Brain, behavior, & immunity - health最新文献

{"title":"Progranulin modulates inflammatory responses to immune challenges by suppressing circulating cytokine levels","authors":"Takashi Matsuwaki,&nbsp;Keitaro Yamanouchi,&nbsp;Masugi Nishihara","doi":"10.1016/j.bbih.2025.101084","DOIUrl":"10.1016/j.bbih.2025.101084","url":null,"abstract":"<div><div>Progranulin (PGRN) is a multifunctional growth factor that is widely expressed throughout the body. It has recently been reported that PGRN haploinsufficiency is a major factor causing frontotemporal lobar dementia. Subsequently, many studies, including ours, have demonstrated the neuroprotective and neurotrophic functions of PGRN. We have also shown that PGRN is involved in voluntary exercise-induced neurogenesis and the suppression of neuroinflammation after traumatic brain injury. Because PGRN is expressed in immune cells in peripheral and central tissues, the main purpose of the present study was to elucidate the role of PGRN in inflammatory responses to immune challenges. Male C57BL/6J wild-type (WT) mice or PGRN-deficient (KO) mice of the same background were used in all experiments. We intraperitoneally injected lipopolysaccharide (LPS, 120 μg/kg) into the animals and measured their body temperature for 9 h during the day and their food intake for 24 h. Although LPS induced a fever response and anorexia in mice of both genotypes, the symptoms were much more severe in the KO mice. LPS is known to induce the secretion of inflammatory cytokines, which transmit immune signals from peripheral to central tissues. Thus, we subsequently determined the serum concentrations of the inflammatory cytokines IL-1β, IL-6, and TNF-α at 0, 1, and 3 h after LPS injection. KO mice showed a significantly stronger induction of IL-6 at 3 h and TNF-α at both 1 and 3 h after injection. IL-1β also tended to have stronger induction at 3 h in KO mice, although the difference was not statistically significant. In WT mice, LPS injection increased PGRN mRNA expression but did not enhance serum PGRN concentration. These results suggest that PGRN suppresses excessive inflammatory responses by moderating the secretion of inflammatory cytokines by functioning inside immune cells.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101084"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756696","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":"Detection of autoantibodies against Interferon Type I in patients with autochthonous West Nile Virus encephalitis","authors":"Jan Braune ,&nbsp;Lorenz Pechstein ,&nbsp;Christian Meisel ,&nbsp;Tim Meyer ,&nbsp;Julia Melchert ,&nbsp;Victor Max Corman ,&nbsp;Christiana Franke ,&nbsp;Thomas Schneider","doi":"10.1016/j.bbih.2025.101085","DOIUrl":"10.1016/j.bbih.2025.101085","url":null,"abstract":"<div><div>West Nile virus (WNV) is a neurotropic flavivirus that has become a global concern because of its rapid geographical spread and its capacity to cause severe disease in humans. Although often asymptomatic, infection can lead to life-threatening neuroinvasive disease (WNND) in a small percentage of cases, particularly among elderly individuals and individuals with compromised immune responses. We present three cases of autochthonous WNND from Germany from 2023 to 2024, which showcase various neurological manifestations and their correlation with immune responses. Two elderly men developed severe encephalitis symptoms, whereas one patient presented with only mild encephalitis symptoms but severe flaccid paresis. Notably, two patients (Patients One and Two) had neutralizing autoantibodies against interferon-α2 and interferon-ω, along with neutralizing antibodies against interferon-β in Patient One. This may implicate impaired viral immunity and severe disease progression. Complete genome sequencing revealed lineage 2 sequences with high similarity to WNV sequences obtained from other patients, birds, and mosquitoes in Germany. Our report raises concerns about the underdiagnosis of WNV in Germany, where human cases remain underreported despite the presence of endemic infections in animals and competent mosquito vectors. Given the increasing prevalence of WNV in Europe, intensified surveillance and awareness are critical. The variability in clinical presentations and the potential for fatal outcomes underscore the importance of early recognition and individualized management strategies.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101085"},"PeriodicalIF":3.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756695","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":"Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging?","authors":"Marieke S. Tollenaar ,&nbsp;Nicole Creasey ,&nbsp;Mirjam C.M. Wever ,&nbsp;Karen Knipping ,&nbsp;Johan Garssen ,&nbsp;Lisanne E.A.M. van Houtum ,&nbsp;Wilma G.M. Wentholt ,&nbsp;Loes Janssen ,&nbsp;Elad Lax ,&nbsp;Bernet M. Elzinga","doi":"10.1016/j.bbih.2025.101080","DOIUrl":"10.1016/j.bbih.2025.101080","url":null,"abstract":"<div><h3>Background</h3><div>Childhood maltreatment is a major risk factor for the development of depression, as well as for imbalances in the immune system, including chronic low-grade inflammation. Less is known about potential immune imbalances in adolescent depression and the role of childhood maltreatment. Furthermore, accelerated epigenetic aging may contribute to the development of inflammation, but has never been examined in the context of adolescent depression.</div></div><div><h3>Methods</h3><div>We investigated childhood maltreatment, inflammation, and epigenetic aging in 78 healthy adolescents and 33 adolescents with a clinically diagnosed depressive disorder. Childhood maltreatment was assessed via self-report, and inflammatory markers (CRP, IL-1β, IL-6, IL-8, sIgA, and TNF-α) were analyzed in saliva. DNA methylation was analyzed in a subsample (<em>n</em> = 48) of both healthy and unmedicated, depressed adolescents to estimate epigenetic age (Horvath and PedBE clocks).</div></div><div><h3>Results</h3><div>The MANOVA showed that depression was significantly associated with the immune markers, but not with epigenetic aging. Post-hoc tests suggested however that IL-8 levels were reduced, while none of the other markers were affected. Unexpectedly, childhood (emotional) maltreatment was significantly associated with epigenetic age <em>de</em>celeration on the PedBE clock (<em>p</em> = .01), and not with inflammation. The inflammatory markers were not associated with either of the epigenetic age clocks.</div></div><div><h3>Conclusions</h3><div>Our results contrast with previous literature in adults, indicating that epigenetic age <em>ac</em>celeration and inflammation are not unequivocal indicators of depression and childhood trauma in adolescents. Future studies with larger, more heterogeneous samples should investigate under which circumstances increased or decreased levels of these biological markers indicate vulnerability for health-related outcomes. Better understanding of these mechanisms in adolescence may help to develop appropriate interventions supporting a healthy development of children who experienced maltreatment or depression.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101080"},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725106","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":"Impact of maternal microbiota imbalance during pregnancy on fetal cerebral neurodevelopment: Is there a link to certain autistic disorders?","authors":"Sylvie Mavel ,&nbsp;Léa Pellé ,&nbsp;Christian R. Andres","doi":"10.1016/j.bbih.2025.101074","DOIUrl":"10.1016/j.bbih.2025.101074","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with a heterogeneous group of psychiatric disorders primarily characterized by impairments in communication and social interactions. ASD typically emerges around 18 months of age. While no single etiology has been identified, theories suggest a combination of genetic predisposition and environmental factors, such as exposure to toxics, viral infections, and neuroinflammatory processes. However, the mechanisms linking environmental risk factors to ASD remain poorly understood, particularly during the prenatal period. Among the various hypotheses, the gut microbiota has been proposed as a potential modulator of nervous system development and function. During pregnancy, the maternal microbiota could trigger gestational inflammatory responses, leading to maternal immune activation (MIA). These deleterious processes could play a causal role in the etiopathogenesis of neurodevelopmental disorders in offspring. The gut microbiota could be the missing link between genetic susceptibility and environmental exposures in certain forms of ASD. The gut microbiome induces the production of microbiota-derived signaling metabolites, immune mediators, gut hormones, and neural signaling via the spinal cord and vagus nerve. This review synthesizes the current knowledge from preclinical rodent models and human studies that investigate the impact of the maternal gut microbiota during pregnancy on ASD risk in offspring. Additionally, the potential roles of the maternal oral and vaginal microbiota are also discussed in the context of this maternal-offspring pairing. Finally, we examine how restoring maternal microbiome balance, through interventions such as pre/probiotics, may help reduce the perinatal risk of certain ASD by positively influencing prenatal environmental factors.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101074"},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720968","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 impact of acute COVID-19 symptoms on insomnia: A longitudinal study among medical students","authors":"Yue Zhu ,&nbsp;Xiaoyang Qin ,&nbsp;Yuhong Lu ,&nbsp;Yuenan Yu ,&nbsp;Rongxun Liu ,&nbsp;Rongxin Zhu ,&nbsp;Kuan-Pin Su ,&nbsp;Fei Wang","doi":"10.1016/j.bbih.2025.101067","DOIUrl":"10.1016/j.bbih.2025.101067","url":null,"abstract":"<div><h3>Objective</h3><div>The COVID-19 pandemic has profoundly disrupted global mental health. Medical students, already vulnerable to high stress, experience heightened psychological distress. This study aimed to investigate the association between acute COVID-19 infection and the development of psychological symptoms in medical students, exploring the role of specific COVID-19 symptoms and lifestyle factors.</div></div><div><h3>Methods</h3><div>A longitudinal study of 2359 medical students assessed psychological symptoms (depression, anxiety, insomnia) before and after COVID-19 infection. Logistic regression models, adjusted for confounders, examined the relationship between COVID-19 status (with or without infection), and the onset of psychological symptoms. The study also explored acute COVID-19 symptoms and lifestyle factors associated with psychological symptoms in the COVID-19 infected (COVID+) group.</div></div><div><h3>Findings</h3><div>The COVID + group exhibited significantly greater increases in depression and insomnia compared to non-infected group. COVID-19 infection was significantly associated with the onset of insomnia post-infection (OR [95 % CI] 1.83 [1.05–3.21]). Moderate to severe acute symptoms, including sleep disturbances (2.20 [1.17–4.14]), decreased attention/memory (2.47 [1.02–6.00]), and breathlessness (2.05 [1.08–3.85]), were identified as risk factors for onset of insomnia. Regular exercise was found to be negatively associated with the onset of insomnia (0.54 [0.33–0.88]).</div></div><div><h3>Conclusion</h3><div>Early intervention targeting these acute-phase risk symptoms is crucial for preventing long-term insomnia. Regular exercise is effective in preventing the development of insomnia in medical students following COVID-19 infection. These findings will assist in formulating targeted interventions to address recurrent infections in the post-pandemic era.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101067"},"PeriodicalIF":3.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725105","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":"Maternal immune activation and antibiotics affect offspring neurodevelopment, behaviour, and microbiome","authors":"Clara Deady ,&nbsp;Jamie FitzGerald ,&nbsp;Nirit Kara ,&nbsp;Martina Mazzocchi ,&nbsp;Adam O'Mahony ,&nbsp;Mara Ioana Ionescu ,&nbsp;Ruth Shanahan ,&nbsp;Saoirse Kelly ,&nbsp;Fiona Crispie ,&nbsp;Paul D. Cotter ,&nbsp;Fergus P. McCarthy ,&nbsp;Cathal McCarthy ,&nbsp;Gerard W. O'Keeffe ,&nbsp;Siobhain M. O'Mahony","doi":"10.1016/j.bbih.2025.101065","DOIUrl":"10.1016/j.bbih.2025.101065","url":null,"abstract":"<div><div><em>In utero</em> exposure to an increased level of maternal inflammation or a disrupted maternal gut microbiome during pregnancy have been linked to several neurodevelopmental disorders in the offspring. Despite the strong links between these two adverse events, few studies looked at the interaction between the maternal gut microbiome and maternal immune activation (MIA) on the neurodevelopmental outcomes in the offspring. Here, we aim to determine if maternal gut microbiome disruption exacerbated the impact of systemic inflammation on brain development, offspring behaviour, and long-term microbiome changes. A low dose of intraperitoneal lipopolysaccharide (LPS) was administered to pregnant Sprague Dawley rats from gestational day 12–18. Concurrently, an antibiotic cocktail (ampicillin, neomycin, vancomycin) was given in the drinking water to disturb the maternal microbiome. Embryos at gestational day 18 were found to have a reduced body size and weight, along with reduced placental weight following exposure to LPS, with some effects also seen with antibiotic exposure. Offspring exposed to LPS <em>in utero</em> were found to have increased anxiety-like behaviours and repetitive-behaviours. No behavioural changes were noted from antibiotic exposure. The expression of 5HT1a receptors in the prefrontal cortex was found to be reduced following LPS exposure. The offspring microbiome varied between the groups, with prenatal antibiotic exposure playing a role in reducing α-diversity and species richness in the periadolescent period. This study highlights the impact of prenatal exposures on different aspects of neurodevelopment. However, additional research is warranted to explore the role of the maternal immune system and microbiome on the offspring development, while also testing the potential therapeutic agents such as probiotics.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101065"},"PeriodicalIF":3.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713961","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":"Childhood trauma and mental health outcomes in Post-COVID Syndrome: Results from a cross-sectional study in Germany","authors":"Andrea Stölting ,&nbsp;Dominik Schröder ,&nbsp;Tim Schmachtenberg ,&nbsp;Inga Schimansky ,&nbsp;Massa Yaqubi-Naqizadah ,&nbsp;Christian Klemann ,&nbsp;Franziska Rebmann ,&nbsp;Marie Mikuteit ,&nbsp;Sandra Steffens ,&nbsp;Georg M.N. Behrens ,&nbsp;Frank Klawonn ,&nbsp;Alexandra Dopfer-Jablonka ,&nbsp;Frank Müller ,&nbsp;Christine Happle","doi":"10.1016/j.bbih.2025.101069","DOIUrl":"10.1016/j.bbih.2025.101069","url":null,"abstract":"<div><h3>Introduction</h3><div>Post-COVID syndrome (PCS) affects approximately 6–10 % of COVID-19 survivors, with complex clinical manifestations and poorly understood pathophysiological mechanisms. While childhood trauma is known to impact long-term health outcomes, its influence on PCS and associated quality of life remains unclear.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, we analyzed data from 641 participants (487 with PCS, 154 without) through the DEFEAT online platform. Childhood trauma was assessed using the Child Trauma Questionnaire-Short Form (CTQ-SF). Depression, anxiety, and health-related quality of life were evaluated using PHQ-9, GAD-7, and EQ-5D-3L. Uni- and multivariate analyses were performed.</div></div><div><h3>Results</h3><div>Overall, 38.8 % of participants reported at least one adverse childhood experience (ACE). Emotional abuse was significantly more frequent in PCS patients compared to controls (21.1 % vs. 12.3 %, p = 0.02). PCS patients showed significantly higher rates of depression (18.9 % vs. 7.1 %, p &lt; 0.001) and anxiety (23.8 % vs. 14.3 %, p = 0.004) compared to non-PCS participants. Health-related quality of life was significantly lower in PCS patients (median 64.9 vs. 90.2, p &lt; 0.001). After adjusting for age, gender, and educational level, childhood trauma was associated with increased depression and anxiety specifically in PCS patients.</div></div><div><h3>Discussion/conclusion</h3><div>Our findings suggest that childhood trauma significantly impacts mental health outcomes and quality of life in PCS patients. The strong association between childhood trauma and adverse mental health outcomes specifically in PCS patients highlights the importance of trauma-informed care approaches. These results emphasize the need for targeted screening and personalized interventions addressing both physiological and psychological aspects of PCS recovery in patients with childhood trauma history.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101069"},"PeriodicalIF":3.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711255","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":"Social anxiety disorder and antibodies against glial cells in the cerebrospinal fluid","authors":"Judith Weiser ,&nbsp;Alexander Rau ,&nbsp;Katharina von Zedtwitz ,&nbsp;Bernd Feige ,&nbsp;Kathrin Nickel ,&nbsp;Simon J. Maier ,&nbsp;Raphael J. Dressle ,&nbsp;Nils Venhoff ,&nbsp;Ludger Tebartz van Elst ,&nbsp;Miriam A. Schiele ,&nbsp;Katharina Domschke ,&nbsp;Harald Prüss ,&nbsp;Dominique Endres","doi":"10.1016/j.bbih.2025.101064","DOIUrl":"10.1016/j.bbih.2025.101064","url":null,"abstract":"<div><h3>Introduction</h3><div>Autoimmune social anxiety disorders have not yet been described in the literature.</div></div><div><h3>Methods</h3><div>Therefore, this case of a patient with possible autoimmune-mediated social anxiety disorder is presented. Due to treatment resistance and high serum streptococcal antibody levels, a comprehensive diagnostic work-up was performed.</div></div><div><h3>Results</h3><div>The 19-year-old female patient presented with predominant social anxiety disorder and secondary depression. Testing for all known characterized neuronal and glial IgG antibodies identified slightly positive (“+”) recoverin IgG antibodies only in the serum (using an immunoassay). Cerebrospinal fluid (CSF) analysis using a tissue-based assay on unfixed mouse brain slices revealed moderate immunoglobulin G (IgG) anti-nuclear binding and a specific strong IgG binding against cell nuclei of the Bergmann glia in the cerebellum. No clear pathology was noted in conventional magnetic resonance imaging (MRI), voxel-based morphometry, and cerebral blood flow. Diffusion microstructure imaging (DMI) revealed a substantial reduction of the intraneurite volume fraction in the cerebellar gray and white matter. This was accompanied by a compensatory increase in free fluid and the extra-neurite volume fraction. Alterations in the striatum were also observed with DMI. Electroencephalography (EEG) showed intermittent generalized slowing with underlying left frontal, right temporal, and left temporo-occipital components (detected via independent component analysis of the EEG). The [¹⁸F]fluorodeoxyglucose positron emission tomography of the whole body detected a slight polyserositis and no malignant tumor.</div></div><div><h3>Discussion</h3><div>This is the first description of a case with evidence of a possible antibody-mediated cerebellar dysfunction associated with social anxiety disorder. The testing for all characterized neuronal/glial antibodies showed only weakly positive recoverin antibodies in the serum, which, however, were not detectable in the CSF. Therefore, novel CSF antibodies directed against cell nuclei of the Bergmann glia in the cerebellum could be assumed. DMI alterations in the cerebellum were in principle compatible with neuroinflammation with edematization and cellular activation. In addition, the further DMI alterations in the striatum and the fronto-temporal generators of EEG slowing suggest an involvement of the “anxiety network”. Further immunopsychiatric research in anxiety disorders might contribute to identifying an autoimmune subtype and potentially immunomodulatory treatment options.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101064"},"PeriodicalIF":3.7,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702820","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":"Immune cell exhaustion and apoptotic markers in major depressive disorder: Effects of in vitro cannabidiol administration","authors":"Muanpetch Rachayon ,&nbsp;Ketsupar Jirakran ,&nbsp;Pimpayao Sodsai ,&nbsp;Chavit Tunvirachaisakul ,&nbsp;Atapol Sughondhabirom ,&nbsp;Jing Li ,&nbsp;Yingqian Zhang ,&nbsp;Michael Maes","doi":"10.1016/j.bbih.2025.101066","DOIUrl":"10.1016/j.bbih.2025.101066","url":null,"abstract":"<div><h3>Background</h3><div>Immune dysregulation is a component of Major Depressive Disorder (MDD). Cannabidiol (CBD) has immunomodulatory and putative antidepressant effects. The relationship between apoptotic and exhaustion immune markers and the clinical features of MDD and the effects of CBD on these markers are still unknown.</div></div><div><h3>Objectives</h3><div>To assess pro-apoptotic (CD95) and T cell exhaustion (TIM3) markers on immune cells in patients with MDD, as well as the impact of in vitro CBD administration on these markers.</div></div><div><h3>Methods</h3><div>We recruited healthy controls and MDD patients and evaluated the immunophenotypes of T/B lymphocytes using flow cytometry in unstimulated and anti-CD3/CD28 stimulated conditions. We evaluated the immune profiles of M1 macrophages, immune-inflammatory response system (IRS), compensatory immunoregulatory system (CIRS), T cell proliferation, and immune-related neurotoxicity (IRN). We investigated the in vitro effects of CBD on immune cell subsets at concentrations of 0.1 μg/mL, 1 μg/mL, and 10.0 μg/mL.</div></div><div><h3>Results</h3><div>The stimulated CD3⁺CD95⁺ cell percentages were substantially correlated with the number of depressive episodes, recurrence of illness, and suicidal behaviors. The stimulated CD8+TIM3+ cell percentages were substantially and inversely associated with the M1, IRS, CIRS, T cell growth, and IRN immune profiles. TIM3+ bearing CD3⁺, CD4⁺ and CD8⁺,cells were significantly suppressed by lower CBD concentrations (0.1–1 μg/mL). TIM3+ and CD95⁺ bearing cells were significantly suppressed by the higher CBD concentrations (10.0 μg/mL).</div></div><div><h3>Discussion</h3><div>Aberrations in immune checkpoint molecular processes impact the features of MDD. CBD significantly impacts apoptotic and exhaustion processes thereby possibly interfering with immune homeostasis.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101066"},"PeriodicalIF":3.7,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679532","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":"Risk factors, protective factors, peripheral biomarkers, and neurocognitive markers associated with mood disorders: An umbrella review of 103 meta-analyses and systematic reviews","authors":"Huixue Wang ,&nbsp;Lijun Ma ,&nbsp;Mi Zhang ,&nbsp;Zhenyue Zu ,&nbsp;Wenzhuo Wei ,&nbsp;Ni Li ,&nbsp;Linxi Yang ,&nbsp;Fenglan Chen ,&nbsp;Chuan Fan ,&nbsp;Kai Wang ,&nbsp;Xiaoming Li","doi":"10.1016/j.bbih.2025.101068","DOIUrl":"10.1016/j.bbih.2025.101068","url":null,"abstract":"<div><h3>Background</h3><div>Mood disorders, including bipolar disorder (BD) and major depressive disorder (MDD), are extensively studied regarding environmental risk factors, protective factors, peripheral biomarkers, and cognitive neurocognitive markers. Our umbrella review of observational studies aims to separately elucidate these associations with BD and MDD.</div></div><div><h3>Methods</h3><div>A comprehensive search of PubMed, Embase, Web of Science, and Cochrane was conducted, with a search end date of October 17, 2024. We included systematic reviews that provided meta-analyses of observational studies that examined associations of potential environmental risk factors, environmental protective factors, peripheral biomarkers and neurocognitive markers with mood disorder. We synthesized data using summary effect estimates (e.g., odds ratio [OR], relative risk [RR]), evaluated quality with AMSTAR 2. This review is registered with PROSPERO (CRD42023439581).</div></div><div><h3>Results</h3><div>Identified 103 articles from 2782 initially screened. In depression, we identified 95 risk factors, 18 protective factors, 19 biomarkers, and 10 neurocognitive markers. For MDD, evidence of association was convincing (class I) history of mental illness (OR 6.77, 95 %CI 5.07–9.04), perinatal domestic violence exposure (OR 3.14, 95 %CI 2.74–3.61), and Mediterranean diet adherence (OR 0.87, 95 %CI 0.84–0.91). For BD, evidence of association was suggestive (class Ⅲ) for cannabis use (OR 2.97, 95 %CI 1.80–4.90), obesity (OR 1.77, 95 %CI 1.40–2.23) were prominent risk factors. The evidence levels of biomarkers and cognitive neuro-markers for BD and MDD are at suggestive (class Ⅲ) or below.</div></div><div><h3>Conclusion</h3><div>This review highlights the complexity of the interrelationship between mood disorders and numerous risk and protective factors. However, the reviewed associations are not necessarily causal. Future research should prioritize prospective high-quality studies to establish causality and thus facilitate the development of targeted interventions and preventive measures for mood disorders.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101068"},"PeriodicalIF":3.7,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687388","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}