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Static and dynamic connectivity structure of white-matter functional networks across the adult lifespan 成年期白质功能网络的静态和动态连接结构。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2025.111252
Zeqiang LinLi , Kang Hu , Qingdong Guo , Shuixia Guo
Aging of the human brain involves intricate biological processes, resulting in complex changes in structure and function. While the effects of aging on gray matter (GM) connectivity are extensively studied, white matter (WM) functional changes have received comparatively less attention. This study examines age-related WM functional dynamics using resting-state fMRI across the adult lifespan. We identified GM and WM functional networks (FNs) using k-means clustering. Static and dynamic analyses of WM functional network connectivity (FNC) were performed to explore age effects on WM-FNs and recurrent patterns of dynamic FNC. We identified 9 WM and 12 GM FNs. Age-related effects on WM FNC strength and WM-GM FNC dynamics included linear positive and U-shaped age trajectories in static FNC strength, and linear negative and inverted U-shaped trajectories in FNC temporal variability. Three distinct brain states with significant age-related differences were identified and validated. These findings were largely replicated in the validation analysis. High integration and low temporal variability in WM-GM FNC may indicate reduced adaptability of the network system in older adults, offering insights into brain aging processes.
人类大脑的衰老涉及复杂的生物过程,导致结构和功能的复杂变化。虽然衰老对灰质(GM)连通性的影响已被广泛研究,但白质(WM)功能的变化受到的关注相对较少。本研究使用静息状态功能磁共振成像检查了成人寿命中与年龄相关的WM功能动态。我们使用k-means聚类识别GM和WM功能网络(FNs)。对WM功能网络连通性(FNC)进行静态和动态分析,探讨年龄对WM- FNC的影响以及动态FNC的循环模式。我们鉴定出9个WM和12个GM FNs。年龄对WM FNC强度和WM- gm FNC动态的影响包括静态FNC强度的线性正、u型年龄轨迹,FNC时间变异性的线性负、倒u型年龄轨迹。三种不同的大脑状态与显著的年龄相关的差异被识别和验证。这些发现在验证分析中得到了很大程度上的重复。WM-GM FNC的高整合和低时间变异性可能表明老年人网络系统的适应性降低,这为大脑衰老过程提供了新的见解。
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引用次数: 0
A multimodal neuroimaging meta-analysis of functional and structural brain abnormalities in attention-deficit/hyperactivity disorder. 注意缺陷/多动障碍患者脑功能和结构异常的多模态神经影像学荟萃分析。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 Epub Date: 2024-11-29 DOI: 10.1016/j.pnpbp.2024.111199
Chao Chen, Shilin Sun, Ruoyi Chen, Zixuan Guo, Xinyue Tang, Guanmao Chen, Pan Chen, Guixian Tang, Li Huang, Ying Wang

Background: Numerous neuroimaging studies utilizing resting-state functional imaging and voxel-based morphometry (VBM) have identified variations in distinct brain regions among individuals with attention-deficit/hyperactivity disorder (ADHD). However, the results have been inconsistent.

Methods: A comprehensive voxel-wise meta-analysis was performed on studies employing resting-state functional imaging and gray matter volume (GMV), examining discrepancies between individuals with ADHD and neurotypical controls (NCs). The analysis utilized the Seed-based d Mapping software.

Results: A systematic review of the literature identified 21 functional imaging studies (595 ADHD and 564 controls) and 50 GMV studies (1907 ADHD and 1611 controls). In general, individuals with ADHD exhibited increased resting-state functional activity in the right parahippocampal gyrus and bilateral orbitofrontal cortex (OFC), as well as decreased resting-state functional activity in the bilateral cingulate cortex (including the posterior cingulate cortex [PCC], median cingulate cortex [MCC], and anterior cingulate cortex [ACC]). The VBM meta-analysis revealed decreased GMV in the bilateral OFC, right putamen (extending to right superior temporal gyrus [STG]), left inferior frontal gyrus (IFG), right superior frontal gyrus (SFG), ACC, and precentral gyrus among individuals with ADHD.

Conclusions: The multimodal meta-analyses indicated that individuals with ADHD exhibit abnormalities in both function and structure in the bilateral OFC. In addition, a few regions exhibited only functional or only structural abnormalities in ADHD, such as in the limbic, prefrontal, primary sensorimotor regions.

背景:许多利用静息状态功能成像和基于体素的形态测量(VBM)的神经影像学研究已经确定了注意缺陷/多动障碍(ADHD)患者不同大脑区域的差异。然而,结果却不一致。方法:对采用静息状态功能成像和灰质体积(GMV)的研究进行全面的体素分析,检查ADHD个体与神经典型对照组(nc)之间的差异。分析使用了基于种子的主题图像排列d映射软件。结果:系统回顾了21项功能成像研究(595例ADHD和564例对照)和50项GMV研究(1907例ADHD和1611例对照)。总体而言,ADHD个体表现出右侧海马旁回和双侧眶额皮质(OFC)静息状态功能活动增加,而双侧扣带皮层(包括后扣带皮层[PCC]、中扣带皮层[MCC]和前扣带皮层[ACC])静息状态功能活动减少。VBM meta分析显示,ADHD患者的双侧OFC、右侧壳核(延伸至右侧颞上回[STG])、左侧额下回(IFG)、右侧额上回(SFG)、ACC和中央前回的GMV下降。结论:多模态荟萃分析表明,ADHD患者在双侧OFC的功能和结构上都表现出异常。此外,ADHD患者的一些区域仅表现出功能性或结构性异常,如边缘区、前额叶区、初级感觉运动区。
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引用次数: 0
Temporoparietal structural-functional coupling abnormalities in drug-naïve first-episode major depressive disorder drug-naïve首发重度抑郁症颞顶结构-功能偶联异常。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111211
Qian Zhang , Aoxiang Zhang , Ziyuan Zhao , Qian Li , Yongbo Hu , Xiaoqi Huang , Graham J. Kemp , Weihong Kuang , Youjin Zhao , Qiyong Gong

Introduction

Major depressive disorder (MDD) is a debilitating and heterogeneous disease. Many MDD patients experience concurrent anxiety symptoms, often referred to as anxious depression (MDD-ANX). The relationships between network alterations in structural connectivity (SC) and functional connectivity (FC) in MDD and its anxiety-related subtype remain areas that require further investigation.

Methods

We investigated SC-FC coupling at the system and regional levels in 80 never-treated first-episode MDD patients and 80 healthy control (HC) subjects. For brain systems and regions showing significant between-group coupling differences, we further conducted subgroup comparisons between MDD-ANX, non-anxious depression (MDD-NANX) and HC. We also investigated topological features at the corresponding levels, and assessed the correlation patterns between significant coupling alterations and the topological and clinical characteristics.

Results

Relative to HC, MDD patients showed increased SC-FC coupling in the temporal system (right hippocampus and left superior temporal gyrus [STG]) but decreased coupling in the parietal system (right postcentral gyrus and left angular gyrus). These systems and regions were further characterized by disturbed inter-module connections and impaired structural network efficiency in MDD. Notably, SC-FC coupling of the right hippocampus was significantly increased in MDD-ANX compared to MDD-NANX, which further showed distinct correlation patterns with structural network efficiency.

Conclusions

Alterations in both SC-FC coupling and topological properties in the temporal and parietal regions provide insights into the interplay between the structural and functional network abnormalities in MDD. SC-FC coupling alterations in the right hippocampus, associated with structural nodal efficiency, may be implicated in the neuropathology of anxious depression.
重度抑郁症(MDD)是一种使人衰弱的异质性疾病。许多重度抑郁症患者会同时出现焦虑症状,通常被称为焦虑性抑郁(MDD- anx)。MDD及其焦虑相关亚型中结构连通性(SC)和功能连通性(FC)的网络改变之间的关系有待进一步研究。方法:我们在80例从未治疗过的首发MDD患者和80例健康对照(HC)中研究了系统和区域层面的SC-FC耦合。对于组间耦合差异显著的脑系统和区域,我们进一步进行了MDD-ANX、非焦虑性抑郁(MDD-NANX)和HC的亚组比较。我们还研究了相应水平的拓扑特征,并评估了显著耦合改变与拓扑和临床特征之间的相关性模式。结果:与HC相比,MDD患者颞系统(右侧海马和左侧颞上回)SC-FC偶联增强,顶叶系统(右侧中央后回和左侧角回)SC-FC偶联减弱。这些系统和区域的进一步特征是模块间连接受到干扰,结构网络效率受损。值得注意的是,与MDD-NANX相比,MDD-ANX的右侧海马SC-FC耦合显著增加,进一步显示出与结构网络效率的明显相关模式。结论:颞和顶叶区域SC-FC耦合和拓扑特性的改变为MDD的结构和功能网络异常之间的相互作用提供了见解。右侧海马体SC-FC偶联改变与结构结效率相关,可能与焦虑性抑郁的神经病理学有关。
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引用次数: 0
Comparative safety of prescribed Esketamine and ketamine in relation to renal and urinary disorders: A pharmacovigilance perspective 处方艾氯胺酮和氯胺酮治疗肾脏和泌尿系统疾病的比较安全性:药物警戒的观点。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111213
S. Chiappini , A. Guirguis , N. Schifano , J.M. Corkery , F. Semeraro , A. Mosca , G. D’Andrea , G. Duccio Papanti , D. Arillotta , G. Floresta , G. Martinotti , F. Schifano
Intranasal esketamine, approved with oral antidepressants for adults with treatment-resistant depression (TRD), is the S-enantiomer of ketamine and has higher potency and affinity for N-Methyl-d-Aspartate receptors. Administered intranasally, it offers rapid absorption and onset, essential for severe depressive symptoms or suicidal impulses. Comparative studies on esketamine and ketamine's urological safety profiles show esketamine has lower or comparable risks of renal and urinary disorders. Ketamine, however, has documented cases of nephrotoxicity and severe urological issues in recreational users.
The study aims to further evaluate and compare these profiles against other antidepressants and antipsychotics using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) data. ADR cases were reported to the FDA up to May 12, 2024, being drugs listed including esketamine, ketamine, quetiapine, aripiprazole, olanzapine, risperidone, citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine, amitriptyline, and clomipramine.
Risperidone showed the highest ADRs (107,418) and serious cases (71,515), with significant renal and urinary disorders reported, including acute kidney injury and urinary incontinence. Olanzapine, quetiapine, and aripiprazole also had high serious ADRs. Venlafaxine and fluoxetine were notable among antidepressants for acute kidney injury. Esketamine and ketamine were associated with lower urinary tract symptoms and nephrolithiasis. Disproportionality analysis revealed ketamine had higher odds of renal and urinary disorders compared to other drug classes, while esketamine had lower or comparable odds.
The data suggest a relatively favorable tolerability profile for these drugs, especially esketamine. However, the results highlight the necessity for more extensive studies to evaluate long-term safety and optimize treatment protocols.
经批准与口服抗抑郁药一起用于治疗成人难治性抑郁症(TRD)的鼻内用艾司氯胺酮是氯胺酮的S-对映体,对N-甲基-d-天冬氨酸受体具有更高的效力和亲和力。氯胺酮经鼻内给药,吸收和起效迅速,对严重抑郁症状或自杀冲动至关重要。关于埃斯氯胺酮和氯胺酮泌尿系统安全性的比较研究表明,埃斯氯胺酮引发肾脏和泌尿系统疾病的风险较低或相当。然而,氯胺酮在娱乐性使用者中却有肾毒性和严重泌尿系统问题的病例记录。这项研究旨在利用美国食品药品管理局(FDA)的不良事件报告系统(FAERS)数据,进一步评估和比较氯胺酮与其他抗抑郁药和抗精神病药的相似性。截至2024年5月12日,向FDA报告的ADR病例包括埃司氯胺酮、氯胺酮、喹硫平、阿立哌唑、奥氮平、利培酮、西酞普兰、艾司西酞普兰、帕罗西汀、氟西汀、舍曲林、度洛西汀、文拉法辛、阿米替林和氯米帕明。利培酮的不良反应(107,418 例)和严重病例(71,515 例)最多,报告的肾脏和泌尿系统疾病也最多,包括急性肾损伤和尿失禁。奥氮平、喹硫平和阿立哌唑的严重药物不良反应发生率也很高。在抗抑郁药中,文拉法辛(Venlafaxine)和氟西汀(Fluoxetine)因急性肾损伤而引人注目。艾司西汀和氯胺酮与下尿路症状和肾结石有关。比例失调分析显示,与其他类药物相比,氯胺酮发生肾脏和泌尿系统疾病的几率更高,而艾司氯胺酮的几率较低或相当。数据表明,这些药物的耐受性相对较好,尤其是艾司氯胺酮。不过,这些结果突出表明,有必要进行更广泛的研究,以评估长期安全性并优化治疗方案。
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引用次数: 0
The neuropharmacology of kratom, a novel psychoactive natural product 一种新型精神活性天然产物——克拉托姆的神经药理学。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111215
MeShell Green , Charles A. Veltri , Walter C. Prozialeck , Oliver Grundmann
Kratom (Mitragyna speciosa, Korth.) is a tropical tree that is indigenous to Southeast Asia. When ingested, kratom leaves or decoctions from the leaves have been reported to produce complex stimulant and opioid-like effects. For generations native populations in Southeast Asia have used kratom products to stave off fatigue, improve mood, alleviate pain and manage symptoms of opioid withdrawal. Over the past 15–20 years, kratom use has spread to Western nations including the United States, where many individuals are using kratom products for the self-management of pain, opioid use disorder, anxiety and depression. The increased use of kratom has triggered a surge in research into the biochemistry, pharmacology and behavioral effects of kratom and its active constituents, especially mitragynine and 7-hydroxymitragynine. In this review, we highlight some of the recent animal studies showing that kratom and its constituent compounds have potential beneficial effects in animal models of pain, anxiety, depression and opioid dependence. We also highlight studies showing that kratom can modulate the functioning of opioid, noradrenergic, serotonergic and dopaminergic systems. The highlighted studies strongly suggest that kratom and its constituents may form the basis for the development of novel therapeutic agents.
Kratom (Mitragyna speciosa, north .)是一种原产于东南亚的热带树木。据报道,当摄入时,苦参叶或苦参叶的煎剂会产生复杂的兴奋剂和阿片样物质。几代人以来,东南亚的土著居民一直使用kratom产品来缓解疲劳、改善情绪、缓解疼痛和控制阿片类药物戒断症状。在过去的15-20 年里,kratom的使用已经蔓延到包括美国在内的西方国家,在那里,许多人使用kratom产品来自我管理疼痛、阿片类药物使用障碍、焦虑和抑郁。kratom使用量的增加引发了对kratom及其活性成分的生物化学、药理学和行为影响的研究激增,特别是米特拉金和7-羟基米特拉金。在这篇综述中,我们重点介绍了最近的一些动物研究,这些研究表明克拉通及其成分化合物对疼痛、焦虑、抑郁和阿片类药物依赖的动物模型有潜在的有益作用。我们还强调研究表明,克拉通可以调节阿片,去甲肾上腺素能,血清素能和多巴胺能系统的功能。突出的研究强烈表明,克拉托姆及其成分可能成为开发新型治疗剂的基础。
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引用次数: 0
A two-sample study on the relationship between polygenic risk score of serotonergic polymorphisms and social phobia: Interpersonal adaptability as a mediator 血清素能多态性多基因风险评分与社交恐惧症关系的双样本研究:人际适应的中介作用。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111220
Yuting Yang , Qi Lan , Wenting Liang , Mingzhu Zhou , Wenping Zhao , Pingyuan Gong

Backgrounds

The influence of serotonin function on social phobia has been well-documented, yet the polygenic risk score of serotonergic polymorphisms for social phobia remains unclear.

Methods

We assessed two aspects of social phobia (i.e., social interaction anxiety and social phobia scrutiny fear) and created a polygenic risk score of seven serotonergic polymorphisms in two independent samples.

Results

The results from both samples indicated that a greater polygenic risk score, denoting a higher risk of anxiety, was associated with higher levels of social interaction anxiety and social phobia scrutinizing fear. Interestingly, the association between polygenic risk score and social interaction anxiety was mediated by interpersonal adaptability.

Conclusion

These findings demonstrate the importance of serotonergic polymorphisms in social phobia and unveil a psychological pathway whereby interpersonal adaptability mediates the effect of serotonergic polymorphisms on social phobia.
背景:血清素功能对社交恐惧症的影响已得到充分证实,但血清素能多态性对社交恐惧症的多基因风险评分仍不清楚:方法:我们评估了社交恐惧症的两个方面(即社交互动焦虑和社交恐惧症审视恐惧),并在两个独立样本中建立了七个血清素能多态性的多基因风险评分:结果:两个样本的结果表明,多基因风险得分越高,表示焦虑风险越高,则社交互动焦虑和社交恐惧症的程度越高。有趣的是,多基因风险得分与社交互动焦虑之间的关联是由人际适应性介导的:这些研究结果证明了血清素能多态性在社交恐惧症中的重要性,并揭示了人际适应性介导血清素能多态性对社交恐惧症影响的心理途径。
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引用次数: 0
Prenatal exposure to valproic acid induces sex-specific alterations in rat cortical and hippocampal neuronal structure and function in vitro 产前暴露于丙戊酸诱导大鼠皮质和海马神经元结构和功能的性别特异性改变。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111222
Olivia O.F. Williams , Madeleine Coppolino , Cecilia B. Micelli , Ryan T. McCallum , Paula T. Henry-Duru , Joshua D. Manduca , Jasmin Lalonde , Melissa L. Perreault
There are substantial differences in the characteristics of males and females with an autism spectrum disorder (ASD), yet there is little knowledge surrounding the mechanistic underpinnings of these differences. The valproic acid (VPA) rodent model is based upon the human fetal valproate spectrum disorder, which is associated with increased risk of developing ASD. This model, which displays significant social, learning, and memory alterations, has therefore been widely used to further our understanding of specific biological features of ASD. However, to date, almost all of the studies employing this model have used male rodents. To fill this knowledge gap, we evaluated sex differences for neuronal activity, morphology, and glycogen synthase kinase-3 (GSK-3) signaling in primary cortical (CTX) and hippocampal (HIP) neurons prepared from rats exposed to VPA in utero. In vivo, sex-specific VPA-induced alterations in the frontal CTX transcriptome at birth were also determined. Overall, VPA induced more robust changes in neuronal function and structure in the CTX than in the HIP. Male- and female-derived primary CTX neurons from rats exposed to prenatal VPA had elevated activity and showed more disorganized firing. In the HIP, only the female VPA neurons showed elevated firing, while the male VPA neurons exhibited disorganized activity. Dendritic arborization of CTX neurons from VPA rats was less complex in both sexes, though this was more pronounced in the females. Conversely, both female and male HIP neurons from VPA rats showed elevated complexity distal to the soma. Female VPA CTX neurons also had an elevated number of dendritic spines. The relative activity of the α and β isoforms of GSK-3 were suppressed in both female and male VPA CTX neurons, with no changes in the HIP neurons. On postnatal day 0, alterations in CTX genes associated with neuropeptides (e.g., penk, pdyn) and receptors (e.g., drd1, adora2a) were seen in both sexes, though they were downregulated in females and upregulated in males. Together these findings suggest that substantial sex differences in neuronal structure and function in the VPA model may have relevance to the reported sex differences in idiopathic ASD.
患有自闭症谱系障碍(ASD)的男性和女性在特征上有很大的差异,但对这些差异的机制基础知之甚少。丙戊酸(VPA)啮齿动物模型是基于人类胎儿丙戊酸谱系障碍,这与发展为ASD的风险增加有关。该模型显示了显著的社交、学习和记忆改变,因此被广泛用于进一步了解ASD的特定生物学特征。然而,到目前为止,几乎所有采用这种模型的研究都使用了雄性啮齿动物。为了填补这一知识空白,我们评估了在子宫内暴露于VPA的大鼠制备的初级皮质(CTX)和海马(HIP)神经元中神经元活性、形态和糖原合成酶激酶3 (GSK-3)信号传导的性别差异。在体内,还确定了出生时vpa诱导的额叶CTX转录组的性别特异性改变。总的来说,VPA在CTX中诱导的神经元功能和结构的变化比在HIP中更强大。暴露于产前VPA的大鼠的雄性和雌性原始CTX神经元活性升高,表现出更多的无组织放电。在HIP中,只有雌性VPA神经元表现出升高的放电,而雄性VPA神经元表现出紊乱的活动。VPA大鼠CTX神经元的树突树突化在两性中都不那么复杂,尽管这在雌性中更为明显。相反,雌性和雄性VPA大鼠的HIP神经元在远端胞体处都表现出更高的复杂性。雌性VPA CTX神经元的树突棘数量也有所增加。GSK-3 α和β亚型的相对活性在雌性和雄性VPA CTX神经元中均受到抑制,而在HIP神经元中无变化。在出生后第0天,与神经肽(例如,penk, pdyn)和受体(例如,drd1, adora2a)相关的CTX基因在两性中都发生了变化,尽管它们在雌性中下调,在雄性中上调。总之,这些发现表明,VPA模型中神经元结构和功能的实质性性别差异可能与报道的特发性ASD的性别差异有关。
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引用次数: 0
Multi-omics data integration reveals novel genes related to autoimmune hypothyroidism in the brain: A molecular basis for the brain–thyroid axis 多组学数据整合揭示了大脑中与自身免疫性甲状腺功能减退症有关的新基因:脑-甲状腺轴的分子基础
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111239
Hong Yu , Zuoxi Li , Xiao Gao , Xuehuan Liu , Weiwei Cui , Ningjun Li , Xinying Lian , Can Li , Jun Liu

Background

The mechanisms underlying the complex relationship between autoimmune hypothyroidism and neurological disorders remain unclear. We conducted a comprehensive analysis of associations between alternative splicing, transcriptomics, and proteomics data and autoimmune hypothyroidism.

Methods

Splicing-wide association studies (SWAS), proteome-wide association studies (PWAS), and transcriptome-wide association studies (TWAS) were used to identify genes and proteins that regulate autoimmune hypothyroidism within the brain axis. We performed TWAS on GTEx V8 thyroid tissue data to identify autoimmune hypothyroidism-associated thyroid axis genes. A FUSION analysis of overlapping genes in the brain and thyroid axes and brain splicing weights was conducted to determine the influence of alternative splicing in the brain on thyroid tissue gene expression.

Results

SWAS identified 223 alternative splicing events, TWAS identified 270 genes, and PWAS revealed five genes (FDPS, PPIL3, PEX6, MMAB, and ALDH2) encoding proteins associated with autoimmune hypothyroidism. Neuroimaging analyses revealed distinct brain-imaging phenotypes associated with these five genes. TWAS of thyroid tissue identified four genes (FDPS, PPIL3, MMAB, and ALDH2) associated with the brain axis related to thyroid tissue. A FUSION analysis indicated that alternative splicing changes in ALDH2 in brain tissue influenced its expression in thyroid tissue.

Conclusion

Integrating brain splicing, proteomic, and transcriptomic data supports the association between specific genes and proteins in the brain and autoimmune hypothyroidism. Additionally, ALDH2 alternative splicing in brain tissue influences its thyroid tissue expression. These findings provide new insights into the molecular basis of autoimmune hypothyroidism, facilitating future pathogenesis research.
背景:自身免疫性甲状腺功能减退与神经系统疾病之间复杂关系的机制尚不清楚。我们对选择性剪接、转录组学和蛋白质组学数据与自身免疫性甲状腺功能减退症之间的关联进行了全面分析。方法:采用剪接全关联研究(SWAS)、蛋白质组全关联研究(PWAS)和转录组全关联研究(TWAS)来鉴定脑轴内调节自身免疫性甲状腺功能减退症的基因和蛋白质。我们对GTEx V8甲状腺组织数据进行TWAS,以鉴定自身免疫性甲状腺功能减退相关的甲状腺轴基因。我们对脑和甲状腺轴的重叠基因和脑剪接权重进行了融合分析,以确定脑选择性剪接对甲状腺组织基因表达的影响。结果:SWAS鉴定了223个备选剪接事件,TWAS鉴定了270个基因,PWAS发现了5个基因(FDPS、PPIL3、PEX6、MMAB和ALDH2)编码与自身免疫性甲状腺功能减退症相关的蛋白。神经影像学分析揭示了与这五个基因相关的不同的脑成像表型。甲状腺组织TWAS鉴定出与甲状腺组织相关的脑轴相关的4个基因(FDPS、PPIL3、MMAB和ALDH2)。一项FUSION分析表明,脑组织中ALDH2的选择性剪接变化影响其在甲状腺组织中的表达。结论:整合脑剪接、蛋白质组学和转录组学数据支持脑中特定基因和蛋白质与自身免疫性甲状腺功能减退症之间的关联。此外,ALDH2在脑组织中的选择性剪接影响其在甲状腺组织中的表达。这些发现为自身免疫性甲状腺功能减退症的分子基础提供了新的见解,为未来的发病机制研究提供了便利。
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引用次数: 0
Structural alterations of thalamic nuclei and their associations with leptin levels in patients with anorexia nervosa 神经性厌食症患者丘脑核的结构改变及其与瘦素水平的关系。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2025.111248
Marie-Louis Wronski , Franziska Gronow , John Schlömer , Fabio Bernardoni , Daniel Geisler , Arne Doose , Dominic Arold , Nadine Schwanke , Franziska Ludwicki , Veit Roessner , Joseph A. King , Stefan Ehrlich

Background

The thalamus is a complex subcortical brain structure that plays a role in various cognitive functions. Few studies have focused on thalamic nuclei-specific alterations and potential neurohormonal involvement in eating disorders including anorexia nervosa (AN).

Methods

We employed a FreeSurfer segmentation tool to compare thalamic nuclei volumes cross-sectionally between females with AN (n = 131, 12–29 years) and age-matched healthy females (HC, n = 131). Potential associations with BMI, leptin, and psychiatric symptoms were analyzed via robust linear regression.

Results

Most thalamic nuclei volumes were reduced in both hemispheres in AN versus HC. The spread of alterations ranged between −39.7 % and +3.8 % (average −9.8 %, ηp2 = 0.16). Left laterodorsal and pulvinar inferior nuclei showed positive associations with leptin in AN. Leptin mediated the effect of BMI on both thalamic nuclei volumes.

Conclusions

In AN, thalamic nuclei are altered to different degrees with laterodorsal nuclei emerging as substantially reduced. Leptin seems to be mechanistically involved in the reduction of some thalamic nuclei, further supporting the investigation of experimental leptin treatment for AN. Effect sizes observed for thalamic nuclei reductions in AN exceed other brain structures as well as other psychiatric disorders, which demonstrates the importance of the thalamus as a target structure in research on AN.
背景:丘脑是一个复杂的大脑皮层下结构,在多种认知功能中发挥作用。很少有研究关注丘脑核特异性改变和潜在的神经激素参与饮食失调,包括神经性厌食症(AN)。方法:我们采用FreeSurfer分割工具对AN女性(n = 131, 12-29岁)和年龄匹配的健康女性(n = 131)的丘脑核体积进行横断面比较。通过稳健线性回归分析BMI、瘦素和精神症状的潜在关联。结果:与HC相比,AN在两个半球的大部分丘脑核体积减小。变异的范围为- 39.7% ~ + 3.8%(平均- 9.8%,ηp2 = 0.16)。在AN中,左鼻外侧核和枕下核与瘦素呈正相关。瘦素介导BMI对丘脑核体积的影响。结论:在AN中,丘脑核有不同程度的改变,外侧核明显减少。瘦素似乎在机制上参与了一些丘脑核的减少,进一步支持实验性瘦素治疗AN的研究。在AN中观察到的丘脑核减少的效应大小超过了其他脑结构以及其他精神疾病,这表明丘脑作为AN研究的目标结构的重要性。
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引用次数: 0
Measuring the effects of ketogenic diet on neuropsychiatric disorder: A scoping review – Letter to the Editor 测量生酮饮食对神经精神障碍的影响:范围审查-致编辑的信。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111246
Agnieszka Mechlińska, Adam Włodarczyk
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引用次数: 0
期刊
Progress in Neuro-Psychopharmacology & Biological Psychiatry
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