Brain, behavior, & immunity - health最新文献

{"title":"Leptin and inflammatory pathways in the Alzheimer's disease continuum: Implications for glial activation and neuropsychiatric symptoms","authors":"Fumihiko Yasuno ,&nbsp;Kazuyuki Nakagome ,&nbsp;Yoshie Omachi ,&nbsp;Yasuyuki Kimura ,&nbsp;Aya Ogata ,&nbsp;Hiroshi Ikenuma ,&nbsp;Junichiro Abe ,&nbsp;Hiroyuki Minami ,&nbsp;Takashi Nihashi ,&nbsp;Kastunori Yokoi ,&nbsp;Saori Hattori ,&nbsp;Nobuyoshi Shimoda ,&nbsp;Kensaku Kasuga ,&nbsp;Takeshi Ikeuchi ,&nbsp;Akinori Takeda ,&nbsp;Takashi Sakurai ,&nbsp;Kengo Ito ,&nbsp;Takashi Kato","doi":"10.1016/j.bbih.2025.101018","DOIUrl":"10.1016/j.bbih.2025.101018","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic peripheral inflammation triggered by adipokine release may extend to the brain, potentially influencing the pathological progression of Alzheimer's disease (AD) and neuropsychiatric symptoms (NPS). However, it remains unclear whether and how leptin contributes to the link between adipose tissue dysfunction and dementia. This study aims to investigate the role of leptin in the connection between adipose-derived inflammatory signaling and cognitive impairment/NPS.</div></div><div><h3>Methods</h3><div>Path analysis was employed to explore how leptin relates to the association between adipose-related metabolic dysfunction and dementia through inflammatory pathways in patients with AD pathology (n = 15). Variables included plasma leptin concentration, body mass index (BMI) as a marker of adiposity, and in vivo assessments of regional neuroinflammation using translocator protein (TSPO)-PET imaging with the tracer ¹¹C-DPA-713 (¹¹C-DPA-713-binding potential [¹¹C-DPA-713-BP_ND]). Cognitive function was measured using the Alzheimer's Disease Assessment Scale-Japanese Cognitive Subscale (ADAS-J cog), while NPS were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q).</div></div><div><h3>Results</h3><div>Regression analysis demonstrated that higher plasma leptin concentrations positively correlated with BMI and significantly predicted ¹¹C-DPA-713-BP_ND in the insula. Additionally, NPI-Q scores were associated with ¹¹C-DPA-713-BP_ND in the insula. Path analysis supported leptin's role linking adiposity to NPS through insular inflammation. The hypothesized model fit the data well under the null hypothesis [χ² (3) = 0.63, p = 0.89].</div></div><div><h3>Discussion</h3><div>These findings underscore the relevance of exploring how leptin and adipose tissue dysfunction interact with neuroinflammatory processes in contributing to NPS in the patients in the AD continuum. Interventions targeting these interactions could represent promising avenues for managing NPS.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101018"},"PeriodicalIF":3.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185372","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}

{"title":"Culturally targeted messaging and racial equity in SARS-CoV-2 antibody testing by multiplex salivary measurement: Protocol overview of a SeroNet investigation","authors":"Todd Lucas ,&nbsp;Christopher D. Heaney ,&nbsp;Steve W. Granger ,&nbsp;Kent D. Key ,&nbsp;Maria Knight Lapinski ,&nbsp;Nicole Jones ,&nbsp;Nigel Paneth ,&nbsp;Ahnalee M. Brincks ,&nbsp;Anurag Dawadi ,&nbsp;Leah Maschino ,&nbsp;Lindsey Rose ,&nbsp;Monicia Summers ,&nbsp;Rachel Weisbrod ,&nbsp;Nora Pisanic ,&nbsp;Olivia Aspiras ,&nbsp;Stefan M.M. Goetz ,&nbsp;Douglas A. Granger","doi":"10.1016/j.bbih.2025.101019","DOIUrl":"10.1016/j.bbih.2025.101019","url":null,"abstract":"<div><div>Better understanding racial disparities observed during the COVID-19 pandemic can be aided by SARS-CoV-2 serology testing. However, racial minorities may be underrepresented in serosurveillance efforts not only due to lack of testing accessibility, but also due to hesitancy towards participating in antibody testing programs stemming from medical mistrust. We designed a randomized control trial to evaluate how non-invasive salivary antibody testing and culturally targeted communication might be used to promote racial equity in uptake of SARS-CoV-2 serology testing during the COVID-19 pandemic. To evaluate these approaches, we recruited African American and White American participants from Flint, Michigan. Participants viewed a novel, animated didactic video about SARS-CoV-2 antibody testing, with half of African Americans viewing a culturally targeted version. We measured cognitive and affective responses that indicated receptivity to SARS-CoV-2 serology testing. We also provided a non-invasive salivary antibody screening opportunity, and we measured screening uptake as a behavioral outcome. Finally, we measured baseline sociodemographic, psychological, and health factors that could affect these responses. In addition to evaluating health communication approaches, multiplex SARS-CoV-2 antibody profiles can be subsequently linked to prescreen measures, and to inflammatory markers that were concomitantly measured in whole saliva. Ultimately, we aim to reduce COVID-19 racial disparities and bolster future pandemic preparedness through promoting equity in understanding and uptake of serology testing.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101019"},"PeriodicalIF":3.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169378","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}

{"title":"Physical activity affects DNA methylation-derived inflammation markers in a community-based Parkinson's disease study","authors":"Yang Cheng Hu ,&nbsp;Keren Zhang ,&nbsp;Kimberly C. Paul ,&nbsp;Jin Zhou ,&nbsp;Jeff M. Bronstein ,&nbsp;Cynthia D.J. Kusters ,&nbsp;Beate R. Ritz","doi":"10.1016/j.bbih.2025.101014","DOIUrl":"10.1016/j.bbih.2025.101014","url":null,"abstract":"<div><h3>Introduction</h3><div>Past studies have connected physical activity (PA) and Parkinson's disease (PD) to chronic inflammation. We use DNA methylation-derived (DNAm) proxies for inflammation to investigate the relationship between PA and chronic inflammation among PD patients.</div></div><div><h3>Methods</h3><div>We collected demographics, lifestyle, and PA status information by interviewing 555 PD patients enrolled in the Parkinson's Environment and Gene (PEG) studies. We used the epigenetic clock website to generate DNAm proxies and performed principal component analysis (PCA) of 22 DNAm cytokine proxies. Using the Mann-Whitney <em>U</em> test, we compared the PC scores of active and sedentary patients. For PCs associated with PA status, we examine associations between PA status, the amount of PA, and PCs for DNAm cytokines using permutation-based tests.</div></div><div><h3>Results</h3><div>Compared to sedentary PD patients, those who reported strenuous PA have lower levels of c-reactive protein (CRP; p &lt; 0.01) and higher levels of Fc receptor-like 2 (FcRL2; p = 0.02). Patients who engaged in moderate PA have lower levels of C-X-C motif chemokine ligand 9 (CXCL9; p = 0.03), 10 (CXCL10; p = 0.02), and 11 (CXCL11; p = 0.01). Among active patients, strenuous PA is non-linearly (convex-shape) associated with the proportions of natural killer cells (NK; p = 0.02) and CD8T cells (p = 0.05) and negatively associated with CRP levels (p = 0.02). We also observe a non-linear association between moderate PA and monocyte counts (p = 0.02).</div></div><div><h3>Conclusion</h3><div>PA may benefit PD patients by reducing chronic inflammation. We also found that strenuous PA may increase the proportions of NK and CD8T cells, though further effort is needed to confirm potential shifts in immune cell subtypes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101014"},"PeriodicalIF":3.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169376","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}

{"title":"Psychoneuroimmunology of Mindfulness: What works, how it works, and for whom?","authors":"Ivana Buric","doi":"10.1016/j.bbih.2025.101022","DOIUrl":"10.1016/j.bbih.2025.101022","url":null,"abstract":"<div><div>As a major risk factor for mental and physical health disorders, chronic stress presents a critical public health challenge. Over the past decades, mindfulness-based interventions (MBIs) have gained empirical support as a promising approach to mitigating its harmful effects. However, important research gaps remain in the psychoneuroimmunology of mindfulness. This article synthesises the current state of research and identifies three central gaps that offer future directions for advancing the field. The first gap concerns the lack of a unified theoretical framework in mindfulness research, which hinders progress and cross-disciplinary integration. Researchers are invited to use the testable INterdiSciPlinary TheoretIcal FRamEwoRk (INSPIRER) that integrates the psychological, neural, and immune mechanisms by which mindfulness produces broad benefits across different levels of observation. The second gap refers to individual differences in responses to MBIs, emphasising the need for precision approaches to discover who benefits most and for whom these interventions may be contraindicated. Baseline levels of psychopathology are some of the participant characteristics that influence responses, but only further identification of participant characteristics and replication of existing ones will allow for more targeted interventions. The final gap addresses adaptations to existing MBIs that may further increase effectiveness or accessibility across diverse populations—such as varying intervention duration and doses of home practice or utilising technology. By addressing these three research gaps, we can advance the field of mindfulness in the 21st century and contribute to the development of cost-effective and personalised interventions that can be applied on a large scale to mitigate the effects of chronic stress and protect human health.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101022"},"PeriodicalIF":3.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147041","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}

{"title":"Altered behaviour and immune response in mice with NHLRC2 p.Asp148Tyr variant","authors":"Anniina E. Hiltunen ,&nbsp;Salla M. Kangas ,&nbsp;Aishwarya Gondane ,&nbsp;Henna Koivisto ,&nbsp;Kari Salokas ,&nbsp;Anne Heikkinen ,&nbsp;Miia H. Salo ,&nbsp;Tapio Röning ,&nbsp;Antti Tallgren ,&nbsp;Virpi Glumoff ,&nbsp;Maria C. Denis ,&nbsp;Niki Karagianni ,&nbsp;Johanna Myllyharju ,&nbsp;Markku Varjosalo ,&nbsp;Heikki Tanila ,&nbsp;Harri M. Itkonen ,&nbsp;Mika Rämet ,&nbsp;Johanna Uusimaa ,&nbsp;Reetta Hinttala","doi":"10.1016/j.bbih.2025.101020","DOIUrl":"10.1016/j.bbih.2025.101020","url":null,"abstract":"<div><div>Fibrosis, neurodegeneration and cerebral angiomatosis (FINCA) is a childhood-onset neurodevelopmental disorder with multi-organ manifestations, including recurrent infections. It is caused by variants in <em>NHLRC2</em>, initiating a cascade of unknown pathological events.</div><div>We investigated the FINCA disease-causing p.Asp148Tyr variant in NHLRC2 by analysing transcriptional changes in mouse embryonic stem cells (mESCs). We conducted behavioural and immunological phenotyping of FINCA mice compound heterozygous for the <em>Nhlrc2</em> knockout allele and p.Asp148Tyr variant and explored their T cell populations and cytokine production in splenocytes. Additionally, we employed proximity-labelling mass spectrometry to identify changes in protein–protein interactions resulting from the p.Asp148Tyr variant in human embryonic kidney cells.</div><div>We discovered significant transcriptional changes in mESCs homozygous for the p.Asp148Tyr variant or <em>Nhlrc2</em> knockout allele compared to wild-type cells, with genes involved in cell metabolism, adhesion, neurodevelopment and immune response. FINCA mice exhibited hyperactivity and decreased exploration of new object in adolescence, and an altered innate immune response, particularly in interferon γ production. By comparing p.Asp148Tyr-induced changes in gene expression in mouse cells and putative interaction partners in human cells, we identified Rho GTPase signalling as a common affected pathway.</div><div>Our study provides insights into the molecular pathways impacted by the p.Asp148Tyr NHLRC2. The FINCA mouse, which recapitulates several features of the human condition, particularly neurodevelopmental and immune response defects, serves as a tool for investigations on the role of environmental triggers in disease pathogenesis. Our results suggest that targeting immune pathways could offer a strategy for therapeutic intervention in FINCA disease.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101020"},"PeriodicalIF":3.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138987","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}

{"title":"The contribution of type-I IFN-mediated neuroinflammation to Parkinson's disease progression","authors":"Shuyan Chen,&nbsp;Peter J. Crack,&nbsp;Juliet M. Taylor","doi":"10.1016/j.bbih.2025.101017","DOIUrl":"10.1016/j.bbih.2025.101017","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by motor dysfunction. Pathological hallmarks of the disease include selective dopaminergic neuronal death, intraneuronal deposits known as Lewy bodies and extensive neuroinflammation within the central nervous system (CNS). Microglia are the key cellular players in mediating this neuroinflammatory response, propagating this neuropathology to exacerbate the neuronal cell death. Growing evidence suggests a role for the type-I interferons (IFN) in driving the neuroinflammatory response in PD, with increased type-I IFN signatures reported in both PD patients and in animal models of the disease. This review will discuss 1) the key players that modulate the neuroinflammatory response in PD and their implications in the CNS 2) the contribution of the type-I IFNs in driving the neuroinflammatory response in PD, and 3) evidence for therapeutically targeting type-I IFN signalling to slow disease progression. A greater understanding of the underlying mechanisms that lead to the elevated neuroinflammatory response in PD could lead to new advances in therapeutic targets that effectively slow the disease progression.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101017"},"PeriodicalIF":3.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115948","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}

{"title":"The effect of dual inflammation on the acute phase clinical outcomes of schizophrenia patients with comorbid COVID-19","authors":"Jiahui Zhu ,&nbsp;Jiamin Shao ,&nbsp;Peng Wang ,&nbsp;Yuan Liu ,&nbsp;Gangming Cheng ,&nbsp;Qi Zhou ,&nbsp;Zhuoran Li ,&nbsp;Jiayi Li ,&nbsp;Mingqia Wang ,&nbsp;Zhuokai Zhang ,&nbsp;Xuan Dong ,&nbsp;Chuan Shi","doi":"10.1016/j.bbih.2025.101015","DOIUrl":"10.1016/j.bbih.2025.101015","url":null,"abstract":"<div><h3>Background and hypothesis</h3><div>Inflammation plays a crucial role in pathological mechanisms in schizophrenia (SZ) and the coronavirus disease 2019 (COVID-19), but the impact of dual inflammation on SZs’ clinical outcomes is poorly understood. This study aimed to investigate whether dual inflammation impacts acute phase outcomes in patients with schizophrenia comorbid with COVID-19 (COVID-SZs).</div></div><div><h3>Study design</h3><div>A total of 114 SZs and 49 COVID-SZs were recruited for this study. Plasma samples were collected and analyzed for levels of routine blood and inflammatory cytokines from all the participants. Then clinical symptoms, cognitive performance, and functional assessments were conducted at recruitment. One-way analysis of covariance examined the differences in inflammatory cytokines and correlation analyses examined the relationship between inflammatory cytokines and clinical outcomes.</div></div><div><h3>Study results</h3><div>After controlling for age, gender, substance use status, and antipsychotic medications, levels of inflammatory cytokines increased in COVID-SZs groups compared to SZs groups. There were significantly higher total Positive and Negative Syndrome Scale (PANSS) scores and positive PANSS scores in COVID-SZs groups compared to SZs. As for cognitive performance, the COVID-SZs group had significantly worse performance in processing speed and attention than the SZs. The COVID-SZs group had significantly worse health status compared to the SZs. There were significantly different correlation patterns between the severity of psychiatric symptoms and inflammatory cytokines in COVID-SZs and SZs group.</div></div><div><h3>Conclusions</h3><div>Findings indicate that dual inflammation exacerbates the acute phase clinical outcome of COVID-SZs. Suggesting a combined anti-inflammatory drug or the use of potentially anti-inflammatory antipsychotics in the acute phase of treatment to mitigate central nervous system damage. Regular monitoring of inflammatory marker levels can help reduce the risk of fluctuating psychiatric symptoms in patients with schizophrenia caused by inflammatory storms.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101015"},"PeriodicalIF":3.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147098","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}

{"title":"Exploring the effects of exercise on immune cell function and tumour infiltration in patients with breast cancer receiving neoadjuvant chemotherapy – a feasibility trial","authors":"Anna Ubink ,&nbsp;Marieke R. ten Tusscher ,&nbsp;Hans J. van der Vliet ,&nbsp;Joeri A.J. Douma ,&nbsp;Tanja D. de Gruijl ,&nbsp;Hetty Bontkes ,&nbsp;Petra Bonnet ,&nbsp;Diede van Ens ,&nbsp;Willemijn Hobo ,&nbsp;Harry Dolstra ,&nbsp;Ellis Barbé ,&nbsp;Susanne van der Velde ,&nbsp;Catharina Willemien Menke-van der Houven van Oordt ,&nbsp;Simone H.C. Havenith ,&nbsp;Annemarie Conijn-Mensink ,&nbsp;Annette A. van Zweeden ,&nbsp;Harm Westdorp ,&nbsp;Joannes F.M. Jacobs ,&nbsp;Laurien M. Buffart","doi":"10.1016/j.bbih.2025.101021","DOIUrl":"10.1016/j.bbih.2025.101021","url":null,"abstract":"<div><div>Pre-clinical studies have shown that exercise can decrease tumour growth through mobilisation, activation, and increased tumour infiltration of natural killer (NK) and CD8⁺ T cells. It is currently unclear whether this can be extrapolated to patients. Therefore, a pilot study was set up to examine the feasibility of obtaining an additional study biopsy and to generate preliminary data on the potential effects of exercise on peripheral immune cell function and tumour immune infiltration. Twenty patients with stage I-III breast cancer receiving neoadjuvant chemotherapy were included (participation rate: 27%). Patients were randomised into the intervention group receiving a six-week supervised aerobic and resistance exercise program or the control group. Blood samples and tumour biopsies were collected before randomisation and after six weeks of chemotherapy. For 8 of 20 (40%) patients, we were able to obtain and analyse biopsies at diagnosis and six-week follow-up. This showed a decrease in CD56⁺ cells/mm² tumour tissue in the three patients of the control group, while it remained stable in most patients of the exercise group. Upon co-culture of peripheral blood mononuclear cells with K562 tumour cells, the exercise group showed increased expression of the degranulation marker CD107a on NK cells (β = 1038.5, 95%CI = 56.9; 2020.2, p = 0.04), and a trend towards increased tumour cell lysis <em>in vitro</em> (β = 18.8%, 95%CI = −3.9; 41.5, p = 0.10) compared to the control group. In conclusion, the study design was feasible with regard to the participation rate, however, revision is needed with regard to the use of a study-related biopsy prior to a sufficiently powered randomised controlled trial.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101021"},"PeriodicalIF":3.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134448","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}

{"title":"Modulating effects of environmental enrichment on stress-induced changes in the gut microbiome","authors":"Kevin B. Smith ,&nbsp;Michael Murack ,&nbsp;James Butcher ,&nbsp;Abby Hinterberger ,&nbsp;Alain Stintzi ,&nbsp;Jacky Liang ,&nbsp;Despina A. Tata ,&nbsp;Nafissa Ismail","doi":"10.1016/j.bbih.2025.101023","DOIUrl":"10.1016/j.bbih.2025.101023","url":null,"abstract":"<div><div>Environmental enrichment (EE) involves adding non-standard stimuli, such as running wheels, mazes, and cage mates, to standard animal living conditions to facilitate physical activity, cognitive stimulation, and socialization. Interestingly, exposure to EE can modulate stress and immune responses. However, it is unclear whether housing environments can modulate the effects of stress on the gut microbiome. This study aimed to explore the effects of three different housing conditions—deprived (DH), social (SH), and enriched (EE)—on the central and peripheral immune responses, the HPA axis, and the gut microbiome in 180 male and female mice. Mice were housed in either the DH, SH, or EE condition for 3 weeks starting from post-natal day 21. At 6 weeks of age, during the pubertal stress-sensitive period, mice were treated with either saline or lipopolysaccharide (LPS), a bacterial endotoxin. Eight hours post-treatment, mice were euthanized, and brain, fecal samples, and trunk blood were collected to examine peripheral and central cytokine levels, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) expressions, along with diversity in the gut microbiome. Contrary to expectations, EE and SH mice showed higher plasma concentrations of TNFα, IL6, and IL12 cytokines than DH mice following LPS treatment, with male mice exhibiting significantly higher levels of these cytokines than their female counterparts. Moreover, EE mice exhibited significantly greater hypothalamic and hippocampal expressions of GR and MR compared to DH mice. The gut microbiome analysis revealed sex-specific beta diversity patterns post-LPS treatment, with male EE and SH mice displaying a more diverse microbiome compared to female counterparts. These findings enhance our understanding of how housing conditions influence the acute immune and stress responses and modulate their effects on the gut microbiome during puberty.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101023"},"PeriodicalIF":3.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124351","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}

{"title":"Reduced SARS-CoV-2 vaccine-specific antibody response associated with high clozapine doses in schizophrenia spectrum disorders","authors":"Itziar Montalvo ,&nbsp;Juan Francisco Delgado ,&nbsp;Albert Rodrigo-Parés ,&nbsp;Teresa Sagués ,&nbsp;Antoni Berenguer-Llergo ,&nbsp;Raquel Rodríguez-González ,&nbsp;Indira Bhambi ,&nbsp;Patricia Pontón ,&nbsp;Germà Julià ,&nbsp;Virginia Soria ,&nbsp;Diego Palao ,&nbsp;Javier Labad","doi":"10.1016/j.bbih.2025.101016","DOIUrl":"10.1016/j.bbih.2025.101016","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia, affecting approximately 1 % of the population worldwide, is associated with increased mortality rates and a reduced life expectancy of 10–20 years. Approximately 30 % of cases are resistant to conventional antipsychotic treatments, necessitating the use of clozapine. Recent evidence suggests that clozapine exerts immunomodulatory effects, with individuals undergoing chronic clozapine treatment exhibiting immune profiles resembling primary immunodeficiencies.</div></div><div><h3>Objective</h3><div>To evaluate the immune response to vaccination with the spike protein of SARS-CoV-2 in schizophrenia patients treated with clozapine, compared to those receiving other antipsychotics.</div></div><div><h3>Methods</h3><div>The study included 98 patients diagnosed with schizophrenia or schizoaffective disorder, of whom 69 were treated with clozapine. Demographic, clinical, and laboratory data were collected for all participants. Anti-spike protein antibodies were measured using the Elecsys® Anti-SARS-CoV-2 S assay.</div></div><div><h3>Results</h3><div>No significant differences were observed in demographic, clinical, or laboratory parameters between the groups. Univariate analysis revealed that spike antibody levels were positively associated with smoking habits and more than two exposures to the virus, while they were negatively associated with the time elapsed since vaccination and clozapine dosage.</div><div>In multivariate analysis, patients receiving clozapine doses &gt;350 mg/day exhibited a significant reduction in anti-spike antibody levels compared to those not treated with clozapine (fold change = 0.49 [0.24–0.97], <em>p</em> = 0.041) and those receiving &lt;200 mg/day of clozapine (fold change = 0.39 [0.17–0.88], <em>p</em> = 0.024).</div></div><div><h3>Conclusion</h3><div>High doses of clozapine (&gt;350 mg/day) in patients with schizophrenia and schizoaffective disorders are associated with a diminished immune response to SARS-CoV-2 spike protein vaccination.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"46 ","pages":"Article 101016"},"PeriodicalIF":3.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124352","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}