,缓解吸毒导致的认知能力下降,从而改善这些疾病的治疗效果。此外,脑源性神经营养因子(BDNF)可以促进前额叶皮层的可塑性,减少寻求毒品的行为。我们研究了工作记忆训练是否能提高前额叶皮层的BDNF水平,以及这种训练是否能预测或防止可卡因或大麻素寻求行为:方法:训练成年雄性大鼠完成 "简单 "或 "复杂 "版本的延迟匹配到样本工作记忆任务。然后,大鼠自行服用可卡因或合成大麻素 WIN55,212-2,并在戒断期间接受诱导药物寻求测试。对前额叶皮层和海马背侧的组织进行了 BDNF 蛋白表达分析:结果:工作记忆任务训练提高了边缘前额叶皮层的内源性 BDNF 蛋白水平,但没有提高海马背侧的内源性 BDNF 蛋白水平。工作记忆训练对两种药物的自我给药均无影响,但可预测戒断期间WIN自我给药和可卡因寻求的程度:这些结果表明,工作记忆训练能促进内源性BDNF,但不会改变寻求毒品或服用毒品的行为。然而,药物暴露前认知表现的个体差异可能预示着未来药物使用的脆弱性。
{"title":"Working Memory Performance Predicts, but Does Not Reduce, Cocaine and Cannabinoid Seeking in Adult Male Rats.","authors":"Sierra J Stringfield, Erin K Kirschmann, Mary M Torregrossa","doi":"10.1093/ijnp/pyae048","DOIUrl":"10.1093/ijnp/pyae048","url":null,"abstract":"<p><strong>Background: </strong>Cognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking.</p><p><strong>Methods: </strong>Adult male rats were trained to perform a \"simple\" or \"complex\" version of a delayed-match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression.</p><p><strong>Results: </strong>Training on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence.</p><p><strong>Conclusions: </strong>These results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance before drug exposure may predict vulnerability to future drug use.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ketamine Prevents Inflammation-Induced Reduction of Human Hippocampal Neurogenesis via Inhibiting the Production of Neurotoxic Metabolites of the Kynurenine Pathway. 氯胺酮通过抑制神经毒性代谢产物犬尿氨酸途径的产生,防止炎症诱导的人类海马神经发生减少。
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-01 DOI: 10.1093/ijnp/pyae041
Gargi Mandal, Madeline Kirkpatrick, Silvia Alboni, Nicole Mariani, Carmine M Pariante, Alessandra Borsini

Background: Understanding the precise mechanisms of ketamine is crucial for replicating its rapid antidepressant effects without inducing psychomimetic changes. Here, we explore whether the antidepressant-like effects of ketamine enantiomers are underscored by protection against cytokine-induced reductions in hippocampal neurogenesis and activation of the neurotoxic kynurenine pathway in our well-established in vitro model of depression in a dish.

Methods: We used the fetal hippocampal progenitor cell line (HPC0A07/03C) to investigate ketamine's impact on cytokine-induced reductions in neurogenesis in vitro. Cells were treated with interleukin- 1beta (IL-1b) (10 ng/mL) or IL-6 (50 pg/mL), alone or in combination with ketamine enantiomers arketamine (R-ketamine, 400 nM) or esketamine (S-ketamine, 400 nM) or antidepressants sertraline (1 mM) or venlafaxine (1 mM).

Results: Resembling the effect of antidepressants, both ketamine enantiomers prevented IL-1b- and IL-6-induced reduction in neurogenesis and increase in apoptosis. This was mediated by inhibition of IL-1b-induced production of IL-2 and IL-13 by R-ketamine and of IL-1b-induced tumor necrosis factor-alpha by S-ketamine. Likewise, R-ketamine inhibited IL-6-induced production of IL-13, whereas S-ketamine inhibited IL-6-induced IL-1b and IL-8. Moreover, both R- and S-ketamine prevented IL-1b-induced increases in indoleamine 2,3-dioxygenase expression as well as kynurenine production, which in turn was shown to mediate the detrimental effects of IL-1b on neurogenesis and apoptosis. In contrast, neither R- nor S-ketamine prevented IL-6-induced kynurenine pathway activation.

Conclusions: Results suggest that R- and S-ketamine have pro-neurogenic and anti-inflammatory properties; however, this is mediated by inhibition of the kynurenine pathway only in the context of IL-1b. Overall, this study enhances our understanding of the mechanisms underlying ketamine's antidepressant effects in the context of different inflammatory phenotypes, ultimately leading to the development of more effective, personalized therapeutic approaches for patients suffering from depression.

背景:了解氯胺酮的确切机制对于复制其快速抗抑郁效果而不诱发精神拟态变化至关重要。在此,我们将在已建立的体外抑郁模型中,探讨氯胺酮对映体的抗抑郁样作用是否通过防止细胞因子诱导的海马神经发生减少和神经毒性犬尿氨酸通路的激活而得到强调:我们使用胎儿海马祖细胞系(HPC0A07/03C)来研究氯胺酮对细胞因子诱导的体外神经发生减少的影响。用白细胞介素1β(IL-1b)(10纳克/毫升)或IL-6(50皮克/毫升)处理细胞,单独或与氯胺酮对映体、氯胺酮(R-氯胺酮,400毫微克)或氯胺酮(S-氯胺酮,400毫微克)或抗抑郁药舍曲林(1毫摩尔)或文拉法辛(1毫摩尔)联合使用:与抗抑郁药的作用相似,两种氯胺酮对映体都能防止IL-1b和IL-6诱导的神经发生减少和细胞凋亡增加。R-氯胺酮抑制了IL-1b诱导的IL-2和IL-13的产生,S-氯胺酮抑制了IL-1b诱导的肿瘤坏死因子-α(TNF-a)的产生。同样,R-氯胺酮能抑制 IL-6 诱导的 IL-13 的产生,而 S-氯胺酮则能抑制 IL-6 诱导的 IL-1b 和 IL-8。此外,R-和S-氯胺酮都能阻止IL-1b诱导的吲哚胺2,3-二氧化酶(IDO)表达的增加以及犬尿氨酸的产生,而犬尿氨酸反过来又能介导IL-1b对神经发生和细胞凋亡的不利影响。相比之下,R-和S-氯胺酮都不能阻止IL-6诱导的犬尿氨酸通路激活:结论:研究结果表明,R-和S-氯胺酮具有促进神经发生和抗炎的特性,但这仅在IL-1b的情况下通过抑制犬尿氨酸通路来实现。总之,这项研究加深了我们对氯胺酮在不同炎症表型下的抗抑郁作用机制的了解,最终将为抑郁症患者开发出更有效的个性化治疗方法。
{"title":"Ketamine Prevents Inflammation-Induced Reduction of Human Hippocampal Neurogenesis via Inhibiting the Production of Neurotoxic Metabolites of the Kynurenine Pathway.","authors":"Gargi Mandal, Madeline Kirkpatrick, Silvia Alboni, Nicole Mariani, Carmine M Pariante, Alessandra Borsini","doi":"10.1093/ijnp/pyae041","DOIUrl":"10.1093/ijnp/pyae041","url":null,"abstract":"<p><strong>Background: </strong>Understanding the precise mechanisms of ketamine is crucial for replicating its rapid antidepressant effects without inducing psychomimetic changes. Here, we explore whether the antidepressant-like effects of ketamine enantiomers are underscored by protection against cytokine-induced reductions in hippocampal neurogenesis and activation of the neurotoxic kynurenine pathway in our well-established in vitro model of depression in a dish.</p><p><strong>Methods: </strong>We used the fetal hippocampal progenitor cell line (HPC0A07/03C) to investigate ketamine's impact on cytokine-induced reductions in neurogenesis in vitro. Cells were treated with interleukin- 1beta (IL-1b) (10 ng/mL) or IL-6 (50 pg/mL), alone or in combination with ketamine enantiomers arketamine (R-ketamine, 400 nM) or esketamine (S-ketamine, 400 nM) or antidepressants sertraline (1 mM) or venlafaxine (1 mM).</p><p><strong>Results: </strong>Resembling the effect of antidepressants, both ketamine enantiomers prevented IL-1b- and IL-6-induced reduction in neurogenesis and increase in apoptosis. This was mediated by inhibition of IL-1b-induced production of IL-2 and IL-13 by R-ketamine and of IL-1b-induced tumor necrosis factor-alpha by S-ketamine. Likewise, R-ketamine inhibited IL-6-induced production of IL-13, whereas S-ketamine inhibited IL-6-induced IL-1b and IL-8. Moreover, both R- and S-ketamine prevented IL-1b-induced increases in indoleamine 2,3-dioxygenase expression as well as kynurenine production, which in turn was shown to mediate the detrimental effects of IL-1b on neurogenesis and apoptosis. In contrast, neither R- nor S-ketamine prevented IL-6-induced kynurenine pathway activation.</p><p><strong>Conclusions: </strong>Results suggest that R- and S-ketamine have pro-neurogenic and anti-inflammatory properties; however, this is mediated by inhibition of the kynurenine pathway only in the context of IL-1b. Overall, this study enhances our understanding of the mechanisms underlying ketamine's antidepressant effects in the context of different inflammatory phenotypes, ultimately leading to the development of more effective, personalized therapeutic approaches for patients suffering from depression.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evidence for the Contribution of the miR-206/BDNF Pathway in the Pathophysiology of Depression. miR-206/BDNF 通路在抑郁症病理生理学中的作用证据
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-01 DOI: 10.1093/ijnp/pyae039
Ya-Bin Zheng, Xiang Jin

Depression is a complex disorder with substantial impacts on individual health and has major public health implications. Depression results from complex interactions between genetic and environmental factors. Epigenetic mechanisms, including DNA methylation, microRNAs (miRNAs), and histone modifications, can produce heritable phenotypic changes without a change in DNA sequence and recently were proven to mediate lasting increases in the risk of depression following exposure to adverse life events. Of these, miRNAs are gaining attention for their role in the pathogenesis of many stress-associated mental disorders, including depression. One such miRNA is microRNA-206 (miR-206), which is a critical candidate for increasing the susceptibility to stress. Although miR-206 is thought to be a typical muscle-specific miRNA, it is expressed throughout the brain, particularly in the hippocampus and prefrontal cortex. Until now, only a few studies have been conducted on rodents to understand the role of miR-206 in stress-related abnormalities in neurogenesis. However, the precise underlying molecular mechanism of miR-206-mediated depression-like behaviors remains largely unknown. Here, we reviewed recent advances in the field of biomedical and clinical research on the role of miR-206 in the pathogenesis of depression from studies using different tissues and various experimental designs and described how abnormalities in miR-206 expression in these tissues can affect neuronal functions. Moreover, we focused on studies investigating the brain-derived neurotrophic factor (BDNF) as a functional target of miR-206, where miR-206 has been implicated in the pathogenesis of depression by suppressing the expression of the BDNF. In summary, these studies confirm the existence of a tight correlation between the pathogenesis of depression and the miR-206/BDNF pathway.

抑郁症是一种复杂的疾病,对个人健康有重大影响,对公共卫生也有重大影响。抑郁症是遗传因素和环境因素复杂相互作用的结果。表观遗传机制,包括 DNA 甲基化(DNAm)、microRNAs(miRNAs)和组蛋白修饰,可以在不改变 DNA 序列的情况下产生可遗传的表型变化,最近已被证实可在暴露于不良生活事件后介导抑郁症风险的持续增加。其中,miRNA 在包括抑郁症在内的许多与压力相关的精神疾病的发病机制中的作用日益受到关注。其中一种 miRNA 是 microRNA-206 (miR-206),它是增加压力易感性的关键候选因子。尽管 miR-206 被认为是一种典型的肌肉特异性 miRNA,但它在整个大脑中都有表达,尤其是在海马体和前额叶皮质(PFC)中。迄今为止,只有少数针对啮齿类动物的研究了解了它在与压力相关的神经发生异常中的作用。然而,miR-206 介导抑郁样行为的确切潜在分子机制在很大程度上仍不为人所知。在此,我们回顾了生物医学和临床研究领域关于 miR-206 在抑郁症发病机制中作用的最新进展,这些研究采用了不同的组织和不同的实验设计,并描述了 miR-206 在这些组织中的表达异常如何影响神经元功能。此外,我们还重点研究了将脑源性神经营养因子(BDNF)作为 miR-206 功能靶点的研究,在这些研究中,miR-206 通过抑制 BDNF 的表达被认为与抑郁症的发病机制有关。总之,这些研究证实了抑郁症的发病机制与 miR-206/BDNF 通路之间存在密切的相关性。
{"title":"Evidence for the Contribution of the miR-206/BDNF Pathway in the Pathophysiology of Depression.","authors":"Ya-Bin Zheng, Xiang Jin","doi":"10.1093/ijnp/pyae039","DOIUrl":"10.1093/ijnp/pyae039","url":null,"abstract":"<p><p>Depression is a complex disorder with substantial impacts on individual health and has major public health implications. Depression results from complex interactions between genetic and environmental factors. Epigenetic mechanisms, including DNA methylation, microRNAs (miRNAs), and histone modifications, can produce heritable phenotypic changes without a change in DNA sequence and recently were proven to mediate lasting increases in the risk of depression following exposure to adverse life events. Of these, miRNAs are gaining attention for their role in the pathogenesis of many stress-associated mental disorders, including depression. One such miRNA is microRNA-206 (miR-206), which is a critical candidate for increasing the susceptibility to stress. Although miR-206 is thought to be a typical muscle-specific miRNA, it is expressed throughout the brain, particularly in the hippocampus and prefrontal cortex. Until now, only a few studies have been conducted on rodents to understand the role of miR-206 in stress-related abnormalities in neurogenesis. However, the precise underlying molecular mechanism of miR-206-mediated depression-like behaviors remains largely unknown. Here, we reviewed recent advances in the field of biomedical and clinical research on the role of miR-206 in the pathogenesis of depression from studies using different tissues and various experimental designs and described how abnormalities in miR-206 expression in these tissues can affect neuronal functions. Moreover, we focused on studies investigating the brain-derived neurotrophic factor (BDNF) as a functional target of miR-206, where miR-206 has been implicated in the pathogenesis of depression by suppressing the expression of the BDNF. In summary, these studies confirm the existence of a tight correlation between the pathogenesis of depression and the miR-206/BDNF pathway.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GluN2B on Adult-Born Granule Cells Modulates (R,S)-Ketamine's Rapid-Acting Effects in Mice. 小鼠成体颗粒细胞上的 GluN2B 可调节(R,S)-氯胺酮的速效作用。
IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-01 DOI: 10.1093/ijnp/pyae036
Nicholas E Bulthuis, Josephine C McGowan, Liliana R Ladner, Christina T LaGamma, Sean C Lim, Claire X Shubeck, Rebecca A Brachman, Ezra Sydnor, Ina P Pavlova, Dong-Oh Seo, Michael R Drew, Christine A Denny

Background: Standard antidepressant treatments often take weeks to reach efficacy and are ineffective for many patients. (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be a rapid-acting antidepressant and to decrease depressive symptoms within hours of administration. While previous studies have shown the importance of the GluN2B subunit of the NMDA receptor on interneurons in the medial prefrontal cortex, no study to our knowledge has investigated the influence of GluN2B-expressing adult-born granule cells.

Methods: Here, we examined whether (R,S)-ketamine's efficacy depends on adult-born hippocampal neurons using a genetic strategy to selectively ablate the GluN2B subunit of the NMDA receptor from Nestin+ cells in male and female mice, tested across an array of standard behavioral assays.

Results: We report that in male mice, GluN2B expression on 6-week-old adult-born neurons is necessary for (R,S)-ketamine's effects on behavioral despair in the forced swim test and on hyponeophagia in the novelty suppressed feeding paradigm, as well on fear behavior following contextual fear conditioning. In female mice, GluN2B expression is necessary for effects on hyponeophagia in novelty suppressed feeding. These effects were not replicated when ablating GluN2B from 2-week-old adult-born neurons. We also find that ablating neurogenesis increases fear expression in contextual fear conditioning, which is buffered by (R,S)-ketamine administration.

Conclusions: In line with previous studies, these results suggest that 6-week-old adult-born hippocampal neurons expressing GluN2B partially modulate (R,S)-ketamine's rapid-acting effects. Future work targeting these 6-week-old adult-born neurons may prove beneficial for increasing the efficacy of (R,S)-ketamine.

背景:标准的抗抑郁治疗通常需要数周时间才能见效,对许多患者无效。(N-甲基-D-天冬氨酸(NMDA)拮抗剂--(R,S)-氯胺酮已被证明是一种速效抗抑郁剂,可在用药后数小时内减轻抑郁症状。以往的研究表明,NMDA 受体(NMDAR)的 GluN2B 亚基对内侧前额叶皮层(mPFC)的中间神经元非常重要,但还没有研究调查过表达 GluN2B 的成体颗粒细胞(abGCs)的影响。方法:在此,我们采用一种遗传策略,选择性地消减雄性和雌性小鼠 Nestin+ 细胞中的 NMDAR GluN2B 亚基,并通过一系列标准行为测定进行了测试,从而研究了(R,S)-氯胺酮的药效是否取决于这些成体海马神经元:我们报告说,在雄性小鼠中,(R,S)-氯胺酮对强迫游泳试验(FST)中的行为绝望和新奇性抑制摄食(NSF)范例中的食欲减退以及情境恐惧条件反射(CFC)后的恐惧行为的影响需要6周大的成体神经元上的GluN2B表达。在雌性小鼠中,GluN2B的表达是影响NSF食欲减退的必要条件。在消减 2 周大的成体神经元中的 GluN2B 时,这些效应并没有得到复制。我们还发现,消减神经发生会增加 CFC 中的恐惧表达,而服用(R,S)-氯胺酮可以缓冲恐惧表达:与之前的研究一致,这些结果表明,表达 GluN2B 的 6 周龄成体海马神经元部分调节了(R,S)-氯胺酮的速效作用。未来针对这些6周大的成神经元开展的工作可能会被证明有利于提高(R,S)-氯胺酮的疗效。
{"title":"GluN2B on Adult-Born Granule Cells Modulates (R,S)-Ketamine's Rapid-Acting Effects in Mice.","authors":"Nicholas E Bulthuis, Josephine C McGowan, Liliana R Ladner, Christina T LaGamma, Sean C Lim, Claire X Shubeck, Rebecca A Brachman, Ezra Sydnor, Ina P Pavlova, Dong-Oh Seo, Michael R Drew, Christine A Denny","doi":"10.1093/ijnp/pyae036","DOIUrl":"10.1093/ijnp/pyae036","url":null,"abstract":"<p><strong>Background: </strong>Standard antidepressant treatments often take weeks to reach efficacy and are ineffective for many patients. (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be a rapid-acting antidepressant and to decrease depressive symptoms within hours of administration. While previous studies have shown the importance of the GluN2B subunit of the NMDA receptor on interneurons in the medial prefrontal cortex, no study to our knowledge has investigated the influence of GluN2B-expressing adult-born granule cells.</p><p><strong>Methods: </strong>Here, we examined whether (R,S)-ketamine's efficacy depends on adult-born hippocampal neurons using a genetic strategy to selectively ablate the GluN2B subunit of the NMDA receptor from Nestin+ cells in male and female mice, tested across an array of standard behavioral assays.</p><p><strong>Results: </strong>We report that in male mice, GluN2B expression on 6-week-old adult-born neurons is necessary for (R,S)-ketamine's effects on behavioral despair in the forced swim test and on hyponeophagia in the novelty suppressed feeding paradigm, as well on fear behavior following contextual fear conditioning. In female mice, GluN2B expression is necessary for effects on hyponeophagia in novelty suppressed feeding. These effects were not replicated when ablating GluN2B from 2-week-old adult-born neurons. We also find that ablating neurogenesis increases fear expression in contextual fear conditioning, which is buffered by (R,S)-ketamine administration.</p><p><strong>Conclusions: </strong>In line with previous studies, these results suggest that 6-week-old adult-born hippocampal neurons expressing GluN2B partially modulate (R,S)-ketamine's rapid-acting effects. Future work targeting these 6-week-old adult-born neurons may prove beneficial for increasing the efficacy of (R,S)-ketamine.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
International Journal of Neuropsychopharmacology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1