Brain, behavior, & immunity - health最新文献_第5页

Alterations in functional connectivity analyzed using MREG in patients with suspected autoimmune psychosis spectrum syndromes 在疑似自身免疫性精神病谱系综合征患者中使用MREG分析功能连通性的改变

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-22 DOI: 10.1016/j.bbih.2025.101111

Katharina von Zedtwitz , Ludger Tebartz van Elst , Isabelle Matteit , Andrea Schlump , Thomas Lange , Kimon Runge , Judith Weiser , Kathrin Nickel , Katharina Domschke , Harald Prüss , Alexander Rau , Marco Reisert , Simon J. Maier , Bernd Feige , Dominique Endres

Introduction

In NMDA-R encephalitis, which is typically accompanied by psychotic symptoms, conventional magnetic resonance imaging (MRI) is often normal, despite widespread alterations in functional connectivity. This is the first functional connectivity study in psychiatric patients with suspected autoimmune psychosis (AP) spectrum syndromes.

Methods

Twenty-eight patients with suspected AP spectrum syndromes who were selected according to the concept of autoimmune psychiatric syndromes (APS) and 28 matched healthy controls (HCs) were examined with ultrafast functional MRI using magnetic resonance encephalography (MREG). Patients were positive for either well-characterized or novel central nervous system antibodies or well-characterized systemic antibodies with autoimmune brain involvement. MREG data were processed using “Analysis of Functional NeuroImages” (AFNI) with the “Functional And Tractographic Connectivity Analysis AFNI toolbox” to analyze connectivity across 170 regions, yielding an analysis of 5995 evaluable connectivities.

Results

After correction for multiple testing, functional connectivity between the left middle cingulate/paracingulate gyri and the right insula (p_adj = 0.025) was significantly reduced in the patient group compared to HCs. Exploratory analyses revealed widespread global functional connectivity alterations in 226 of all connections (corresponding to 3.8 %). Notably, of these altered connections, 99 % showed reduced connectivity, while 1 % showed hyperconnectivity. The medial pulvinar of the left thalamus emerged as the most disconnected hub with altered connectivity to 33 other regions. Overall, 46 % of all analyzed regions exhibited at least one altered functional connectivity, with 19 % of hubs located in the cerebellum, 11 % in the frontal brain, and 9 % in the thalami. After correction for multiple comparisons, increased connectivity between the left insula and the left superior temporal gyrus correlated with the Beck Depression Inventory scores (p_adj = 0.043).

Discussion

Patients with suspected AP spectrum syndromes exhibit altered insular functional connectivity associated with the severity of depressive symptoms. Broader changes identified via hypothesis-generating analyses highlighted major hubs in the cerebellum, frontal brain, and thalamus. These findings suggest that functional MRI may serve as an additional tool for detecting patients with AP/APS. Future studies in more homogeneous autoimmune-mediated patient groups may help delineate specific connectivity signatures in functional networks.

NMDA-R脑炎通常伴有精神病性症状，尽管功能连通性普遍改变，但常规磁共振成像（MRI）通常正常。这是首次对疑似自身免疫性精神病（AP）谱系综合征的精神病患者进行功能连通性研究。方法采用超快功能磁共振脑电图（MREG）对28例疑似AP谱综合征患者（根据自身免疫性精神综合征（APS）概念选择）和28例匹配的健康对照（hc）进行检查。患者的特异性抗体或新型中枢神经系统抗体或特异性全身抗体伴自身免疫性脑受累均呈阳性。使用“功能神经图像分析”（AFNI）和“功能和神经束图连接分析AFNI工具箱”对MREG数据进行处理，分析170个区域的连接，产生5995个可评估的连接。结果经多次校正后，与hc相比，患者组左侧中扣带/副扣带回与右侧脑岛之间的功能连通性（padj = 0.025）显著降低。探索性分析显示，在所有连接中有226个存在广泛的全球功能连接改变（对应3.8%）。值得注意的是，在这些改变的连接中，99%的人表现出连接减少，而1%的人表现出超连接。左丘脑的内侧枕侧是最不连接的中枢，与其他33个区域的连接发生了变化。总的来说，46%的分析区域表现出至少一种功能连接的改变，其中19%的中枢位于小脑，11%位于额脑，9%位于丘脑。经过多次比较校正后，左脑岛和左颞上回之间的连通性增加与贝克抑郁量表得分相关（padj = 0.043）。疑似AP谱系综合征的患者表现出与抑郁症状严重程度相关的岛岛功能连通性改变。通过假设生成分析确定的更广泛的变化突出了小脑、额脑和丘脑的主要中枢。这些发现提示功能性MRI可作为检测AP/APS患者的附加工具。未来对更均匀的自身免疫介导的患者群体的研究可能有助于描述功能网络中的特定连接特征。

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引用次数: 0

High dietary phosphate intake induces anxiety in normal male mice 高膳食磷酸盐摄入可引起正常雄性小鼠的焦虑

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-19 DOI: 10.1016/j.bbih.2025.101112

Pavel Yanev , Thomas A. Ujas , Han-Kyul Kim , Teppei Fujikawa , Noriyoshi Isozumi , Eiichiro Mori , Jadwiga Turchan-Cholewo , Connor Stuart , Rowan Sturgill , Shari G. Birnbaum , Ann M. Stowe , Wanpen Vongpatanasin

Background

Diet is increasingly recognized as an important risk factor for mental health. Inorganic phosphate (Pi) is currently used as a flavor enhancer or preservative at an unregulated amount in the western diet despite evidence that excessive dietary Pi intake associates with metabolic and cardiovascular disorders. The impact of high Pi on brain function remains poorly understood. This study aimed to evaluate the effects of chronic consumption of high dietary phosphate on behavior, neurovascular health, and neuroimmune populations, and cortical gene expression in key brain regions associated with emotional regulation.

Methods

Adult C57BL/6 male mice were fed either a normal phosphate (NP) or high phosphate (HP) diet for 12 weeks. Behavioral assessments included the open field test (OFT) and fear conditioning. Histological analyses assessed neuronal densities and vascularization. Flow cytometry quantified brain-resident immune cell populations and microglia. Unbiased analysis of hippocampal gene expression was performed using RNA sequencing (RNA-Seq).

Results

HP-fed mice exhibited increased anxiety-like behaviors compared to NP-fed controls, as indicated by increased thigmotaxis (i.e., more time close to the walls and, consequently, less time spent in the central area, HP: 164 ± 61 vs. NP: 215 ± 54 s, P = 0.03) in the OFT and increased time freezing regardless of stimulus type during fear conditioning. Neuronal density is significantly decreased in the hypothalamus of HP-fed mice (21.9 % ± 4.5 % vs. 16.4 ± 2.9 %, P = 0.02) but without concomitant differences in brain vascularization. Immunophenotyping showed that HP-diet significantly reduced TCRβ⁺ T cells and NK1.1⁺ NK cells (both P < 0.05), suggesting diet-induced alterations in neuroimmune homeostasis. RNA-Seq identified significant alterations in gene expression in the hippocampus, including upregulation of Neat1 and Stat3 and downregulation of Igf2, which are implicated in stress regulation, neurodegeneration, synaptic plasticity and immune system pathways.

Conclusions

Collectively, this study highlights that habitual consumption of high dietary phosphate in mice may induce chronic anxiety, accompanied by significant changes in the neuronal and brain-resident immune populations. The data point to a potential link between dietary Pi, neuroinflammation, and the pathogenesis of anxiety and depression in otherwise healthy young male mice. Given the prevalence of phosphate additives in processed foods, these findings have important public health implications supporting the regulation of Pi in the food industry.

饮食越来越被认为是心理健康的一个重要风险因素。无机磷酸盐（Pi）目前在西方饮食中被用作风味增强剂或防腐剂，但用量不受监管，尽管有证据表明，饮食中摄入过多的Pi与代谢和心血管疾病有关。高π值对大脑功能的影响仍然知之甚少。本研究旨在评估长期摄入高磷饮食对行为、神经血管健康、神经免疫群体以及与情绪调节相关的关键脑区皮质基因表达的影响。方法C57BL/6成年雄性小鼠分别饲喂正常磷（NP）和高磷（HP）饲粮12周。行为评估包括开放式测试（OFT）和恐惧条件反射。组织学分析评估神经元密度和血管化。流式细胞术定量脑驻留免疫细胞群和小胶质细胞。采用RNA测序（RNA- seq）对海马基因表达进行无偏分析。结果与NP喂养的对照组相比，shp喂养的小鼠表现出了更多的焦虑样行为，这表明，在恐惧条件反射期间，无论刺激类型如何，外脑的移动性增加（即更多的时间接近墙壁，因此在中心区域花费的时间更少，HP: 164±61 vs NP: 215±54 s, P = 0.03），时间冻结增加。hp喂养小鼠下丘脑神经元密度显著降低（21.9%±4.5% vs. 16.4±2.9%,P = 0.02），但脑血管化未出现差异。免疫表型分析显示，hp饮食显著降低了TCRβ+ T细胞和NK1.1+ NK细胞（P < 0.05），提示饮食诱导了神经免疫稳态的改变。RNA-Seq发现海马中基因表达的显著改变，包括Neat1和Stat3的上调以及Igf2的下调，这些基因表达与应激调节、神经退行性变、突触可塑性和免疫系统通路有关。综上所述，本研究强调，小鼠习惯性摄入高磷饮食可能会诱发慢性焦虑，并伴随神经元和脑内免疫群体的显著变化。这些数据表明，在健康的年轻雄性小鼠中，饮食Pi、神经炎症以及焦虑和抑郁的发病机制之间存在潜在的联系。鉴于磷酸盐添加剂在加工食品中的普遍存在，这些发现具有重要的公共卫生意义，支持对食品工业中的Pi进行监管。

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引用次数: 0

The roles of exosomes in the pathogenesis and treatment of coronary heart disease with depression and/or anxiety 外泌体在冠心病伴抑郁和/或焦虑的发病机制和治疗中的作用

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-19 DOI: 10.1016/j.bbih.2025.101113

Jiecheng Huang , Ying Piao , Xin Jiang , Jingjin Liu

Coronary heart disease (CHD) patients have been found to also possess high anxiety and depression rates, which have been considered as significant risk factors for the disease. One possible underlying biological mechanism behind anxiety/depression being associated with CHD may be exosomes, extracellular vesicles produced by cells throughout the body. These exosomes contain various proteins and miRNAs that could exert a variety of physiological and pathological effects. However, the precise role they play in CHD with anxiety/depression has still not been fully elucidated. In this review, we summarized the current research on exosome involvement in the pathogenesis of CHD with anxiety/depression, particularly focusing on inflammatory responses, neuroendocrine signaling, sympathetic nervous system (SNS) regulation, platelet activation, and endothelial injury. In particular, for inflammatory responses, exosomes have been associated with increased pro-inflammatory cytokine release, such as interleukin (IL)-1β, while for neuroendocrine signaling, the miRNAs miR-135a-5p and miR-320a have been implicated in increasing glucocorticoid signaling. As for SNS regulation, exosome miRNAs are involved in downregulating Nrf2, leading to increased sympathetic nerve excitation, while inhibiting exosome production counteracts platelet activation, in turn lowering thrombosis risk for CHD. Endothelial dysfunction could be promoted by exosomes carrying miR-155. On the other hand, exosome contents exert beneficial effects that could be used for treatment strategies, such as miR-1246 alleviating hypoxia-induced myocardial tissue damage, as well as miR-188–3p lowering nigrostriatal autophagy. Overall, identifying the roles that exosomes play in CHD with concurrent anxiety/depression pathogenesis, as well as potential alleviation, may be greatly beneficial for formulating effective treatment strategies.

冠心病（CHD）患者也有很高的焦虑和抑郁率，这被认为是该疾病的重要危险因素。焦虑/抑郁与冠心病相关的一个潜在生物学机制可能是外泌体，即由全身细胞产生的细胞外囊泡。这些外泌体含有多种蛋白质和mirna，可以发挥各种生理和病理作用。然而，它们在冠心病伴焦虑/抑郁中的确切作用仍未完全阐明。在这篇综述中，我们总结了目前关于外泌体参与冠心病伴焦虑/抑郁发病机制的研究，特别关注炎症反应、神经内分泌信号、交感神经系统（SNS）调节、血小板激活和内皮损伤。特别是，对于炎症反应，外泌体与促炎细胞因子释放增加有关，如白细胞介素(IL)-1β，而对于神经内分泌信号，mirna miR-135a-5p和miR-320a与糖皮质激素信号的增加有关。在SNS调控方面，外泌体miRNAs参与下调Nrf2，导致交感神经兴奋增加，而抑制外泌体产生抵消血小板活化，进而降低冠心病血栓形成风险。携带miR-155的外泌体可促进内皮功能障碍。另一方面，外泌体内容物具有有益的作用，可用于治疗策略，如miR-1246减轻缺氧诱导的心肌组织损伤，miR-188-3p降低黑质纹状体自噬。总之，确定外泌体在冠心病并发焦虑/抑郁发病机制中的作用，以及潜在的缓解，可能对制定有效的治疗策略非常有益。

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引用次数: 0

Dynamic immune dysregulation in severe mental illness: Exaggerated innate and attenuated adaptive immune responses following SARS-CoV-2 vaccination 严重精神疾病的动态免疫失调：接种SARS-CoV-2后先天性免疫反应的夸大和适应性免疫反应的减弱

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-19 DOI: 10.1016/j.bbih.2025.101114

Tim Rietberg , Kawtar El Abdellati , Alexandre Lucas , Margot Lemarinier , Steven Fried , Jean-Romain Richard , Ryad Tamouza , Violette Coppens , Manuel Morrens , Marion Leboyer , Livia De Picker

Background

Immune dysregulation in severe mental illness (SMI) is usually characterised using static measurements. As such, how the immune system of SMI patients responds to real-world challenges remains largely unknown. Prior studies suggest that patients may exhibit an exaggerated innate and attenuated adaptive immune response, but in vivo studies are lacking.

Objectives

This study aimed to assess immune responses to SARS-CoV-2 vaccination in SMI patients compared to non-psychiatric controls (NPCs). We investigated post-vaccination changes in cytokine and antibody levels, their associations, and secondary measures including tryptophan-kynurenine pathway metabolites and psychiatric symptoms.

Methods

We collected blood samples of 72 SMI patients and 127 NPCs before and after the first and second vaccine dose administrations to quantify cytokines (IL1β, IL6, IL8, IL10) and anti-SARS-CoV-2 antibodies (Spike, S1, S2, S1RBD, Nucleocapsid). We used linear mixed models to assess whether post-vaccination changes in biomarker levels differ between SMI patients and NPCs, and to evaluate associations among biomarkers.

Results

SMI patients showed significantly greater increases in IL1β (F(394.3) = 30.03, P_FDR < 0.001) and IL8 (F(384.4) = 15.28, P_FDR = 0.005) levels following the first vaccine dose and smaller increases in Spike (F(508.7) = 8.58, P_FDR = 0.005), S1 (F(506.9) = 19.76, P_FDR < 0.0001) and S2 (F(507.8) = 20.96, P_FDR < 0.0001) antibody levels after two vaccine doses when compared to NPCs. Higher cytokine levels were associated with lower antibody response in SMI patients.

Conclusion

Our findings provide in vivo evidence for exaggerated innate and attenuated adaptive immune responses to vaccination in SMI patients. The study underscores the need for longitudinal, experimental approaches in immunopsychiatry to better characterise the dynamic dysregulation of both the innate and the adaptive immune system in this population.

背景：严重精神疾病（SMI）中的免疫失调通常使用静态测量来表征。因此，重度精神障碍患者的免疫系统如何应对现实世界的挑战在很大程度上仍然未知。先前的研究表明，患者可能表现出夸大的先天免疫反应和减弱的适应性免疫反应，但缺乏体内研究。目的：本研究旨在评估重度精神障碍患者与非精神疾病对照组（npc）对SARS-CoV-2疫苗接种的免疫反应。我们调查了疫苗接种后细胞因子和抗体水平的变化及其相关性，以及包括色氨酸-犬尿氨酸途径代谢物和精神症状在内的次要指标。方法采集72例重度精神分裂症患者和127例非典型肺炎患者在第一次和第二次疫苗接种前后的血液样本，定量细胞因子（il - 1β、il - 6、il - 8、il - 10）和抗sars - cov -2抗体（Spike、S1、S2、S1RBD、Nucleocapsid）。我们使用线性混合模型来评估SMI患者和npc接种疫苗后生物标志物水平的变化是否存在差异，并评估生物标志物之间的相关性。结果smi患者在第一次接种疫苗后il - 1β (F(394.3) = 30.03, PFDR < 0.001)和il - 8 （F(384.4) = 15.28, PFDR = 0.005）水平显著升高，两剂疫苗后Spike （F(508.7) = 8.58, PFDR = 0.005）、S1 （F(506.9) = 19.76, PFDR < 0.0001）和S2 （F(507.8) = 20.96, PFDR < 0.0001）抗体水平升高较小。在重度精神分裂症患者中，较高的细胞因子水平与较低的抗体反应相关。结论我们的研究结果为重度精神分裂症患者接种疫苗后先天免疫反应增强和适应性免疫反应减弱提供了体内证据。该研究强调了免疫精神病学纵向实验方法的必要性，以更好地表征该人群中先天性和适应性免疫系统的动态失调。

{"title":"Dynamic immune dysregulation in severe mental illness: Exaggerated innate and attenuated adaptive immune responses following SARS-CoV-2 vaccination","authors":"Tim Rietberg , Kawtar El Abdellati , Alexandre Lucas , Margot Lemarinier , Steven Fried , Jean-Romain Richard , Ryad Tamouza , Violette Coppens , Manuel Morrens , Marion Leboyer , Livia De Picker","doi":"10.1016/j.bbih.2025.101114","DOIUrl":"10.1016/j.bbih.2025.101114","url":null,"abstract":"<div><h3>Background</h3><div>Immune dysregulation in severe mental illness (SMI) is usually characterised using static measurements. As such, how the immune system of SMI patients responds to real-world challenges remains largely unknown. Prior studies suggest that patients may exhibit an exaggerated innate and attenuated adaptive immune response, but in vivo studies are lacking.</div></div><div><h3>Objectives</h3><div>This study aimed to assess immune responses to SARS-CoV-2 vaccination in SMI patients compared to non-psychiatric controls (NPCs). We investigated post-vaccination changes in cytokine and antibody levels, their associations, and secondary measures including tryptophan-kynurenine pathway metabolites and psychiatric symptoms.</div></div><div><h3>Methods</h3><div>We collected blood samples of 72 SMI patients and 127 NPCs before and after the first and second vaccine dose administrations to quantify cytokines (IL1β, IL6, IL8, IL10) and anti-SARS-CoV-2 antibodies (Spike, S1, S2, S1RBD, Nucleocapsid). We used linear mixed models to assess whether post-vaccination changes in biomarker levels differ between SMI patients and NPCs, and to evaluate associations among biomarkers.</div></div><div><h3>Results</h3><div>SMI patients showed significantly greater increases in IL1β (F(394.3) = 30.03, <em>P</em><sub><em>FDR</em></sub> < 0.001) and IL8 (F(384.4) = 15.28, <em>P</em><sub><em>FDR</em></sub> = 0.005) levels following the first vaccine dose and smaller increases in Spike (F(508.7) = 8.58, <em>P</em><sub><em>FDR</em></sub> = 0.005), S1 (F(506.9) = 19.76, <em>P</em><sub><em>FDR</em></sub> < 0.0001) and S2 (F(507.8) = 20.96, <em>P</em><sub><em>FDR</em></sub> < 0.0001) antibody levels after two vaccine doses when compared to NPCs. Higher cytokine levels were associated with lower antibody response in SMI patients.</div></div><div><h3>Conclusion</h3><div>Our findings provide in vivo evidence for exaggerated innate and attenuated adaptive immune responses to vaccination in SMI patients. The study underscores the need for longitudinal, experimental approaches in immunopsychiatry to better characterise the dynamic dysregulation of both the innate and the adaptive immune system in this population.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101114"},"PeriodicalIF":3.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inflammatory predictors of Post-COVID fatigue covid - 19后疲劳的炎症预测因素

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-17 DOI: 10.1016/j.bbih.2025.101109

A. Nuber-Champier , G. Breville , P. Voruz , I. Jacot de Alcântara , P.H. Lalive , G. Allali , L. Benzakour , K.-O. Lövblad , O. Braillard , M. Nehme , M. Coen , J. Serratrice , J.-L. Reny , J. Pugin , I. Guessous , B.N. Landis , A. Cionca , F. Assal , J.A. Péron

The biological mechanisms underlying objective and subjective fatigue in post-COVID syndrome remain unclear. This study investigates whether immune responses during the acute phase of SARS-CoV-2 infection predict fatigue dimensions 6–9 months post-infection. We analyzed serum immune markers from 54 hospitalized patients (mean age: 58.69 ± 10.90 yrs; female: 31 %) and assessed their association with chronic fatigue using general linear mixed models. Elevated levels of IL-1RA, IFNγ, TNFα, and monocyte percentage during acute infection predicted increased physical and total fatigue. Additionally, higher TNFα levels (r = −0.40, p = .019) correlated with reduced awareness of cognitive fatigue. These findings highlight the role of acute inflammation in the persistence of post-COVID fatigue.

新冠肺炎后综合征主客观疲劳的生物学机制尚不清楚。本研究探讨SARS-CoV-2感染急性期的免疫反应是否能预测感染后6-9个月的疲劳维度。我们分析了54例住院患者（平均年龄：58.69±10.90岁，女性：31%）的血清免疫标志物，并使用一般线性混合模型评估其与慢性疲劳的关系。急性感染期间IL-1RA、IFNγ、TNFα和单核细胞百分比的升高预示着身体和总疲劳的增加。此外，较高的TNFα水平（r = - 0.40, p = 0.019）与认知疲劳意识降低相关。这些发现强调了急性炎症在covid后疲劳持续中的作用。

引用次数: 0

Networks and clusters of immunometabolic biomarkers and depression-associated features in middle-aged and older community-dwelling US adults with and without depression 美国中老年社区居民中有或无抑郁症的免疫代谢生物标志物的网络和集群以及抑郁相关特征

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-17 DOI: 10.1016/j.bbih.2025.101103

Asma Hallab , The Health and Aging Brain Study (HABS-HD) Study Team

Introduction

Therapy-resistant depression is associated with higher levels of systemic inflammation and increased odds of metabolic disorders. It is, therefore, crucial to identify the biomarkers of high-risk individuals and understand the key features of depression-immunometabolic networks.

Methods

The multiethnic ≥50-year-old study population is a subset of the Health and Aging Brain Study: Health Disparities (HABS-HD) study. Spearman's rank correlation network analysis was performed between immunological, metabolic, and subscales of the Geriatric Depression Scale (GDS). Significant correlations were then evaluated using a multivariable linear regression analysis, including testing for non-linearity and clinical cutoffs.

Results

Two clusters were formed: the first included the immunometabolic biomarkers, and the second included the different subscales of GDS. The two clusters were significantly correlated at six edges. IL-6 and HbA1c were significantly correlated with anhedonic and melancholic features. Abdominal circumference and BMI were significantly correlated with anhedonic features. In the subgroup without current depression, IL-6 and Abdominal circumference maintained a significant edge with anhedonic features. TNF-alpha/melancholia and IL-6/cognitive concerns were additional relevant edges in older adults. The observed correlations remained statistically significant in the confounder-adjusted regression analysis and followed specific patterns.

Conclusions

Symptom clustering showed its superiority over relying on dichotomized depression diagnoses for identifying relevant immunometabolic biomarkers. This study is a first step toward understanding the particularities of immunometabolic depression for better risk stratification and to direct personalized preventive and therapeutic strategies in multiethnic aging populations.

治疗抵抗性抑郁症与更高水平的全身性炎症和代谢紊乱的几率增加有关。因此，确定高危个体的生物标志物和了解抑郁症免疫代谢网络的关键特征是至关重要的。方法多民族≥50岁的研究人群是健康与衰老脑研究：健康差异（HABS-HD）研究的一个子集。在老年抑郁量表（GDS）的免疫、代谢和亚量表之间进行Spearman等级相关网络分析。然后使用多变量线性回归分析评估显著相关性，包括非线性检验和临床截止点。结果形成两类：一类是免疫代谢生物标志物，一类是GDS各亚量表。两类聚类在6条边显著相关。IL-6、HbA1c与快乐缺乏症、忧郁症特征显著相关。腹围和BMI与快感缺乏特征显著相关。在没有当前抑郁的亚组中，IL-6和腹围保持明显的边缘，具有快感缺乏特征。在老年人中，tnf - α /忧郁症和IL-6/认知问题是额外的相关优势。在混杂校正回归分析中，观察到的相关性仍然具有统计学意义，并遵循特定的模式。结论症状聚类在识别相关免疫代谢生物标志物方面优于依赖抑郁症二分类诊断。这项研究是了解免疫代谢抑郁症的特殊性的第一步，可以更好地进行风险分层，并指导多民族老龄化人群的个性化预防和治疗策略。

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引用次数: 0

Viral infections and risk of mental illness: A Mendelian randomization study 病毒感染与精神疾病风险：一项孟德尔随机研究

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-16 DOI: 10.1016/j.bbih.2025.101104

Jian-Wei Huang , Yi-Fei Wang , Miao Tang , Qian-Qian Cui , Ying Guo , Shuang-Qi Gao

Background

Prior epidemiological evidence suggests associations between viral infections and psychiatric disorders, yet causal relationships remain insufficiently characterized. This study aims to investigate potential causal links using genetic instrumental variables.

Methods

A two-sample Mendelian randomization (MR) analysis was conducted using pooled European-ancestry genomic data. Exposures included hepatitis B virus (HBV), human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human papillomavirus (HPV), and Epstein-Barr virus (EBV) infections. Outcomes encompassed generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), schizophrenia (SCH), major depressive disorder (MDD), and manic episodes. Causal estimates were primarily derived via inverse variance weighting (IVW), with robustness assessed through MR-Egger regression, weighted median, and pleiotropy-robust methods. Heterogeneity and horizontal pleiotropy were evaluated via Cochran's Qstatistic, MR-Egger intercept, and sensitivity plots.

Results

HBV infection was associated with reduced GAD risk (OR = 0.94; 95 % CI [0.91, 0.97]; P = 0.0012). Similarly, HIV and SARS-CoV-2 infections exhibited protective effects against OCD (OR = 0.84; 95 % CI [0.72, 0.97]; P = 0.019 and OR = 0.78; 95 % CI [0.61, 0.99]; P = 0.039). HPV infection decreased SCH risk (OR = 0.84; 95 % CI [0.76, 0.92]; P = 0.0005). Conversely, EBV infection elevated MDD risk (OR = 1.00; 95 % CI [1.00, 1.01]; P = 0.0015). Sensitivity analyses confirmed minimal pleiotropy (Q > 0.05; MR-Egger intercept P > 0.1).

Conclusions

This MR analysis provides genetic evidence supporting causal roles of specific viral infections in psychiatric disorders. Findings underscore the clinical relevance of viral prevention strategies for mental health outcomes.

背景先前的流行病学证据表明病毒感染与精神疾病之间存在关联，但因果关系仍未充分表征。本研究旨在利用遗传工具变量探讨潜在的因果关系。方法采用双样本孟德尔随机化（MR）分析，收集欧洲人祖先基因组数据。暴露包括乙型肝炎病毒（HBV）、人类免疫缺陷病毒（HIV）、严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）、人乳头瘤病毒（HPV）和eb病毒（EBV）感染。结果包括广泛性焦虑症（GAD）、强迫症（OCD）、精神分裂症（SCH）、重度抑郁症（MDD）和躁狂发作。因果估计主要通过逆方差加权（IVW）得出，并通过MR-Egger回归、加权中位数和多效性稳健方法评估稳健性。异质性和水平多效性通过Cochran’s q统计量、MR-Egger截距和敏感性图进行评估。结果shbv感染与GAD风险降低相关（OR = 0.94; 95% CI [0.91, 0.97]; P = 0.0012）。同样，HIV和SARS-CoV-2感染对强迫症表现出保护作用（OR = 0.84; 95% CI [0.72, 0.97]; P = 0.019和OR = 0.78; 95% CI [0.61, 0.99]; P = 0.039）。HPV感染降低了SCH风险（OR = 0.84; 95% CI [0.76, 0.92]; P = 0.0005）。相反，EBV感染会增加MDD的风险（OR = 1.00; 95% CI [1.00, 1.01]; P = 0.0015）。敏感性分析证实了最小的多效性（Q > 0.05； MR-Egger截距P >； 0.1）。结论：磁共振分析提供了支持特定病毒感染在精神疾病中的因果作用的遗传证据。研究结果强调了病毒预防策略与心理健康结果的临床相关性。

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引用次数: 0

Vegetable intake is associated with lower psychological stress via increased anti-inflammatory responses in pregnant women with chronic diseases 慢性疾病孕妇的蔬菜摄入通过增加抗炎反应与降低心理压力相关

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-16 DOI: 10.1016/j.bbih.2025.101106

Rosa S. Wong , Keith T.S. Tung , Patrick Ip

Women with chronic diseases are susceptible to inflammation and stress during pregnancy. Dietary factors such as vegetable consumption can influence the level of inflammation markers in the body, which research has shown to be associated with stress levels. This study examined the moderating role of vegetable intake in the association between chronic disease history and stress levels via anti-inflammatory cytokine interleukin-10 (IL-10) in pregnant women. We recruited 239 pregnant women from antenatal clinics and used an electronic food frequency questionnaire to survey their vegetable intake. Plasma samples were collected at enrollment and assayed for IL-10. Perceived stress scale was completed one month after the assessment of dietary intake. The relationships among chronic disease history, vegetable intake, IL-10 levels, and stress levels were explored using moderated mediation analysis. Pregnant women with chronic diseases demonstrated elevated stress levels and decreased IL-10 levels compared to those without chronic conditions. However, a significant interaction was observed between vegetable intake and chronic disease history in modulating IL-10 levels (B = 0.09, p = 0.007). Specifically, consuming vegetables was positively associated with IL-10 levels in women with chronic diseases, while this association was not observed in women without chronic conditions. When consuming high levels of vegetables, women with chronic diseases were found to experience lower stress levels than those without (B = −0.43; Boot SE = 0.28; LLCI = −1.06; ULCI = −0.01). It is crucial for pregnant women with chronic diseases to consume a vegetable-rich diet, which could benefit their mental health by potentially reducing inflammation during pregnancy.

患有慢性疾病的妇女在怀孕期间容易受到炎症和压力的影响。饮食因素，如蔬菜的摄入量，可以影响体内炎症标志物的水平，研究表明，这与压力水平有关。本研究通过抗炎细胞因子白细胞介素-10 （IL-10）在孕妇中研究了蔬菜摄入量在慢性疾病史和应激水平之间的调节作用。我们从产前诊所招募了239名孕妇，并使用电子食物频率问卷调查她们的蔬菜摄入量。在入组时收集血浆样本并检测IL-10。在饮食摄入评估后一个月完成感知压力量表。采用有调节的中介分析探讨慢性疾病史、蔬菜摄入量、IL-10水平和应激水平之间的关系。与没有慢性疾病的孕妇相比，患有慢性疾病的孕妇表现出压力水平升高和IL-10水平降低。然而，蔬菜摄入量和慢性疾病史在调节IL-10水平方面存在显著的相互作用（B = 0.09, p = 0.007）。具体来说，在患有慢性疾病的女性中，食用蔬菜与IL-10水平呈正相关，而在没有慢性疾病的女性中没有观察到这种关联。当食用大量蔬菜时，患有慢性疾病的妇女的压力水平低于没有蔬菜的妇女（B = - 0.43; Boot SE = 0.28; LLCI = - 1.06; ULCI = - 0.01）。对于患有慢性疾病的孕妇来说，食用富含蔬菜的饮食是至关重要的，这可以通过潜在地减少怀孕期间的炎症来有益于她们的心理健康。

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引用次数: 0

Dysregulated miR-1246 and miR-1253 link inflammatory protein markers in plasma to major depressive disorder in female adolescents miR-1246和miR-1253失调将血浆炎症蛋白标志物与女性青少年重度抑郁症联系起来

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-16 DOI: 10.1016/j.bbih.2025.101108

Kristine Johannessen , Dušan Braný , Dana Dvorská , Michaela Krivošová , Miloslav Oppa , Igor Ondrejka , Ján Strnádel , Nikola Ferencová , Ingrid Tonhajzerová , Zuzana Danková , Erika Halašová , Juraj Mokrý , Betina Elfving

Major depressive disorder (MDD) in adolescents is a prevalent psychiatric condition worldwide with severe consequences. Growing evidence shows that microRNAs (miRNAs) regulate many processes hypothesized to be involved in the pathogenesis of MDD including inflammation, suggesting their suitability as biomarkers. Still, more research is needed regarding miRNAs as biomarkers and the role of inflammation in adolescents with MDD.

This study applied the NanoString nCounter technology to identify dysregulated miRNAs in plasma from hospitalized female adolescents with MDD compared to healthy controls, as well as before and after antidepressant treatment. A multiplexed immunoassay was also performed to assess the plasma levels of 27 inflammatory proteins. A total of 33 patients and 14 healthy controls were included in the study.

miR-1246 and miR-1253 were downregulated in female adolescents with MDD compared to healthy controls, suggesting their potential as diagnostic biomarkers. Additionally, miR-496 was downregulated with treatment, indicating its potential as a prognostic biomarker. Moreover, increased levels of PDGF-BB and IL-7 were seen in adolescents with MDD compared to healthy controls, while IL-9 and MIP-1β levels decreased with antidepressant treatment. Finally, the expression of specific miRNAs were found to correlate with the levels of several inflammatory proteins.

In summary, miR-1246, miR-1253, and miR-496 are suggested as potential diagnostic and prognostic biomarkers. Furthermore, this study contributes in more detail to our understanding of miRNAs, inflammation, and MDD in female adolescents.

青少年重度抑郁障碍（MDD）是一种世界范围内普遍存在的严重后果的精神疾病。越来越多的证据表明，microRNAs （miRNAs）调节了许多被假设参与MDD发病机制的过程，包括炎症，这表明它们作为生物标志物的适用性。尽管如此，关于mirna作为生物标志物和炎症在青少年重度抑郁症中的作用，还需要更多的研究。本研究应用NanoString nCounter技术鉴定住院的MDD女性青少年血浆中与健康对照者以及抗抑郁治疗前后的失调mirna。采用多重免疫分析法评估27种炎症蛋白的血浆水平。研究共纳入33名患者和14名健康对照者。与健康对照组相比，miR-1246和miR-1253在患有重度抑郁症的女性青少年中下调，这表明它们具有作为诊断性生物标志物的潜力。此外，miR-496在治疗过程中下调，表明其作为预后生物标志物的潜力。此外，与健康对照相比，MDD青少年患者的PDGF-BB和IL-7水平升高，而IL-9和MIP-1β水平在抗抑郁治疗后下降。最后，发现特定mirna的表达与几种炎症蛋白的水平相关。总之，miR-1246、miR-1253和miR-496被认为是潜在的诊断和预后生物标志物。此外，这项研究有助于我们更详细地了解女性青少年的mirna、炎症和MDD。

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引用次数: 0

Memory under siege: the cognitive costs of smoking and vaping 被围困的记忆：吸烟和电子烟的认知成本

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-09-15 DOI: 10.1016/j.bbih.2025.101102

Brian G. Oliver , Qi Wang , Rochelle A. Yarak , Tharathip Hikasem , Catherine A. Gorrie , Chenju Yi , Hui Chen

Memory function is critically essential across all life stages, yet it is increasingly compromised by exposure to airborne pollutants due to human behaviours. This review examines the adverse impacts of tobacco smoke and e-cigarette vapour on memory function, emphasising the risks to younger populations. Both pollutants are potent oxidants that induce oxidative stress and inflammatory responses in the brain, leading to synaptic injury and neuronal apoptosis. These processes compromise neuronal integrity and function, potentially resulting in early-onset dementia. Additionally, third-hand exposure to tobacco smoke and e-cigarette vapour, through re-exposure to toxic chemicals on surfaces or clothing, poses significant risks, especially to toddlers. Epigenetic mechanisms, including DNA methylation and histone modification, further exacerbate these effects by altering gene expression critical for brain development and function. This review highlights the necessity for further research to develop risk-reduction strategies to protect cognitive health from these pollutants.

记忆功能在生命的各个阶段都是至关重要的，但由于人类的行为，它越来越多地受到空气中污染物的影响。这篇综述研究了烟草烟雾和电子烟蒸汽对记忆功能的不利影响，强调了对年轻人的风险。这两种污染物都是强效氧化剂，可诱导脑内氧化应激和炎症反应，导致突触损伤和神经元凋亡。这些过程损害了神经元的完整性和功能，可能导致早发性痴呆。此外，通过再次接触表面或衣服上的有毒化学物质，三手接触烟草烟雾和电子烟蒸汽会带来重大风险，尤其是对幼儿。表观遗传机制，包括DNA甲基化和组蛋白修饰，通过改变对大脑发育和功能至关重要的基因表达，进一步加剧了这些影响。这篇综述强调了进一步研究制定降低风险策略以保护认知健康免受这些污染物影响的必要性。

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引用次数: 0