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Virtual stressors with real impact: what virtual reality-based biobehavioral research can teach us about typical and atypical stress responsivity. 具有真实影响的虚拟压力源:基于虚拟现实的生物行为学研究能告诉我们什么是典型和非典型压力反应。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-17 DOI: 10.1038/s41398-024-03129-x
Elizabeth A Shirtcliff, Tor T Finseth, Eliot H Winer, David C Glahn, Roselynn A Conrady, Stacy S Drury

Stress contributes to transdiagnostic morbidity and mortality across a wide range of physical and mental health problems. VR tasks have been validated as stressors with robust effect sizes for VR-based stressors to evoke stress across the most common autonomic and adrenocortical stress biomarkers. However, meta-analytic validation of VR stressors have resulted in inconsistent logic: why should something that isn't real evoke a very real suite of stress responses? This review posits that conceptually addressing this question requires differentiating a cause, "stressor", from effects, "stress". Stress comprises a series of well-delineated perturbations in biological systems, such as autonomic and adrenocortical biomarkers in response to stressors. Despite their ubiquity, decades of literature have back-calculated stressor intensity based on the magnitude of a stress response. This causal directionality is not logical, yet remains pervasive because seemingly objective stress indices have generated a wealth of findings showing how stress gets under the skin and skull. This has created challenges for providing clear guidance and strategies to measure acute stressor intensity. Binary thinking about whether something is (not) real has stifled advances in understanding how to measure the dosage of a stressful environment. As a function of being programmed, individualizable, and titrated, virtual reality (VR) based stressors offer the field a platform for quantifying the dose of a stressor and generating reliable dose-response curves. This also raises the possibility to safely and ethically integrate psychosocial stressor administration into clinical and therapeutic settings. For example, Social Evaluative Threat experiments effectively trigger a stress response both in a laboratory setting and in built environments, while also upholding hard-fought trust and rapport with care providers. By focusing attention on the measurement of the stressor, VR paradigms can advance tangible understanding of stressors themselves and the pathways to the stress response.

压力会导致各种身心健康问题的跨诊断发病率和死亡率。VR任务作为压力源已经得到验证,基于VR的压力源在最常见的自律神经和肾上腺皮质压力生物标志物中唤起压力的效应大小很强。然而,对 VR 压力源的元分析验证却产生了不一致的逻辑:为什么不真实的东西会唤起一系列非常真实的压力反应?本综述认为,要从概念上解决这个问题,就必须区分原因("压力源")和影响("压力")。压力包括生物系统中一系列明确界定的扰动,例如自律神经和肾上腺皮质生物标志物对压力源的反应。尽管压力无处不在,但几十年来的文献都是根据压力反应的大小来反向计算压力源的强度。这种因果方向性不符合逻辑,但仍然普遍存在,因为看似客观的压力指数已经产生了大量的研究结果,显示压力是如何侵入皮肤和头骨的。这就为提供明确的指导和策略来测量急性应激源强度带来了挑战。关于某件事情是否真实的二元思维阻碍了人们对如何测量压力环境剂量的理解。基于虚拟现实(VR)的应激源具有可编程、可个性化和可滴定的功能,为该领域提供了一个量化应激源剂量和生成可靠剂量-反应曲线的平台。这也为安全、合乎伦理地将社会心理应激源应用于临床和治疗提供了可能。例如,社会评价威胁实验在实验室环境和人造环境中都能有效触发应激反应,同时还能维护与护理提供者之间来之不易的信任和融洽关系。通过将注意力集中在应激源的测量上,虚拟现实范例可以促进对应激源本身和应激反应途径的切实了解。
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引用次数: 0
A systematic review and meta-analysis of nitric oxide-associated arginine metabolites in schizophrenia. 一氧化氮相关精氨酸代谢物在精神分裂症中的系统回顾和荟萃分析。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-17 DOI: 10.1038/s41398-024-03157-7
Angelo Zinellu, Sara Tommasi, Ciriaco Carru, Salvatore Sotgia, Arduino A Mangoni

There is increasing interest in the pathophysiological role of arginine metabolism in schizophrenia, particularly in relation to the modulation of the endogenous messenger nitric oxide (NO). The assessment of specific arginine metabolites that, unlike NO, are stable can provide useful insights into NO regulatory enzymes such as isoform 1 of dimethylarginine dimethylaminohydrolase (DDAH1) and arginase. We investigated the role of arginine metabolomics in schizophrenia by conducting a systematic review and meta-analysis of the circulating concentrations of arginine metabolites associated with DDAH1, arginase, and NO synthesis [arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), dimethylamine, and ornithine] in this patient group. We searched PubMed, Scopus, and Web of Science from inception to the 31st of May 2023 for studies investigating arginine metabolites in patients with schizophrenia and healthy controls. The JBI Critical Appraisal Checklist for analytical studies and GRADE were used to assess the risk of bias and the certainty of evidence, respectively (PROSPERO registration number: CRD42023433000). Twenty-one studies were identified for analysis. There were no significant between-group differences in arginine, citrulline, and SDMA. By contrast, patients with schizophrenia had significantly higher ADMA (DDAH1 substrate, standard mean difference, SMD = 1.23, 95% CI 0.86-1.61, p < 0.001; moderate certainty of evidence), dimethylamine (DDAH1 product, SMD = 0.47, 95% CI 0.24-0.70, p < 0.001; very low certainty of evidence), and ornithine concentrations (arginase product, SMD = 0.32, 95% CI 0.16-0.49, p < 0.001; low certainty of evidence). In subgroup analysis, the pooled SMD for ornithine was significantly different in studies of untreated, but not treated, patients. Our study suggests that DDAH1 and arginase are dysregulated in schizophrenia. Further studies are warranted to investigate the expression/activity of these enzymes in the brain of patients with schizophrenia and the effects of targeted treatments.

人们越来越关注精氨酸代谢在精神分裂症中的病理生理作用,尤其是与调节内源性信使一氧化氮(NO)有关的作用。与一氧化氮不同,特定精氨酸代谢物是稳定的,对其进行评估可为了解一氧化氮调控酶(如二甲基精氨酸二甲基氨水解酶同工酶 1(DDAH1)和精氨酸酶)提供有用的信息。我们通过对精神分裂症患者群体中与 DDAH1、精氨酸酶和 NO 合成相关的精氨酸代谢物 [精氨酸、瓜氨酸、不对称二甲基精氨酸 (ADMA)、对称二甲基精氨酸 (SDMA)、二甲胺和鸟氨酸] 的循环浓度进行系统回顾和荟萃分析,研究了精氨酸代谢组学在精神分裂症中的作用。我们检索了 PubMed、Scopus 和 Web of Science 从开始到 2023 年 5 月 31 日有关精神分裂症患者和健康对照组精氨酸代谢物的研究。分析研究的 JBI 关键评估清单和 GRADE 分别用于评估偏倚风险和证据的确定性(PROSPERO 注册号:CRD42023433000)。共确定了 21 项研究用于分析。精氨酸、瓜氨酸和 SDMA 在组间无明显差异。相比之下,精神分裂症患者的 ADMA(DDAH1 底物,标准均值差异,SMD = 1.23,95% CI 0.86-1.61,p
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引用次数: 0
Psychological interventions for suicidal behavior in adolescents: a comprehensive systematic review. 针对青少年自杀行为的心理干预:全面系统回顾。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-16 DOI: 10.1038/s41398-024-03132-2
Ainoa García-Fernández, Teresa Bobes-Bascarán, Clara Martínez-Cao, Leticia González-Blanco, Jennifer Fernández-Fernández, Paula Zurrón-Madera, Elisa Seijo Zazo, Luis Jiménez-Treviño, María Paz García-Portilla, Julio Bobes, Pilar A Sáiz

Background: Recent evidence indicates that the risk of death by suicide in teenagers has increased significantly worldwide. Consequently, different therapeutic interventions have been proposed for suicidal behavior in this particular population. Therefore, the main objective of this study is to provide an updated review of the existing psychological interventions for the treatment of suicide attempts (SA) in adolescents and to analyze the efficacy of such interventions.

Methods: A systematic review was conducted following PRISMA guidelines. The studies were identified by searching PubMed, PsychINFO, Web of Science, and Scopus databases from 2016 to 2022. According to the inclusion criteria, a total of 40 studies that tested the efficacy of different psychological interventions were selected.

Results: Various psychological interventions for adolescents with suicidal behaviors were identified. Most of those present promising results. However, to summarize results from recent years, dialectical behavior therapy (DBT) was the most common and the only treatment shown to be effective for adolescents at high risk of suicide and SA. In contrast, empirical evidence for other psychological interventions focusing on deliberate self-harm (SH) is inconclusive.

Conclusions: Interventions specifically designed to reduce suicidal risk in adolescents have multiplied significantly in recent years. There are a few promising interventions for reducing suicidal behaviors in adolescents evaluated by independent research groups. However, replication and dismantling studies are needed to identify the effects of these interventions and their specific components. An important future challenge is to develop brief and effective interventions to reduce the risk of death by suicide among the adolescent population.

背景:最近的证据表明,全世界青少年自杀死亡的风险显著增加。因此,针对这一特殊人群的自杀行为,人们提出了不同的治疗干预措施。因此,本研究的主要目的是对治疗青少年自杀未遂(SA)的现有心理干预措施进行最新综述,并分析这些干预措施的疗效:方法:按照 PRISMA 指南进行了系统性回顾。方法:根据PRISMA指南开展了一项系统性综述,通过检索2016年至2022年的PubMed、PsychINFO、Web of Science和Scopus数据库确定了相关研究。根据纳入标准,共筛选出40项测试不同心理干预效果的研究:结果:研究发现了针对有自杀行为的青少年的各种心理干预措施。其中大多数都取得了可喜的成果。然而,总结近年来的研究结果,辩证行为疗法(DBT)是最常见的,也是唯一被证明对高自杀风险青少年和 SA 有效的治疗方法。相比之下,其他针对蓄意自残(SH)的心理干预的经验证据并不确定:近年来,专门用于降低青少年自杀风险的干预措施大幅增加。经独立研究小组评估,有几种减少青少年自杀行为的干预措施很有希望。然而,要确定这些干预措施及其具体组成部分的效果,还需要进行复制和拆解研究。未来的一项重要挑战是制定简短有效的干预措施,以降低青少年自杀死亡的风险。
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引用次数: 0
Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study. 氯胺酮和拉莫三嗪在负面情绪处理过程中的功能活动和连接特征:一项双盲随机对照 fMRI 研究。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-14 DOI: 10.1038/s41398-024-03120-6
Marvin S Meiering, David Weigner, Matti Gärtner, Luisa Carstens, Christian Keicher, Rita Hertrampf, Christian F Beckmann, Maarten Mennes, Andreas Wunder, Anne Weigand, Simone Grimm

Ketamine is a highly effective antidepressant (AD) that targets the glutamatergic system and exerts profound effects on brain circuits during negative emotional processing. Interestingly, the effects of ketamine on brain measures are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Examining the antagonistic effects of ketamine and lamotrigine on glutamate transmission holds promise to identify effects of ketamine that are mediated through changes in the glutamatergic system. Investigating this modulation in relation to both the acute and sustained effects of ketamine on functional activity and connectivity during negative emotional processing should therefore provide novel insights. 75 healthy subjects were investigated in a double-blind, single-dose, randomized, placebo-controlled, parallel-group study with three treatment conditions (ketamine, lamotrigine pre-treatment, placebo). Participants completed an emotional face viewing task during ketamine infusion and 24 h later. Acute ketamine administration decreased hippocampal and Default Mode Network (DMN) activity and increased fronto-limbic coupling during negative emotional processing. Furthermore, while lamotrigine abolished the ketamine-induced increase in functional connectivity, it had no acute effect on activity. Sustained (24 h later) effects of ketamine were only found for functional activity, with a significant reduction in the posterior DMN. This effect was blocked by pretreatment with lamotrigine. Our results suggest that both the acute increases in fronto-limbic coupling and the delayed decrease in posterior DMN activity, but not the attenuated limbic and DMN recruitment after ketamine, are mediated by altered glutamatergic transmission.

氯胺酮是一种高效抗抑郁药(AD),它以谷氨酸能系统为靶点,在负面情绪处理过程中对大脑回路产生深远影响。有趣的是,氯胺酮对大脑测量的影响对拉莫三嗪的预处理调节很敏感,而拉莫三嗪能抑制谷氨酸的释放。通过研究氯胺酮和拉莫三嗪对谷氨酸传递的拮抗作用,有望发现氯胺酮通过谷氨酸能系统变化介导的作用。因此,研究氯胺酮在负面情绪处理过程中对功能活动和连接性的急性和持续影响时的这种调节作用,将能提供新的见解。在一项双盲、单剂量、随机、安慰剂对照、平行组研究中,75 名健康受试者接受了三种治疗条件(氯胺酮、拉莫三嗪预处理、安慰剂)的调查。受试者在氯胺酮输注期间和24小时后完成一项情绪面孔观察任务。在负性情绪处理过程中,急性氯胺酮给药降低了海马和默认模式网络(DMN)的活动,增加了前边缘耦合。此外,虽然拉莫三嗪能消除氯胺酮引起的功能连接性增加,但它对活动没有急性影响。氯胺酮的持续影响(24 小时后)只体现在功能活动上,后部 DMN 的功能活动显著减少。这种效应在使用拉莫三嗪进行预处理后被阻断。我们的研究结果表明,氯胺酮导致的前边缘耦合的急性增加和DMN后部活动的延迟减少,而不是边缘和DMN招募的减弱,是由谷氨酸能传递的改变介导的。
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引用次数: 0
Association of plasma arachidonic acid levels with a bipolar disorder and the effects of a FADS gene variant. 血浆花生四烯酸水平与双相情感障碍的关系以及 FADS 基因变异的影响。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-14 DOI: 10.1038/s41398-024-03141-1
Takuma Ashizawa, Takeo Saito, Tomo Okochi, Kohei Ninomiya, Kenta Ito, Rei Aoki, Masashi Ikeda, Nakao Iwata

Recent genome-wide association studies (GWASs) have identified fatty acid desaturase (FADS) genes, which code key enzymes involved in polyunsaturated fatty acid (PUFA) desaturation as susceptibility genes for bipolar disorder (BD). Several quantitative changes in PUFAs suggest their involvement in BD pathogenesis. Therefore, this study aimed to clarify the relationship between BD and PUFAs by conducting lipidomics covariating with the FADS gene variant (rs174550), which is associated with PUFA levels and BD susceptibility. The concentrations of 23 fatty acids were measured using plasma samples from the BD group (n = 535) and the control group (n = 107). Differences in each PUFA concentration ratio were compared between the two groups. Also, differences in each PUFA concentration ratio were compared for each genotype in rs174550. Our results showed that the BD group had significantly lower concentrations of linoleic acid (LA) (β = -0.36, p = 0.023) and arachidonic acid (AA) (β = -0.18, p = 0.013) than the control group. Concerning the effect of FADS on the PUFA concentration ratio, carriers of C-allele at rs174550 had significantly decreased γ-linolenic acid and AA concentration ratios. A previous GWAS reported that the presence of a C-allele at rs174550 increased the BD risk. This direction is consistent with the lipidomic results of the present study. In conclusion, both the FADS and BD were considered to regulate the AA concentration. Thus, as the FADS gene variant is crucial for conducting lipidomics of BD we believe that the allele frequency of FADS must be analyzed.

最近的全基因组关联研究(GWAS)发现,脂肪酸去饱和酶(FADS)基因是双相情感障碍(BD)的易感基因,该基因编码参与多不饱和脂肪酸(PUFA)去饱和的关键酶。多不饱和脂肪酸的一些定量变化表明它们与躁狂症的发病机制有关。因此,本研究旨在通过与 FADS 基因变异(rs174550)相关的脂质组学研究来阐明双相情感障碍与 PUFAs 之间的关系,因为 FADS 基因变异与 PUFA 水平和双相情感障碍易感性相关。利用 BD 组(535 人)和对照组(107 人)的血浆样本测量了 23 种脂肪酸的浓度。比较了两组之间每种 PUFA 浓度比率的差异。此外,还比较了 rs174550 各基因型的 PUFA 浓度比差异。结果显示,BD 组的亚油酸(LA)(β = -0.36,p = 0.023)和花生四烯酸(AA)(β = -0.18,p = 0.013)浓度明显低于对照组。关于 FADS 对 PUFA 浓度比的影响,rs174550 的 C-等位基因携带者的γ-亚麻酸和 AA 浓度比显著降低。之前的一项全球基因组研究报告指出,rs174550的C等位基因会增加BD风险。这一方向与本研究的脂质体结果一致。总之,FADS 和 BD 都被认为能调节 AA 浓度。因此,由于 FADS 基因变异对开展 BD 脂质组学研究至关重要,我们认为必须对 FADS 的等位基因频率进行分析。
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引用次数: 0
Divergent gene expression patterns in alcohol and opioid use disorders lead to consistent alterations in functional networks within the dorsolateral prefrontal cortex. 酒精和阿片类药物使用障碍的基因表达模式不同,导致背外侧前额叶皮层内的功能网络发生一致的改变。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-14 DOI: 10.1038/s41398-024-03143-z
Martha MacDonald, Pablo A S Fonseca, Kory R Johnson, Erin M Murray, Rachel L Kember, Henry R Kranzler, R Dayne Mayfield, Daniel da Silva

Substance Use Disorders (SUDs) manifest as persistent drug-seeking behavior despite adverse consequences, with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) representing prevalent forms associated with significant mortality rates and economic burdens. The co-occurrence of AUD and OUD is common, necessitating a deeper comprehension of their intricate interactions. While the causal link between these disorders remains elusive, shared genetic factors are hypothesized. Leveraging public datasets, we employed genomic and transcriptomic analyses to explore conserved and distinct molecular pathways within the dorsolateral prefrontal cortex associated with AUD and OUD. Our findings unveil modest transcriptomic overlap at the gene level between the two disorders but substantial convergence on shared biological pathways. Notably, these pathways predominantly involve inflammatory processes, synaptic plasticity, and key intracellular signaling regulators. Integration of transcriptomic data with the latest genome-wide association studies (GWAS) for problematic alcohol use (PAU) and OUD not only corroborated our transcriptomic findings but also confirmed the limited shared heritability between the disorders. Overall, our study indicates that while alcohol and opioids induce diverse transcriptional alterations at the gene level, they converge on select biological pathways, offering promising avenues for novel therapeutic targets aimed at addressing both disorders simultaneously.

物质使用失调症(SUD)表现为不顾不良后果的持续吸毒行为,其中酒精使用失调症(AUD)和阿片类药物使用失调症(OUD)是与高死亡率和经济负担相关的流行形式。酒精使用障碍和阿片类药物使用障碍并发的情况很常见,因此有必要深入了解它们之间错综复杂的相互作用。虽然这些疾病之间的因果联系仍然难以捉摸,但人们假设存在共同的遗传因素。利用公共数据集,我们采用了基因组和转录组分析来探索与 AUD 和 OUD 相关的背外侧前额叶皮层内的保守和独特的分子通路。我们的研究结果揭示了这两种疾病在基因水平上的适度转录组重叠,但在共同的生物通路上却有很大的趋同性。值得注意的是,这些通路主要涉及炎症过程、突触可塑性和关键的细胞内信号调节因子。将转录组数据与最新的全基因组关联研究(GWAS)相结合,不仅证实了我们的转录组发现,还证实了这两种疾病之间有限的共同遗传性。总之,我们的研究表明,虽然酒精和阿片类药物会在基因水平上诱发不同的转录改变,但它们在特定的生物通路上趋于一致,这为同时治疗这两种疾病的新型治疗靶点提供了前景广阔的途径。
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引用次数: 0
Temporal dynamics of negative emotional memory reprocessing during sleep. 睡眠中负面情绪记忆再处理的时间动态。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-13 DOI: 10.1038/s41398-024-03146-w
Serik Tabarak, Ximei Zhu, Peng Li, Frederik D Weber, Le Shi, Yimiao Gong, Kai Yuan, Yanping Bao, Tengteng Fan, Suxia Li, Jie Shi, Lin Lu, Jiahui Deng

Memory reprocessing during sleep is a well-established phenomenon in numerous studies. However, it is unclear whether the intensity of memory reprocessing is consistently maintained throughout the night or exhibits dynamic changes. This study investigates the temporal dynamics of negative emotional memory reprocessing during sleep, with a specific focus on slow oscillation (SO)-spindle coupling and its role in memory reprocessing. In the first experiment (N = 40, mean age = 22.5 years), we detected the negative emotional memory reprocessing strength in each sleep cycle, we found that the 2nd sleep cycle after negative emotional memory learning constitute the most sensitive window for memory reprocessing, furthermore, SO-spindle coupling signals in this window plays a role in stabilizing negative emotional memory. To verify the role of SO-spindle coupling in negative emotional memory reprocessing, we utilized transcranial alternating current stimulation (tACS) to disrupt SO-spindle coupling during the 2nd sleep cycle (N = 21, mean age = 19.3 years). Notably, the outcomes of the tACS intervention demonstrated a significant reduction in the recognition of negative emotional memories. These findings offer new insights into the mechanisms that regulate emotional memory consolidation during sleep and may have implications for addressing psychiatric disorders associated with pathological emotional memory.

睡眠中的记忆再加工是众多研究中公认的一种现象。然而,记忆再处理的强度是在整个夜间持续保持还是呈现动态变化,目前尚不清楚。本研究调查了睡眠中负面情绪记忆再处理的时间动态,特别关注慢振荡(SO)-纺锤体耦合及其在记忆再处理中的作用。在第一个实验中(N = 40,平均年龄 = 22.5 岁),我们检测了每个睡眠周期中负性情绪记忆再处理的强度,发现负性情绪记忆学习后的第二个睡眠周期是记忆再处理最敏感的窗口期,而且该窗口期中的慢振荡-纺锤体耦合信号在稳定负性情绪记忆中发挥作用。为了验证SO-纺锤体耦合在负性情绪记忆再处理中的作用,我们利用经颅交变电流刺激(tACS)来破坏第二个睡眠周期中的SO-纺锤体耦合(21人,平均年龄19.3岁)。值得注意的是,经颅交变电流刺激(tACS)干预的结果表明,负面情绪记忆的识别能力显著下降。这些发现为研究睡眠期间情绪记忆巩固的调节机制提供了新的视角,并可能对解决与病理性情绪记忆相关的精神疾病产生影响。
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引用次数: 0
Modulation of neural oscillations in escitalopram treatment: a Canadian biomarker integration network in depression study. 艾司西酞普兰治疗对神经振荡的调节:加拿大抑郁症生物标志物整合网络研究。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-12 DOI: 10.1038/s41398-024-03110-8
Benjamin Schwartzmann, Raaj Chatterjee, Yasaman Vaghei, Lena C Quilty, Timothy A Allen, Stephen R Arnott, Sravya Atluri, Pierre Blier, Prabhjot Dhami, Jane A Foster, Benicio N Frey, Stefan Kloiber, Raymond W Lam, Roumen Milev, Daniel J Müller, Claudio N Soares, Chloe Stengel, Sagar V Parikh, Gustavo Turecki, Rudolf Uher, Susan Rotzinger, Sidney H Kennedy, Faranak Farzan

Current pharmacological agents for depression have limited efficacy in achieving remission. Developing and validating new medications is challenging due to limited biological targets. This study aimed to link electrophysiological data and symptom improvement to better understand mechanisms underlying treatment response. Longitudinal changes in neural oscillations were assessed using resting-state electroencephalography (EEG) data from two Canadian Biomarker Integration Network in Depression studies, involving pharmacological and cognitive behavioral therapy (CBT) trials. Patients in the pharmacological trial received eight weeks of escitalopram, with treatment response defined as ≥ 50% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS). Early (baseline to week 2) and late (baseline to week 8) changes in neural oscillation were investigated using relative power spectral measures. An association was found between an initial increase in theta and symptom improvement after 2 weeks. Additionally, late increases in delta and theta, along with a decrease in alpha, were linked to a reduction in MADRS after 8 weeks. These late changes were specifically observed in responders. To assess specificity, we extended our analysis to the independent CBT cohort. Responders exhibited an increase in delta and a decrease in alpha after 2 weeks. Furthermore, a late (baseline to week 16) decrease in alpha was associated with symptom improvement following CBT. Results suggest a common late decrease in alpha across both treatments, while modulatory effects in theta may be specific to escitalopram treatment. This study offers insights into electrophysiological markers indicating a favorable response to antidepressants, enhancing our comprehension of treatment response mechanisms in depression.

目前治疗抑郁症的药物在实现缓解方面的疗效有限。由于生物靶点有限,开发和验证新药具有挑战性。本研究旨在将电生理数据与症状改善联系起来,以更好地了解治疗反应的内在机制。研究人员利用两项加拿大抑郁症生物标记物整合网络研究(包括药物治疗和认知行为治疗试验)中的静息态脑电图(EEG)数据,对神经振荡的纵向变化进行了评估。药物试验中的患者接受为期八周的艾司西酞普兰治疗,治疗反应的定义是蒙哥马利-阿斯伯格抑郁量表(MADRS)下降≥50%。研究人员使用相对功率谱测量方法调查了神经振荡的早期(基线至第 2 周)和晚期(基线至第 8 周)变化。结果发现,θ的初期增加与两周后症状改善之间存在关联。此外,delta 和 theta 的后期增加以及 alpha 的减少与 8 周后 MADRS 的降低有关。这些晚期变化在应答者中被特别观察到。为了评估特异性,我们将分析扩展到独立的 CBT 群体。反应者在 2 周后表现出 delta 增加和 alpha 减少。此外,晚期(基线至第 16 周)α下降与 CBT 后症状改善有关。研究结果表明,在两种治疗方法中,α的后期下降是共同的,而θ的调节作用可能是艾司西酞普兰治疗所特有的。这项研究深入揭示了表明对抗抑郁药物产生良好反应的电生理标志物,从而加深了我们对抑郁症治疗反应机制的理解。
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引用次数: 0
Endocannabinoid concentrations in major depression: effects of childhood maltreatment and relation to hippocampal volume. 重度抑郁症患者的内源性大麻素浓度:童年虐待的影响以及与海马体体积的关系。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-12 DOI: 10.1038/s41398-024-03151-z
Raegan Mazurka, Kate L Harkness, Stefanie Hassel, Niclas Stensson, Nikita Nogovitsyn, Jordan Poppenk, Jane A Foster, Scott D Squires, Jessie Rowe, Roumen V Milev, Katherine E Wynne-Edwards, Gustavo Turecki, Stephen C Strother, Stephen R Arnott, Raymond W Lam, Susan Rotzinger, Sidney H Kennedy, Benicio N Frey, Leah M Mayo

Evidence from preclinical animal models suggests that the stress-buffering function of the endocannabinoid (eCB) system may help protect against stress-related reductions in hippocampal volume, as is documented in major depressive disorder (MDD). However, stress exposure may also lead to dysregulation of this system. Thus, pathways from marked stress histories, such as childhood maltreatment (CM), to smaller hippocampal volumes and MDD in humans may depend on dysregulated versus intact eCB functioning. We examined whether the relation between MDD and peripheral eCB concentrations would vary as a function of CM history. Further, we examined whether eCBs moderate the relation of CM/MDD and hippocampal volume. Ninety-one adults with MDD and 62 healthy comparison participants (HCs) were recruited for a study from the Canadian Biomarker Integration Network in Depression program (CAN-BIND-04). The eCBs, anandamide (AEA) and 2-arachidonylglycerol (2-AG), were assessed from blood plasma. Severe CM history was assessed retrospectively via contextual interview. MDD was associated with eCBs, though not all associations were moderated by CM or in the direction expected. Specifically, MDD was associated with higher AEA compared to HCs regardless of CM history, a difference that could be attributed to psychotropic medications. MDD was also associated with higher 2-AG, but only for participants with CM. Consistent with hypotheses, we found lower left hippocampal volume in participants with versus without CM, but only for those with lower AEA, and not moderate or high AEA. Our study presents the first evidence in humans implicating eCBs in stress-related mechanisms involving reduced hippocampal volume in MDD.

来自临床前动物模型的证据表明,内源性大麻素(eCB)系统的压力缓冲功能可能有助于防止与压力相关的海马体积缩小,这在重度抑郁障碍(MDD)中得到了证实。然而,压力暴露也可能导致该系统失调。因此,从明显的压力史(如童年虐待(CM))到较小的海马体积和人类MDD的路径可能取决于eCB功能失调还是完好。我们研究了 MDD 与外周 eCB 浓度之间的关系是否会因 CM 历史而变化。此外,我们还研究了 eCB 是否会缓和 CM/MDD 与海马体积之间的关系。我们从加拿大抑郁症生物标记物整合网络项目(CAN-BIND-04)中招募了 91 名患有 MDD 的成人和 62 名健康对比参与者(HCs)进行研究。研究人员从血浆中评估了 eCBs、anandamide (AEA) 和 2-arachidonylglycerol (2-AG)。严重中风病史通过背景访谈进行回顾性评估。多发性抑郁症与 eCBs 有关,但并非所有的关联都会受到 CM 的调节,也并非所有的关联都会朝着预期的方向发展。具体而言,与 HCs 相比,无论是否有 CM 史,MDD 都与较高的 AEA 相关,这种差异可能是由于精神药物所致。MDD 也与较高的 2-AG 相关,但仅针对有 CM 史的参与者。与假设一致的是,我们发现患有CM的参与者与未患有CM的参与者相比,左侧海马体积较小,但只有那些AEA较低的参与者才会出现这种情况,而中度或高度AEA的参与者则不会出现这种情况。我们的研究首次在人类中提出证据,证明 eCB 与压力相关机制有关,涉及 MDD 患者海马体积的缩小。
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引用次数: 0
Glutamate concentration of medial prefrontal cortex is inversely associated with addictive behaviors: a translational study. 内侧前额叶皮层的谷氨酸浓度与成瘾行为成反比:一项转化研究。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-12 DOI: 10.1038/s41398-024-03145-x
Hui Zhou, Tiantian Hong, Xi Chen, Conghui Su, Binyu Teng, Wan Xi, Jean Lud Cadet, Yihong Yang, Fengji Geng, Yuzheng Hu

In both preclinical and clinical settings, dysregulated frontostriatal circuits have been identified as the underlying neural substrates of compulsive seeking/taking behaviors manifested in substance use disorders and behavioral addictions including internet gaming disorder (IGD). However, the neurochemical substrates for these disorders remain elusive. The lack of comprehensive cognitive assessments in animal models has hampered our understanding of neural plasticity in addiction from these models. In this study, combining data from a rat model of compulsive taking/seeking and human participants with various levels of IGD severity, we investigated the relationship between regional glutamate (Glu) concentration and addictive behaviors. We found that Glu levels were significantly lower in the prelimbic cortex (PrL) of rats after 20-days of methamphetamine self-administration (SA), compared to controls. Glu concentration after a punishment phase negatively correlated with acute drug-seeking behavior. In addition, changes in Glu levels from a drug naïve state to compulsive drug taking patterns negatively correlated with drug-seeking during both acute and prolonged abstinence. The human data revealed a significant negative correlation between Glu concentration in the dorsal anterior cingulate cortex (dACC), the human PrL counterpart, and symptoms of IGD. Interestingly, there was a positive correlation between Glu levels in the dACC and self-control, as well as mindful awareness. Further analysis revealed that the dACC Glu concentration mediated the relationship between self-control/mindful awareness and IGD symptoms. These results provide convergent evidence for a protective role of dACC/PrL in addiction, suggesting interventions to enhance dACC glutamatergic functions as a potential strategy for addiction prevention and treatment.

在临床前和临床环境中,前额纹状体回路失调已被确定为物质使用障碍和行为成瘾(包括网络游戏障碍(IGD))中强迫性寻求/摄取行为的潜在神经基质。然而,这些障碍的神经化学底物仍然难以捉摸。动物模型缺乏全面的认知评估,这阻碍了我们从这些模型中了解成瘾的神经可塑性。在本研究中,我们结合强迫性服用/寻求大鼠模型和不同严重程度 IGD 的人类参与者的数据,研究了区域谷氨酸(Glu)浓度与成瘾行为之间的关系。我们发现,与对照组相比,甲基苯丙胺自我给药 20 天后,大鼠前边缘皮层(PrL)的谷氨酸浓度明显降低。惩罚阶段后的 Glu 浓度与急性觅药行为呈负相关。此外,从药物天真状态到强迫性吸毒模式的 Glu 水平变化与急性和长期戒断期间的觅药行为呈负相关。人类数据显示,与人类PrL相对应的背侧前扣带回皮层(dACC)中的Glu浓度与IGD症状呈显著负相关。有趣的是,dACC 中的 Glu 浓度与自我控制以及心智意识之间存在正相关。进一步的分析表明,dACC Glu浓度在自我控制/正念意识与IGD症状之间起着中介作用。这些结果为dACC/PrL在成瘾中的保护作用提供了聚合证据,表明增强dACC谷氨酸能功能的干预措施是预防和治疗成瘾的一种潜在策略。
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引用次数: 0
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Translational Psychiatry
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