Brain, Behavior, and Immunity最新文献

{"title":"A Phenome-Wide association study (PheWAS) of genetic risk for C-reactive protein in children of European Ancestry: Results from the ABCD study","authors":"Sara A. Norton , Aaron J. Gorelik , Sarah E. Paul , Emma C. Johnson , David AA Baranger , Jayne L Siudzinski , Zhaolong Adrian Li , Erin Bondy , Hailey Modi , Nicole R. Karcher , Tamara Hershey , Alexander S. Hatoum , Arpana Agrawal , Ryan Bogdan","doi":"10.1016/j.bbi.2025.04.012","DOIUrl":"10.1016/j.bbi.2025.04.012","url":null,"abstract":"<div><h3>Background</h3><div>C-reactive protein (CRP) is a moderately heritable marker of systemic inflammation that is associated with adverse physical and mental health outcomes. Identifying factors associated with genetic liability to elevated CRP in childhood may inform our understanding of variability in CRP that could be targeted to prevent and/or delay the onset of related health outcomes.</div></div><div><h3>Methods</h3><div>We conducted a phenome-wide association study (PheWAS) of genetic risk for elevated CRP (i.e. CRP polygenic risk score [PRS]) among children genetically similar to European ancestry reference populations (median analytic n = 5,509, range = 120–5,556) from the Adolescent Brain and Cognitive Development<sup>SM</sup> (ABCD) Study baseline assessment. Associations between CRP PRS and 2,377 psychosocial and neuroimaging phenotypes were estimated using independent mixed effects models nested by recruitment site (or scanner) and family, with ancestral genomic principal components (n = 10), age, and sex, as well as global brain metrics (when relevant) included as fixed effect covariates. <em>Post hoc</em> analyses examined whether: (1) covarying for measured body mass index (BMI) or removing the shared genetic architecture between CRP and BMI altered phenotypic associations, (2) sex moderated CRP PRS associations, and (3) associations were unconfounded by assortative mating or passive gene-environment correlations (using <em>within-family</em> analyses). Multiple testing was adjusted for using Bonferroni and false discovery rate (FDR) correction.</div></div><div><h3>Results</h3><div>Nine phenotypes were positively associated with CRP PRS after multiple testing correction: five weight- and eating-related phenotypes (e.g. BMI, overeating), three phenotypes related to caregiver somatic problems (e.g. caregiver somatic complaints), as well as weekday video watching (all <em>p</em>s = 1.2 x 10<sup>-7</sup> − 2.5 x 10<sup>-4</sup>, all <em>p<sub>FDR</sub></em>s = 0.0002–0.05). No neuroimaging phenotypes were associated with CRP PRS (all <em>p</em>s = 0.0003–0.998; all <em>p<sub>FDR</sub></em>s = 0.08–0.998) after correction for multiple testing. Eating and weight-related phenotypes remained associated with CRP PRS in within-family analyses. Covarying for BMI resulted in largely consistent results, and sex did not moderate any CRP PRS associations. Removing the shared genetic variance between CRP and BMI attenuated all relationships; associations with weekday video watching, caregiver somatic problems and caregiver report that the child is overweight remained significant while associations with waist circumference, weight, and caregiver report that child overeats did not.</div></div><div><h3>Discussion</h3><div>Genetic liability to elevated CRP is associated with higher weight, eating, and weekday video watching during childhood as well as caregiver somatic problems. These associations were consistent with direct genetic effects (i.","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 487-496"},"PeriodicalIF":8.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glymphatic function and choroid plexus volume is associated with systemic inflammation and oxidative stress in major depressive disorder","authors":"Wenyue Gong ,&nbsp;Qinghua Zhai ,&nbsp;Yiwen Wang ,&nbsp;Azi Shen ,&nbsp;Yinghong Huang ,&nbsp;Kaiyu Shi ,&nbsp;Yingying Huang ,&nbsp;Moxuan Song ,&nbsp;Rui Yan ,&nbsp;Zhijian Yao ,&nbsp;Qing Lu","doi":"10.1016/j.bbi.2025.04.008","DOIUrl":"10.1016/j.bbi.2025.04.008","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory processes were recognized as key factors in the pathophysiology of major depressive disorder (MDD). The choroid plexus (ChP) and glymphatic system played central roles in immune interactions between the brain and periphery. However, their specific roles in MDD and their relationship with systemic inflammation and oxidative stress remained unclear.</div></div><div><h3>Methods</h3><div>This study finally included 665 MDD patients and 338 healthy controls. Clinical data and MRI scans were collected, and some patients also underwent blood routine and biochemical tests. ChP volume was manually segmented, and the diffusion tensor imaging along the perivascular space (DTI-ALPS) index, reflecting glymphatic function, was obtained through the FSL pipeline. The differences in these dices between groups were compared, and their associations with systemic inflammation and oxidative stress were analyzed.</div></div><div><h3>Results</h3><div>MDD patients showed increased ChP volume (total: <em>d</em> = 0.316, <em>p</em> &lt; 0.001; left: <em>d</em> = 0.317, <em>p</em> &lt; 0.001; right: <em>d</em> = 0.268, <em>p</em> = 0.003) and decreased DTI-ALPS index (<em>d</em> = −0.144, <em>p</em> = 0.022), with a negative correlation between them (<em>ρ</em> = −0.135, <em>p &lt;</em> 0.001). In MDD patients, lower DTI-ALPS index was correlated with higher LHR (<em>ρ</em> = −0.107, <em>p</em> = 0.025) and MHR (<em>ρ</em> = −0.126, <em>p</em> = 0.008). Larger right ChP volume was associated with higher MLR (<em>ρ</em> = 0.107, <em>p</em> = 0.009), SIRI (<em>ρ</em> = 0.086, <em>p</em> = 0.036), PIV (<em>ρ</em> = 0.086, <em>p</em> = 0.036), MHR (<em>ρ</em> = 0.136, <em>p</em> = 0.004), and PHR (<em>ρ</em> = 0.126, <em>p</em> = 0.008), while larger total ChP volume was correlated with higher MHR (<em>ρ</em> = 0.097, <em>p</em> = 0.042) and PHR (<em>ρ</em> = 0.114, <em>p</em> = 0.017).</div></div><div><h3>Conclusion</h3><div>MDD appeared to be accompanied by an increase in ChP volume and a decrease in glymphatic function, and these changes were related to systemic inflammation and oxidative stress.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 266-275"},"PeriodicalIF":8.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human leukocyte antigen (HLA) class I and II genetic relationships with brain imaging measures: A systematic review and meta-analysis","authors":"Lusi Zhang ,&nbsp;Chengmin Yang ,&nbsp;Wenjing Zhang ,&nbsp;Su Lui ,&nbsp;Jeffrey R. Bishop","doi":"10.1016/j.bbi.2025.04.011","DOIUrl":"10.1016/j.bbi.2025.04.011","url":null,"abstract":"<div><div>This systematic review and <em>meta</em>-analysis synthesizes current evidence on associations between genetic polymorphisms of human leukocyte antigen (HLA) class I and II molecules, which play key roles in antigen presentation and immune response regulation, and brain imaging phenotypes across various neurological and psychiatric conditions. The strongest associations were observed in multiple sclerosis (MS), where HLA-DRB1*15:01 was linked to increased lesion volume and disease progression. Meta-analyses revealed significant pooled effect sizes for both T1 and T2 lesion volumes. Emerging evidence also suggests that variants in HLA class I and II genes contribute to brain structural changes associated with age-related cognitive decline, schizophrenia, and Gulf War illness. Our findings revealed stronger patterns of association between HLA class II polymorphisms with brain imaging implications as compared to class I in neurodegenerative conditions. Considering HLA class II roles in exogenous protein/peptide presentation, this highlights the potential importance of neuroimmune-environmental interactions as contributing factors to disease pathogenesis and progression. Population-based studies from the UK Biobank highlight the potential influence of HLA class I and II genetic polymorphisms on brain structure beyond disease-specific contexts, suggesting broader implications for neurodevelopment and neurodegeneration. Despite these emerging insights, the limited availability of studies using imaging modalities beyond structural MRI, along with inconsistent findings within specific diseases and across conditions, underscores the need for further investigation into the mechanistic contributions of specific genetic variants on impacting brain structural and functional outcomes. Future research should include larger, more diverse study cohorts and employ advanced genotyping technologies to provide a more comprehensive investigations of HLA’s role on brain health across the lifespan.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 336-351"},"PeriodicalIF":8.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with inflammatory cytokines in family caregivers of allogeneic hematopoietic stem cell transplantation (HSCT) recipients","authors":"Lena J. Lee,&nbsp;Jennifer J. Barb,&nbsp;Elisa H. Son,&nbsp;Li Yang,&nbsp;Chantal Gerrard,&nbsp;Gwenyth R. Wallen","doi":"10.1016/j.bbi.2025.04.013","DOIUrl":"10.1016/j.bbi.2025.04.013","url":null,"abstract":"<div><h3>Background</h3><div>Family caregiving has been proposed as chronic stress that may lead to immune health risks through increased systemic inflammation. Cytokines are key modulators of inflammation via a complex network of interactions. However, most studies examined only a single to a few cytokines to determine whether they correlate with psychobehavioral variables of interest. This study aimed to investigate factors influencing multiple inflammatory cytokines in family caregivers of allogeneic hematopoietic stem cell transplantation (HSCT) recipients.</div></div><div><h3>Methods</h3><div>Baseline data from a randomized controlled clinical trial at the National Institutes of Health Clinical Center were collected from caregivers of allogeneic HSCT recipients. The 20 serum cytokine levels were measured using multiplexed cytokine immunoassays. Multiple linear regression was conducted.</div></div><div><h3>Results</h3><div>Caregivers (N = 45) were 44.6 ± 15.4 years of age; primarily female (87 %), White (66 %), non-Hispanic (82 %), and a spouse/partner of the HSCT recipient (56 %). Caring for HSCT recipients with hematologic malignancy predicted higher IL-12/IL-23p40 than caring for non-malignant HSCT recipients (<em>β</em> = 0.291, <em>p</em> = 0.044). Medication use was associated with higher IL-15 (<em>β</em> = 0.425, <em>p</em> = 0.017). Caregiver BMI overweight (<em>β</em> = 0.342, <em>p</em> = 0.043) or obese (<em>β</em> = 0.411, <em>p</em> = 0.010), taking prescribed medications (<em>β</em> = 0.521, <em>p</em> = 0.007), caregiving 8 to 16 h (<em>β</em> = 0.396, <em>p</em> = 0.027) or more than 16 h per day (<em>β</em> = 0.510, <em>p</em> = 0.006) predicted higher TNF-α than the counterparts.</div></div><div><h3>Discussion</h3><div>These findings suggest inflammatory responses may be associated with providing care to an HSCT recipient, especially in caregivers who take medications, provide more hours of care a day and care for patients with hematologic malignancies. The results highlight a physiological response of stress and bring to light the importance of developing interventions focused on reducing time spent caregiving, such as a respite care program for family caregivers.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 362-369"},"PeriodicalIF":8.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fueling the fire in the lung-brain axis: The salience network connects allergen-provoked TH17 responses to psychological stress in asthma","authors":"Estelle T. Higgins ,&nbsp;William W. Busse ,&nbsp;Stephane Esnault ,&nbsp;Bradley T. Christian ,&nbsp;Danika R. Klaus ,&nbsp;Julia C. Bach ,&nbsp;Corrina J. Frye ,&nbsp;Melissa A. Rosenkranz","doi":"10.1016/j.bbi.2025.04.004","DOIUrl":"10.1016/j.bbi.2025.04.004","url":null,"abstract":"<div><h3>Background</h3><div>Asthma, a highly prevalent chronic inflammatory disease of the airways, results in an average of 10 deaths per day in the U.S., and psychological stress hinders its effective management. Threat-sensitive neurocircuitry, active during psychological stress, may intensify airway inflammatory responses and contribute to poor clinical outcomes. However, the neural mechanisms and descending pathways connecting acute stress and inflammatory responses to allergen exposure remain poorly understood. We hypothesized that stress-induced engagement of the salience network would prime Th17 immune pathways and potentiate airway inflammation.</div></div><div><h3>Methods</h3><div>We measured brain glucose metabolism during the Trier Social Stress Test (TSST) and a non-stressful control task using [¹⁸F]fluorodeoxyglucose positron emission tomography (PET) in 28 adults (18F) with asthma. Salivary cortisol was collected to quantify physiological stress responses. Before and after airway provocation with a whole-lung allergen challenge (WL-AG), airway inflammation was assessed using fraction of exhaled nitric oxide (FeNO), sputum % eosinophils, and expression of Th17-related cytokine mRNA in the airway.</div></div><div><h3>Results</h3><div>As expected, the WL-AG increased all inflammatory biomarkers. Acute stress significantly increased salivary cortisol (<em>t</em>(27.3) = -27.3, <em>p</em> &lt; 0.01), but did not significantly affect airway inflammation overall. Instead, more robust cortisol responses to stress predicted increased glucose metabolism in the amygdala, insula, and dorsal anterior cingulate cortex, key nodes in the salience network, as well as increased IL-23A mRNA expression (<em>t</em>(22.1) = 2.38, <em>p</em> = 0.026) and FeNO (<em>t</em>(21.5) = 2.17, <em>p</em> = 0.041). Moreover, differential increases in amygdala and dACC glucose metabolism predicted differential increases IL-23A mRNA expression following WL-AG. In addition, compared to low chronic stress, high chronic stress was associated with enhanced IL-17A mRNA expression in response to acute stress and WL-AG.</div></div><div><h3>Conclusions</h3><div>Individual differences in salience network and cortisol responses to acute stress predict enhanced allergen challenge-provoked Th17-related responses, advancing our understanding of the efferent arm of the lung-brain axis in asthma. This work underscores the importance of translational research for the development of novel interventions that target stress-sensitive brain and immune pathways.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 276-288"},"PeriodicalIF":8.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EZH2-mediated suppression of TIMP1 in spinal GABAergic interneurons drives microglial activation via MMP-9-TLR2/4-NLRP3 signaling in neuropathic pain","authors":"Li Wan ,&nbsp;Haiyue Guo ,&nbsp;Fan Hu ,&nbsp;Yinbing Pan ,&nbsp;Shuo Yang ,&nbsp;Chun-Yi Jiang ,&nbsp;Wentao Liu ,&nbsp;Xuefeng Wu ,&nbsp;Xudong Wu","doi":"10.1016/j.bbi.2025.04.007","DOIUrl":"10.1016/j.bbi.2025.04.007","url":null,"abstract":"<div><div>Effective management of neuropathic pain remains a significant challenge due to the limited understanding of its underlying mechanisms. We found that the FDA-approved enhancer of zeste homolog 2 (EZH2) inhibitor, EPZ6438, can prevent the development of neuropathic pain caused by chronic constriction injury (CCI). Therefore, we utilized EPZ6438 as a probe to investigate the molecular events involved in the early stage of neuropathic pain. RNA-seq analysis reveals that EPZ6438 significantly upregulates <em>Timp1</em> transcription in the spinal cord of mice. As a specific endogenous inhibitor of MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP1) levels significantly decrease in the cerebrospinal fluid of both neuropathic pain patients and the CCI rat models. Importantly, intrathecal administration of mouse recombinant TIMP1 protein (rmTIMP1) reverses CCI-induced mechanical and thermal hyperalgesia. Mechanistically, substance P released from primary sensory neurons suppresses TIMP1 in spinal GABAergic interneurons by elevating EZH2 expression, which enhances H3K27me3 enrichment at the <em>Timp1</em> promoter. Blocking spinal NK1R effectively prevents the downregulation of TIMP1 and alleviates CCI-induced hyperalgesia. The imbalance between TIMP1 and MMP-9 leads to NLRP3 activation in spinal microglia and increases IL-1β maturation via TLR2/4 pathway. TIMP1 injection eliminates MMP-9-induced NLRP3 activation and blocks hyperalgesia, suggesting that TIMP1 is a critical gatekeeper in preventing neuroinflammation during neuropathic pain development.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 234-255"},"PeriodicalIF":8.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do biological alterations precede the onset of psychosis? A systematic review and meta-analysis of immune, cardiometabolic, prolactin and HPA axis alterations in clinical high-risk for psychosis","authors":"Claudia Aymerich ,&nbsp;Borja Pedruzo ,&nbsp;Gonzalo Salazar de Pablo ,&nbsp;Javier Labad ,&nbsp;Robert McCutcheon ,&nbsp;Toby Pillinger ,&nbsp;Miguel Ángel González-Torres ,&nbsp;Vanessa Sanchez-Gistau ,&nbsp;Dominic Oliver ,&nbsp;Daniel Alonso-Alconada ,&nbsp;Pablo Navalón ,&nbsp;Gisela Sugranyes ,&nbsp;Eduard Vieta ,&nbsp;Celso Arango ,&nbsp;Philip McGuire ,&nbsp;Paolo Fusar-Poli ,&nbsp;Ana Catalan","doi":"10.1016/j.bbi.2025.04.009","DOIUrl":"10.1016/j.bbi.2025.04.009","url":null,"abstract":"<div><div>First episode psychosis (FEP) individuals show biological abnormalities preceding antipsychotic treatment. However, it remains unclear whether such alterations are also present before the onset of psychosis. We aim to provide estimates of standardized mean differences for immune, cardiometabolic, prolactin, and HPA axis parameters in individuals at clinical high-risk for psychosis (CHR-P) compared to healthy controls (HC) and FEP individuals, and between CHR-P transitioning to psychosis (CHR-T) compared non-transitioning (CHR-NT). A multistep literature search was performed from database inception until September 25, 2023. PRISMA/MOOSE-compliant and pre-registered (PROSPERO: CRD42024507670) systematic review identified studies reporting on immune, cardiovascular or endocrine parameters in CHR-P samples compared with HC or FEP samples or comparing CHR-T vs CHR-NT. Inter-group differences in magnitude of effect were estimated using Hedges g and estimates were pooled using random-effects <em>meta</em>-analysis. Heterogeneity was high for most outcomes. 37 studies were included, total sample 2509 CHR-P, 710 FEP, and 1444 HC individuals. A statistically significant elevation of pro-inflammatory proteins was found among CHR-P compared with HC (k = 12; N = 1710; g = 0.16; p &lt; 0.01) and FEP (k = 7; g = 0.15; p = 0.04) subjects. Interleukin-6 (IL-6) was increased in CHR-P compared to HC (k = 9; N = 1243; g = 0.54; p &lt; 0.01), and interleukin-4 (IL-4) was increased in CHR-T compared with CHR-NT (k = 2; N = 318; g = 0.36; p &lt; 0.01). CHR-P exhibited stronger cortisol awakening response than FEP subjects (k = 3; N = 173; g = 0.51; p = 0.01). CHR-P and FEP individuals did not show statistically significant differences in terms of prolactin levels. An inflammatory state (particularly marked by elevated IL-6 and IL-4 levels) and HPA axis alterations are present in CHR-P individuals.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 219-233"},"PeriodicalIF":8.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between peripheral inflammation and body mass index on white matter integrity and free water in bipolar II depression","authors":"Yuan Cao ,&nbsp;Paulo Lizano ,&nbsp;Meng Li ,&nbsp;Nils Opel ,&nbsp;Zümrüt Duygu Sen ,&nbsp;Lejla Colic ,&nbsp;Huan Sun ,&nbsp;Xiaoqin Zhou ,&nbsp;Merita Aruci ,&nbsp;Tara Chand ,&nbsp;Xipeng Long ,&nbsp;Gaoju Deng ,&nbsp;Jingshi Mu ,&nbsp;Shuo Guo ,&nbsp;Huaiqiang Sun ,&nbsp;Qiyong Gong ,&nbsp;Changjian Qiu ,&nbsp;Martin Walter ,&nbsp;Zhiyun Jia","doi":"10.1016/j.bbi.2025.04.005","DOIUrl":"10.1016/j.bbi.2025.04.005","url":null,"abstract":"<div><div>Immuno-metabolic dysregulation is implicated in mood disorders and elucidating non-invasive brain correlates may aid clinical translation of pathomechanism. This study aims to investigate the interrelationship between peripheral inflammation and body mass index (BMI) and their effects on white matter (WM) microstructure and free water (FW) in bipolar II depression (BDII-D). Voxel-wise FW and FW-corrected fractional anisotropy (FAt) were compared between 146 BDII-D and 151 healthy controls (HCs) using FSL Randomise. Partial correlations were used to explore associations between BMI, peripheral inflammation, FW measures, and psychiatric symptoms. Moderation analysis examined the interrelationships among BMI, peripheral inflammation, and FW measures. BDII-D showed lower FAt in the genu of the corpus callosum (CC) and bilateral anterior corona radiata, and higher FW in the body of the CC compared with HCs. Higher BMI was linked to lower global FAt (q &lt; 0.001), while higher peripheral inflammation was associated with higher global FW (q ≤ 0.01) in BDII-D. Lower FAt in the genu of the CC and higher FW in the body of CC were significantly related to higher BMI, inflammation, and greater depressive symptoms (q &lt; 0.05). Low-grade Inflammation moderated the relationship between higher BMI and lower FAt in the genu of the CC in BDII-D (B = −3.094e−05, <em>p</em> &lt; 0.001). We found evidence for a mechanistic link between immune-metabolic dysregulation and altered connection in BDII-D. Next to mediating BMI effects on WM integrity, there seems to exist specific relationships between inflammation and BMI with different MR-based tract markers that need further investigation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 208-218"},"PeriodicalIF":8.8,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher blood–brain barrier leakage in schizophrenia-spectrum disorders: A comparative dynamic contrast-enhanced magnetic resonance imaging study with healthy controls","authors":"Joanna Moussiopoulou ,&nbsp;Vladislav Yakimov ,&nbsp;Lukas Roell ,&nbsp;Boris-Stephan Rauchmann ,&nbsp;Hannah Toth ,&nbsp;Julian Melcher ,&nbsp;Iris Jäger ,&nbsp;Isabel Lutz ,&nbsp;Marcel S. Kallweit ,&nbsp;Boris Papazov ,&nbsp;Emanuel Boudriot ,&nbsp;Klaus Seelos ,&nbsp;Amir Dehsarvi ,&nbsp;Mattia Campana ,&nbsp;Florian Raabe ,&nbsp;Isabel Maurus ,&nbsp;Lisa Löhrs ,&nbsp;Matthias Brendel ,&nbsp;Sophia Stöcklein ,&nbsp;Peter Falkai ,&nbsp;Elias Wagner","doi":"10.1016/j.bbi.2025.04.003","DOIUrl":"10.1016/j.bbi.2025.04.003","url":null,"abstract":"<div><h3>Background</h3><div>Blood-brain barrier (BBB) disruptions are presumed to be implicated in schizophrenia-spectrum disorders (SSDs). Previous studies focused on cerebrospinal fluid (CSF) markers, which are imprecise for detecting subtle BBB disruption. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables sensitive investigation of subtle BBB leakage in vivo, yet remains unexplored in SSD research. We hypothesized higher leakage in SSDs compared to healthy controls (HCs), indicating a clinical sub-phenotype.</div></div><div><h3>Methods</h3><div>Forty-one people with SSDs and forty age- and sex-matched HCs were included in this cross-sectional study employing DCE-MRI, clinical characterization, cognitive assessment, blood and CSF analyses. The volume transfer constant K_trans, calculated using the Patlak method to estimate the contrast agent transfer between blood and extravascular space, was compared between groups to detect differences in BBB leakage.</div></div><div><h3>Results</h3><div>Individuals with SSDs showed higher BBB leakage compared to HCs in a widespread pattern, in brain regions typically affected in SSDs. No significant association was detected between leakage and measures of cognition, symptom severity, peripheral inflammation markers and albumin CSF/serum ratio.</div></div><div><h3>Conclusions</h3><div>This is the first study to date reporting BBB leakage in SSDs compared to HCs in multiple brain regions implicated in the disorder. These findings provide insights into disease mechanisms, highlighting the need for further investigation into the role of the BBB in SSDs.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 256-265"},"PeriodicalIF":8.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulation of microglia leads to a rapid antidepressant effect by triggering astrocytic P2Y1Rs and promoting BDNF-mediated neurogenesis in the hippocampus","authors":"Hanxiao Wang ,&nbsp;Xu Lu ,&nbsp;Ying Ye ,&nbsp;Chen Huang ,&nbsp;Yunli Fang ,&nbsp;Rongrong Yang ,&nbsp;Micona Sun ,&nbsp;Jie Ren ,&nbsp;Rongrong Song ,&nbsp;Feng Xu ,&nbsp;Jianbin Su ,&nbsp;Hongxiang Hong ,&nbsp;Chao Huang","doi":"10.1016/j.bbi.2025.04.010","DOIUrl":"10.1016/j.bbi.2025.04.010","url":null,"abstract":"<div><div>Reversing the decline of microglia in the dentate gyrus of stressed animals has antidepressant effects, but the molecular mechanisms are unclear. Since microglia normally interact with astrocytes and astrocytic purinergic 2Y1 receptor (P2Y1R) signaling plays an important role in regulating cellular crosstalk, we hypothesize that astrocytic P2Y1R signaling may mediate the antidepressant effects of microglia stimulation. Our results showed that a single injection of low-dose lipopolysaccharide (LPS) (100 μg/kg) elicited rapid antidepressant effects and a significant increase in adenosine triphosphate (ATP) levels in the dentate gyrus in chronically stressed mice, and that these effects of LPS were abolished by chemogenetic inhibition of microglia. Depletion of endogenous ATP, non-specific antagonization of purinergic receptors, or specific inhibition of P2Y1Rs, but not other purinergic receptors, by MRS2179 in the hippocampus abolished the antidepressant effects of low-dose LPS. Conditional gene knockout data showed that the antidepressant effect of low-dose LPS could not be observed in mice lacking P2Y1Rs in astrocytes but not in forebrain neurons. Chemogenetic inhibition of microglia in the dentate gyrus, specific deletion of P2Y1Rs in astrocytes and the absence of ATP abolished the increase in doublecortin (DCX)⁺ cells and brain-derived neurotrophic factor (BDNF) induced by a low dose of LPS in the dentate gyrus of stressed mice, and infusion of BDNF antibodies into the hippocampus simultaneously abolished the pro-neurogenesis and antidepressant effects of microglia stimulation in stressed mice. Taken together, these results suggest that ATP signaling mobilized by microglia stimulation has an antidepressant effect by triggering astrocytic P2Y1R-dependent synthesis of BDNF.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 134-151"},"PeriodicalIF":8.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}