Brain, Behavior, and Immunity最新文献

{"title":"Discovery of novel blood–brain barrier neuropathology in schizophrenia and bipolar disorder midbrain","authors":"Yunting Zhu ,&nbsp;Gerardo Mendez Victoriano ,&nbsp;Maree J Webster ,&nbsp;Frank A. Middleton ,&nbsp;Paul T. Massa ,&nbsp;Christine Fuller ,&nbsp;Cynthia Shannon Weickert","doi":"10.1016/j.bbi.2026.106292","DOIUrl":"10.1016/j.bbi.2026.106292","url":null,"abstract":"<div><div>Elevated pro-inflammatory cytokines and increased macrophage densities have been found in ∼ 35–50 % of schizophrenia and bipolar disorder brains. However, the influence of neuroinflammation on the blood–brain barrier (BBB) in these serious mental illnesses remains unclear. Here, we measured and compared multiple BBB-associated molecules in the ventral midbrain, including chemokines, macrophage markers, adhesion molecules, tight junction proteins, and basement membrane proteins in people with schizophrenia (n = 35), or bipolar disorder (n = 34), and controls (n = 33), stratified by inflammatory status. Both mRNA and protein levels of macrophage chemokine (CCL2) and macrophage scavenger receptor (CD163) were significantly elevated in the neuroinflammatory schizophrenia (high) compared to all the low inflammatory subgroups. Adhesion molecule mRNAs (ICAM1 and PECAM1) were increased in both schizophrenia and bipolar disorder high inflammatory subgroups, but PECAM1 protein was only elevated in schizophrenia, while ICAM1 protein was decreased in bipolar disorder. We found lower collagen IV (ColIV) protein levels in bipolar disorder. Tight junction protein claudin-5 (CLDN5) mRNA was elevated in both schizophrenia and bipolar disorder high inflammatory subgroups, while occludin (OCLN) mRNA was decreased in schizophrenia, especially in the high inflammatory subgroup. CLDN5 immunostaining revealed increased fragmented blood vessels with bursts of CLDN5 + processes surrounding and appearing to emanate from endothelial cells in schizophrenia and bipolar disorder high inflammation subgroup. Collectively, the high inflammatory individuals in both schizophrenia and/or bipolar disorder display more signs of BBB alterations, including increased macrophage chemoattraction, changed adhesion molecules, and altered tight junction proteins, though they have distinct molecular signatures of BBB pathology in the midbrain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106292"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008993","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":"Prenatal-lactational alcohol exposure induces sex-specific CX3CL1/CX3CR1 dysregulation linked to neuroendocrine imbalance and cardiovascular risk","authors":"Dina Medina-Vera ,&nbsp;Alba García-Baos ,&nbsp;Mireia Medrano ,&nbsp;Laura Martín-Chaves ,&nbsp;Jorge Rodríguez-Capitán ,&nbsp;Fernando Rodríguez de Fonseca ,&nbsp;Antonia Serrano ,&nbsp;Manuel Jiménez-Navarro ,&nbsp;Olga Valverde ,&nbsp;Francisco Javier Pavón-Morón","doi":"10.1016/j.bbi.2026.106463","DOIUrl":"10.1016/j.bbi.2026.106463","url":null,"abstract":"<div><div>Fetal alcohol spectrum disorder is associated with lasting neurodevelopmental and cardiovascular dysfunctions. The fractalkine axis CX₃CL1/CX₃CR1, a chemokine and its sole known receptor expressed in microglia and myeloid/endothelial cells, coordinates neuroimmune and vascular responses. We tested whether prenatal-lactational alcohol exposure (PLAE) is associated with sex-specific dysregulation of this axis along with integrated behavioral, neuroendocrine, inflammatory, and cardiovascular signatures.</div><div>Pregnant C57BL/6 dams consumed 20% ethanol using a drinking-in-the-dark (DID) paradigm throughout gestation and lactation. Adult offspring (PND60–70) underwent behavioral testing (elevated plus maze and tail suspension test); plasma profiling of corticosterone, cytokines/chemokines, endothelial/coagulation markers, and matrix-remodeling enzymes; and cardiac transcriptional assays for stress- and inflammation-related genes (including <em>Cx3cr1</em>). Analyses were stratified by sex.</div><div>PLAE females exhibited increased anxiety-like behavior, two-fold higher plasma CX₃CL1, and upregulated cardiac <em>Cx3cr1</em> compared with control females. PLAE males showed no behavioral or endocrine changes but evidence of matrix remodeling (elevated proMMP-9, reduced sP-Selectin). Across sexes, PLAE was associated with a proinflammatory/endothelial-activation profile (elevated IL13, IL18, and PAI-1, reduced CXCL16, higher proMMP-9) and altered cardiac expression of <em>Nr3c2</em>, <em>Tnfrsf1a</em>, <em>Tlr4</em>, and <em>Nfkbia</em>, compatible with early vascular risk. Independent of exposure, females exhibited reduced immobility and higher corticosterone, IL5, IL13, sE-Selectin, and thrombomodulin. Plasma CX₃CL1 correlated inversely with exploratory and stress-coping behaviors, and positively with corticosterone, inflammatory/vascular markers, and cardiac <em>Cx3cr1</em> and <em>Tnfrsf1a</em>.</div><div>PLAE is associated with sex-specific dysregulation of the CX₃CL1/CX₃CR1 axis and convergent neuroimmune-vascular signatures indicative of subclinical endothelial dysfunction. These associative findings support the hypothesis that fractalkine-pathway modulation may mitigate long-term neurobehavioral and cardiovascular vulnerability after PLAE, warranting causal testing.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106463"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075710","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":"Wolf in sheep’s clothing: leveraging sheep to study how maternal immune activation contributes to neurodevelopmental disorders","authors":"Olivia C. Campbell,&nbsp;John R. Lukens","doi":"10.1016/j.bbi.2026.106474","DOIUrl":"10.1016/j.bbi.2026.106474","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106474"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075711","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":"Depression-related chronic stress promotes ovarian cancer progression via metabolic dysfunction and IRF1-mediated immune suppression","authors":"Yeqing Zheng ,&nbsp;Cheng Qian ,&nbsp;Shan Wu ,&nbsp;Bin Li ,&nbsp;Lin Zhang ,&nbsp;Wenjun Cheng","doi":"10.1016/j.bbi.2026.106471","DOIUrl":"10.1016/j.bbi.2026.106471","url":null,"abstract":"<div><div>Depression is highly prevalent among patients with ovarian cancer, but its impact on tumor progression and the underlying mechanisms remain unclear. This study aimed to investigate the relationship between depression and ovarian cancer progression, and evaluate the potential therapeutic value of antidepressant drugs. Clinical data analysis of patients with ovarian cancer revealed a significantly elevated risk of depression in this population. Animal experiments using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) models have confirmed that depression-related chronic stress induces depressive-like behaviors in mice and is associated with significant enhancement of ovarian cancer growth and metastasis. Mechanistically, single-cell RNA sequencing and metabolomics demonstrated that chronic stress downregulated interferon regulatory factor 1 (<em>IRF1</em>) expression in tumor cells. <em>IRF1</em> suppression inhibited the immune effector cells infiltration, such as macrophages, while inducing abnormal lipid metabolism and glutathione pathway dysfunction. Notably, combining antidepressant drugs with platinum-based chemotherapy reversed these pathological changes. This combination therapy upregulated <em>IRF1</em> expression, restored <em>CCR2⁺</em> macrophage infiltration, and delayed ovarian cancer progression in mice. Clinical validation further confirmed that high <em>IRF1</em> expression was correlated with prolonged overall survival (OS) in patients with ovarian cancer. These findings suggest that depression may be associated with ovarian cancer progression by remodeling the immune-metabolic microenvironment. This study highlights antidepressant therapy combined with anti-tumor treatment as a potential strategy for ovarian cancer patients with comorbid depression.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106471"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075665","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":"PPARγ in microglia helps protect adolescent male mice from harmful effects of stress during early development","authors":"Zhe Liu ,&nbsp;Jiutai Wang ,&nbsp;Yan Ge ,&nbsp;Yu Wang ,&nbsp;Hanyi Ling ,&nbsp;Yan Liu ,&nbsp;Jinqiang Zhang ,&nbsp;Zili You ,&nbsp;Yue Han","doi":"10.1016/j.bbi.2026.106483","DOIUrl":"10.1016/j.bbi.2026.106483","url":null,"abstract":"<div><div>Deficiency in the expression or activity of the nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) has been observed in autism spectrum disorder, bipolar disorder and Alzheimer’s disease. Here we showed that separating mouse pups from their mothers for three hours daily during the first two weeks of life downregulated PPARγ, leading to pro-inflammatory polarization and activation of microglia in the hippocampus, which results in more severe responses to subsequent chronic restraint stress in adolescent animals. These effects of maternal separation were reversed by activating PPARγ with pioglitazone at 30 mg/kg/day for one week, which also stimulated hippocampal neurogenesis. Knocking out PPARγ specifically in microglia reduced neural activity and dendritic spine density in the cortex and hippocampus and led to depressive-like behaviors in mice. These results suggest that PPARγ expression enables microglia to “remember” previous exposure to stress and thereby influence responses to future stress. The findings may help guide interventions against stress and related psychological disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106483"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164229","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":"Post-infection mental illness: Mapping pathways of vulnerability and resilience in VIRAL-MInds","authors":"Eva Wachtelaer ,&nbsp;Chloë Trippaers ,&nbsp;Ole A. Andreassen ,&nbsp;Ingrid Torp Johansen ,&nbsp;Nils Eiel Steen ,&nbsp;Helga Ask ,&nbsp;Dana Tzur Bitan ,&nbsp;Amit Kramer ,&nbsp;Sara Poletti ,&nbsp;Federica Colombo ,&nbsp;Livia De Picker","doi":"10.1016/j.bbi.2026.106291","DOIUrl":"10.1016/j.bbi.2026.106291","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106291"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002843","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":"The impact of adverse childhood experiences on gut microbiota and markers of inflammation is mediated by obesity and depression","authors":"Liisa Hantsoo ,&nbsp;Eileen Ford ,&nbsp;Elliot S. Friedman ,&nbsp;Fuhua Hao ,&nbsp;Andrew D. Patterson ,&nbsp;Kyle Bittinger ,&nbsp;Gary D. Wu ,&nbsp;Babette S. Zemel ,&nbsp;Ceylan Tanes","doi":"10.1016/j.bbi.2026.106479","DOIUrl":"10.1016/j.bbi.2026.106479","url":null,"abstract":"<div><h3>Background</h3><div>Adverse childhood experiences (ACEs) are associated with poor health outcomes in adulthood including obesity, psychiatric symptoms, and elevated levels of inflammatory markers. Our previous work found ACEs are associated with altered gut microbiota composition. In the present work, we examined ACE associations with gut microbiota and peripheral measures of inflammation in pregnant women with or without obesity, and explored potential modifying factors including diet and depressive symptoms.</div></div><div><h3>Methods</h3><div>Female participants were recruited in the third trimester of pregnancy as part of a larger growth study of African-American infants. Participants were categorized as healthy weight (BMI &lt; 25) or obese (BMI ≥ 30) based on their early pregnancy BMI. They completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and Center for Epidemiologic Studies Depression Scale (CES-D). Stool samples, blood, and dietary data were collected in the third trimester. Shotgun metagenomic sequencing was performed on DNA isolated from stool. Statistical models assessed relationships between gut microbiota and ACE. A false discovery rate (fdr) adjusted p-value q &lt; 0.1 was considered statistically significant.</div></div><div><h3>Results</h3><div>107 women completed questionnaires and provided stool in the third trimester. ACEs were positively associated with BMI and depressive symptom severity but not with gut microbiota composition. Depressive symptoms were significantly negatively associated with abundance of gut <em>Bifidobacterium longum</em> (q = 0.02) and positively associated with <em>Bacteroides thetaiotaomicron</em> (q = 0.02). Path analysis revealed that ACEs predicted pre-pregnancy BMI which predicted elevated inflammatory markers. ACEs also predicted more severe depressive symptoms in pregnancy, which was associated with gut microbiome composition. Finally, ACEs interacted with dietary intake of sugar and whole grains to impact markers of inflammation, the gut microbiome, and enzymes produced by gut microbiota.</div></div><div><h3>Discussion</h3><div>ACEs led to two risk pathways in pregnancy: one in which high pre-pregnancy BMI was linked with high levels of serum inflammatory markers during pregnancy, and the other in which greater depressive symptom severity was associated with alterations to the gut microbiome. Further, data suggested ACEs may influence the metabolic potential of the gut microbiome.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106479"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131149","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":"Inflammatory biomarkers as predictors of fetal brain resilience or vulnerability to prenatal maternal anxiety","authors":"Xiang Zhou ,&nbsp;Die Zhang ,&nbsp;Chaoqiang Liu ,&nbsp;Helen Chen ,&nbsp;Yap-Seng Chong ,&nbsp;Marielle V. Fortier ,&nbsp;Peter D. Gluckman ,&nbsp;Anqi Qiu","doi":"10.1016/j.bbi.2026.106477","DOIUrl":"10.1016/j.bbi.2026.106477","url":null,"abstract":"<div><div>Prenatal maternal anxiety has been associated with altered neurodevelopmental outcomes in offspring, yet the biological mechanisms underlying this relationship remain poorly understood. This study investigated whether maternal inflammatory biomarkers moderate the association between prenatal anxiety and offspring brain and behavioral development. Using data from a prospective longitudinal cohort, we assessed maternal anxiety and circulating inflammatory markers at late mid-pregnancy, followed by neonatal brain MRI (n = 159) and cognitive assessments at 24 months (n = 340). Our findings revealed that interferon-gamma (IFN-γ) moderated the association between prenatal maternal anxiety and neonatal right globus pallidus volume, with higher IFN-γ levels linked to a larger pallidus volume and better cognitive outcomes at 24 months, even in the context of elevated anxiety. Similarly, both high and low levels of maternal monocyte chemoattractant protein-1 (MCP-1) altered the relationship between prenatal anxiety and neonatal brain morphology within the striatal–cortical circuit, including bilateral caudate volumes and cortical thickness in the sensorimotor and temporal regions. These results suggest that extreme MCP-1 levels may amplify vulnerability or promote resilience in fetal brain development. Higher MCP-1 levels were also associated with improved language development at 24 months. Together, these findings highlight the potential roles of inflammatory biomarkers in shaping the fetal brain’s sensitivity to maternal anxiety, offering potential mechanisms for early risk identification and intervention strategies.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106477"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149099","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":"Midbrain microglial and macrophage mRNAs distinguish neuroinflammatory schizophrenia from bipolar disorder","authors":"Gerardo Mendez-Victoriano ,&nbsp;Yunting Zhu ,&nbsp;Yasmine Kostoglou ,&nbsp;Adam K. Walker ,&nbsp;Frank Middleton ,&nbsp;Paul T. Massa ,&nbsp;Bart J.L. Eggen ,&nbsp;Maree J. Webster ,&nbsp;Iris E.C. Sommer ,&nbsp;Cynthia S. Weickert","doi":"10.1016/j.bbi.2026.106276","DOIUrl":"10.1016/j.bbi.2026.106276","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Increased microglial/macrophage transcripts are found in the midbrains of people with a neuroinflammatory subtype of schizophrenia. However, it is unknown in which immune cell population these transcripts are mostly expressed, nor do we know if transcriptional changes in microglial/macrophage markers are also found in the midbrain of neuroinflammatory bipolar disorder.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Here, we determined the extent of microglial/macrophage changes in the ventral midbrain (at the level of the oculomotor nerve exit) of a large cohort of people with schizophrenia and bipolar disorder, defined as either low or high-inflammation, compared to controls. We aimed to confirm in which cell-type cluster our transcripts were expressed (microglia vs macrophages). First, we mapped the cellular expression of putative microglial/macrophage markers via snRNA-seq. Then, mRNA levels of 11 microglial/macrophage markers were measured and compared via RT-PCR from human post-mortem midbrains of 61 healthy controls, 63 schizophrenia cases, and 33 bipolar disorder cases.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;7/11 mRNAs (&lt;em&gt;IBA1&lt;/em&gt;, &lt;em&gt;CD11B&lt;/em&gt;, &lt;em&gt;CX3CR1&lt;/em&gt;, &lt;em&gt;P2RY12&lt;/em&gt;, &lt;em&gt;CD64&lt;/em&gt;, &lt;em&gt;CD40&lt;/em&gt;, &amp; &lt;em&gt;TMEM119&lt;/em&gt;) were mainly expressed in microglial cell clusters; 2 mRNAs were in the macrophage cell cluster (&lt;em&gt;CD32C, CD86&lt;/em&gt;); 1 mRNA was broadly expressed (&lt;em&gt;HEXB&lt;/em&gt;), and &lt;em&gt;CD68&lt;/em&gt; mRNA was too low to confirm cellular source by snRNA-seq. Across groups, transcripts associated with microglia activation and motility were significantly increased in high-inflammation schizophrenia (&lt;em&gt;IBA1, CD11B&lt;/em&gt;; all &lt;em&gt;p&lt;/em&gt; ≤ 0.001) and significantly decreased in high-inflammation bipolar disorder (&lt;em&gt;P2RY12&lt;/em&gt;, &lt;em&gt;CX3CR1&lt;/em&gt;; all &lt;em&gt;p&lt;/em&gt; ≤ 0.01) compared to low-inflammation controls. Transcripts associated with microglial and macrophage activation via FcγR-IgG/Immune complex antigen binding were significantly increased in high-inflammatory schizophrenia (&lt;em&gt;CD64&lt;/em&gt; &amp; &lt;em&gt;CD32C&lt;/em&gt;) and high-inflammatory bipolar disorder (&lt;em&gt;CD32C&lt;/em&gt;) (all &lt;em&gt;p&lt;/em&gt; ≤ 0.01). Transcripts associated with increased cytokine response (&lt;em&gt;CD40 &amp; CD86&lt;/em&gt;) and phagocytosis (&lt;em&gt;CD68&lt;/em&gt;) were significantly increased in high-inflammatory schizophrenia and divergently changed in high-inflammatory bipolar disorder (&lt;em&gt;CD40&lt;/em&gt; increased&lt;em&gt;/CD86&lt;/em&gt; decreased) (all &lt;em&gt;p&lt;/em&gt; ≤ 0.05). Overall, the number of CD68 + cells with reactive-like morphology was increased in high-inflammation schizophrenia compared to all the low-inflammation groups (all p ≤ 0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our findings strengthen the contention that microglia and macrophages are activated in schizophrenia and disrupted in bipolar disorder midbrains of high-inflammatory subgroups. This suggests that optimal immune-based treatments targeting schizophrenia and bipolar disorder patients may differ when restor","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106276"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997279","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":"Altered gene expression associated with postoperative delirium in patients undergoing surgery and anesthesia","authors":"Maria Heinrich ,&nbsp;Anna-Rosa Krüger ,&nbsp;Sreyoshi Chatterjee ,&nbsp;Anna Fournier ,&nbsp;Florian Lammers-Lietz ,&nbsp;Roland Krause ,&nbsp;Peter Nürnberg ,&nbsp;Reinhard Schneider ,&nbsp;Georg Winterer ,&nbsp;Maik Pietzner ,&nbsp;Claudia Spies","doi":"10.1016/j.bbi.2026.106283","DOIUrl":"10.1016/j.bbi.2026.106283","url":null,"abstract":"<div><div>Postoperative delirium is a severe complication associated with poor overall and especially neurocognitive prognosis after anesthesia and surgery. As a systemic phenomenon, peripheral immune response to surgical trauma may play a central role. Although analysis of differential gene expression in peripheral immune cells could provide insights into immune dysregulation in postoperative delirium (POD), no sufficiently powered prospective cohort study has yet been conducted.</div><div>We performed gene expression analysis in N = 599 cognitively healthy male and female patients ≥65 years who provided blood samples for microarray-based gene-expression data before major elective surgery and on the first postoperative day. Patients were followed up for delirium until the seventh postoperative day. We identified differentially expressed genes in POD using a multivariable linear regression framework adjusted for sex, age, body mass index, preoperative physical status, duration of anesthesia and operative procedure.</div><div>Preoperative gene expression did not differ significantly in patients who were later diagnosed with POD. However, we identified a total of 1,063 unique significantly associated genes which differed in baseline-corrected mRNA abundance among POD patients after surgery (n = 394 upregulated, n = 681 downregulated). This set was significantly enriched for genes related to cellular and humoral immune response, RNA metabolism and platelet function.</div><div>Post-, but not preoperative gene expression in peripheral immune cells has been found to be altered in patients with POD. Whereas most enriched pathways were related to immune response and acute phase reaction, few molecular alterations were found, which may reflect nervous system alterations and warrant further investigation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106283"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988364","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}