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Acute stress selectively blunts reward anticipation but not consumption: An ERP study 急性压力选择性地削弱了奖励预期,而不是消耗:一项ERP研究
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-11-01 DOI: 10.1016/j.ynstr.2023.100583
Wei Yi , Yantao Chen , Linlin Yan , Nils Kohn , Jianhui Wu

Stress-induced dysfunction of reward processing is documented to be a critical factor associated with mental illness. Although many studies have attempted to clarify the relationship between stress and reward, few studies have investigated the effect of acute stress on the temporal dynamics of reward processing. The present study applied event-related potentials (ERP) to examine how acute stress differently influences reward anticipation and consumption. In this study, seventy-eight undergraduates completed a two-door reward task following a Trier Social Stress Task (TSST) or a placebo task. The TSST group showed higher cortisol levels, perceived stress, anxiety, and negative affect than the control group. For the control group, a higher magnitude of reward elicited a reduced cue-N2 but increased stimulus-preceding negativity (SPN), suggesting that controls were sensitive to reward magnitude. In contrast, these effects were absent in the stress group, suggesting that acute stress reduces sensitivity to reward magnitude during the anticipatory phase. However, the reward positivity (RewP) and P3 of both groups showed similar patterns, which suggests that acute stress has no impact on reward responsiveness during the consummatory phase. These findings suggest that acute stress selectively blunts sensitivity to reward magnitude during the anticipatory rather than the consummatory phase.

应激诱导的奖励处理功能障碍是与精神疾病相关的一个关键因素。尽管许多研究试图澄清压力和奖励之间的关系,但很少有研究调查急性压力对奖励加工的时间动态的影响。本研究应用事件相关电位(ERP)研究急性应激对奖赏预期和消费的不同影响。在这项研究中,78名大学生在完成特里尔社会压力任务(TSST)或安慰剂任务后完成了双门奖励任务。与对照组相比,TSST组表现出更高的皮质醇水平、感知压力、焦虑和负面情绪。在对照组中,较高的奖励强度引起的线索- n2减少,但刺激前负性(SPN)增加,表明对照组对奖励强度敏感。相反,这些影响在应激组中不存在,这表明急性应激降低了预期阶段对奖励大小的敏感性。然而,两组的奖励积极性(RewP)和P3表现出相似的模式,这表明急性应激对完满期的奖励反应没有影响。这些发现表明,急性应激在预期阶段而不是完成阶段选择性地减弱了对奖励大小的敏感性。
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引用次数: 0
The double-edged sword of the hippocampus-ventromedial prefrontal cortex resting-state connectivity in stress susceptibility and resilience: A prospective study 海马体-腹内侧前额叶皮层静息状态连接在应激易感性和恢复力中的双刃剑:一项前瞻性研究
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-11-01 DOI: 10.1016/j.ynstr.2023.100584
Jingjing Chang , Di Song , Rongjun Yu

The hippocampus has long been considered a pivotal region implicated in both stress susceptibility and resilience. A wealth of evidence from animal and human studies underscores the significance of hippocampal functional connectivity with the ventromedial prefrontal cortex (vmPFC) in these stress-related processes. However, there remains a scarcity of research that explores and contrasts the roles of hippocampus-vmPFC connectivity in stress susceptibility and resilience when facing a real-life traumatic event from a prospective standpoint. In the present study, we investigated the contributions of undirected and directed connectivity between the hippocampus and vmPFC to stress susceptibility and resilience within the context of the COVID-19 pandemic. Our findings revealed that the left hippocampus-left vmPFC connectivity prior to the pandemic exhibited a negative correlation with both stress susceptibility and resilience. Specifically, individuals with stronger left hippocampus-left vmPFC connectivity reported experiencing fewer stress-related feelings during the outbreak period of the epidemic but displayed lower levels of stress resilience five months later. Our application of spectral dynamic causal modeling unveiled an additional inhibitory connectivity pathway from the left hippocampus to the left vmPFC in the context of stress susceptibility, which was notably absent in stress resilience. Furthermore, we observed a noteworthy positive association between self-inhibition of the vmPFC and stress susceptibility, with this effect proving substantial enough to predict an individual's susceptibility to stress; conversely, these patterns did not manifest in the realm of stress resilience. These findings enrich our comprehension of stress susceptibility and stress resilience and might have implications for innovative approaches to managing stress-related disorders.

长期以来,海马体一直被认为是影响压力敏感性和恢复力的关键区域。来自动物和人类研究的大量证据强调了海马与腹内侧前额叶皮层(vmPFC)功能连接在这些应激相关过程中的重要性。然而,从前瞻性的角度探索和对比海马体- vmpfc连接在面对现实生活创伤事件时压力易感性和恢复力中的作用的研究仍然很少。在本研究中,我们研究了在COVID-19大流行背景下,海马和vmPFC之间的定向和定向连接对应激敏感性和恢复力的贡献。我们的研究结果显示,在大流行之前,左侧海马体-左侧vmPFC的连通性与压力敏感性和恢复力都呈负相关。具体来说,左侧海马体-左侧vmPFC连通性较强的个体报告说,在疫情爆发期间,与压力相关的感受较少,但五个月后表现出较低的压力恢复能力。我们应用谱动态因果模型揭示了应激易感性背景下从左侧海马体到左侧vmPFC的额外抑制连接通路,这在应激恢复力中是明显缺失的。此外,我们观察到vmPFC的自我抑制与压力易感性之间存在显著的正相关,这种影响足以预测个体对压力的易感性;相反,这些模式并没有在压力恢复能力领域表现出来。这些发现丰富了我们对压力易感性和压力恢复力的理解,并可能对管理压力相关疾病的创新方法产生影响。
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引用次数: 0
Controlling intrusive thoughts of future fears under stress 在压力下控制对未来恐惧的侵入性想法
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-11-01 DOI: 10.1016/j.ynstr.2023.100582
Stephanie M. Ashton , Tom Smeets , Conny W.E.M. Quaedflieg

Negative outlooks of our future may foster unwanted and intrusive thoughts. To some extent, individuals have control over their ability to suppress intrusions and downregulate their frequency. Acute stress impairs intentional suppression, leading to an increased frequency of intrusions. The aim of this study was to gain insight into the mechanism underlying stress-induced impairments in intentional suppression of intrusions by investigating the combined and independent roles of the two major stress hormones, noradrenaline and cortisol. Healthy participants (N = 181) were administered propranolol (to block the noradrenergic response), metyrapone (to block the cortisol response), or a placebo before being exposed to the Maastricht Acute Stress Test. Intrusive thoughts of autobiographical future fears were then measured via the Imagine/No-Imagine task. Results demonstrated that the stress response was successfully altered because of the drug and stress manipulations. In all groups, repeated suppression of future fears reduced intrusions. Across the sample, an enhanced decrease over time was associated with greater attenuation of anxiety towards the related fears. The groups did not differ in the total frequency of intrusions. Though, trait anxiety increased the total number of intrusions. Our findings show that stress hormones did not influence the ability to suppress intrusions. However, our results do add support to previous research linking anxiety to memory control deficits. When using autobiographical content, future research should focus on the quality and characteristics of the individual memories to explain more of the variation observed in intentional memory control.

对未来的消极看法可能会滋生不想要的和侵入性的想法。在某种程度上,个体可以控制自己抑制干扰和下调频率的能力。急性应激损害有意抑制,导致入侵频率增加。本研究的目的是通过研究两种主要应激激素去甲肾上腺素和皮质醇的联合和独立作用,来深入了解应激诱导的损伤在故意抑制入侵中的机制。健康参与者(N = 181)在接受马斯特里赫特急性压力测试之前被给予心得安(阻断去甲肾上腺素能反应)、美替拉酮(阻断皮质醇反应)或安慰剂。然后通过想象/不想象任务测量自传式未来恐惧的侵入性想法。结果表明,由于药物和压力的操纵,应激反应成功地改变了。在所有的小组中,反复抑制对未来的恐惧减少了干扰。在整个样本中,随着时间的推移,这种增强的减少与对相关恐惧的焦虑的更大衰减有关。两组在入侵的总频率上没有差异。然而,特质焦虑增加了入侵的总数。我们的研究结果表明,应激激素不影响抑制入侵的能力。然而,我们的结果确实支持了先前将焦虑与记忆控制缺陷联系起来的研究。当使用自传体内容时,未来的研究应该关注个体记忆的质量和特征,以解释在有意记忆控制中观察到的更多变化。
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引用次数: 0
Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats 产前感染和青少年社会逆境对雄性大鼠小胶质细胞、突触密度和行为的影响
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-10-19 DOI: 10.1016/j.ynstr.2023.100580
Cyprien G.J. Guerrin , Kavya Prasad , Daniel A. Vazquez-Matias , Jing Zheng , Maria Franquesa-Mullerat , Lara Barazzuol , Janine Doorduin , Erik F.J. de Vries

Maternal infection during pregnancy and childhood social trauma have been associated with neurodevelopmental and affective disorders, such as schizophrenia, autism spectrum disorders, bipolar disorder and depression. These disorders are characterized by changes in microglial cells, which play a notable role in synaptic pruning, and synaptic deficits. Here, we investigated the effect of prenatal infection and social adversity during adolescence – either alone or in combination – on behavior, microglia, and synaptic density. Male offspring of pregnant rats injected with poly I:C, mimicking prenatal infection, were exposed to repeated social defeat during adolescence. We found that maternal infection during pregnancy prevented the reduction in social behavior and increase in anxiety induced by social adversity during adolescence. Furthermore, maternal infection and social adversity, alone or in combination, induced hyperlocomotion in adulthood. Longitudinal in vivo imaging with [11C]PBR28 positron emission tomography revealed that prenatal infection alone and social adversity during adolescence alone induced a transient increase in translocator protein TSPO density, an indicator of glial reactivity, whereas their combination induced a long-lasting increase that remained until adulthood. Furthermore, only the combination of prenatal infection and social adversity during adolescence induced an increase in microglial cell density in the frontal cortex. Prenatal infection increased proinflammatory cytokine IL-1β protein levels in hippocampus and social adversity reduced anti-inflammatory cytokine IL-10 protein levels in hippocampus during adulthood. This reduction in IL-10 was prevented if rats were previously exposed to prenatal infection. Adult offspring exposed to prenatal infection or adolescent social adversity had a higher synaptic density in the frontal cortex, but not hippocampus, as evaluated by synaptophysin density. Interestingly, such an increase in synaptic density was not observed in rats exposed to the combination of prenatal infection and social adversity, perhaps due to the long-lasting increase in microglial density, which may lead to an increase in microglial synaptic pruning. These findings suggest that changes in microglia activity and cytokine release induced by prenatal infection and social adversity during adolescence may be related to a reduced synaptic pruning, resulting in a higher synaptic density and behavioral changes in adulthood.

妊娠期和儿童期的母亲感染社会创伤与神经发育和情感障碍有关,如精神分裂症、自闭症谱系障碍、双相情感障碍和抑郁症。这些疾病的特征是小胶质细胞的变化,小胶质细胞在突触修剪和突触缺陷中发挥着显著作用。在这里,我们研究了产前感染和青春期社会逆境(单独或联合)对行为、小胶质细胞和突触密度的影响。注射poly I:C的怀孕大鼠的雄性后代,模仿产前感染,在青春期暴露于反复的社会失败中。我们发现,怀孕期间的母亲感染阻止了青春期社会逆境引起的社交行为的减少和焦虑的增加。此外,母亲感染和社会逆境,无论是单独还是组合,都会导致成年后的过度运动。[11C]PBR28正电子发射断层扫描的纵向体内成像显示,单独的产前感染和青春期的社会逆境诱导了转运蛋白TSPO密度的短暂增加,TSPO密度是神经胶质反应性的指标,而它们的组合诱导了持续到成年的长期增加。此外,只有产前感染和青春期社会逆境的结合才导致额叶皮层小胶质细胞密度增加。在成年期,产前感染增加了海马中的促炎细胞因子IL-1β蛋白水平,而社会逆境降低了海马中抗炎细胞因子IL-10蛋白水平。如果大鼠先前暴露于产前感染,则可以防止IL-10的这种减少。根据突触素密度评估,暴露于产前感染或青少年社会逆境的成年后代额叶皮层的突触密度较高,但海马体的突触密度不高。有趣的是,在暴露于产前感染和社会逆境的大鼠中没有观察到突触密度的这种增加,可能是由于小胶质细胞密度的长期增加,这可能导致小胶质细胞突触修剪的增加。这些发现表明,产前感染和青春期社会逆境诱导的小胶质细胞活性和细胞因子释放的变化可能与突触修剪减少有关,从而导致成年后突触密度和行为变化增加。
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引用次数: 0
High emotional reactivity is associated with activation of a molecularly distinct hippocampal-amygdala circuit modulated by the glucocorticoid receptor 高情绪反应性与糖皮质激素受体调节的分子不同的海马杏仁核回路的激活有关
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-10-16 DOI: 10.1016/j.ynstr.2023.100581
Qiang Wei , Vivek Kumar , Shannon Moore, Fei Li, Geoffrey G. Murphy, Stanley J. Watson , Huda Akil

Emotions are characterized not only by their valence but also by whether they are stable or labile. Yet, we do not understand the molecular or circuit mechanisms that control the dynamic nature of emotional responses. We have shown that glucocorticoid receptor overexpression in the forebrain (GRov) leads to a highly reactive mouse with increased anxiety behavior coupled with greater swings in emotional responses. This phenotype is established early in development and persists into adulthood. However, the neural circuitry mediating this lifelong emotional lability remains unknown. In the present study, optogenetic stimulation in ventral dentate gyrus (vDG) of GRov mice led to a greater range and a prolonged duration of anxiety behavior. cFos expression analysis showed that the amplified behavioral response to vDG activation in GRov mice is coupled to increased neuronal activity in specific brain regions. Relative to wild type mice, GRov mice displayed glutamatergic/GABAergic activation imbalance in ventral CA1 (vCA1) and selectively increased glutamatergic activation in the basal posterior amygdaloid complex. Moreover, forebrain GR overexpression led to increased activation of molecularly distinct subpopulations of neurons within the hippocampus and the posterior basolateral amygdala (pBLA) as evident from the increased cFos co-labeling in the calbindin1+ glutamatergic neurons in vCA1 and in the DARPP-32/Ppp1r1b+ glutamatergic neurons in pBLA. We propose that a molecularly distinct hippocampal-amygdala circuit is shaped by stress early in life and tunes the dynamics of emotional responses.

情绪的特征不仅在于它们的价态,还在于它们是稳定的还是不稳定的。然而,我们不了解控制情绪反应动态性质的分子或电路机制。我们已经表明,前脑中的糖皮质激素受体过度表达(GRov)会导致高度反应性小鼠焦虑行为增加,情绪反应波动更大。这种表型在发育早期就形成了,并一直持续到成年。然而,介导这种终生情绪不稳定的神经回路仍然未知。在本研究中,GRov小鼠腹侧齿状回(vDG)的光遗传学刺激导致焦虑行为的范围更大,持续时间更长。cFos表达分析表明,GRov小鼠对vDG激活的放大行为反应与特定脑区神经元活性的增加有关。与野生型小鼠相比,GRov小鼠在腹侧CA1(vCA1)表现出谷氨酸能/GABA能激活失衡,并选择性增加基底后杏仁核复合体的谷氨酸能激活。此外,前脑GR过表达导致海马和后基底外侧杏仁核(pBLA)内神经元的分子不同亚群的激活增加,这从vCA1中的钙结合蛋白1+谷氨酸能神经元和pBLA中的DARPP-32/Pp1r1b+谷氨酸能神经元中的cFos共标记增加中可以明显看出。我们提出,一个分子上不同的海马杏仁核回路是由生命早期的压力形成的,并调节情绪反应的动力学。
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引用次数: 0
Epigenetic age acceleration as a biomarker for impaired cognitive abilities in adulthood following early life adversity and psychiatric disorders 表观遗传年龄加速作为成年早期生活逆境和精神障碍后认知能力受损的生物标志物
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-10-15 DOI: 10.1016/j.ynstr.2023.100577
John M. Felt , Natan Yusupov , Karra D. Harrington , Julia Fietz , Zhenyu “Zach” Zhang , Martin J. Sliwinski , Nilam Ram , Kieran J. O'Donnell , BeCOME Working Group , Michael J. Meaney , Frank W. Putnam , Jennie G. Noll , Elisabeth B. Binder , Chad E. Shenk

Background

Early life adversity and psychiatric disorders are associated with earlier declines in neurocognitive abilities during adulthood. These declines may be preceded by changes in biological aging, specifically epigenetic age acceleration, providing an opportunity to uncover genome-wide biomarkers that identify individuals most likely to benefit from early screening and prevention.

Methods

Five unique epigenetic age acceleration clocks derived from peripheral blood were examined in relation to latent variables of general and speeded cognitive abilities across two independent cohorts: 1) the Female Growth and Development Study (FGDS; n = 86), a 30-year prospective cohort study of substantiated child sexual abuse and non-abused controls, and 2) the Biological Classification of Mental Disorders study (BeCOME; n = 313), an adult community cohort established based on psychiatric disorders.

Results

A faster pace of biological aging (DunedinPoAm) was associated with lower general cognitive abilities in both cohorts and slower speeded abilities in the BeCOME cohort. Acceleration in the Horvath clock was significantly associated with slower speeded abilities in the BeCOME cohort but not the FGDS. Acceleration in the Hannum clock and the GrimAge clock were not significantly associated with either cognitive ability. Accelerated PhenoAge was associated with slower speeded abilities in the FGDS but not the BeCOME cohort.

Conclusions

The present results suggest that epigenetic age acceleration has the potential to serve as a biomarker for neurocognitive decline in adults with a history of early life adversity or psychiatric disorders. Estimates of epigenetic aging may identify adults at risk of cognitive decline that could benefit from early neurocognitive screening.

背景早期生活中的逆境和精神障碍与成年期神经认知能力的早期下降有关。在这些下降之前,生物衰老可能会发生变化,特别是表观遗传学年龄加速,这为揭示全基因组生物标志物提供了机会,这些生物标志物可以识别最有可能从早期筛查和预防中受益的个体。方法在两个独立的队列中,检测了来自外周血的五个独特的表观遗传学年龄加速时钟与一般和加速认知能力的潜在变量的关系:1)女性生长发育研究(FGDS;n=86),这是一项为期30年的前瞻性队列研究,对证实的儿童性虐待和非虐待对照进行研究,和2)精神障碍生物学分类研究(BeCOME;n=313),一个基于精神障碍建立的成人社区队列。结果生物衰老速度较快(DunedinPoAm)与两个队列中较低的一般认知能力和BeCOME队列中较慢的加速能力有关。Horvath时钟的加速与BeCOME队列中较慢的加速能力显著相关,但与FGDS无关。Hannum时钟和GrimAge时钟的加速与这两种认知能力都没有显著关联。在FGDS中,加速表型年龄与较慢的加速能力有关,但在BeCOME队列中则不然。结论目前的研究结果表明,表观遗传年龄加速有可能成为有早期生活逆境或精神障碍史的成年人神经认知能力下降的生物标志物。表观遗传学衰老的估计可能会识别出有认知能力下降风险的成年人,这可能受益于早期神经认知筛查。
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引用次数: 0
Psychosocial stress-induced intestinal permeability in healthy humans: What is the evidence? 健康人的心理社会压力引起的肠道通透性:证据是什么?
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-10-06 DOI: 10.1016/j.ynstr.2023.100579
Danique La Torre , Lukas Van Oudenhove , Tim Vanuytsel , Kristin Verbeke

An impaired intestinal barrier function can be detrimental to the host as it may allow the translocation of luminal antigens and toxins into the subepithelial tissue and bloodstream. In turn, this may cause local and systemic immune responses and lead to the development of pathologies. In vitro and animal studies strongly suggest that psychosocial stress is one of the factors that can increase intestinal permeability via mast-cell dependent mechanisms. Remarkably, studies have not been able to yield unequivocal evidence that such relation between stress and intestinal permeability also exists in (healthy) humans. In the current Review, we discuss the mechanisms that are involved in stress-induced intestinal permeability changes and postulate factors that influence these alterations and that may explain the translational difficulties from in vitro and animal to human studies. As human research differs highly from animal research in the extent to which stress can be applied and intestinal permeability can be measured, it remains difficult to draw conclusions about the presence of a relation between stress and intestinal permeability in (healthy) humans. Future studies should bear in mind these difficulties, and more research into in vivo methods to assess intestinal permeability are warranted.

肠道屏障功能受损可能对宿主有害,因为它可能会使管腔抗原和毒素转移到上皮下组织和血液中。反过来,这可能会引起局部和系统免疫反应,并导致病理的发展。体外和动物研究强烈表明,心理社会压力是通过肥大细胞依赖机制增加肠道通透性的因素之一。值得注意的是,研究未能得出明确的证据,证明压力和肠道通透性之间的关系也存在于(健康)人类中。在目前的综述中,我们讨论了应激诱导的肠道通透性变化的机制,以及影响这些变化的假设因素,这些因素可能解释了从体外和动物到人类研究的转化困难。由于人类研究与动物研究在施加压力和测量肠道通透性的程度上有很大不同,因此很难得出关于(健康)人类压力与肠道通透性之间存在关系的结论。未来的研究应该考虑到这些困难,有必要对评估肠道通透性的体内方法进行更多的研究。
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引用次数: 0
Pre-COVID brain network topology prospectively predicts social anxiety alterations during the COVID-19 pandemic COVID-19前大脑网络拓扑可预测COVID-19大流行期间社交焦虑的变化
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-10-01 DOI: 10.1016/j.ynstr.2023.100578
Qingyuan Li , Xun Zhang , Xun Yang , Nanfang Pan , Xiao Li , Graham J. Kemp , Song Wang , Qiyong Gong

Background

Social anxiety (SA) is a negative emotional response that can lead to mental health issues, which some have experienced during the coronavirus disease 2019 (COVID-19) pandemic. Little attention has been given to the neurobiological mechanisms underlying inter-individual differences in SA alterations related to COVID-19. This study aims to identify neurofunctional markers of COVID-specific SA development.

Methods

110 healthy participants underwent resting-state magnetic resonance imaging and behavioral tests before the pandemic (T1, October 2019 to January 2020) and completed follow-up behavioral measurements during the pandemic (T2, February to May 2020). We constructed individual functional networks and used graph theoretical analysis to estimate their global and nodal topological properties, then used Pearson correlation and partial least squares correlations examine their associations with COVID-specific SA alterations.

Results

In terms of global network parameters, SA alterations (T2-T1) were negatively related to pre-pandemic brain small-worldness and normalized clustering coefficient. In terms of nodal network parameters, SA alterations were positively linked to a pronounced degree centrality pattern, encompassing both the high-level cognitive networks (dorsal attention network, cingulo-opercular task control network, default mode network, memory retrieval network, fronto-parietal task control network, and subcortical network) and low-level perceptual networks (sensory/somatomotor network, auditory network, and visual network). These findings were robust after controlling for pre-pandemic general anxiety, other stressful life events, and family socioeconomic status, as well as by treating SA alterations as categorical variables.

Conclusions

The individual functional network associated with SA alterations showed a disrupted topological organization with a more random state, which may shed light on the neurobiological basis of COVID-related SA changes at the network level.

背景社交焦虑(SA)是一种负面情绪反应,可能导致心理健康问题,一些人在2019冠状病毒病(新冠肺炎)大流行期间曾经历过这种情况。很少关注与新冠肺炎相关的SA改变个体间差异的神经生物学机制。本研究旨在确定新冠肺炎特异性SA发展的神经功能标志物。方法110名健康参与者在疫情前(2019年10月T1至2020年1月)接受了静息状态磁共振成像和行为测试,并在疫情期间(2020年2月T2至5月)完成了后续行为测量。我们构建了单个函数网络,并使用图论分析来估计它们的全局和节点拓扑性质,然后使用Pearson相关性和偏最小二乘相关性来检查它们与新冠病毒特异性SA变化的关联。结果在全局网络参数方面,SA改变(T2-T1)与疫情前大脑小世界度和归一化聚类系数呈负相关。在节点网络参数方面,SA的改变与显著的程度中心性模式呈正相关,包括高级认知网络(背侧注意网络、扣带回盖任务控制网络、默认模式网络、记忆检索网络、额顶叶任务控制网络和皮层下网络)和低级感知网络(感觉/体动网络、听觉网络和视觉网络)。在控制了疫情前的普遍焦虑、其他压力生活事件和家庭社会经济地位,并将SA变化视为分类变量后,这些发现是有力的。结论与SA改变相关的个体功能网络表现出一种更随机的拓扑组织破坏,这可能为新冠肺炎相关SA改变在网络水平上的神经生物学基础提供线索。
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引用次数: 0
Greater maltreatment severity is associated with smaller brain volume with implication for intellectual ability in young children 虐待程度越严重,大脑体积越小,这对幼儿的智力有影响。
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-09-23 DOI: 10.1016/j.ynstr.2023.100576
Judith Joseph , Claudia Buss , Andrea Knop , Karin de Punder , Sibylle M. Winter , Birgit Spors , Elisabeth Binder , John-Dylan Haynes , Christine Heim

Background

Childhood maltreatment profoundly alters trajectories of brain development, promoting markedly increased long-term health risks and impaired intellectual development. However, the immediate impact of maltreatment on brain development in children and the extent to which altered global brain volume contributes to intellectual development in children with maltreatment experience is currently unknown. We here utilized MRI data obtained from children within 6 months after the exposure to maltreatment to assess the association of maltreatment severity with global brain volume changes. We further assessed the association between maltreatment severity and intellectual development and tested for the mediating effect of brain volume on this association.

Method

We used structural MRI (3T) in a sample of 49 children aged 3–5 years with maltreatment exposure, i.e. emotional and physical abuse and/or neglect within 6 months, to characterize intracranial and tissue-specific volumes. Maltreatment severity was coded using the Maternal Interview for the Classification of Maltreatment. IQ was tested at study entry and after one year using the Snijders Oomen Nonverbal Test.

Results

Higher maltreatment severity was significantly correlated with smaller intracranial volume (r = -.393, p = .008), which was mainly driven by lower total brain volume (r = -.393, p = .008), which in turn was primarily due to smaller gray matter volume (r = -.454, p = .002). Furthermore, smaller gray matter volume was associated with lower IQ at study entry (r = -.548, p < .001) and predicted IQ one year later (r = -.493, p = .004). The observed associations were independent of potential confounding variables, including height, socioeconomic status, age and sex.

Importance

We provide evidence that greater maltreatment severity in early childhood is related to smaller brain size at a very young age with significant consequences for intellectual ability, likely setting a path for far-reaching long-term disadvantages. Insights into the molecular and neural processes that underlie the impact of maltreatment on brain structure and function are urgently needed to derive mechanism-driven targets for early intervention.

背景:儿童时期的虐待严重改变了大脑发育的轨迹,导致长期健康风险显著增加,智力发育受损。然而,目前尚不清楚虐待对儿童大脑发育的直接影响,以及有虐待经历的儿童的整体大脑容量变化在多大程度上促进了智力发育。在这里,我们利用从暴露于虐待后6个月内的儿童身上获得的MRI数据来评估虐待严重程度与整体脑容量变化的关系。我们进一步评估了虐待严重程度与智力发展之间的关系,并测试了脑容量对这种关系的中介作用。方法:我们对49名3-5岁的虐待儿童(即6个月内的情感和身体虐待和/或忽视)进行了结构MRI(3T),以表征颅内和组织特异性体积。使用母亲访谈法对虐待行为的严重程度进行编码。在研究开始时和一年后使用Snijders-Oomen非言语测试对IQ进行了测试,研究开始时,灰质体积越小,智商越低(r=-0.548,p=0.004)。观察到的相关性与潜在的混杂变量无关,包括身高、社会经济地位、年龄和性别。重要性:我们提供的证据表明,儿童早期虐待的严重程度越高,与很小的时候大脑体积越小有关,这对智力产生了重大影响,可能会导致深远的长期不利影响。迫切需要深入了解虐待对大脑结构和功能影响的分子和神经过程,以获得早期干预的机制驱动目标。
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引用次数: 0
Chronic stress promotes basal ganglia disinhibition by increasing the excitatory drive of direct-pathway neurons 慢性应激通过增加直接通路神经元的兴奋驱动来促进基底神经节的去抑制
IF 5 2区 医学 Q1 NEUROSCIENCES Pub Date : 2023-09-22 DOI: 10.1016/j.ynstr.2023.100571
Diana Rodrigues , Patricia Monteiro

Chronic stress (CS) is a well-recognized triggering factor in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS), two neuropsychiatric disorders characterized by the presence of stereotypic motor symptoms. Planning and execution of motor actions are controlled by the dorsal striatum, a brain region that promotes or suppresses motor movement by activating striatal neurons from the direct- or indirect-pathway, respectively. Despite the dorsal striatum being affected in motor disorders and by CS exposure, how CS affects the two opposing pathways is not fully understood. Here, we report that CS in mice selectively potentiates the direct-pathway, while sparing the indirect-pathway. Specifically, we show that CS both increases excitation and reduces inhibition over direct-pathway neurons in the dorsomedial striatum (DMS). Furthermore, inhibitory interneurons located in the DMS also display reduced excitatory drive after chronic stress, thus amplifying striatal disinhibition. Altogether, we propose a model where both increased excitatory drive and decreased inhibitory drive in the striatum causes disinhibition of basal ganglia's motor direct pathway - a mechanism that might explain the emergence of motor stereotypies and tic disorders under stress.

慢性压力(CS)是公认的强迫症(OCD)和抽动秽语综合征(TS)的触发因素,这两种神经精神疾病的特征是存在刻板的运动症状。运动动作的计划和执行由背侧纹状体控制,背侧纹状体是一个大脑区域,通过分别从直接或间接途径激活纹状体神经元来促进或抑制运动。尽管背侧纹状体在运动障碍和CS暴露中受到影响,但CS如何影响两种相反的途径尚不完全清楚。在这里,我们报道了CS在小鼠中选择性地增强直接途径,同时保留间接途径。具体而言,我们发现CS既增加了对背内侧纹状体(DMS)直接通路神经元的兴奋,又减少了对其的抑制。此外,位于DMS中的抑制性中间神经元在慢性应激后也表现出兴奋性驱动减弱,从而增强纹状体的去抑制作用。总之,我们提出了一个模型,在该模型中,纹状体中兴奋性驱动的增加和抑制性驱动的减少都会导致基底神经节运动直接通路的去抑制,这一机制可能解释了压力下运动刻板印象和抽动障碍的出现。
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引用次数: 0
期刊
Neurobiology of Stress
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