Brain, Behavior, and Immunity最新文献

{"title":"A recent history of immune cell sex differences in the peripheral nervous system in persistent pain states.","authors":"Madelene Faye S Ho, Olivia Farkas, Andre Vilela Faria, Jason R Plemel, Bradley J Kerr","doi":"10.1016/j.bbi.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.05.004","url":null,"abstract":"<p><p>Pain is entwined with inflammation, and biological sex often influences mechanisms of the immune system. Due to possible differences in inflammatory mechanisms, women are predisposed to autoimmune diseases and chronic pain. Despite sex as a critical variable in clinical cases of autoimmune conditions and its pain comorbidities, fundamental investigations have long underrepresented female subjects in their studies. Fundamental research in the 2010 s, however, identified a binary sex specific mechanism for pain in rodents: male pain is microglia-driven while female pain is T cell-driven. Since then, studies have expanded in neuro-immunology to indicate that the sex differences and immune cells involved in these processes take on more elaborate roles when expanded to other causal modalities and anatomical levels of neuropathic and inflammatory pain. In this mini-review, we highlight updated roles for macrophages, T cells, and B cells in the peripheral nervous system during persistent pain conditions: neuropathic pain and inflammatory pain. We discuss sex similarities and sex differences in these cell types. By parsing out the sex specific roles of immune cells in persistent pain states we may be better positioned to find immune-based therapies that can effectively target chronic pain in sex-biased autoimmune conditions.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963982","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":"Childhood adversity as a risk factor for autoimmune disease: A systematic review and meta-analysis with implications for psychiatry","authors":"Jehanita Jesuthasan ,&nbsp;Cameron J. Watson ,&nbsp;Danish Hafeez ,&nbsp;Katharine Lynch-Kelly ,&nbsp;Andrea Danese ,&nbsp;Thomas A. Pollak","doi":"10.1016/j.bbi.2025.04.036","DOIUrl":"10.1016/j.bbi.2025.04.036","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune diseases are a heterogeneous category of disorders caused by an interaction between genetic and environmental factors which lead to a dysregulated immune response. Childhood adversity is an environmental risk factor with enduring effects on the immune system and may therefore be implicated in the aetiology of autoimmune disorders. This systematic review and <em>meta</em>-analysis sought to examine the association between childhood adversity and autoimmune disease in adulthood.</div></div><div><h3>Methods</h3><div>Electronic databases (MEDLINE, PsycINFO, Embase, and Web of Science) were searched for peer-reviewed studies in English, examining rates of childhood adversity in adults with a diagnosis of any autoimmune disease. This study was registered with PROSPERO, CRD42023439745.</div></div><div><h3>Findings</h3><div>The <em>meta</em>-analysis included 45 effect sizes from 27 studies (<em>Ncases</em> = 8,728, <em>Ncontrol</em> = 3,298,392). Results revealed a small effect (<em>SMD</em> = 0.30, 95 % CI [0.20–0.40], <em>p</em> &lt; 0.001) of exposure to childhood adversity on autoimmune disease in adulthood. Heterogeneity was very high, and Egger’s test and funnel plot inspection suggested that publication bias may be present. Rheumatoid arthritis (<em>SMD =</em> 0.48, 95 % CI [0.20–0.76], <em>p</em> &lt; 0.001), psoriasis (<em>SMD</em> = 0.30, 95 % CI [0.17–0.43], <em>p</em> &lt; 0.001), multiple sclerosis (<em>SMD =</em> 0.20, 95 % CI [0.01–0.38], <em>p</em> = 0.008), and inflammatory bowel disease (<em>SMD =</em> 0.31, 95 % CI [0.04–0.58], <em>p</em> = 0.024) were each associated with childhood adversity. Systemic lupus erythematosus was not (<em>SMD =</em> 0.17, 95 % CI [-0.06–0.41], <em>p</em> = 0.141). Twenty-one studies were assessed as being at high risk of bias.</div></div><div><h3>Interpretation</h3><div>There is evidence of an association between a history of childhood adversity and autoimmune disorders. This exposure may contribute to the elevated comorbidity between autoimmune diseases and severe mental illnesses. Due to the heterogeneity of the evidence and the high risk of bias in numerous studies, however, results should be treated with caution. Possible mechanisms underlying the relationship and implications for treatment and prevention of autoimmune diseases are discussed.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 643-653"},"PeriodicalIF":8.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941965","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":"Activation of central cannabinoid type 2 receptors, but not on peripheral immune cells, is required for endocannabinoid-mediated neuroprotection in Parkinson’s disease","authors":"Leyre Ayerra ,&nbsp;Miguel Angel Abellanas ,&nbsp;Clara Vidaurre ,&nbsp;Leyre Basurco ,&nbsp;Adriana Tavira ,&nbsp;Esther Luquin ,&nbsp;Pedro Clavero ,&nbsp;Elisa Mengual ,&nbsp;Maria Collantes ,&nbsp;Ivan Peñuelas ,&nbsp;Samuel Ruiz de Martin-Esteban ,&nbsp;Uwe Grether ,&nbsp;Cecilia J. Hillard ,&nbsp;Julian Romero ,&nbsp;Sandra Hervás-Stubbs ,&nbsp;Maria S. Aymerich","doi":"10.1016/j.bbi.2025.04.037","DOIUrl":"10.1016/j.bbi.2025.04.037","url":null,"abstract":"<div><div>Neuroinflammation is a key feature of Parkinson’s disease (PD). The cannabinoid receptor type 2 (CB2R) is expressed by cells of the innate and adaptive immune systems. Inhibition of monoacylglycerol lipase (MAGL) with JZL184 increases the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG), which is neuroprotective for dopaminergic neurons. The aim of this study was to determine whether the neuroprotective effect of MAGL inhibition is mediated by CB2R activation on specific immune cell populations. Experimental parkinsonism was induced by chronic administration of MPTP and probenecid. A specific increase in CD4⁺ T cell infiltration was detected in the midbrain of parkinsonian mice and was reduced by administration of JZL184. JZL184 had no effect in CB2R KO mice, suggesting that CB2R is required for neuroprotection. In the brain, CB2R expression was restricted to myeloid cells and lymphocytes, and increased in microglia under parkinsonian conditions. Administration of a central CB2R agonist, JWH133, exerted a beneficial effect similar to that of JZL184, whereas the peripheral agonist RO304 lacked neuroprotective activity. These results were confirmed using chimeric mice. <em>In silico</em> analysis, showed that transcripts related to 2-AG biosynthesis are downregulated in the midbrain microglia from PD patients. Our results show that activation of CB2R in the brain prevents nigrostriatal degeneration, CD4⁺ T cell infiltration and TNFα production in the midbrain of parkinsonian mice. The reduced 2-AG signaling in microglia from PD patients suggests that activation of microglial CB2R may be an interesting strategy for the treatment of PD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 600-611"},"PeriodicalIF":8.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907763","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":"Role of early life adversities in inflammation-related neuropsychiatric comorbidity in obesity","authors":"Juliette Montet ,&nbsp;Sandra Dexpert ,&nbsp;Muriel Darnaudéry ,&nbsp;Cédric Beau ,&nbsp;Damien Forestier ,&nbsp;Patrick Ledaguenel ,&nbsp;Eric Magne ,&nbsp;Bruno Aouizerate ,&nbsp;Lucile Capuron","doi":"10.1016/j.bbi.2025.04.039","DOIUrl":"10.1016/j.bbi.2025.04.039","url":null,"abstract":"<div><div>A growing body of data highlights the key role of adiposity-related inflammation in the development of neuropsychiatric comorbidity in obesity. Nevertheless, despite similar levels of inflammation, only a subgroup of obese subjects is afflicted with neuropsychiatric symptoms, suggesting the contribution of additional vulnerability factors. In light of previous work suggesting the involvement of early life adversity (ELA), this study aims to determine whether ELA promotes the emergence of inflammation-related neuropsychiatric symptoms in a sample of obese subjects.</div><div>Eighty-two adults afflicted with obesity (BMI &gt; 30 kg/m²) and twenty-one lean individuals (BMI &lt; 25 kg/m²) were recruited. Depressive symptoms, fatigue and neurobehavioral symptoms were assessed through semi-structured interviews and validated self-reports. ELA was measured using the Childhood Trauma Questionnaire (CTQ). Systemic inflammation was determined through serum concentrations of high-sensitivity C-reactive protein (hsCRP).</div><div>In the whole population under study, hsCRP concentrations were significantly associated with neuropsychiatric symptoms, consistent with the increased prevalence of neuropsychiatric comorbidity in obese subjects. Significant associations were also found between ELA severity and neuropsychiatric symptoms. Although they did not influence hsCRP levels, ELA antecedents in obese subjects were associated with more marked mood, fatigue and cognitive symptoms. Among ELA, sexual abuse was the only significant predictor of the association between hsCRP levels and neuropsychiatric comorbidity in obesity. These findings support the hypothesis that ELA represents a potent vulnerability factor for the development of neuropsychiatric comorbidity in obese subjects with chronic inflammation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 612-619"},"PeriodicalIF":8.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912606","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":"PACAP a mediator of inflammation following trauma exposure and mild traumatic brain injury: Differential effects in males and females","authors":"Shane W. Adams ,&nbsp;Aoife O’Donovan ,&nbsp;Thomas C. Neylan ,&nbsp;Victor May ,&nbsp;Sayamwong E. Hammack ,&nbsp;Kerry Ressler ,&nbsp;Odette A. Harris ,&nbsp;Sabra S. Inslicht","doi":"10.1016/j.bbi.2025.04.038","DOIUrl":"10.1016/j.bbi.2025.04.038","url":null,"abstract":"<div><div>Individual differences in systemic responses to trauma exposure, posttraumatic stress disorder (PTSD), and/or mild traumatic brain injury (mTBI) may help account for differential risk of adverse sequalae in females and heterogeneity in pathophysiology, symptoms, and treatment responses. Accordingly, this study investigated sex differences in the association between neuroendocrine (pituitary adenylate cyclase-activating polypeptide [PACAP]) and inflammatory markers following lifespan trauma exposure, PTSD, and mTBI in 71 trauma-exposed veteran and non-veteran males (<em>n</em> = 41) and females (<em>n</em> = 30). Two mediation models were proposed and evaluated, informed by an existing theoretical model. Both mediation models examined elevated PACAP as a key variable that may be associated with elevated inflammatory cytokine interleukin-6 (IL-6). The first model evaluated this effect following psychological trauma exposure and the second following mTBI. Trauma exposure and mTBI accounted for a large proportion of sex differences in PACAP and inflammation independent of the effects of time since the events (<em>M</em> = 8–11 years), PTSD symptom severity and diagnostic status, suggesting potentially long-term impacts of trauma exposure and mTBI on systemic pathophysiological responses regardless of PTSD symptom variations. Specifically, PACAP mediated the relationship between cumulative trauma exposure and IL-6 as well as mTBI history and IL-6, with a stronger mediating effect of PACAP on mTBI (<em>β</em> = 0.352) than trauma exposure (<em>β</em> = 0.149). Sex differences were observed in which males with mTBI histories had significantly elevated PACAP levels (Hedges’ g = 0.79) and females with mTBI histories had significantly elevated IL-6 levels (Hedges’ g = 1.03). PACAP was uniquely associated with trauma exposure in females (<em>β</em> = 0.56) and mTBI in males (<em>β</em> = 0.35). Conversely, IL-6 was uniquely associated with mTBI in females (<em>β</em> = 0.47–0.61) and trauma exposure in males (<em>β</em> = 0.42–0.54). For both sexes, childhood emotional neglect was uniquely associated with PACAP and inflammation later in life. This study presents preliminary evidence of the association between PACAP and inflammation following both trauma exposure and mTBI, which was differentially related in males and females. Although further study is needed, findings have the potential to help explicate heterogeneous presentations and differential risk of trauma-related pathology and mTBI that could lead to more targeted and effective treatments.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 589-599"},"PeriodicalIF":8.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899941","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":"Exercise-induced β₂-adrenergic receptor activation enhances effector lymphocyte mobilization in humans and suppresses lymphoma growth in mice through NK-cells.","authors":"Kyle A Smith, Helena Batatinha, Grace M Niemiro, Forrest L Baker, Tiffany M Zúñiga, Douglass Diak, Preteesh L Mylabathula, Timothy M Kistner, Dan Davini, Emely Hoffman, Jamie N Colombo, Michael Seckeler, Richard A Bond, Emmanuel Katsanis, Richard J Simpson","doi":"10.1016/j.bbi.2025.04.040","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.04.040","url":null,"abstract":"<p><p>Signaling through the β₂-adrenergic receptor (β2-AR) mobilizes immune cells during exercise and is implicated in tumor lymphocyte infiltration. We investigated mechanisms governing immune cell mobilization in humans and the role of adrenergic signaling in anti-cancer responses to a murine lymphoma. Human studies included double-blind, placebo-controlled, crossover trials with beta blocker drugs and a phosphodiesterase inhibitor during steady-state and graded exercise. β₁ + β₂-AR blockade reduced lymphocyte and NK-cell mobilization during steady-state exercise, while β₁-AR blockade enhanced the mobilization of NK-cells. Combining a β₁-AR antagonist with a phosphodiesterase-4 (PDE4) inhibitor during graded exercise further increased mobilization of CD8 + T-cells, γδ T-cells, and monocytes. Isoproterenol infusion also elevated lymphocyte and NK-cell levels similarly to exercise at 70 % VO_2max. Single cell RNA sequencing revealed complex signaling downstream of cAMP that relate to lymphocyte activation and effector function. In murine models of voluntary wheel running, β₂-AR signaling and NK-cells were critical for exercise-induced protection against B-cell lymphoma, as β₂-AR blockade or NK-cell depletion abrogated these effects. These findings highlight the pivotal role of β₂-AR signaling in mobilizing cytotoxic immune cells and protecting against tumor progression through exercise, suggesting potential therapeutic strategies combining exercise with adrenergic modulation to enhance immune responses.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966739","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 immune system: An effective therapeutic target for duloxetine","authors":"Nathalie Castanon","doi":"10.1016/j.bbi.2025.04.035","DOIUrl":"10.1016/j.bbi.2025.04.035","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 510-511"},"PeriodicalIF":8.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886586","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":"Beneficial and adverse effects of THC on cognition in the HIV-1 transgenic rat model: Importance of exploring task- and sex-dependent outcomes","authors":"Samantha M. Ayoub ,&nbsp;Sunitha Vemuri ,&nbsp;Elizabeth B. Hoang ,&nbsp;Neal A. Jha ,&nbsp;Arpi Minassian ,&nbsp;Jared W. Young","doi":"10.1016/j.bbi.2025.04.030","DOIUrl":"10.1016/j.bbi.2025.04.030","url":null,"abstract":"<div><div>HIV-associated neurocognitive impairment (NCI) is an untreated concern among people living with HIV (PLWH). Cannabis use in PLWH may complicate outcomes on cognition, with evidence to suggest function-dependent effects that are modulated by several factors including use patterns (e.g., frequency of use) and demographic influences (e.g., age). Animal studies can control for these factors.</div><div>Here, we characterized the impact of the primary psychoactive ingredient in cannabis (delta-9-tetrahydrocannabinol; THC), on function-dependent cognitive outcomes in HIV-1 transgenic (Tg) rats using cross-species translatable assays. Female and male HIV-1Tg rats and their controls were tested in the rat Iowa Gambling Task (IGT; to measure risk-based decision-making), and the Probabilistic Reversal Learning Task (PRLT; to measure learning and cognitive flexibility). Rats were tested at baseline, then retested following acute and chronic exposures to THC (0, 0.3, 3 mg/kg, intraperitoneal injection).</div><div>At baseline, HIV-1Tg rats took longer to make decisions, but exhibited intact cognition across tasks, suggestive of a speed-accuracy trade-off and early cognitive deficits. Both acute and chronic THC exposures produced selective effects on primary performance measures in HIV-1Tg rats, including enhanced learning performance but worsened risk-based decision-making, not observed in controls.</div><div>This work confirms function-dependent effects of THC on cognitive function in an animal model of HIV using cross-species translatable tasks used in the clinic. Findings are consistent with evidence for function-dependent cannabis effects observed in HIV, and suggest THC may drive cannabis-induced changes observed on cognitive performance in PLWH. These data may serve as guidance for clinicians prescribing cannabis to patients with HIV, and for further research exploring the interactive effects of HIV and cannabinoid treatment on cognitive function.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 571-588"},"PeriodicalIF":8.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899940","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":"Decreased excitatory and increased inhibitory transmission in the hippocampal CA1 drive neuroinflammation-induced cognitive impairments in mice","authors":"Xin-miao Wu ,&nbsp;Cui-na Shi ,&nbsp;Kai Liu ,&nbsp;Xiao-yi Hu ,&nbsp;Qiu-li He ,&nbsp;Hao Yao ,&nbsp;Di Fan ,&nbsp;Da-qing Ma ,&nbsp;Jian-jun Yang ,&nbsp;Jin-chun Shen ,&nbsp;Mu-huo Ji","doi":"10.1016/j.bbi.2025.04.027","DOIUrl":"10.1016/j.bbi.2025.04.027","url":null,"abstract":"<div><div>Neuroinflammation is one of crucial pathogenic mechanisms underlying Alzheimer’s disease, sepsis-associated encephalopathy, and postoperative cognitive dysfunction. These diseases or conditions are often accompanied by typical clinical manifestations of cognitive impairments, including impaired learning and memory but underlying mechanisms are unknown. Hence, effective treatments are not available. In the current study, mice received intraperitoneal administrations of LPS (0.5 mg/kg, daily, Escherichia coli<!--> <!-->O55:B5) for seven consecutive days and after which, different cohorts were used for behavioral assessments with open field, Y maze, and novel object recognition test or for electrophysiology recordings of mEPSC, mIPSC or LTP in <em>ex vivo</em> preparations. Their hippocampi were harvested for immunostaining or Western blotting of PSD95, vGLUT1, vGAT, gephyrin, PV, and SST. <em>In vivo</em> optical fiber calcium recording was used to evaluate the neuronal excitability. During the early stage of neuroinflammation induced by LPS, there was a decrease of excitatory afferent synapses and transmission in the CA1. During the later stage of neuroinflammation, there was an increase of inhibitory afferent synapses and transmission in the CA1, resulting in excessive inhibition on excitatory neurons. Both of them contributed to the decreased hippocampal neuronal excitability and impaired LTP, ultimately leading to cognitive impairments. Overexpression of CREB in the early stage or inactivation of PV-positive interneurons in the later stage in the CA1 both improved cognitive impairments. Our work suggests that negating decreased excitatory and increased inhibitory afferent in the hippocampus may improve cognitive impairments relate to neuroinflammation associated with neurological diseases.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 416-428"},"PeriodicalIF":8.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874411","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":"Cell-type-specific and inflammatory DNA methylation patterns associated with PTSD","authors":"Alicia K. Smith ,&nbsp;Seyma Katrinli ,&nbsp;Adam X. Maihofer ,&nbsp;Allison E. Aiello ,&nbsp;Dewleen G. Baker ,&nbsp;Marco P. Boks ,&nbsp;Leslie A. Brick ,&nbsp;Chia-Yen Chen ,&nbsp;Shareefa Dalvie ,&nbsp;Negar Fani ,&nbsp;Catherine B. Fortier ,&nbsp;Joel Gelernter ,&nbsp;Elbert Geuze ,&nbsp;Charles F. Gillespie ,&nbsp;Jasmeet P. Hayes ,&nbsp;Suzi Hong ,&nbsp;Ronald C. Kessler ,&nbsp;Anthony P. King ,&nbsp;Nastassja Koen ,&nbsp;Karestan C. Koenen ,&nbsp;Anthony S. Zannas","doi":"10.1016/j.bbi.2025.04.031","DOIUrl":"10.1016/j.bbi.2025.04.031","url":null,"abstract":"<div><h3>Background</h3><div>Epigenetic modifications, including DNA methylation (DNAm), can change in response to traumatic stress exposure, and may help to distinguish between individuals with and without PTSD. Here, we examine the DNAm patterns specific to immune cell types and inflammation in those with PTSD.</div></div><div><h3>Methods</h3><div>This study includes 3,277 participants from 11 cohorts participating in the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup. DNAm was assayed from blood with the MethylationEPIC BeadChip. A standardized QC pipeline was applied and used to impute cell composition. Within each cohort, we identified cell-type-specific DNAm patterns associated with PTSD, controlling for sex (if applicable), age, and ancestry. Meta-analyses were performed from summary statistics.</div></div><div><h3>Results</h3><div>PTSD cases had lower proportions of B cells and NK cells as well as higher proportions of neutrophils when compared to trauma-exposed controls. Overall, we identified 96 PTSD-associated CpGs across six types of immune cells. Most of these differences were identified in B cells, with 95 % exhibiting lower methylation levels in those with PTSD. Interestingly, the PTSD-associated CpGs annotated to a gene in B cells were enriched in a recent GWAS of PTSD (p &lt; 0.0001).</div></div><div><h3>Conclusions</h3><div>This study identifies novel PTSD-associated CpGs in individual immune cell types and supports the role of immune dysregulation and inflammation in PTSD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 540-548"},"PeriodicalIF":8.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886469","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}