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Clinical and biological markers of electroconvulsive therapy effectiveness: a narrative review. 电休克治疗有效性的临床和生物学标志物:叙述性回顾。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-10 DOI: 10.1038/s41398-026-03900-2
David Zilles-Wegner, Iven-Alex von Mücke-Heim, Antoine Yrondi, Akihiro Takamiya

Electroconvulsive therapy (ECT) is the most effective treatment for several particularly severe or pharmacotherapy-resistant psychiatric disorders, and a growing number of studies have investigated factors influencing the effectiveness of ECT. The objective of this article is to review the current evidence on clinical and biological markers potentially related to response to ECT and to outline perspectives for future research. In depressive disorders, the presence of clinical characteristics such as higher age, psychotic and psychomotor symptoms, and the absence of comorbid personality disorders are associated with a particularly good response to ECT. However, these clinical factors alone explain only a part of the variance of treatment outcome. Biomarkers at the genetic/epigenetic, immune inflammatory, and brain imaging levels are now providing promising and, in part, converging findings on both the mechanism of action and predictors of response to ECT. Taken together, these findings suggest a close relationship between specific clinical symptoms, the immune inflammatory, and neuroplastic mechanisms of ECT. While genetic studies consistently indicate a higher genetic risk load in patients referred for ECT, findings regarding the predictive value of polygenic risk scores and also epigenetic markers for ECT response remain inconsistent. In the future, combining clinical features and biomarkers could help define subgroups of psychiatric disorders with distinct pathophysiology and reliably predict treatment outcomes at the individual patient level. For now, it may be assumed that different and possibly age-dependent prototypical forms of depressive disorders exist, which are characterized by specific clinical (psychotic and psychomotor symptoms) and inflammatory markers (higher levels of IL-6 and CRP) and show a differential response to treatment modalities.

电惊厥治疗(ECT)是几种特别严重或药物治疗难治性精神疾病最有效的治疗方法,越来越多的研究调查了影响ECT疗效的因素。本文的目的是回顾目前的临床和生物学标志物可能与ECT反应相关的证据,并概述未来研究的前景。在抑郁症中,临床特征的存在,如年龄较大,精神病和精神运动症状,以及无共病人格障碍,与ECT的良好反应相关。然而,这些临床因素本身只能解释部分治疗结果的差异。遗传/表观遗传、免疫炎症和脑成像水平的生物标志物目前在ECT的作用机制和反应预测方面提供了有希望的发现,并且在一定程度上趋同于这些发现。综上所述,这些发现提示在特定的临床症状、免疫炎症和ECT的神经可塑性机制之间存在密切的关系。虽然遗传学研究一致表明,接受ECT治疗的患者存在较高的遗传风险负荷,但关于多基因风险评分和表观遗传标记对ECT反应的预测价值的发现仍不一致。在未来,结合临床特征和生物标志物可以帮助定义具有不同病理生理学的精神疾病亚群,并在个体患者水平上可靠地预测治疗结果。目前,可以假设存在不同且可能与年龄相关的抑郁症原型形式,其特征是特定的临床(精神病和精神运动症状)和炎症标志物(较高水平的IL-6和CRP),并对治疗方式表现出不同的反应。
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引用次数: 0
Understanding betel nut addiction: a review of harmful consequences, underlying neurobiology, and emerging intervention strategies. 了解槟榔成瘾:有害后果的回顾,潜在的神经生物学,和新兴的干预策略。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-09 DOI: 10.1038/s41398-026-03875-0
Mengying Shao, Lizhen Zhuang, Saifei Xie, Taohua Pan, Yan Xie, Shuhang Fan, Jincai Guo, Hui Xie

Betel nut is the fourth most commonly used psychoactive substance globally and is particularly prevalent in the Asia-Pacific region. Betel nut chewing is closely associated with a variety of health hazards, including oral cancer, cardiovascular diseases, and metabolic syndrome. This article reviews the epidemiological characteristics, health hazards, neurobiological mechanisms, and intervention strategies of betel nut addiction. The major active component in betel nut, arecoline, leads to addiction by modulating the cholinergic, dopaminergic, and glutamatergic systems, with the involvement of the gut-brain axis and immune-inflammatory responses. In terms of intervention strategies, pharmacological treatments (such as nicotinic receptor modulators), neuromodulation techniques (such as real-time functional magnetic resonance imaging neurofeedback), cognitive-behavioral therapy, and public health policies have shown potential efficacy. Future research should focus on the development of precision medicine strategies and interdisciplinary integrated intervention models.

槟榔是全球第四大最常用的精神活性物质,在亚太地区尤为普遍。嚼槟榔与多种健康危害密切相关,包括口腔癌、心血管疾病和代谢综合征。本文综述了槟榔成瘾的流行病学特征、健康危害、神经生物学机制和干预策略。槟榔中的主要活性成分槟榔碱,通过调节胆碱能、多巴胺能和谷氨酸能系统,参与肠脑轴和免疫炎症反应,导致成瘾。在干预策略方面,药物治疗(如尼古丁受体调节剂)、神经调节技术(如实时功能磁共振成像神经反馈)、认知行为治疗和公共卫生政策已显示出潜在的疗效。未来的研究应着眼于发展精准医学策略和跨学科综合干预模式。
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引用次数: 0
METTL3-mediated m6A modification regulates CDKN1A to attenuate chronic sleep deprivation-induced cognitive impairment and neuronal apoptosis in rats. mettl3介导的m6A修饰调节CDKN1A减轻慢性睡眠剥夺诱导的大鼠认知功能障碍和神经元凋亡。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-09 DOI: 10.1038/s41398-026-03855-4
Fei Xing, Xiao-Shan Shi, Han-Wen Gu, Pan-Miao Liu, Lei Lei, Min Jia, Xing-Ming Wang, Mu-Huo Ji, Jian-Jun Yang

Chronic sleep deprivation (CSD) can induce cognitive impairment, but its molecular mechanism remains unclear. In this study, initial m⁶A RNA sequencing of the hippocampal CA3 region in CSD rats, coupled with differential gene expression analysis of the total RNA fraction, revealed downregulation of METTL3, which was consistent with impaired performance in the Morris Water Maze (MWM) and confirmed by qRT-PCR and Western blot. Further investigation showed that, in HT-22 cells, METTL3 knockdown exacerbated rapamycin-induced apoptosis. RNA sequencing of METTL3-knockdown cells identified gene modules and specific differentially expressed genes associated with METTL3 loss. Differential expression analysis revealed that CDKN1A was significantly upregulated following METTL3 knockdown. Methylated RNA immunoprecipitation followed by qPCR (MeRIP-qPCR) further showed that METTL3 knockdown reduced the m⁶A methylation level of CDKN1A mRNA. In vivo, METTL3 overexpression in CSD rats reduced CDKN1A levels, decreased neuronal apoptosis, improved spatial memory, and alleviated CA3 neuronal damage. In vitro, METTL3 knockdown upregulated CDKN1A and promoted apoptosis in HT-22 cells, while CDKN1A knockdown reversed this effect. Collectively, our results demonstrate that METTL3 downregulation promotes CSD-induced cognitive impairment by driving CDKN1A-dependent neuronal apoptosis, thereby identifying the METTL3/CDKN1A axis as a potential therapeutic target.

慢性睡眠剥夺可诱发认知障碍,但其分子机制尚不清楚。在本研究中,通过对CSD大鼠海马CA3区的初始m 26 A RNA测序,结合总RNA片段的差异基因表达分析,发现METTL3下调,这与Morris水迷宫(MWM)中表现受损一致,并通过qRT-PCR和Western blot证实。进一步研究表明,在HT-22细胞中,METTL3敲低加剧了雷帕霉素诱导的细胞凋亡。METTL3敲除细胞的RNA测序鉴定了与METTL3缺失相关的基因模块和特异性差异表达基因。差异表达分析显示,CDKN1A在METTL3敲低后显著上调。甲基化RNA免疫沉淀和qPCR (MeRIP-qPCR)进一步表明,METTL3敲除降低了CDKN1A mRNA的m 26 A甲基化水平。在体内,CSD大鼠METTL3过表达可降低CDKN1A水平,减少神经元凋亡,改善空间记忆,减轻CA3神经元损伤。在体外,METTL3敲低可上调CDKN1A并促进HT-22细胞的凋亡,而CDKN1A敲低可逆转这一作用。总之,我们的研究结果表明,METTL3下调通过驱动CDKN1A依赖的神经元凋亡来促进csd诱导的认知障碍,从而确定METTL3/CDKN1A轴是一个潜在的治疗靶点。
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引用次数: 0
Cerebellar astrocytic alterations in depression. 抑郁症患者小脑星形细胞的改变。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-09 DOI: 10.1038/s41398-026-03866-1
Christa Hercher, Gina Abajian, Maria Antonietta Davoli, Gustavo Turecki, Naguib Mechawar

Accumulating evidence suggests dysfunction of cerebellar-cerebral circuits in depression. However, the potential cellular and molecular alterations associated with depression in the cerebellum remain largely uncharacterized. While postmortem findings in the cerebral cortex indicate astrocyte dysregulation in depressed individuals who died by suicide (DS), the extent to which depression potentially alters cerebellar astrocytes is not well understood. In this study, two canonical astrocyte markers, glial fibrillary acidic protein (GFAP) and aldehyde Dehydrogenase-1 Family member L1 (ALDH1L1) were used to quantify cerebellar astrocyte subtypes, Bergmann glia (BG) in the Purkinje cell layer (PCL), velate astrocytes in the granule cell layer (GCL), and fibrous astrocytes in the white matter (WM). Purkinje cells (PCs) were also quantified due to their close association with BG. To assess potential dysregulation of astrocyte communication, we examined connexins, channel proteins essential in forming a functional network between astrocytes. Astrocytic connexins were visualized using single molecule in situ hybridization targeting connexin 30 (Cx30) and connexin 43 (Cx43), followed by immunolabeling for ALDH1L1. Our analysis revealed significant increases in ALDH1L1+ astrocyte densities in DS specific to the PCL compared to control individuals. Astrocytic connexins were significantly downregulated in DS, with Cx43 showing marked reductions in both PCL and GCL. Overall, our findings suggest that BG in the PCL and velate astrocytes in the GCL are particularly vulnerable in the depressive phenotype. Furthermore, this study supports previous findings in the cerebral cortex and extends astrocytic dysfunction to the cerebellum suggesting a widespread disruption of astrocyte-mediated communication across the brain in depression.

越来越多的证据表明抑郁症患者的小脑回路功能障碍。然而,与小脑抑郁相关的潜在细胞和分子改变在很大程度上仍未被表征。虽然在死于自杀的抑郁症患者的大脑皮层中发现星形胶质细胞失调,但抑郁症对小脑星形胶质细胞的潜在改变程度尚不清楚。本研究采用胶质纤维酸性蛋白(GFAP)和醛脱氢酶-1家族成员L1 (ALDH1L1)这两种典型星形胶质细胞标志物,定量测定了小脑星形胶质细胞亚型,即浦肯野细胞层(PCL)中的Bergmann胶质细胞(BG)、颗粒细胞层(GCL)中的velate星形胶质细胞和白质(WM)中的纤维状星形胶质细胞。由于浦肯野细胞(PCs)与BG密切相关,我们也对其进行了定量。为了评估星形胶质细胞通讯的潜在失调,我们检查了连接蛋白,即星形胶质细胞之间形成功能网络所必需的通道蛋白。采用靶向连接蛋白30 (Cx30)和连接蛋白43 (Cx43)的单分子原位杂交技术对星形胶质细胞连接蛋白进行可视化,然后对ALDH1L1进行免疫标记。我们的分析显示,与对照个体相比,PCL特异性DS中ALDH1L1+星形细胞密度显著增加。星形细胞连接蛋白在DS中显著下调,Cx43在PCL和GCL中均明显降低。总的来说,我们的研究结果表明,PCL中的BG和GCL中的velate星形胶质细胞在抑郁表型中特别脆弱。此外,该研究支持了先前在大脑皮层的发现,并将星形细胞功能障碍扩展到小脑,表明抑郁症中星形细胞介导的大脑通信广泛中断。
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引用次数: 0
The role of lipids in neuromodulation for psychiatric disorders: A narrative review. 脂质在精神疾病神经调节中的作用:叙述性综述。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-08 DOI: 10.1038/s41398-026-03873-2
D M Karaszewska, M van Kesteren, I Bergfeld, A Lok, J Assies, A Dols, P van den Munckhof, R Schuurman, D Denys, R J T Mocking

Lipids are highly abundant in the brain and play key roles in membrane regulation, neurotransmission, neurogenesis, and inflammation. The same processes are involved in neuromodulation mechanisms. While neuromodulation therapies have shown promising outcomes for treatment-resistant psychiatric disorders, the factors determining individual variability in treatment response remain poorly understood. Furthermore, the potential impact of neurometabolic factors in predicting response has been largely overlooked. This narrative review aims to evaluate the role of lipids in psychiatric neuromodulation. Particularly glycerophospholipids, sphingolipids and polyunsaturated fatty acids (PUFAs) have been described as important mediators. Current evidence suggests a bidirectional relationship between lipids and neuromodulation therapies such as electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS). Neuromodulation effects are associated with lipid metabolism changes, including phospholipids, sphingolipids, and fatty acids. ECT is associated with an increase in lipid peroxidation and alterations of cholesterol and fatty acid levels, while rTMS is associated with normalization of sphingolipids and phospholipids levels. Solely one study investigated the relation between deep brain stimulation and lipids, showing an association with sphingolipid metabolism. To our knowledge, this is the first comprehensive review to consolidate findings on the relationship between lipids and neuromodulation. By mapping this emerging field, these findings might be a first step towards investigating whether lipids could be a potential biomarker for response prediction in the future. As most findings are preliminary, with variability across studies, further investigation is warranted and current findings should be interpreted in the context of their limitations.

脂质在大脑中非常丰富,在膜调节、神经传递、神经发生和炎症中起着关键作用。同样的过程也涉及到神经调节机制。虽然神经调节疗法在治疗难治性精神疾病方面显示出良好的效果,但决定治疗反应个体差异的因素仍然知之甚少。此外,神经代谢因素在预测反应方面的潜在影响在很大程度上被忽视了。这篇叙述性综述旨在评估脂质在精神神经调节中的作用。特别是甘油磷脂、鞘脂和多不饱和脂肪酸(PUFAs)被认为是重要的介质。目前的证据表明,脂质与神经调节疗法(如电休克疗法(ECT)和重复经颅磁刺激(rTMS))之间存在双向关系。神经调节作用与脂质代谢变化有关,包括磷脂、鞘脂和脂肪酸。ECT与脂质过氧化的增加以及胆固醇和脂肪酸水平的改变有关,而rTMS与鞘脂和磷脂水平的正常化有关。只有一项研究调查了深部脑刺激与脂质之间的关系,显示与鞘脂代谢有关。据我们所知,这是第一个综合性的综述,巩固了脂质和神经调节之间的关系。通过绘制这一新兴领域的地图,这些发现可能是研究脂质是否可以作为未来反应预测的潜在生物标志物的第一步。由于大多数研究结果都是初步的,在不同的研究中存在差异,因此有必要进一步调查,目前的研究结果应在其局限性的背景下进行解释。
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引用次数: 0
Prenatal and postnatal effects of gestational immune activation on synaptic and neurodevelopmental pathways via epigenetic mechanisms. 妊娠期免疫激活通过表观遗传机制对突触和神经发育通路的产前和产后影响。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-07 DOI: 10.1038/s41398-026-03884-z
Bohan Zhu, Gaoshan Li, Justin M Saunders, Lynette B Naler, Thomas M Hadlock, Chenlong Wang, Adolfo García-Sastre, Javier González-Maeso, Chang Lu

Epidemiological research suggests that maternal immune activation (MIA) during early gestation is a significant risk factor for neurodevelopmental and psychiatric disorders in offspring. Epigenetic factors and chromatin-related phenomena remain highly dynamic throughout prenatal and early postnatal development, offering a substrate through which environmental insults can exert lasting effects on gene regulation. Here, we used a mouse MIA model induced by infection with a mouse-adapted influenza A/WSN/33 (H1N1) virus to investigate the long-term molecular consequences of maternal infection on adult offspring. To separately assess prenatal and postnatal effects of MIA, we cross-fostered half of the pups from each influenza-infected or mock-treated dam at birth. We then profiled histone modifications (H3K27ac, H3K4me3) and transcriptome changes in neuronal nuclei isolated from the frontal cortex of adult offspring. Our results revealed considerable overlap between the prenatal and postnatal effects of MIA on enhancer activity, suggesting a sustained regulatory trajectory across developmental stages. Prenatal MIA was specifically associated with changes in gene regulatory elements related to forebrain and telencephalon development, while postnatal MIA primarily affected pathways involved in axonogenesis and synapse organization. Cross-species enrichment analysis further revealed that MIA-responsive enhancers and promoters are significantly enriched at GWAS loci for neuropsychiatric disorders. Together, these findings support a model in which MIA contributes to disease risk through enduring epigenetic reprogramming of gene regulatory networks in the developing brain.

流行病学研究表明,妊娠早期母体免疫激活(MIA)是后代神经发育和精神疾病的重要危险因素。表观遗传因素和染色质相关现象在产前和产后早期发育过程中保持高度动态,提供了一种底物,通过这种底物,环境损害可以对基因调控产生持久影响。在这里,我们使用小鼠感染小鼠适应型流感a /WSN/33 (H1N1)病毒诱导的小鼠MIA模型来研究母体感染对成年后代的长期分子影响。为了分别评估MIA的产前和产后影响,我们在出生时交叉培养了来自每个流感感染或模拟治疗的母鼠的一半幼崽。然后,我们分析了从成年后代额叶皮层分离的神经元核的组蛋白修饰(H3K27ac, H3K4me3)和转录组变化。我们的研究结果显示,MIA对增强子活性的产前和产后影响之间存在相当大的重叠,表明在发育阶段存在持续的调节轨迹。产前MIA与前脑和端脑发育相关的基因调控元件的变化特别相关,而产后MIA主要影响轴突发生和突触组织相关的通路。跨物种富集分析进一步表明,神经精神疾病的GWAS位点显著富集了mia响应增强子和启动子。总之,这些发现支持MIA通过发育中的大脑中基因调控网络的持久表观遗传重编程来增加疾病风险的模型。
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引用次数: 0
Effects of post-stress corticosterone on hippocampal excitability and behavior involving hyperpolarization-activated cation channel 1 function. 应激后皮质酮对涉及超极化激活阳离子通道1功能的海马兴奋性和行为的影响。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-07 DOI: 10.1038/s41398-026-03871-4
Chung Sub Kim, Jiwon Kim, Sandali Michael

Single Prolonged Stress (SPS) is a widely used rodent model for investigating the consequences of acute traumatic stress, but outcomes in mice are often variable across strains and behavioral domains. Because corticosterone (CORT) release is a central feature of the stress response, we combined SPS with post-stress CORT administration (SPS + CORT) to capture this hormonal component and unmask latent phenotypes. Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are highly expressed in the dorsal CA1 (dCA1) hippocampus, where they regulate neuronal excitability. We previously demonstrated that acute CORT enhances hyperpolarization-activated current (Ih) in vitro; here, we tested its in vivo contribution to stress-related behavioral and physiological outcomes. Male mice (8-9 weeks old) were exposed to SPS followed by vehicle or CORT. Behavioral assays-including the open field, Y-maze, and contextual fear conditioning-revealed that SPS + CORT mice displayed impaired spatial working memory and deficits in contextual recall and fear extinction, resembling core PTSD-like features. Whole-cell recordings from dCA1 neurons showed decreased input resistance, reduced action potential firing, and elevated Ih, which were normalized by the HCN channel blocker ZD7288. Overexpression of HCN1 in SPS mice reproduced both behavioral and physiological phenotypes seen in SPS + CORT mice, whereas genetic deletion of HCN1 in SPS + CORT mice reduced Ih and rescued the behavioral abnormalities. Together, these findings identify HCN1 channels as a critical mediator linking post-stress glucocorticoid signaling to maladaptive hippocampal plasticity and PTSD-like outcomes.

单一延长应激(SPS)是一种广泛使用的啮齿动物模型,用于研究急性创伤应激的后果,但小鼠的结果在不同品系和行为领域往往是可变的。由于皮质酮(CORT)释放是应激反应的核心特征,我们将SPS与应激后CORT给药(SPS + CORT)结合起来,以捕获这种激素成分并揭示潜在的表型。超极化激活的环核苷酸门控1 (HCN1)通道在海马背侧CA1 (dCA1)中高度表达,在那里它们调节神经元的兴奋性。我们之前在体外证明急性CORT增强超极化激活电流(Ih);在这里,我们测试了它在体内对压力相关行为和生理结果的贡献。雄性小鼠(8-9周龄)暴露于SPS,然后是车辆或CORT。行为学测试——包括空旷场、y形迷宫和情境恐惧条件反射——显示,SPS + CORT小鼠表现出空间工作记忆受损、情境回忆和恐惧消退的缺陷,类似于核心ptsd样特征。dCA1神经元的全细胞记录显示输入电阻降低,动作电位放电减少,Ih升高,HCN通道阻滞剂ZD7288使其归一化。在SPS小鼠中,HCN1的过表达再现了SPS + CORT小鼠的行为和生理表型,而在SPS + CORT小鼠中,HCN1的基因缺失减少了Ih并挽救了行为异常。总之,这些发现确定了HCN1通道是连接应激后糖皮质激素信号与适应不良海马可塑性和ptsd样结果的关键介质。
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引用次数: 0
The Habenula's role in major depressive disorder: recent insights from preclinical and human studies. Habenula在重度抑郁症中的作用:来自临床前和人体研究的最新见解。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-07 DOI: 10.1038/s41398-026-03867-0
Feiteng Lin, Kayleigh Casmey, Sierra A Codeluppi-Arrowsmith, Gustavo Turecki

The habenula is a small epithalamic structure composed of two distinct subregions, the medial (MHb) and lateral (LHb) habenula. It serves as a critical hub for integrating fronto-limbic and brainstem signals to regulate motivation, mood, and reward processing. Therefore, it is unsurprising that dysfunction of the habenula has been implicated in several mood disorders including major depressive disorder (MDD), a debilitating mood disorder marked by low mood and feelings of hopelessness. This review synthesizes recent advances in understanding the habenula's neurocircuitry, molecular landscape, and role in MDD pathophysiology, while evaluating its potential as a therapeutic target. Specifically, emerging evidence highlights subregion-specific pathology. Indeed, in MDD and in animal models of depression, the MHb has been shown to exhibit marked downregulation of calcium-dependent activator protein for secretion 2 (CAPS2) and deficits in nicotinic acetylcholine receptor-mediated signaling. While in the LHb, dysregulated expression profiles of inward-rectifying potassium channel Kir4.1, the β isoform of calcium/calmodulin-dependent protein kinase II (CaMKIIβ), protein phosphatase 2 A (PP2A), and small nucleolar RNA SNORA69 have been found in animal models of depression and MDD postmortem studies. Structural imaging and postmortem neurohistological studies in MDD patients have further revealed habenular volume changes, reduced neuronal cell counts, diminished cell area, and abnormal functional connectivity. As research unravels the habenula's complexities, its potential in treating mood disorders grows increasingly salient, offering new avenues for intervention in mental health.

缰是一个小的上皮结构,由两个不同的亚区组成,内侧(MHb)和外侧(LHb)缰。它是整合额边缘和脑干信号来调节动机、情绪和奖励处理的关键枢纽。因此,毫不奇怪,缰带功能障碍与多种情绪障碍有关,包括重度抑郁症(MDD),一种以情绪低落和绝望感为特征的衰弱性情绪障碍。本文综述了缰状核的神经回路、分子结构和在重度抑郁症病理生理中的作用,同时评估了缰状核作为治疗靶点的潜力。具体而言,新出现的证据强调了分区域特异性病理。事实上,在重度抑郁症和抑郁症的动物模型中,MHb表现出钙依赖性激活蛋白分泌2 (CAPS2)的显著下调和烟碱乙酰胆碱受体介导的信号传导缺陷。而在LHb中,在抑郁症和重度抑郁症动物模型的死后研究中发现了向内校正钾通道Kir4.1、钙/钙调素依赖性蛋白激酶II (CaMKIIβ)、蛋白磷酸酶2a (PP2A)和小核核RNA SNORA69的表达谱失调。MDD患者的结构成像和死后神经组织学研究进一步揭示了habenular体积改变,神经元细胞计数减少,细胞面积减少,功能连接异常。随着研究揭开缰带的复杂性,缰带在治疗情绪障碍方面的潜力日益突出,为干预心理健康提供了新的途径。
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引用次数: 0
Target-Specificity and repeatability in neuro-cardiac-guided TMS for heart-brain coupling. 神经心脏引导经颅磁刺激治疗心脑耦合的靶特异性和可重复性。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-07 DOI: 10.1038/s41398-026-03879-w
Zi-Jian Feng, Sandra Martin, Ole Numssen, Konstantin Weise, Ying Jing, Gerasimos Gerardos, Carla Martin, Gesa Hartwigsen, Thomas R Knösche

The dorsolateral prefrontal cortex (DLPFC) is a principal target for transcranial magnetic stimulation (TMS) in treating major depressive disorder, with therapeutic effects thought to be mediated by its connectivity with the subgenual anterior cingulate cortex. As both regions are involved in autonomic regulation, short-term heart rate changes following DLPFC stimulation may serve as physiological markers to identify stimulation targets. We employed neuro-cardiac guided TMS in a cohort of healthy participants to examine the effects of stimulation intensity and DLPFC target specificity on heart-brain coupling (HBC). We used generalized additive models to assess nonlinear effects of stimulation intensity and target location on HBC, while accounting for pain ratings and other side effects. Intra-subject repeatability across three sessions was evaluated using intraclass correlation coefficients. We observed a non-linear modulation of HBC depending on stimulation intensity and target location, with greater effects at the F3 lateral and F3 posterior targets compared to sham. By evaluating these effects across sessions within participants, we demonstrate the robustness of our results beyond the influence of pain and other side effects on HBC modulation. Exploratory analyses of the directionality show a consistent decrease in HR only at the F3 lateral target with suprathreshold stimulation. These results demonstrate that HBC is modulated in a target- and intensity-specific manner, with particularly consistent effects at F3 lateral sites within the DLPFC. The findings enhance the understanding of TMS-modulated heart-brain interactions, offering a potential framework for optimizing individualized rTMS treatment protocols for depression.

背外侧前额叶皮层(DLPFC)是经颅磁刺激(TMS)治疗重度抑郁症的主要靶点,其治疗效果被认为是由其与亚属前扣带皮层的连连介导的。由于这两个区域都参与自主调节,DLPFC刺激后的短期心率变化可以作为识别刺激目标的生理标记。我们在一组健康参与者中采用神经心脏引导的经颅磁刺激(TMS)来研究刺激强度和DLPFC靶特异性对心脑耦合(HBC)的影响。我们使用广义加性模型来评估刺激强度和靶位置对HBC的非线性影响,同时考虑疼痛等级和其他副作用。使用组内相关系数评估三个疗程的受试者内重复性。我们观察到HBC的非线性调节取决于刺激强度和靶位置,与假手术相比,F3侧靶和F3后靶的影响更大。通过在参与者中评估这些效果,我们证明了我们的结果的稳健性,超出了疼痛和其他副作用对HBC调节的影响。方向性的探索性分析表明,只有在阈上刺激的F3侧靶处,心率才会持续下降。这些结果表明,HBC以靶向和强度特异性的方式进行调节,在DLPFC内的F3侧位具有特别一致的影响。这些发现增强了对经颅磁刺激调节的心脑相互作用的理解,为优化抑郁症的个体化经颅磁刺激治疗方案提供了一个潜在的框架。
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引用次数: 0
Blood circulating cell-free mitochondrial DNA as a potential biomarker for major depressive disorder: a meta-analysis. 血液循环无细胞线粒体DNA作为重度抑郁症的潜在生物标志物:一项荟萃分析。
IF 6.2 1区 医学 Q1 PSYCHIATRY Pub Date : 2026-02-06 DOI: 10.1038/s41398-026-03865-2
Yaman Zhang, Mingzhe Zhao, Shijie Song, Qiyuan Chen, Yi Meng, Xueli Yu, Wei Wei, Wei Deng, Wanjun Guo, Tao Li, Xueyu Qi

Background: Mitochondrial dysfunction has been implicated in major depressive disorder (MDD), but reliable, measurable biomarkers remain elusive. As a minimally invasive and quantifiable biomarker, circulating cell-free mitochondrial DNA (ccf-mtDNA) in blood offers potential for objective assessment of mitochondrial stress in MDD. However, evidence linking regarding the association between ccf-mtDNA levels and MDD is limited and inconsistent.

Methods: We systematically searched eight databases, including PubMed, EMBASE, and major Chinese repositories. Thirteen studies with 1370 participants (837 individuals with MDD and 533 controls) were included per PRISMA guidelines. P-values were synthesized using the Lipták-Stouffer Z-score method. Sensitivity and fail-safe N analyses assessed the robustness of the findings and publication bias, and stratified analyses examined the effects of age, antidepressant use, and geographic region.

Results: Across studies, elevated blood ccf-mtDNA levels were significantly associated with MDD (p = 0.013). Stratified analyses revealed stronger associations in older adults (≥60 years old; p = 0.0009), unmedicated patients (p = 4.99 × 10⁻⁶), and North American cohorts (p = 4.29 × 10⁻¹¹), but not in younger individuals (p = 0.83), medicated patients (p = 0.97), and Asian/European samples (p = 0.72, p = 0.99). Sensitivity analyses indicated moderate instability overall but confirmed data robustness in key subgroups.

Conclusions: This is the first meta-analysis to establish a significant link between elevated blood ccf-mtDNA and MDD, highlighting age and antidepressant exposure as critical modulators. These findings support the potential of blood ccf-mtDNA to serve as a biomarker for late-life and drug-naïve depression, with implications for objective diagnosis and personalized treatment.

背景:线粒体功能障碍与重度抑郁症(MDD)有关,但可靠、可测量的生物标志物仍然难以捉摸。作为一种微创和可量化的生物标志物,血液中循环无细胞线粒体DNA (ccf-mtDNA)为MDD患者线粒体应激的客观评估提供了可能。然而,关于ccf-mtDNA水平与MDD之间关联的证据有限且不一致。方法:系统检索PubMed、EMBASE和主要中文资源库等8个数据库。根据PRISMA指南纳入了13项研究,共1370名参与者(837名重度抑郁症患者和533名对照组)。p值采用Lipták-Stouffer Z-score法合成。敏感性和故障安全N分析评估了研究结果的稳健性和发表偏倚,分层分析检查了年龄、抗抑郁药使用和地理区域的影响。结果:在所有研究中,血液ccf-mtDNA水平升高与MDD显著相关(p = 0.013)。分层分析显示,在老年人(≥60岁;p = 0.0009)、未接受药物治疗的患者(p = 4.99 × 10毒血症)和北美人群(p = 4.29 × 10毒血症)中,这种关联更强,但在年轻人(p = 0.83)、接受药物治疗的患者(p = 0.97)和亚洲/欧洲样本(p = 0.72, p = 0.99)中没有这种关联。敏感性分析显示总体不稳定,但在关键亚组中证实数据稳健性。结论:这是第一个建立血液ccf-mtDNA升高与MDD之间显著联系的荟萃分析,强调年龄和抗抑郁药物暴露是关键的调节因子。这些发现支持了血液ccf-mtDNA作为晚年和drug-naïve抑郁症的生物标志物的潜力,对客观诊断和个性化治疗具有重要意义。
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引用次数: 0
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Translational Psychiatry
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