Pub Date : 2025-09-25DOI: 10.1016/j.bbih.2025.101110
A.S. Padhye , I.J. Koralnik , B.A. Hanson , L. Visvabharathy , R.K. DeLisle , G. Tachas
Background
SARS-CoV-2 responsible for COVID-19 caused a global pandemic, with billions of infections, millions of deaths and ongoing manifestations post COVID-19. “Long Covid”, a Post-Acute Sequelae of COVID-19 (PASC), is an ongoing global healthcare problem, affecting all age groups, with many manifestations, and occurring despite vaccines and antivirals. Neurologic manifestations of PASC (Neuro-PASC) such as brain fog can last for years and are amongst the most debilitating and prevalent. There is a need for diagnostic tools and treatments.
Methods
Plasma samples from 48 non-hospitalized PASC patients with diagnosed Neuro-PASC symptoms (NP), 20 convalescent control (CC) subjects, and 24 unvaccinated healthy control (HC) subjects, was used to generate data on over 7000 proteins using the SomaLogic® proteomics platform. ProViz® software was used to perform T-tests, U-Tests, ANOVA and Kruskalis-Wallis tests at a Bonferroni p < 0.05 and a Benjamini-Hochberg corrected False Discovery Rate <0.02, and box plots and knowhow used to identify diagnostic biomarkers and therapeutic targets.
Results
C5a, TGFβ1, and Gliomedin, used together differentiated patients with Neuro-PASC from control subjects with 94 % sensitivity and 86 % specificity, a 90 % accuracy. Additional biomarkers, Gal3ST1, IFNλ1, and GHRH, improved accuracy to 94 %, and a combination of 5 more biomarkers, LFA-3, FASLG + Transgelin-1 and GPNMB + IGHG1, improved accuracy close to 100 %. These markers are suggestive of pathways involved in Neuro-PASC pathogenesis. A dozen partly overlying biomarkers were modulated to which there are FDA approved drugs.
Conclusion
C5a, TGFβ1, Gliomedin expressed highly in serum could be developed as a diagnostic tool, and with clinical assessment used to personalize treatments with repurposed novel drugs.
{"title":"Blood diagnostic biomarkers for neurologic manifestations of long COVID","authors":"A.S. Padhye , I.J. Koralnik , B.A. Hanson , L. Visvabharathy , R.K. DeLisle , G. Tachas","doi":"10.1016/j.bbih.2025.101110","DOIUrl":"10.1016/j.bbih.2025.101110","url":null,"abstract":"<div><h3>Background</h3><div>SARS-CoV-2 responsible for COVID-19 caused a global pandemic, with billions of infections, millions of deaths and ongoing manifestations post COVID-19. “Long Covid”, a Post-Acute Sequelae of COVID-19 (PASC), is an ongoing global healthcare problem, affecting all age groups, with many manifestations, and occurring despite vaccines and antivirals. Neurologic manifestations of PASC (Neuro-PASC) such as brain fog can last for years and are amongst the most debilitating and prevalent. There is a need for diagnostic tools and treatments.</div></div><div><h3>Methods</h3><div>Plasma samples from 48 non-hospitalized PASC patients with diagnosed Neuro-PASC symptoms (NP), 20 convalescent control (CC) subjects, and 24 unvaccinated healthy control (HC) subjects, was used to generate data on over 7000 proteins using the SomaLogic® proteomics platform. ProViz® software was used to perform T-tests, U-Tests, ANOVA and Kruskalis-Wallis tests at a Bonferroni p < 0.05 and a Benjamini-Hochberg corrected False Discovery Rate <0.02, and box plots and knowhow used to identify diagnostic biomarkers and therapeutic targets.</div></div><div><h3>Results</h3><div>C5a, TGFβ1, and Gliomedin, used together differentiated patients with Neuro-PASC from control subjects with 94 % sensitivity and 86 % specificity, a 90 % accuracy. Additional biomarkers, Gal3ST1, IFNλ1, and GHRH, improved accuracy to 94 %, and a combination of 5 more biomarkers, LFA-3, FASLG + Transgelin-1 and GPNMB + IGHG1, improved accuracy close to 100 %. These markers are suggestive of pathways involved in Neuro-PASC pathogenesis. A dozen partly overlying biomarkers were modulated to which there are FDA approved drugs.</div></div><div><h3>Conclusion</h3><div>C5a, TGFβ1, Gliomedin expressed highly in serum could be developed as a diagnostic tool, and with clinical assessment used to personalize treatments with repurposed novel drugs.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101110"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325427","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}
Pub Date : 2025-09-25DOI: 10.1016/j.bbih.2025.101115
Ethiane Segabinazi , Fernando R. Tocantins , Talita Glaser , Tamires Maglio , Nathalia C. Oliveira , Andrelissa Gorete Castanha , Fabiele Baldino Russo , Paulo Emílio Corrêa Leite , Anita Brito , Camila Vieira Molina , Gabriela Prado Paludo , Raquel de Oliveira Souza , Simone Ravena Maia Alves , Marielton dos Passos Cunha , Henning Ulrich , Edison Luiz Durigon , Paola Minoprio , Patricia C.B. Beltrão-Braga
NeuroCOVID-19 has emerged as a significant global health concern, presenting a wide spectrum of neurological manifestations, including headaches, brain fog and anosmia. While mounting evidence indicates that SARS-CoV-2 infection compromises central nervous system (CNS) function, the precise processes underlying these effects remain incompletely understood. Although neurons have been extensively studied, astrocytes – critical regulators of brain homeostasis - have been largely overlooked in this context. In this study, we position astrocytes as central players in the neuropathological landscape of neuroCOVID-19, challenging their traditionally supportive role. We evaluated the frequent neurological symptoms in a Brazilian cohort of COVID-19 patients and investigated whether SARS-CoV-2 infection of cortical astrocytes induces neuroinflammation, glutamatergic imbalance, vasoregulatory disruption, and apoptosis as likely pathogenic processes. Among 162 COVID-19-positive patients, headache (53.09 %), brain fog (42.15 %), and anosmia (38.72 %) were the most commonly reported symptoms. Using human-induced pluripotent stem cell (hiPSC)-derived astrocytes, we found that SARS-CoV-2 infection promotes a pronounced pro-inflammatory response, evidenced by elevated levels of IL-6, IL-15, and IL-4 in the culture supernatant. Infected astrocytes also showed reduced mRNA expression of KLK1 and EAAT1, key genes involved in vasodilation and glutamate clearance, respectively. Additionally, a significant increase in cleaved caspase-3-positive cells indicated enhanced apoptosis. Overall, these findings demonstrate that SARS-CoV-2 disrupts astrocyte homeostatic functions, leading to neuroinflammation, excitatory neurotransmission dysregulation, and cell death that may, hypothetically, underlie the neurological sequelae of COVID-19. By reframing astrocytes as active protagonists, this study highlights their essential role in CNS vulnerability. It also suggests potential targets for the future investigation in the development of therapies against the neurological complications of COVID-19.
{"title":"Astroglia-mediated neuroinflammation as a putative mechanism of neurological outcomes in COVID-19? Insights from a Brazilian cohort","authors":"Ethiane Segabinazi , Fernando R. Tocantins , Talita Glaser , Tamires Maglio , Nathalia C. Oliveira , Andrelissa Gorete Castanha , Fabiele Baldino Russo , Paulo Emílio Corrêa Leite , Anita Brito , Camila Vieira Molina , Gabriela Prado Paludo , Raquel de Oliveira Souza , Simone Ravena Maia Alves , Marielton dos Passos Cunha , Henning Ulrich , Edison Luiz Durigon , Paola Minoprio , Patricia C.B. Beltrão-Braga","doi":"10.1016/j.bbih.2025.101115","DOIUrl":"10.1016/j.bbih.2025.101115","url":null,"abstract":"<div><div>NeuroCOVID-19 has emerged as a significant global health concern, presenting a wide spectrum of neurological manifestations, including headaches, brain fog and anosmia. While mounting evidence indicates that SARS-CoV-2 infection compromises central nervous system (CNS) function, the precise processes underlying these effects remain incompletely understood. Although neurons have been extensively studied, astrocytes – critical regulators of brain homeostasis - have been largely overlooked in this context. In this study, we position astrocytes as central players in the neuropathological landscape of neuroCOVID-19, challenging their traditionally supportive role. We evaluated the frequent neurological symptoms in a Brazilian cohort of COVID-19 patients and investigated whether SARS-CoV-2 infection of cortical astrocytes induces neuroinflammation, glutamatergic imbalance, vasoregulatory disruption, and apoptosis as likely pathogenic processes. Among 162 COVID-19-positive patients, headache (53.09 %), brain fog (42.15 %), and anosmia (38.72 %) were the most commonly reported symptoms. Using human-induced pluripotent stem cell (hiPSC)-derived astrocytes, we found that SARS-CoV-2 infection promotes a pronounced pro-inflammatory response, evidenced by elevated levels of IL-6, IL-15, and IL-4 in the culture supernatant. Infected astrocytes also showed reduced mRNA expression of <em>KLK1</em> and <em>EAAT1</em>, key genes involved in vasodilation and glutamate clearance, respectively. Additionally, a significant increase in cleaved caspase-3-positive cells indicated enhanced apoptosis. Overall, these findings demonstrate that SARS-CoV-2 disrupts astrocyte homeostatic functions, leading to neuroinflammation, excitatory neurotransmission dysregulation, and cell death that may, hypothetically, underlie the neurological sequelae of COVID-19. By reframing astrocytes as active protagonists, this study highlights their essential role in CNS vulnerability. It also suggests potential targets for the future investigation in the development of therapies against the neurological complications of COVID-19.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101115"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268332","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}
Pub Date : 2025-09-22DOI: 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 (padj = 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 (padj = 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.
{"title":"Alterations in functional connectivity analyzed using MREG in patients with suspected autoimmune psychosis spectrum syndromes","authors":"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","doi":"10.1016/j.bbih.2025.101111","DOIUrl":"10.1016/j.bbih.2025.101111","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>After correction for multiple testing, functional connectivity between the left middle cingulate/paracingulate gyri and the right insula (p<sub>adj</sub> = 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<sub>adj</sub> = 0.043).</div></div><div><h3>Discussion</h3><div>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.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101111"},"PeriodicalIF":3.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268835","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}
Pub Date : 2025-09-19DOI: 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。
{"title":"High dietary phosphate intake induces anxiety in normal male mice","authors":"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","doi":"10.1016/j.bbih.2025.101112","DOIUrl":"10.1016/j.bbih.2025.101112","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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).</div></div><div><h3>Results</h3><div>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, <em>P</em> = 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 %, <em>P</em> = 0.02) but without concomitant differences in brain vascularization. Immunophenotyping showed that HP-diet significantly reduced TCRβ<sup>+</sup> T cells and NK1.1<sup>+</sup> NK cells (both <em>P</em> < 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.</div></div><div><h3>Conclusions</h3><div>Collectively, this study highlights that habitual consumption of high dietary phosphate in mice may induce chronic anxiety<em>,</em> 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.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101112"},"PeriodicalIF":3.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121291","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}
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.
{"title":"The roles of exosomes in the pathogenesis and treatment of coronary heart disease with depression and/or anxiety","authors":"Jiecheng Huang , Ying Piao , Xin Jiang , Jingjin Liu","doi":"10.1016/j.bbih.2025.101113","DOIUrl":"10.1016/j.bbih.2025.101113","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101113"},"PeriodicalIF":3.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121290","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}
Pub Date : 2025-09-19DOI: 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, PFDR < 0.001) and IL8 (F(384.4) = 15.28, PFDR = 0.005) levels following the first vaccine dose and smaller increases in Spike (F(508.7) = 8.58, PFDR = 0.005), S1 (F(506.9) = 19.76, PFDR < 0.0001) and S2 (F(507.8) = 20.96, PFDR < 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.
{"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}
Pub Date : 2025-09-17DOI: 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。
{"title":"Inflammatory predictors of Post-COVID fatigue","authors":"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","doi":"10.1016/j.bbih.2025.101109","DOIUrl":"10.1016/j.bbih.2025.101109","url":null,"abstract":"<div><div>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, <em>p</em> = .019) correlated with reduced awareness of cognitive fatigue. These findings highlight the role of acute inflammation in the persistence of post-COVID fatigue.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101109"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159156","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}
Pub Date : 2025-09-17DOI: 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.
{"title":"Networks and clusters of immunometabolic biomarkers and depression-associated features in middle-aged and older community-dwelling US adults with and without depression","authors":"Asma Hallab , The Health and Aging Brain Study (HABS-HD) Study Team","doi":"10.1016/j.bbih.2025.101103","DOIUrl":"10.1016/j.bbih.2025.101103","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101103"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221577","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}
Pub Date : 2025-09-16DOI: 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。
{"title":"Viral infections and risk of mental illness: A Mendelian randomization study","authors":"Jian-Wei Huang , Yi-Fei Wang , Miao Tang , Qian-Qian Cui , Ying Guo , Shuang-Qi Gao","doi":"10.1016/j.bbih.2025.101104","DOIUrl":"10.1016/j.bbih.2025.101104","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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).</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101104"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121155","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}
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