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Long-term cognitive training enhances fluid cognition and brain connectivity in individuals with MCI. 长期认知训练可增强 MCI 患者的流体认知能力和大脑连通性。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-23 DOI: 10.1038/s41398-024-03153-x
Elveda Gozdas, Bárbara Avelar-Pereira, Hannah Fingerhut, Lauren Dacorro, Booil Jo, Leanne Williams, Ruth O'Hara, S M Hadi Hosseini

Amnestic mild cognitive impairment (aMCI) is a risk factor for Alzheimer's disease (AD). Multi-domain cognitive training (CT) may slow cognitive decline and delay AD onset. However, most work involves short interventions, targeting single cognitive domains or lacking active controls. We conducted a single-blind randomized controlled trial to investigate the effect of a 6-month, multi-domain CT on Fluid Cognition, functional connectivity in memory and executive functioning networks (primary outcomes), and white matter microstructural properties (secondary outcome) in aMCI. Sixty participants were randomly assigned to either a multi-domain CT or crossword training (CW) group, and thirty-four participants completed the intervention. We found a significant group-by-time interaction in Fluid Cognition (p = 0.007, F (1,28) = 8.26, Cohen's d = 0.38, 95% confidence interval [CI]: 2.45-14.4), with 90% of CT patients showing post-intervention improvements (p < 0.01, Cohen's d = 0.7). The CT group also showed better post-intervention Fluid Cognition than healthy controls (HCs, N = 45, p = 0.045). Functional connectivity analyses showed a significant group-by-time interaction (Cohen's d ≥ 0.8) in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal cortex (IPC) networks. Specifically, CT displayed post-intervention increases whereas CW displayed decreases in functional connectivity. Moreover, increased connectivity strength between the left DLPFC and medial PFC was associated with improved Fluid Cognition. At a microstructural level, we observed a decline in fiber density (FD) for both groups, but the CT group declined less steeply (1.3 vs. 2%). The slower decline in FD for the CT group in several tracts, including the cingulum-hippocampus tract, was associated with better working memory. Finally, we identified regions in cognitive control and memory networks for which baseline functional connectivity and microstructural properties were associated with changes in Fluid Cognition. Long-term, multi-domain CT improves cognitive functioning and functional connectivity and delays structural brain decline in aMCI (ClinicalTrials.gov number: NCT03883308).

失忆性轻度认知障碍(aMCI)是阿尔茨海默病(AD)的一个风险因素。多领域认知训练(CT)可减缓认知能力下降,延缓阿尔茨海默病的发病。然而,大多数研究都是针对单一认知领域的短期干预,或者缺乏积极的对照。我们进行了一项单盲随机对照试验,研究为期 6 个月的多领域 CT 对 aMCI 患者的流体认知、记忆和执行功能网络的功能连接(主要结果)以及白质微结构特性(次要结果)的影响。60名参与者被随机分配到多领域CT或填字游戏训练(CW)组,34名参与者完成了干预。我们发现,在流体认知(P = 0.007,F (1,28) = 8.26,Cohen's d = 0.38,95% 置信区间 [CI]:2.45-14.4)方面,组与组之间存在明显的交互作用,90% 的 CT 患者在干预后表现出改善(P = 0.007,F (1,28) = 8.26,Cohen's d = 0.38,95% 置信区间 [CI]:2.45-14.4)。
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引用次数: 0
Association between maternal perinatal stress and depression and infant DNA methylation in the first year of life. 母亲围产期压力和抑郁与婴儿出生后第一年 DNA 甲基化之间的关系。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-22 DOI: 10.1038/s41398-024-03148-8
Sarina Abrishamcar, Beryl C Zhuang, Mara Thomas, Nicole Gladish, Julia L MacIsaac, Meaghan J Jones, Elinor Simons, Theo J Moraes, Piush J Mandhane, Jeffrey R Brook, Padmaja Subbarao, Stuart E Turvey, Edith Chen, Gregory E Miller, Michael S Kobor, Anke Hüls

Maternal stress and depression during pregnancy and the first year of the infant's life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown. Here we aim to determine whether prenatal stress and depression are associated with differences in cord blood mononuclear cell DNAm (CBMC-DNAm) in newborns (n = 119) and whether postnatal stress and depression are associated with differences in peripheral blood mononuclear cell DNAm (PBMC-DNAm) in children of 12 months of age (n = 113) from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Stress was measured using the 10-item Perceived Stress Scale (PSS) and depression was measured using the 20-item Center for Epidemiologic Studies Depression Questionnaire (CESD). Both stress and depression were measured longitudinally at 18 weeks and 36 weeks of pregnancy and six months and 12 months postpartum. We conducted epigenome-wide association studies (EWAS) using robust linear regression followed by a sensitivity analysis in which we bias-adjusted for inflation and unmeasured confounding using the bacon and cate methods. To quantify the cumulative effect of maternal stress and depression, we created composite prenatal and postnatal adversity scores. We identified a significant association between prenatal stress and differential CBMC-DNAm at 8 CpG sites and between prenatal depression and differential CBMC-DNAm at 2 CpG sites. Additionally, we identified a significant association between postnatal stress and differential PBMC-DNAm at 8 CpG sites and between postnatal depression and differential PBMC-DNAm at 11 CpG sites. Using our composite scores, we further identified 2 CpG sites significantly associated with prenatal adversity and 7 CpG sites significantly associated with postnatal adversity. Several of the associated genes, including PLAGL1, HYMAI, BRD2, and ERC2 have been implicated in adverse fetal outcomes and neuropsychiatric disorders. These data further support the finding that differential DNAm may play a role in the relationship between maternal mental health and child health.

怀孕期间和婴儿出生后第一年的产妇压力和抑郁影响着很大一部分母亲。孕产妇压力和抑郁与胎儿和儿童的不良结局以及儿童 DNA 甲基化(DNAm)差异有关。然而,孕产妇压力和抑郁与儿童不良健康结果之间的生物机制在很大程度上仍然未知。在此,我们旨在确定产前压力和抑郁是否与新生儿(n = 119)脐带血单核细胞 DNAm(CBMC-DNAm)的差异有关,以及产后压力和抑郁是否与加拿大健康婴儿纵向发展(CHILD)队列中 12 个月大儿童(n = 113)外周血单核细胞 DNAm(PBMC-DNAm)的差异有关。压力用 10 项感知压力量表 (PSS) 测量,抑郁用 20 项流行病学研究中心抑郁问卷 (CESD) 测量。压力和抑郁均在怀孕 18 周和 36 周以及产后 6 个月和 12 个月时进行纵向测量。我们使用稳健线性回归法进行了全表观基因组关联研究(EWAS),然后进行了敏感性分析,在分析中,我们使用培根法和凯特法对通货膨胀和未测量的混杂因素进行了偏差调整。为了量化母亲压力和抑郁的累积效应,我们创建了产前和产后逆境综合评分。我们发现,产前压力与 8 个 CpG 位点的 CBMC-DNAm 差异之间以及产前抑郁与 2 个 CpG 位点的 CBMC-DNAm 差异之间存在显着关联。此外,我们还发现,产后应激与 8 个 CpG 位点的 PBMC-DNAm 差异之间存在显著关联,产后抑郁与 11 个 CpG 位点的 PBMC-DNAm 差异之间存在显著关联。通过综合评分,我们进一步确定了 2 个与产前逆境显著相关的 CpG 位点和 7 个与产后逆境显著相关的 CpG 位点。包括 PLAGL1、HYMAI、BRD2 和 ERC2 在内的几个相关基因与胎儿不良结局和神经精神疾病有关。这些数据进一步支持了差异 DNAm 可能在孕产妇心理健康与儿童健康之间的关系中发挥作用这一发现。
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引用次数: 0
Resting-state brain activation patterns and network topology distinguish human sign and goal trackers. 静息态大脑激活模式和网络拓扑结构区分了人类标志和目标追踪者。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-22 DOI: 10.1038/s41398-024-03162-w
Martino Schettino, Marika Mauti, Chiara Parrillo, Ilenia Ceccarelli, Federico Giove, Antonio Napolitano, Cristina Ottaviani, Marialuisa Martelli, Cristina Orsini

The "Sign-tracker/Goal-tracker" (ST/GT) is an animal model of individual differences in learning and motivational processes attributable to distinctive conditioned responses to environmental cues. While GT rats value the reward-predictive cue as a mere predictor, ST rats attribute it with incentive salience, engaging in aberrant reward-seeking behaviors that mirror those of impulse control disorders. Given its potential clinical value, the present study aimed to map such model onto humans and investigated resting state functional magnetic resonance imaging correlates of individuals categorized as more disposed to sign-tracking or goal-tracking behavior. To do so, eye-tracking was used during a translationally informed Pavlovian paradigm to classify humans as STs (n = 36) GTs (n = 35) or as Intermediates (n = 33), depending on their eye-gaze towards the reward-predictive cue or the reward location. Using connectivity and network-based approach, measures of resting state functional connectivity and centrality (role of a node as a hub) replicated preclinical findings, suggesting a major involvement of subcortical areas in STs, and dominant cortical involvement in GTs. Overall, the study strengthens the translational value of the ST/GT model, with important implications for the early identification of vulnerable phenotypes for psychopathological conditions such as substance use disorder.

标志追踪者/目标追踪者"(ST/GT)是一种动物模型,用于研究学习和动机过程中的个体差异,这些差异可归因于对环境线索的独特条件反射。GT大鼠认为奖励预测线索只是一个预测器,而ST大鼠则认为它具有激励显著性,会做出与冲动控制障碍相似的异常奖励寻求行为。鉴于其潜在的临床价值,本研究旨在将这种模型映射到人类身上,并调查被归类为更倾向于标志追踪或目标追踪行为的个体的静息状态功能磁共振成像相关性。为此,研究人员在翻译巴甫洛夫范式中使用了眼动跟踪技术,将人类分为STs(36人)、GTs(35人)或中间人(33人),这取决于他们对奖励预测线索或奖励位置的注视情况。利用连接性和基于网络的方法,静息状态功能连接性和中心性(节点作为枢纽的作用)测量结果与临床前研究结果一致,表明STs主要涉及皮层下区域,而GTs则主要涉及皮层。总之,这项研究加强了ST/GT模型的转化价值,对早期识别药物使用障碍等精神病理学疾病的易感表型具有重要意义。
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引用次数: 0
Novel therapeutic targets for major depressive disorder related to oxidative stress identified by integrative multi-omics and multi-trait study. 通过多组学和多性状综合研究发现与氧化应激有关的重度抑郁症新治疗靶点
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-19 DOI: 10.1038/s41398-024-03126-0
Xiaojun Shao, Yuan Wang, Zhongli Geng, Guangming Liang, Xiaotong Zhu, Lu Liu, Ming Meng, Li Duan, Gang Zhu

Oxidative stress (OS) is strongly implicated in the pathophysiology of major depressive disorder (MDD) but the molecular mechanisms remain largely unknown. The purpose of this study is to identify genes related to both OS and MDD, and further to evaluate the utility of these genes as diagnostic markers and potential treatment targets. We searched datasets related to MDD from the Gene Expression Omnibus (GEO) database for differentially expressed genes (DEGs) also related to OS according to GeneCards. Bioinformatics analyses and machine learning algorithms were used to identify hub genes mediating OS-MDD interactions. A summary data-based Mendelian randomization (SMR) approach was employed to identify possible causal genes for MDD from blood tissue eQLT data. These investigations identified 32 genes mediating OS-MDD interactions, while SMR analysis identified KCNE1 (OR = 1.057, 95%CI = 1.013-1.102, P value = 0.010), MAPK3 (OR = 1.023, 95%CI = 1.004-1.043, P value = 0.020), and STIP1 (OR = 0.792, 95%CI = 0.641-0.979, P value = 0.031) as OS-related causal genes for MDD. These genes may thus serve as useful diagnostic markers and potential therapeutic targets.

氧化应激(OS)与重度抑郁症(MDD)的病理生理学密切相关,但其分子机制在很大程度上仍不为人所知。本研究的目的是找出与 OS 和 MDD 相关的基因,并进一步评估这些基因作为诊断标志物和潜在治疗靶点的效用。我们从基因表达总库(Gene Expression Omnibus,GEO)数据库中搜索了与 MDD 相关的数据集,根据 GeneCards 寻找与 OS 同样相关的差异表达基因(DEGs)。生物信息学分析和机器学习算法用于识别介导 OS-MDD 相互作用的枢纽基因。采用基于数据摘要的孟德尔随机化(SMR)方法,从血液组织eQLT数据中找出可能与MDD相关的因果基因。这些研究发现了32个介导OS-MDD相互作用的基因,而SMR分析发现KCNE1(OR = 1.057,95%CI = 1.013-1.102,P值 = 0.010)、MAPK3(OR = 1.023,95%CI = 1.004-1.043,P值 = 0.020)和STIP1(OR = 0.792,95%CI = 0.641-0.979,P值 = 0.031)是与OS相关的MDD致病基因。因此,这些基因可作为有用的诊断标记和潜在的治疗靶点。
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引用次数: 0
Longitudinal association of homocysteine with depressive and anxiety symptoms among urban adults: healthy aging in neighborhoods of diversity across the life span study. 同型半胱氨酸与城市成年人抑郁和焦虑症状的纵向联系:跨寿命多样性社区健康老龄化研究。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-19 DOI: 10.1038/s41398-024-03111-7
Michael F Georgescu, May A Beydoun, Christian A Maino Vieytes, Marie T Fanelli-Kuczmarski, Jason Ashe, Hind A Beydoun, Sharmin Hossain, Nicole Noren Hooten, Michele K Evans, Alan B Zonderman

Longitudinal associations of homocysteine (HCY) with depressive symptoms scores among urban adults remain under-studied, especially across sex, race and levels of anxiety. We examined longitudinal associations of homocysteine (HCY) with depressive symptoms scores among urban adults, before and after stratifying by sex, race and anxiety level, using data from 1460 Healthy Aging in Neighborhoods of Diversity across the Lifespan Study (HANDLS) participants aged 30-64 y at v1 (2004-2009), followed across 3 visits up to 2017. In addition to LnHcyv1, we used group-based trajectory models predicting z-transformed likelihood of greater LnHcy with age (Hcytraj). Total and domain-specific depression symptoms were scored using Center for Epidemiologic Studies Depression (CES-D) scale. Mixed-effects linear regression models and Cox proportional hazards models were utilized. A positive association was found between baseline LnHcyv1 and CES-D total scores in reduced socio-demographic- adjusted Model 1 (β (standard error [SE]) = + 2.337 (0.902), P = 0.010), a relationship slightly attenuated in fully adjusted Model 2 (Model 1 adjusting for lifestyle and health factors) with a β (SE) = + 1.825 (0.883), P = 0.039. Individuals with lower anxiety levels experienced faster CES-D domain 2 score annualized increase over time (interpersonal problems) with higher LnHcyv1 (β (SE) = 0.041 (0.018), P = 0.024). Hcytraj was linked to incident elevated depressive symptoms (CES-D total score ≥16) overall (fully adjusted model: HR = 1.09, 95% CI: 1.03-1.14, P = 0.001), particularly among women and those living in poverty. Baseline and "high trajectory" of LnHcy were positively associated with depressive symptoms and elevated depressive symptom incidence, in a sex-, race-, poverty status- and anxiety-level specific manner.

对于同型半胱氨酸(HCY)与城市成年人抑郁症状得分之间的纵向关系,尤其是不同性别、种族和焦虑程度的同型半胱氨酸与抑郁症状得分之间的纵向关系的研究仍然不足。我们研究了城市成年人中同型半胱氨酸(HCY)与抑郁症状评分的纵向关系,在按性别、种族和焦虑程度分层之前和之后,我们使用了 1460 名年龄在 30-64 岁的 "跨生命周期多样性社区健康老龄化研究"(Healthy Aging in Neighborhoods of Diversity across the Lifespan Study,HANDLS)参与者的数据,这些参与者的年龄在 v1 阶段(2004-2009 年)为 30-64 岁,我们对他们进行了 3 次随访,直至 2017 年。除了 LnHcyv1 之外,我们还使用了基于群体的轨迹模型来预测随着年龄增长 LnHcy 变大的 z 变形可能性(Hcytraj)。采用流行病学研究中心抑郁(CES-D)量表对总的和特定领域的抑郁症状进行评分。研究采用了混合效应线性回归模型和 Cox 比例危险模型。在降低社会-人口因素调整后的模型 1 中(β(标准误差 [SE])= + 2.337 (0.902),P = 0.010),基线 LnHcyv1 与 CES-D 总分之间存在正相关,在完全调整后的模型 2(模型 1 调整了生活方式和健康因素)中,这种关系略有减弱,β(标准误差)= + 1.825 (0.883),P = 0.039。焦虑水平较低的个体随着时间的推移,CES-D 领域 2 分数(人际关系问题)的年增长率较快,LnHcyv1 较高(β (SE) = 0.041 (0.018),P = 0.024)。总体而言,Hcytraj 与抑郁症状升高(CES-D 总分≥16)有关(完全调整模型:HR = 1.09,95% CI:1.03-1.14,P = 0.001),尤其是在女性和贫困人群中。LnHcy的基线和 "高轨迹 "与抑郁症状和抑郁症状发生率的升高呈正相关,具体方式与性别、种族、贫困状况和焦虑程度有关。
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引用次数: 0
Visual body size estimation in adolescent anorexia nervosa: Behavioural and neurophysiological data suggest intact visual perception and biased emotional attention. 青少年厌食症患者的视觉体型估计:行为学和神经生理学数据表明,视觉感知和情感注意存在偏差。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-18 DOI: 10.1038/s41398-024-03144-y
Hugo Romero Frausto, Isabel Rahder, Anke W Dalhoff, Kati Roesmann, Georg Romer, Markus Junghöfer, Ida Wessing

Body image disturbance is a key symptom of anorexia nervosa (AN). AN patients report body dissatisfaction and overestimate their own body size in several tasks. This study aimed to clarify whether this overestimation arises from deficits in visual perception. To this end, 36 adolescent restrictive-type AN patients and 42 matched healthy controls performed metric and depictive body size estimation (BSE) tasks. Magneto- and electroencephalography were measured during the size estimation of 66 computer-generated body pictures varying in size from underweight to overweight. AN patients versus controls showed overestimation across self-referential metric and depictive BSE tasks, but similar performance in a depictive BSE task without self-reference and similar early neurophysiological responses. Starting mid-latency (200 ms), AN patients showed relatively more neural activity in response to underweight body pictures and less neural activity in response to higher-weight body pictures in distributed brain regions. A secondary comparison of AN patients with slight vs. distinct overestimation during self-referential BSE uncovered relatively stronger neural responses to body pictures corresponding to the estimated body mass index. These results suggest that body image disturbances in adolescent restrictive-type AN patients depend on self-reference and do not represent a deficit of visual perception, but rather biased emotional attention.

身体形象障碍是神经性厌食症(AN)的一个主要症状。厌食症患者对自己的身体不满意,并在多项任务中高估了自己的体型。本研究旨在阐明这种高估是否源于视觉感知的缺陷。为此,36 名青少年限制型自闭症患者和 42 名匹配的健康对照者进行了度量和描述性体型估计(BSE)任务。在对计算机生成的 66 幅从体重不足到超重不等的人体图片进行体型估计时,对磁场和脑电图进行了测量。自闭症患者与对照组相比,在自我参照的度量和描绘性 BSE 任务中表现出高估,但在没有自我参照的描绘性 BSE 任务中表现相似,早期神经生理反应也相似。从中频(200 毫秒)开始,在分布式脑区,自闭症患者对体重不足的人体图片的神经活动相对较多,而对体重较高的人体图片的神经活动较少。对自我参照 BSE 中轻微高估与明显高估的 AN 患者进行二次比较,发现他们对与估计体重指数相对应的身体图片的神经反应相对较强。这些结果表明,青少年限制型自闭症患者的身体形象障碍取决于自我参照,并不代表视觉感知的缺陷,而是情绪注意力的偏差。
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引用次数: 0
Harnessing the sensing and stimulation function of deep brain-machine interfaces: a new dawn for overcoming substance use disorders. 利用深度脑机接口的传感和刺激功能:克服药物使用障碍的新曙光。
IF 5.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-17 DOI: 10.1038/s41398-024-03156-8
Danyang Chen, Zhixian Zhao, Jian Shi, Shengjie Li, Xinran Xu, Zhuojin Wu, Yingxin Tang, Na Liu, Wenhong Zhou, Changmao Ni, Bo Ma, Junya Wang, Jun Zhang, Li Huang, Zheng You, Ping Zhang, Zhouping Tang

Substance use disorders (SUDs) imposes profound physical, psychological, and socioeconomic burdens on individuals, families, communities, and society as a whole, but the available treatment options remain limited. Deep brain-machine interfaces (DBMIs) provide an innovative approach by facilitating efficient interactions between external devices and deep brain structures, thereby enabling the meticulous monitoring and precise modulation of neural activity in these regions. This pioneering paradigm holds significant promise for revolutionizing the treatment landscape of addictive disorders. In this review, we carefully examine the potential of closed-loop DBMIs for addressing SUDs, with a specific emphasis on three fundamental aspects: addictive behaviors-related biomarkers, neuromodulation techniques, and control policies. Although direct empirical evidence is still somewhat limited, rapid advancements in cutting-edge technologies such as electrophysiological and neurochemical recordings, deep brain stimulation, optogenetics, microfluidics, and control theory offer fertile ground for exploring the transformative potential of closed-loop DBMIs for ameliorating symptoms and enhancing the overall well-being of individuals struggling with SUDs.

药物使用失调症(SUD)给个人、家庭、社区和整个社会带来了深重的生理、心理和社会经济负担,但现有的治疗方案仍然有限。深部脑机接口(DBMI)通过促进外部设备与深部大脑结构之间的高效互动,从而实现对这些区域神经活动的细致监测和精确调节,提供了一种创新方法。这一开创性范例有望彻底改变成瘾性疾病的治疗现状。在这篇综述中,我们将仔细研究闭环 DBMIs 在治疗成瘾性疾病方面的潜力,重点关注三个基本方面:成瘾行为相关生物标记物、神经调控技术和控制策略。虽然直接的经验证据仍然有限,但是电生理和神经化学记录、深部脑刺激、光遗传学、微流控理论等前沿技术的快速发展为探索闭环 DBMI 在改善症状和提高与药物滥用作斗争的个体的整体福祉方面的变革潜力提供了肥沃的土壤。
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引用次数: 0
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
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Translational Psychiatry
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