Brain, Behavior, and Immunity最新文献

{"title":"Altered gut microbiome function in ADHD: More Prevotella, less vitamin B12 biosynthesis, and beneficial modulation by synbiotic treatment","authors":"Miranda Stiernborg ,&nbsp;Liu L. Yang ,&nbsp;Elin Skott ,&nbsp;MaiBritt Giacobini ,&nbsp;Philippe A. Melas ,&nbsp;Justine W Debelius ,&nbsp;Catharina Lavebratt","doi":"10.1016/j.bbi.2026.106259","DOIUrl":"10.1016/j.bbi.2026.106259","url":null,"abstract":"<div><div>The effect of psychostimulant medication in ADHD on the gut microbiome remains unknown. Oral Synbiotic 2000, comprising multiple lactic acid bacteria and dietary fibers, reduces psychiatric symptoms and plasma immune markers in ADHD, but its impact on the gut microbiome is unexplored. This study aimed to (i) study the fecal bacterial microbiome, focusing on species and bacterial gene modules, in ADHD patients and neurotypical controls, and (ii) examine microbiome changes attributable to Synbiotic 2000. Fecal samples were collected from 147 participants at baseline, and 106 completers at follow-up from a randomized placebo-controlled trial of Synbiotic 2000 conducted in children and adults with ADHD. At baseline, adult samples were compared to those of 52 adult controls, and patients on psychostimulants were compared to those not on psychostimulants in adults and children separately. The fecal microbiome was sequenced using shallow shotgun sequencing and analyzed for diversity and differential abundance using machine learning. Plasma short-chain fatty acids (SCFAs) and serum vitamin B12 levels were measured. At baseline, adult ADHD patients had significantly different abundances of four species compared to controls. In children, those on psychostimulants exhibited a higher abundance of species from the genus <em>Prevotella</em>, alongside a lower abundance of the vitamin B12-synthesis module, M00122, than those not on such medication. The lower M00122 abundance was associated with a looser stool consistency, implicating a shorter colonic transit time. Synbiotic 2000 did not affect taxonomic or functional α-diversity in adults or children. However, looser baseline stool consistency was linked to greater increases in evenness in the Synbiotic group over time. There was a significant Synbiotic-specific effect on taxonomic and functional β-diversity, not only the increased abundance of the Synbiotic 2000 species<em>.</em> Plasma levels of formic acid and propionic acid increased towards control levels in the Synbiotic group. In conclusion, distinct species were differently abundant in adults with ADHD compared to controls. The implications of the lower abundance of the vitamin B12-synthesis module, in children on psychostimulant medication, for the gut ecosystem and host intestine remain to be elucidated. Synbiotic 2000 influenced the taxonomy and functionality of the fecal microbiome and increased plasma SCFA levels towards normal. Further research is warranted to explore the clinical implications of microbiome modulation in the treatment of ADHD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106259"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916990","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":"Using social risk factors to predict allostatic biotypes of depression: A latent profile and multinomial regression analysis","authors":"Jay O’Shields ,&nbsp;Helisha Soni ,&nbsp;Orion Mowbray","doi":"10.1016/j.bbi.2025.106243","DOIUrl":"10.1016/j.bbi.2025.106243","url":null,"abstract":"<div><h3>Objective</h3><div>Major depression is often difficult to treat, particularly among individuals exposed to psychosocial risks like childhood maltreatment, loneliness, and recent stress. These experiences may lead to biological dysregulation consistent with allostatic load theory. This study explored whether distinct biological profiles among adults with depression are associated with specific psychosocial and health-related factors.</div></div><div><h3>Method</h3><div>Data were drawn from the Midlife in the United States study (MIDUS), including 367 participants with clinically significant depressive symptoms (CES-D ≥ 16). Latent profile analysis identified biological profiles based on 23 biomarkers across seven systems: inflammation, glucose, sympathetic and parasympathetic nervous systems, HPA-axis, cardiovascular, and lipids. Multinomial regression models examined associations between profile membership and psychosocial (childhood maltreatment, loneliness, recent stress), health (alcohol use, smoking, exercise), and demographic variables (sex, race/ethnicity, age, education).</div></div><div><h3>Results</h3><div>A five-profile solution best fit the data: High Inflammation &amp; Glucose (<em>n</em> = 74), Low PNS (<em>n</em> = 83), High PNS (<em>n</em> = 73), Healthy Depression (<em>n</em> = 67), and High HPA-Axis (<em>n</em> = 70). Childhood maltreatment significantly predicted membership in the High Inflammation &amp; Glucose and Low PNS profiles compared to the Healthy Depression group, even after controlling for health behaviors and demographics. Loneliness and recent stress were not significant predictors.</div></div><div><h3>Conclusion</h3><div>Childhood maltreatment is a predictor of biological dysregulation in depression, differentially predicting profiles characterized by inflammatory and metabolic vs parasympathetic functioning. These may represent different vulnerability pathways from social experiences to depressive illness. Incorporating measurement strategies specific to these pathways may aide in selecting treatment options for people who have depression and a history of childhood maltreatment.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106243"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145826944","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":"Corrigendum to “Acute effects of interferon-alpha on cellular anabolic and catabolic processes are associated with the development of fatigue during Interferon-alpha-based therapy for Hepatitis-C: A preliminary study” [Brain Behav. Immun. 123 (2025) 717–724]","authors":"Eva Periche-Tomas ,&nbsp;Annamaria Cattaneo ,&nbsp;Nadia Cattane ,&nbsp;Claudia Bone ,&nbsp;Jeremy Tibble ,&nbsp;Edward T. Bullmore ,&nbsp;Carmine Pariante ,&nbsp;Neil A. Harrison","doi":"10.1016/j.bbi.2026.106287","DOIUrl":"10.1016/j.bbi.2026.106287","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106287"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028432","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":"Acute ischaemic stroke alters the composition and function of circulating B cells","authors":"Mehwish Younas ,&nbsp;Harry R. Deijnen ,&nbsp;Ruth Stephens ,&nbsp;Alison Harris ,&nbsp;Thomas O. Williams ,&nbsp;Sabrina Tamburrano ,&nbsp;Ian E. Prise ,&nbsp;Craig J. Smith ,&nbsp;Stuart M. Allan ,&nbsp;Laura McCulloch ,&nbsp;John R. Grainger ,&nbsp;Barry W. McColl","doi":"10.1016/j.bbi.2025.106244","DOIUrl":"10.1016/j.bbi.2025.106244","url":null,"abstract":"<div><div>Distinct B cell populations are found in circulation, including those with innate-like properties, that have varied functions in pathogen protection, vaccination and immunoregulation. The effects of tissue injury on circulating B cell populations are poorly explored. Here we show that, following acute ischaemic stroke (AIS), a common cause of neurological disability associated with systemic immune dysfunction, the circulating B cell compartment has altered functionality, alongside marked reductions in marginal zone (MZ)-like B cells, an innate-like B cell subset. Of note, release of Immunoglobulin (Ig) M, a key innate-like B cell-derived factor important in anti-bacterial responses, and regulatory cytokines including IL-6 and IL-10, was impaired upon stimulation of sorted B cells from AIS patients. B cells express adrenergic receptors (ARs), in both control and AIS patients, and release of the β2-AR agonist noradrenaline (NA) is elevated acutely following stroke. <em>In vitro</em> exposure of B cells from healthy individuals to NA recapitulated some of the functional modulation observed in AIS patients. Moreover, increased cell death of MZ-like B cells was observed in response to NA. Secondary infection is a common post-stroke complication that could be responsible for altered B cell characteristics. However, in line with the impact of NA on B cell populations, alterations were largely driven by stroke rather than secondary infection. Taken together, these findings demonstrate that neuroimmune factors are an important signal that could rapidly modify defined B cell populations early after tissue injury and highlight altered innate-like B cell function as a previously unappreciated characteristic of the systemic immunological response to acute stroke.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106244"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843673","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":"Subacute loss of olfactory neurons following SARS-CoV-2 infection in hamsters","authors":"Clara Bourgon ,&nbsp;Laetitia Merle-Nguyen ,&nbsp;Juliette Jacquelin ,&nbsp;Isis Leguay ,&nbsp;Luc Jouneau ,&nbsp;Bernard Klonjkowski ,&nbsp;Sophie Le Poder ,&nbsp;Nicolas Meunier","doi":"10.1016/j.bbi.2026.106274","DOIUrl":"10.1016/j.bbi.2026.106274","url":null,"abstract":"<div><div>The loss of smell has been a hallmark of the COVID-19 pandemic. Odorant detection relies on neurons present in the olfactory epithelium supported by sustentacular cells. The latter are massively infected by SARS-CoV-2 along with infiltration of innate immune cells and desquamation of the olfactory epithelium. This destruction leads to release of olfactory epithelium cells into the lumen of the nasal cavity, but the extent of the loss of mature olfactory neurons remains to be clarified. In this study, we compared the spatiotemporal evolution of the olfactory epithelium during SARS-CoV-2 infection with associated smell impairment in hamsters. The olfactory performance of infected hamsters decreases as early as 2 days post-infection (dpi), then gradually recovers through 17 dpi. While the infection is mostly resolved after 4 dpi in the nasal cavity, we observed a subacute decrease of the mature olfactory neuron population which almost completely disappear at 11 dpi. Furthermore, regeneration of the olfactory epithelium does not start until 8 dpi and leads to a high fraction of immature olfactory neurons. The delayed regeneration and persistent alteration of the olfactory neuron population was correlated with a prolonged expression of inflammatory cytokines and a rapid decrease of the levels of anti-inflammatory markers linked to regeneration. Overall, our results suggest that the regeneration process is altered in some areas of the olfactory epithelium leading to delayed recovery of the epithelium. The later may explain the prolonged smell alteration linked to SARS-CoV-2 infection.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106274"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965370","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":"Daily affect and behavior in relation to inflammatory and metabolic health: An ambulatory assessment study","authors":"Noa van Zwieten ,&nbsp;George Aalbers ,&nbsp;Femke Lamers ,&nbsp;Erik J. Giltay ,&nbsp;Manon H.J. Hillegers ,&nbsp;Brenda W.J.H. Penninx","doi":"10.1016/j.bbi.2026.106282","DOIUrl":"10.1016/j.bbi.2026.106282","url":null,"abstract":"<div><h3>Background</h3><div>Daily life stress is associated with biological dysregulations including elevated inflammatory markers and poorer metabolic (immunometabolic) health, but it remains unclear how they are connected to daily life affect and behaviors. We examined whether daily life affect and behaviors were associated with immunometabolic health, and whether associations were moderated by the presence of a current depression/anxiety diagnosis.</div></div><div><h3>Methods</h3><div>In the Netherlands Study of Depression and Anxiety, participants (n = 357) with and without depression/anxiety self-reported positive affect (PA) and negative affect (NA) 5x/day while continuously wearing a research-grade actigraphy device for 14 days. We quantified four affect variables (i.e., M and SD of PA and NA) and three behavioral variables (i.e., minutes spent in moderate-to-vigorous physical activity [MVPA], sleep duration, and relative amplitude [RA; measure of circadian rhythmicity]), averaged across 14 days. We used linear regression analyses to explore their associations with three immunometabolic health outcomes: (1) inflammation index (based on C-Reactive Protein and Interleukin-6 levels), (2) metabolic index (based on five metabolic syndrome components), and (3) BMI (Body Mass Index), and examined if these associations were moderated by the presence of a current depression/anxiety diagnosis.</div></div><div><h3>Results</h3><div>Analyses showed that higher MVPA and RA were consistently associated with lower inflammation index (B = −0.19; B = −0.12), metabolic index (B = −0.14, B = −0.15), and BMI (B = −1.23; B = −1.30) (all <em>p</em>’s &lt; 0.011). Longer sleep duration was associated with lower BMI (B = −0.80, <em>p</em> = 0.027). Affect variables were not associated with immunometabolic health outcomes (<em>p</em>’s &gt; 0.05). Associations were independent of mental health status (<em>p</em>’s &gt; 0.05).</div></div><div><h3>Conclusions</h3><div>Our findings suggest that more minutes spent in MVPA and a more pronounced circadian rhythm, assessed with actigraphy, are important correlates of better immunometabolic health, and highlight the potential of ambulatory assessment in understanding immunometabolic health.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106282"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973932","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":"Effects of Dopaminergic Therapy with Levodopa (L-DOPA) on Fear and Anxiety-Related Circuits and Symptoms in Patients with Depression and Higher Inflammation","authors":"Genevieve E. Craig ,&nbsp;Neeti D. Mehta ,&nbsp;Mandakh Bekhbat ,&nbsp;Kate P. Revill ,&nbsp;Michael J. Lucido ,&nbsp;Changdo Hong ,&nbsp;Evanthia C. Wommack ,&nbsp;Wendy M. Baer ,&nbsp;Ebrahim Haroon ,&nbsp;Andrew H. Miller ,&nbsp;Zhihao Li ,&nbsp;Jennifer C. Felger","doi":"10.1016/j.bbi.2025.106252","DOIUrl":"10.1016/j.bbi.2025.106252","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Inflammatory biomarkers such as cytokines and C-reactive protein (CRP) are reliably elevated in patients with major depressive disorder (MDD) as well as fear and anxiety-related disorders. Moreover, inflammatory biomarkers have been associated with lower functional connectivity (FC) in reward and threat-related circuits that contribute to symptom severity. Prior work has linked low FC in reward circuitry and symptoms of anhedonia to inflammation effects on striatal dopamine (DA), including our studies involving administration of the DA precursor, levodopa (L-DOPA). Nevertheless, the mechanisms of inflammation associations with fear and anxiety-related circuits and symptoms are not fully understood. Given recent interest in DA in the amygdala in anxiety and the effects of inflammation, we examined a potential role for DA in relationships between inflammation, lower right amygdala-ventromedial prefrontal cortex (vmPFC) FC, and symptoms of anxiety and post-traumatic stress disorder (PTSD). Leveraging data from our studies in medically-stable, unmedicated adults with a primary MDD diagnosis, we tested the hypothesis that acute (250 mg; Study 1, n = 30) and sub-chronic (150–450 mg/day/week; Study 2, n = 18) L-DOPA (administered with carbidopa) versus placebo would increase right amygdala-vmPFC resting state (rs)FC (using a targeted, &lt;em&gt;a priori&lt;/em&gt; approach) in patients with higher (but not lower) inflammation, in relation to comorbid anxiety and PTSD symptoms. In patients enrolled to have a range of CRP concentrations and rsFC before and after acute, within-subject challenge with both L-DOPA and placebo (double-blind, randomized order ∼ 1-week apart; Study 1), a CRP by treatment interaction (F[1,28] = 1.33, p &lt; 0.05) revealed that right amygdala-vmPFC rsFC was increased by L-DOPA versus placebo only in patients with CRP &gt; versus ≤ 2 mg/L (p &lt; 0.05). In MDD patients recruited to have CRP &gt; 2 mg/L in Study 2, L-DOPA increased right amygdala-vmPFC rsFC versus placebo (F[1,12] = 9.24, p &lt; 0.05), with two of three L-DOPA doses (150 and 450 mg/day) increasing rsFC versus placebo at a predetermined threshold of ≥ 20 %. Repeated L-DOPA versus placebo further decreased self-reported anxiety symptoms and state anxiety (F[2,16] = 11.87, p &lt; 0.01), with all three L-DOPA doses significantly decreasing state anxiety (p &lt; 0.05). Right amygdala-vmPFC rsFC responses to L-DOPA also associated with greater reductions in state anxiety (r = -0.72, p &lt; 0.05). Similarly, L-DOPA decreased PTSD symptom severity versus placebo across all four PTSD symptom clusters (B-E) in patients with significant PTSD symptoms at baseline (n = 11; all p &lt; 0.05), with right amygdala-vmPFC rsFC responses to L-DOPA versus placebo negatively correlating with improved Intrusion symptoms (r = -0.81, p &lt; 0.05). These findings suggest a role for DA in the effects of inflammation on fear and anxiety-related circuits and symptoms, while supporting the use of ","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106252"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888626","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":"IL-17A-mediated copper accumulation participates in chronic neuropathic pain-induced cognitive impairment by enhancing microglial synaptic pruning","authors":"Jie Liu,&nbsp;Zheng Li,&nbsp;Xiaoling Peng,&nbsp;Wei Zhao,&nbsp;Tiantian Chu,&nbsp;Jie Ju,&nbsp;Jihao Ren,&nbsp;Feng Gao","doi":"10.1016/j.bbi.2025.106208","DOIUrl":"10.1016/j.bbi.2025.106208","url":null,"abstract":"<div><div>Chronic neuropathic pain is frequently accompanied by cognitive impairment, which seriously influence the quality of the patient’s life. The stability of synapse is the basis for maintaining neural circuits. And overactive microglia can prune normal synapses through phagocytosis, leading to cognitive impairment. This study aims to investigate the role of microglial synaptic pruning in chronic neuropathic pain-induced cognitive impairment, and explore the mechanisms of microglial activation through Interleukin-17A (IL-17A) activation and copper accumulation. We found that chronic neuropathic pain resulted in cognitive impairment, and microglial activation, abnormal microglial synaptic pruning, synaptic loss in hippocampus. Depleting microglia ameliorated the activations of microglial and complement pathways, and rescued synaptic loss and cognitive impairment. The copper was accumulated in hippocampus, and copper chelator tetrathiomolybdate (TTM) inhibited microglial and complement activations and rescued synaptic loss and cognitive impairment. Further research found that suppressing mitochondrial oxidative stress response inhibited copper accumulation-induced microglial activation. Finally, IL-17A was found to be increased in serum and hippocampus. IL-17A neutralization antibody (anti-IL-17A Abs) alleviated copper accumulation by inhibiting six transmembrane epithelial antigens of prostate 4 (STEAP4) / copper transporter 1 (CTR1), and inhibited microglial and complement activation, interrupting abnormal synaptic elimination and ameliorating cognitive impairment. Our results suggest that IL-17A can induce copper accumulation in microglia through STEAP4/CTR1, the latter promotes complement-mediated microglia synaptic pruning, reducing synapse number, and ultimately resulting in cognitive impairment. These provide a new potential therapeutic target for the treatment of chronic neuropathic pain-induced cognitive impairment.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106208"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687030","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":"Brain-immune correlates of quality of life in adolescents with chronic musculoskeletal pain","authors":"Saül Pascual-Diaz ,&nbsp;Maria Suñol ,&nbsp;Marie-Eve Hoeppli ,&nbsp;Emma Biggs ,&nbsp;Christopher D. King ,&nbsp;Nima Aghaeepour ,&nbsp;Martin S. Angst ,&nbsp;Edward Ganio ,&nbsp;Amelie Cambriel ,&nbsp;Dorien Feyaerts ,&nbsp;Brice Gaudilliere ,&nbsp;Jennifer N. Stinson ,&nbsp;Massieh Moayedi ,&nbsp;Robert C. Coghill ,&nbsp;Laura E. Simons ,&nbsp;Marina López-Solà","doi":"10.1016/j.bbi.2025.106225","DOIUrl":"10.1016/j.bbi.2025.106225","url":null,"abstract":"<div><div>Chronic musculoskeletal (MSK) pain affects a substantial proportion of youth, with 5 % reporting high-impact symptoms. Chronic pain in youth leads to multifaceted negative consequences that profoundly affect adolescents’ quality of life (QoL) and future outcomes. Recent studies suggest that neuro-immune interactions significantly contribute to chronic pain. However, how systemic immune dysregulation influences brain function, and how these brain changes affect well-being and functioning in chronic pain remains unclear. This study aims to examine the convergence between immune function and brain processing during a multisensory task to identify novel mechanistic pathways that may explain reduced QoL in adolescents with chronic MSK pain (N = 129). We used a multisensory fMRI task designed to mimic the unpleasant sensory experiences that adolescents and adults with chronic pain often encounter in daily life. Higher task-evoked activation in the rostral anterior cingulate and dorsomedial prefrontal cortices (rACC–dmPFC), which support threat appraisal and response regulation, was associated with lower physical QoL (pFWE = 0.005). Lower physical QoL was also associated with augmented functional connectivity between the rACC-dmPFC region and sensory processing areas in the somatosensory (pFWE = 0.002) and visual (pFWE = 0.049) cortices. Higher systemic pro-inflammatory activity in immature neutrophils was also associated with lower physical QoL (p = 0.01). Furthermore, task-evoked brain activation in the rACC-dmPFC partially mediated the relationship between neutrophil-mediated inflammatory responses and reduced physical QoL. These findings suggest a potential neuro-immune pathway through which systemic immune alterations may affect brain function and QoL in adolescents with chronic MSK pain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106225"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797426","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":"Developmental origins of immune function: Maternal prenatal mood is associated with infant immune cell gene expression","authors":"Gabrielle R. Rinne ,&nbsp;Christine Dunkel Schetter ,&nbsp;Susan Jackman ,&nbsp;Steve W. Cole","doi":"10.1016/j.bbi.2025.106230","DOIUrl":"10.1016/j.bbi.2025.106230","url":null,"abstract":"<div><div>The in-utero environment shapes offspring mental and physical health trajectories over the lifespan, likely through developmental adaptations to fetal biological systems. Offspring immune system development is a putative pathway through which the prenatal environment influences offspring health. The current study tested associations of maternal prenatal depressive and anxiety symptoms with infant pro-inflammatory and antiviral gene expression in a sample of 118 mother-infant pairs enrolled in a longitudinal study. Mothers reported on depressive and anxiety symptoms during interviews in early, mid, and late pregnancy. About one month after birth, trained research staff collected dried blood spots from infants during a heel stick procedure (<em>M</em> = 1.3 months, <em>SD</em> = 1.1 months). Infant dried blood spots were assayed for genome-wide transcriptional profiles using RNAseq. We evaluated associations of maternal prenatal depressive and anxiety symptoms with infant genome-wide transcriptional profiles and used bioinformatics analyses to identify upstream transcriptional pathways of differentially expressed genes. Higher maternal depressive symptom levels over the course of pregnancy were associated with upregulation of the pro-inflammatory NF-κB transcription control pathway and downregulation of the antiviral IRF control pathway in infants. In contrast, anxiety symptoms were associated with downregulation of the antiviral transcriptional control pathway in infants but were not associated with differences in the pro-inflammatory transcriptional control pathway. However, the association of anxiety symptoms with antiviral transcriptional control pathways was no longer significant with adjustment for depressive symptoms. These findings suggest that depressive symptoms during pregnancy may influence infant immune function via inflammatory and antiviral transcriptional control pathways, with potential implications for subsequent health.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106230"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803186","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}