Brain, Behavior, and Immunity最新文献

{"title":"Telomere-mitochondrial dynamics differ depending on childhood maltreatment history, catabolic postpartum state, and developmental period","authors":"R. Nehir Mavioglu ,&nbsp;Anja M. Gumpp ,&nbsp;Elisabeth M. Hummel ,&nbsp;Dirk A. Moser ,&nbsp;Ole Ammerpohl ,&nbsp;Alexander Behnke ,&nbsp;Matthias Mack ,&nbsp;Iris-Tatjana Kolassa","doi":"10.1016/j.bbi.2025.05.022","DOIUrl":"10.1016/j.bbi.2025.05.022","url":null,"abstract":"<div><div>Telomere attrition, a hallmark of aging, is linked to high-energy demand states like early development and biological or psychological stress. Metabolic regulation of telomere length (TL) may occur in these states as part of an energetic trade-off, prioritizing immediate needs over long-term requirements such as telomere maintenance, though this has not been observed in healthy humans. We examined associations between TL and mitochondrial bioenergetics, density, and DNA markers in immune cells of women at 1-week (<em>n</em> = 175) and 1-year postpartum (<em>n</em> = 106), depending on their history of childhood maltreatment (CM), and in their newborns (<em>n</em> = 132). At 1-week postpartum, a catabolic state of high energy demand, women with lower mitochondrial energy production efficiency exhibited shorter TL. One year later, these dynamics appeared only in women with a history of CM. In newborns, TL was shorter when mitochondrial density-normalized routine and ATP production-related respiration was higher. Mitochondrial DNA copy number was associated with TL in both mothers and newborns, regardless of the energetic state. Our findings suggest that telomere-mitochondrial dynamics can adapt to the body’s energetic needs.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 267-278"},"PeriodicalIF":8.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149118","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":"BBI commentary: Breaking barriers: How maternal bacteria influences foetal neurodevelopment","authors":"Philip W.J. Burnet","doi":"10.1016/j.bbi.2025.05.019","DOIUrl":"10.1016/j.bbi.2025.05.019","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 52-53"},"PeriodicalIF":8.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107642","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":"Intravenous SARS-CoV-2 Spike protein induces neuroinflammation and alpha-Synuclein accumulation in brain regions relevant to Parkinson’s disease","authors":"Cara Sophie Schreiber ,&nbsp;Lucas Navarro Ramil ,&nbsp;Juliette Bieligk ,&nbsp;Robert Meineke ,&nbsp;Guus Rimmelzwaan ,&nbsp;Christopher Käufer ,&nbsp;Franziska Richter","doi":"10.1016/j.bbi.2025.05.021","DOIUrl":"10.1016/j.bbi.2025.05.021","url":null,"abstract":"<div><div>Background: Coronavirus disease 2019 (COVID-19) frequently presents with neurological symptoms in human patients and leads to long-lasting brain pathology in a hamster model. There is no overt SARS-CoV-2 virus replication in central neurons. Whether viral proteins are sufficient to cause this pathology requires further investigations. The SARS-CoV-2 Spike-protein S1-subunit (S1-protein) has recently gained interest for causing neuroinflammation and accelerating aggregation of alpha-Synuclein (aSyn) in vitro. Here, we show the impact of S1-protein in a broad spectrum of brain regions after injection via three different application routes in C57/BL6 mice. Methods: S1-protein was administered either intranasally, intravenously or intracerebrally. We quantified aSyn immunoreactivity and phosphorylated aSyn (pS129), microglia and astrocyte reactivity, ACE2/Neuropilin-1 receptor expression, and parvalbumin-positive interneurons in limbic system, basal ganglia, and cortical regions 14 days post-application. Plasma cytokine profiles were assessed 6 days post-injection. Results: While intracerebral injection resulted in decreased aSyn immunoreactivity with increased pS129 in males, intravenous injection led to increased levels of aSyn immunoreactivity and microglia cell density, predominantly in brain regions associated with Parkinson’s disease pathology. Intranasal application of S1-protein induced microgliosis in some brain regions but resulted in sex-dependent alterations of aSyn levels, with increases in females and decreases in males. All routes showed sex-dependent alterations in astrocytic reactivity, receptor expression, and parvalbumin-positive interneurons. Conclusion: Our results demonstrate that S1-protein itself leads to neuroinflammation, altered aSyn homeostasis, and disruption of inhibitory circuits in a route- and sex-dependent manner. These findings indicate the possibility of S1-protein being a crucial agent for both neuroinflammatory processes and altered protein regulation mechanisms. S1-protein trapped in tissue reservoirs could therefore explain symptoms occurring or persisting beyond viral clearance (Post COVID-19 condition).</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 102-123"},"PeriodicalIF":8.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126693","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 greater splanchnic nerve preferentially regulates neutrophils over macrophages in a rat model of septic peritonitis","authors":"Kathia T. Kato ,&nbsp;Gabriela C.S. Ferreira ,&nbsp;Dennyson L.M. Fonseca ,&nbsp;Eduardo H. Moretti ,&nbsp;Isis F.L. Trzan ,&nbsp;Igor Salerno Filgueiras ,&nbsp;Adriel L. Nobile ,&nbsp;Anny S. Adri ,&nbsp;Monique T. Fonseca ,&nbsp;Rayssa N. Souza ,&nbsp;Caroline M. Matos ,&nbsp;Manoela O.R. Sales ,&nbsp;Caroline A. Lino ,&nbsp;Mariana M. Teramoto ,&nbsp;Sandra M. Muxel ,&nbsp;Otávio Cabral-Marques ,&nbsp;Alexandre A. Steiner","doi":"10.1016/j.bbi.2025.05.015","DOIUrl":"10.1016/j.bbi.2025.05.015","url":null,"abstract":"<div><div>The sympathetic splanchnic nerve is a major player in immunoregulation, but its specific roles during infection have yet to be elucidated. Here, we evaluated how bilateral ablation of the greater splanchnic nerve (SplancX) impacts bacterial burden and immune function in a rat model of <em>E. coli</em>-induced septic peritonitis. SplancX had a major effect on bacterial burden within 24 h, reducing it to 4 % in the peritoneum and to 8 % in the spleen of what was found in the sham-operated controls. Such a major effect was not explained by gross changes in the infiltration of these sites with innate immune cells (neutrophils and macrophages), as assessed by flow cytometry. Single-cell RNA sequencing was then employed to evaluate the cellular activation programs of leukocyte subsets. Of the nine cellular clusters identified in the peritoneum of the infected rats, three of them had a transcriptional signature of activated neutrophils and two of them corresponded to quiescent neutrophils with an immunosuppressive signature. SplancX shifted the balance between these neutrophil subsets in a way consistent with heightened immunity, <em>i.e.</em>, the activated neutrophils were augmented whereas the quiescent neutrophils were reduced in the SplancX group. The remainder of the clusters consisted of macrophages and erythrocytes, none of which changed in a way that could account for the observed effects on bacterial clearance. Confirming that SplancX resulted in heightened neutrophil activation, protein markers of neutrophil degranulation and NETosis were found to be elevated in the peritoneal lavage of the SplancX group. Taken together, the data show that the splanchnic nerve exerts a major effect on bacterial clearance in the acute phase of infection, presumably owing to selective changes in the balance between microbicidal and quiescent subsets of neutrophils.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 30-41"},"PeriodicalIF":8.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099806","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":"SORLA Orchestrates microglial dynamics for enhanced neuroprotection and recovery following ischemic stroke","authors":"Sehui Ma ,&nbsp;Tongmei Zhang ,&nbsp;Junkai Lv ,&nbsp;Shiqi Liang ,&nbsp;Shuaizhu Zhao ,&nbsp;Xinyue Nan ,&nbsp;Ziyue Dou ,&nbsp;Jun Yang ,&nbsp;Youming Lu ,&nbsp;Rong Liu ,&nbsp;Hao Li","doi":"10.1016/j.bbi.2025.05.016","DOIUrl":"10.1016/j.bbi.2025.05.016","url":null,"abstract":"<div><div>This study identifies a novel function of Sortilin-related receptor with A-type repeats (SORLA), traditionally linked to Alzheimer’s Disease (AD) as a high-risk gene and associated with neuronal function, in modulating microglial responses to ischemic stroke. We discovered that SORLA expression is significantly reduced in microglia following stroke, a change linked to increased brain injury and diminished neurological recovery. Utilizing SORLA knockout and overexpression models, we demonstrated its essential role in adjusting microglial inflammatory responses. Notably, microglial-specific overexpression of SORLA not only promoted anti-inflammatory actions and effective phagocytosis but also surpassed traditional concepts of microglial polarization. This overexpression mitigated brain damage and enhanced neurofunctional recovery post-stroke, highlighting the neuroprotective potential of SORLA. This breakthrough challenges the prevailing understanding the role of SORLA and opens new therapeutic possibilities for stroke recovery, indicating its wider relevance for neurodegenerative disease management.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 70-86"},"PeriodicalIF":8.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101442","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 of immune-inflammatory biomarkers during pregnancy and the postpartum period with postpartum depression symptoms: A cross-sectional and longitudinal retrospective analysis","authors":"Kaipeng Xie ,&nbsp;Shengyuan Jiang ,&nbsp;Yixiao Wang ,&nbsp;Haiyan Chen ,&nbsp;Xiaoli Wu ,&nbsp;Bo Xu","doi":"10.1016/j.bbi.2025.05.014","DOIUrl":"10.1016/j.bbi.2025.05.014","url":null,"abstract":"<div><h3>Background</h3><div>Postpartum depression (PPD) is characterized by feelings of sadness, hopelessness, and disinterest in daily activities, leading to detrimental effects on both maternal and child well-being. We aimed to investigate the associations between blood immune-inflammatory biomarkers during pregnancy and the postpartum period and the risk of PPD.</div></div><div><h3>Methods</h3><div>In this study, we included postpartum women who underwent routine blood tests during second and third trimester visits as well as postpartum reviews. Immune-inflammatory biomarkers were assessed at three time points: neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI), and pan-immune-inflammatory value (PIV). PPD symptoms were assessed at five to eight weeks postpartum using the Edinburgh Postnatal Depression Scale (EPDS). Multivariable logistic regression, restricted cubic spline (RCS) regression, and subgroup and sensitivity analyses were used to examine the relationships between immune-inflammatory biomarkers and PPD symptoms.</div></div><div><h3>Results</h3><div>Of the 17,500 women eligible for analysis, 2,576 (14.72 %) exhibited PPD symptoms. During the postpartum period, maternal lymphocyte count was associated with decreased odds of PPD symptoms (OR = 0.86, 95 % CI: [0.80, 0.93]), whereas NLR, PLR, and SII were associated with increased odds of PPD symptoms after Bonferroni correction (OR = 1.19, 95 % CI: [1.06, 1.34]; OR = 1.40, 95 % CI: [1.21, 1.61]; OR = 1.18, 95 % CI: [1.07, 1.30], respectively). The relationships showed significant linear trends (all <em>P</em> for nonlinear &gt; 0.05). Subgroup analyses demonstrated that cesarean delivery could modify the association between NLR and PPD symptoms (<em>P</em> for interaction = 0.034). The significant association between NLR and PPD symptoms was observed only in women without cesarean delivery (OR = 1.31, 95 % CI: [1.13, 1.52]). Sensitivity analyses showed that the main findings remained robust.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that lymphocyte count, NLR, PLR, and SII during the postpartum period are independent risk factors for PPD symptoms. Monitoring these biomarkers could aid in clinical decision-making and the implementation of effective PPD management strategies.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 42-51"},"PeriodicalIF":8.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099807","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":"Early life adversity promotes a milieu in favor of catabolic bone turnover in females: Mycobacterium vaccae NCTC 11659 proofs protective in preclinical studies","authors":"Tamara Schimmele ,&nbsp;Dominik Langgartner ,&nbsp;Dorothea Gebauer ,&nbsp;Giulia Mazzari ,&nbsp;Julian Probst ,&nbsp;Giulia Weingast ,&nbsp;Anita Ignatius ,&nbsp;Gaia Tabacco ,&nbsp;Anda Mihaela Naciu ,&nbsp;Maria Vittoria Messina ,&nbsp;Andrea Palermo ,&nbsp;Stefan O. Reber ,&nbsp;Melanie Haffner-Luntzer","doi":"10.1016/j.bbi.2025.05.009","DOIUrl":"10.1016/j.bbi.2025.05.009","url":null,"abstract":"<div><div>Despite early clinical studies supporting the hypothesis that early life adversity (ELA) negatively affects the bone and despite typical ELA-associated disorders, including post-traumatic stress disorder (PTSD) and major depressive disorder (MD), are associated with osteoporosis and increased bone fracture risk, preclinical studies do not support this association. However, previous studies were only conducted in male but not female mice. In the current study we showed that ELA, induced by the classical maternal separation (MS) paradigm, facilitated femoral osteoclast activity specifically in female but not male mice. This was associated with a transient decline in both intestinal alpha diversity and Firmicutes/Bacteroidetes ratio, suggesting that the microbiome-gut-bone axis is involved in these effects. Moreover, ELA long-lastingly increased the femoral mRNA expression of the proinflammatory cytokine interleukin-6 (IL-6) and the osteoclastic markers Cathepsin K and RANKL. Importantly, all sex-specific ELA effects on bone were absent in female mice administered with <em>M. vaccae</em> NCTC (National Collection of Type Cultures) 11659 following ELA exposure. Finally, our clinical data indicate strong associations between ELA and development of an osteopenic/osteoporotic bone phenotype in postmenopausal women undergoing bone diagnostics. Together, our preclinical and clinical findings indicate that i) ELA negatively affects the bone, ii) these effects are specific for female sex, iii) the negative effects of ELA on female bone are associated with transient changes in the composition of the intestinal microbiome followed by long-lasting activation of the immune system and the HPA axis, together setting the stage for a facilitated catabolic bone turnover and development of an osteopenic/osteoporotic bone phenotype, iv) developing immunoregulatory approaches, such as repeated s.c. administrations with immunoregulatory microorganisms, have potential for prevention/treatment of ELA-related bone disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 54-69"},"PeriodicalIF":8.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092819","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":"Dr. Linda R. Watkins: A pioneer who rewrote the science of pain and neuroimmune signaling","authors":"Mark R. Hutchinson ,&nbsp;Erin D. Milligan ,&nbsp;Peter M. Grace","doi":"10.1016/j.bbi.2025.05.013","DOIUrl":"10.1016/j.bbi.2025.05.013","url":null,"abstract":"<div><div>Dr. Linda R. Watkins, a Distinguished Professor at the University of Colorado Boulder, fundamentally altered the understanding of pain and neuroimmune signaling. As she concludes her tenure as Associate Editor of Brain, Behavior, and Immunity, this tribute reflects<!--> <!-->on her revolutionary discoveries. She pioneered the concept that glial cells actively participate in pain states, challenging neuron-centric dogma. Her work elucidated the roles of cytokines like IL-1β and IL-10, the chemokine fractalkine (CX3CL1), and the Toll-Like Receptor 4 (TLR4) in glial reactivity, sickness behavior, and unwanted opioid effects (tolerance, hyperalgesia). As a dedicated mentor and collaborator, particularly with Steve Maier, she fosters interdisciplinary research. Watkins champions translational science, co-founding Xalud Therapeutics to develop immune therapies like IL-10 gene therapy, leaving a profound legacy in neuroscience.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 685-688"},"PeriodicalIF":8.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070635","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":"A role for fibroblast and mural cell subsets in a nerve ligation model of neuropathic pain?","authors":"Sara Villa-Hernandez ,&nbsp;Julia Vlachaki Walker ,&nbsp;Zoe Hore ,&nbsp;Laura Fedele ,&nbsp;Irene Zebochin ,&nbsp;Yuening Li ,&nbsp;Harvey Davis ,&nbsp;Takashi Kanda ,&nbsp;Fumitaka Shimizu ,&nbsp;Leonie S. Taams ,&nbsp;Franziska Denk","doi":"10.1016/j.bbi.2025.05.012","DOIUrl":"10.1016/j.bbi.2025.05.012","url":null,"abstract":"<div><div>Neuropathic pain is a particularly intractable type of chronic pain that can result from physical nerve damage due to surgery or entrapment. Here, we present data which suggest that a particular subclass of fibroblast and mural cells may be implicated in the sensory neuron dysfunction that is characteristic of this pain state.</div><div>In a mouse model of traumatic painful neuropathy, we used cell sorting, nerve tissue clearing and RNA sequencing to study stromal cells. With cell sorting (n = 4 mouse nerves) and tissue clearing (n = 5), we show that fibroblasts and mural cells positive for the platelet-derived growth factor receptor beta (<em>Pdgfrb</em>) gene are increased in number for at least two months post-nerve damage. Moreover, single cell RNA sequencing data (n = 4) from our own lab and those of three other laboratories reveal that Pdgfrb+ cells express high levels of known and putative pro-algesic mediators. Bulk sequencing of sorted Pdgfrb+ fibroblasts (n = 10) and Pdgfrb+/Cd146+ mural cells (n = 11) further indicate that many of these mediators are upregulated in neuropathy.</div><div>We go on to demonstrate that a human nerve pericyte line releases a selection of these pro-algesic mediators at protein level. Moreover, conditioned media from stimulated human pericytes induces intra-cellular changes in human induced pluripotent stem cell derived sensory neurons (n = 5 independent differentiations); these changes (phosphorylation of the transcription factor signal transducer and activator of transcription 3, STAT3) have been previously linked to sensory neuron activation.</div><div>In summary, our data indicate that stromal cell abnormalities should be considered when developing novel strategies to tackle neuropathic pain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 15-29"},"PeriodicalIF":8.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092818","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":"Blood immuno-metabolic biomarker signatures of depression and affective symptoms in young adults","authors":"Nicholas A. Donnelly ,&nbsp;Ruby S.M. Tsang ,&nbsp;Éimear M. Foley ,&nbsp;Holly Fraser ,&nbsp;Aimee L. Hanson ,&nbsp;Golam M. Khandaker","doi":"10.1016/j.bbi.2025.05.011","DOIUrl":"10.1016/j.bbi.2025.05.011","url":null,"abstract":"<div><h3>Background</h3><div>Depression is associated with alterations in immuno-metabolic biomarkers, but it remains unclear whether these alterations are limited to specific markers, and whether there are subtypes of depression and depressive symptoms which are associated with specific patterns of immuno-metabolic dysfunction.</div></div><div><h3>Methods</h3><div>To investigate whether immuno-metabolic biomarkers could be used to profile subtypes of depression, we applied regression, clustering, and machine learning to a dataset comprising depression diagnosis, depressive and anxiety symptoms, and blood-based immunological and metabolic biomarkers (n = 118). We measured inflammatory proteins, cell counts, lipids, hormones, and metabolites from up to n = 4161 participants (2363 female, 337 with depression) aged 24 years from the Avon Longitudinal Study of Parents and Children birth cohort.</div></div><div><h3>Results</h3><div>Depression at age 24 was associated with both altered concentrations of immuno-metabolic markers, and increased extreme-valued inflammatory markers. Inflammatory and metabolic biomarkers show distinct, opposing associations with somatic and anxiety symptoms. We identified two latent components representing the relationship between blood biomarkers, symptoms, and covariates, one characterised by higher somatic symptoms and inflammatory markers (neutrophils, WBC, IL-6), and the other characterised by higher anxiety and worry and lower inflammatory markers (CRP, WBC, IL-6). Individuals with higher somatic-inflammatory component scores had greater depressive symptoms severity over the next five years. Immuno-metabolic biomarkers predicted depression diagnosis (Balanced Accuracy = 0.580) and depression with high somatic symptoms (Balanced Accuracy = 0.575) better than chance, but not depression with high anxiety symptoms (Balanced Accuracy = 0.479).</div></div><div><h3>Conclusions</h3><div>Alterations in immuno-metabolic homeostasis is present in young adults with depression well before the typical age of onset of cardiometabolic diseases. The relationships between affective symptoms and blood immuno-metabolic biomarkers indicate two biotypes of depressive symptoms (somatic-inflamed vs anxious-non-inflamed). These patterns are relevant for prognosis and prediction, highlighting the potential usefulness of immuno-metabolic biomarkers for depression subtyping.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 673-684"},"PeriodicalIF":8.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070634","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}