Brain, Behavior, and Immunity最新文献

{"title":"Chronic constriction of the sciatic nerve does not induce mood-related comorbidities in female mice","authors":"Marion Gaborit ,&nbsp;Quentin Leboulleux ,&nbsp;Noemie Willem ,&nbsp;Coline Sagot ,&nbsp;Stephane Doridot ,&nbsp;Karin Herbeaux ,&nbsp;Melanie Kremer ,&nbsp;Amandine Bery ,&nbsp;Katia Befort ,&nbsp;Dominique Massotte","doi":"10.1016/j.bbi.2026.106286","DOIUrl":"10.1016/j.bbi.2026.106286","url":null,"abstract":"<div><h3>Background</h3><div>Neuropathic pain affects around 7–8% of the population and is associated with a high level of lifetime anxio-depressive comorbidities. Despite the higher incidence of the pathology in women, preclinical studies using rodents almost exclusively focused on males so far.</div></div><div><h3>Methods</h3><div>Sciatic nerve cuffing is a well-characterized model of neuropathy in which anxio-depressive comorbidities develop over time in male mice. In order to examine potential sex-differences in this model, we compared the alterations in the mechanical sensitivity using von Frey testing and used three ethologically relevant tests to explore their well-being (nest building), social behaviour (dyadic social interaction), and depression-like state (splash test) seven weeks after surgery. We also examined sex-related differences in neuroinflammation by quantifying changes in cytokine expression in the brainstem, a region critically involved in descending pain modulation.</div></div><div><h3>Results/conclusion</h3><div>Both male and female mice developed mechanical hypersensitivity following cuff surgery. However, no alteration in nest building ability, social dyadic interaction or grooming activity was observed in female mice seven weeks after surgery. Our data therefore suggest sex differences in the development of comorbidities associated with mechanical hypersensitivity. In addition, we evidenced in the brainstem sex-related differences in the expression of cytokines relevant to human neuropathy. Altogether, these results emphasize the need for additional comparisons between males and females to better grasp the role of neuroinflammation in pain sensitization and associated comorbidities.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106286"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988410","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 GLP-1R ameliorates microglial pyroptosis after spinal cord injury by restoring FANCC expression","authors":"Guangshen Li ,&nbsp;Yang Luo ,&nbsp;Tianyu Zhu ,&nbsp;Chunmao Chen ,&nbsp;Zhanyang Qian ,&nbsp;Haijun Li","doi":"10.1016/j.bbi.2026.106295","DOIUrl":"10.1016/j.bbi.2026.106295","url":null,"abstract":"<div><div>Secondary spinal cord injury (SCI) involves neuroinflammatory mechanisms such as microglial pyroptosis, which aggravates neural impairment via NLRP3 inflammasome activation. Although liraglutide (Lr) is commonly used for managing blood glucose, it also exhibits anti-inflammatory effects. Previous studies from our group have shown that glucagon-like peptide-1 receptor (GLP-1R) activation in microglia attenuates neuroinflammation and promotes functional recovery after SCI, the precise mechanism linking GLP-1R to the inhibition of pyroptosis remained unclear. Here, we report that high-dose Lr (independent of its metabolic effects) significantly improves functional and histological outcomes in a murine SCI model, and these benefits are abolished in GLP-1R^−/− mice. In vitro, RNA sequencing, combined with pharmacological and genetic approaches, revealed that Lr, via the PI3K/Akt/transcription factor EB (TFEB) axis, by upregulates Fanconi anemia complementation group C (FANCC) to suppress pyroptosis. Crucially, FANCC knockdown both elevated p38 phosphorylation and blocked the anti-pyroptotic effect of Lr, thereby establishing FANCC as an essential downstream mediator. This signaling cascade culminates in the inhibition of p38-dependent NLRP3 inflammasome activation. Collectively, our work defines a novel GLP-1R/PI3K/Akt/TFEB/FANCC/p38 pathway through which Lr alleviates secondary SCI, identifying FANCC as a pivotal neuroprotective node and supporting the translational potential of GLP-1R modulation in SCI.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106295"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043882","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":"Modulation of HMGB1-mediated neuroinflammation and synaptic plasticity by ethyl pyruvate reduces methamphetamine reward and motivation in male rats","authors":"Huizhen Liu ,&nbsp;Fangmin Wang ,&nbsp;Zhongyu Zhang ,&nbsp;Xiaolei Huang ,&nbsp;Shanshan Chen ,&nbsp;Yuting Wang ,&nbsp;Yiying Zhou ,&nbsp;Tingting Wu ,&nbsp;Manqing Wu ,&nbsp;Baobao Shi ,&nbsp;Miaojun Lai ,&nbsp;Huifen Liu ,&nbsp;Wenhua Zhou","doi":"10.1016/j.bbi.2026.106481","DOIUrl":"10.1016/j.bbi.2026.106481","url":null,"abstract":"<div><h3>Background</h3><div>Methamphetamine (METH) addiction involves neuroinflammatory cascades and maladaptive synaptic plasticity in reward circuits. While high-mobility group box 1 (HMGB1) and its downstream neuroinflammatory pathways contribute to neuropsychiatric disorders, their therapeutic potential in METH addiction remains unexplored. This study investigated whether ethyl pyruvate (EP, an HMGB1 inhibitor) attenuates METH reinforcement and associated neurotoxicity in the rat infralimbic cortex (IL).</div></div><div><h3>Methods</h3><div>Male rats self-administering METH received systemic EP (0, 50, or 80 mg/kg, i.p.). Reinforcement, motivation, and reinforcing efficacy were assessed using fixed-ratio 1 (FR1), progressive ratio (PR), and dose–response paradigms. Western blotting quantified HMGB1-TLR4/MyD88/PI3K/Akt/NF-κB signaling, pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and synaptic proteins in the IL. Neuronal TLR4 and HMGB1 expression, apoptosis (TUNEL, cleaved caspase-3), and pyroptosis (cleaved caspase-1) were assessed by immunofluorescence staining. In vivo calcium dynamics in IL CaMKIIα⁺ neurons were recorded via fiber photometry, and synaptic transmission was assessed via patch-clamp recordings of spontaneous excitatory postsynaptic currents (sEPSCs). Region-specific effects were confirmed by local microinjections of EP.</div></div><div><h3>Results</h3><div>Systemic EP treatment reduced METH intake and motivation and downshifted the dose–response curve without affecting natural reward. EP reversed METH-induced HMGB1 nuclear-to-cytoplasmic translocation and neuronal TLR4 expression, and suppressed downstream neuroinflammatory signaling and cytokine release. Furthermore, EP also reduced METH-associated neuronal apoptosis and pyroptosis in the IL. It also restored calcium homeostasis in IL CaMKIIα⁺ neurons, normalized expression of key synaptic proteins (e.g., NR2A/B, GluA2, PSD95, SNAP25), and reversed METH-induced hyperexcitability (increased sEPSC frequency/amplitude) in IL pyramidal neurons. Critically, local IL microinjection of EP replicated these systemic effects, confirming the IL as a key site of action.</div></div><div><h3>Conclusion</h3><div>The HMGB1 inhibitor EP attenuated METH reinforcement and motivation by targeting the IL to disrupt a neuroinflammatory cascade, prevent apoptosis and pyroptosis, and restore synaptic homeostasis. These findings identify HMGB1 inhibitors as a novel therapeutic target for mitigating the neuropathology and motivational drive underlying METH addiction.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106481"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177735","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":"An extraverted behavior intervention improves immune gene expression","authors":"Ramona L. Martinez ,&nbsp;Sonja Lyubomirsky ,&nbsp;Steve W. Cole","doi":"10.1016/j.bbi.2026.106299","DOIUrl":"10.1016/j.bbi.2026.106299","url":null,"abstract":"<div><h3>Background</h3><div>Social connection is critical to both psychological well-being and optimal immune function. The present study tested whether a behavioral intervention to increase social connection (promoting extraverted behavior) might reduce a threat-related immunoregulatory gene expression program known as the Conserved Transcriptional Response to Adversity (CTRA). The CTRA is characterized by elevated inflammatory gene expression and reduced innate antiviral gene expression in response to beta adrenergic signaling and has been associated with adverse social conditions such as loneliness and ostracism.</div></div><div><h3>Methods</h3><div>In an 8-week intervention (with 6-week behavior change protocol), participants from a campus community (<em>N</em> = 119; 87 % undergraduate; 9 % graduate; 4 % staff) were randomized to act more extraverted (sociable; Extraversion condition) or track routine daily activities (Control condition). Participants reported on psychological outcomes and provided dried blood spots for RNA sampling at pre-test (Week 0), post-test (Week 8), and 1-month follow-up (Week 12). Multilevel models tested condition differences in CTRA expression over time and examined mediation via psychological outcomes.</div></div><div><h3>Results</h3><div>Pre-registered analyses of pre-specified CTRA indicator genes showed no significant effects. Secondary genome-wide bioinformatic analyses of NF-κB, IRF, and CREB transcription control pathways found significantly greater reductions in CTRA-characteristic gene regulation among the Extraversion group relative to controls. These effects were partially mediated by reductions in loneliness. However, the intervention effect on CTRA gene regulation was not sustained at 1-month follow-up.</div></div><div><h3>Implications</h3><div>Extraverted behavior may improve immune regulation by enhancing perceived social connection. Further research should replicate these findings and enhance the durability of effects.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106299"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028391","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":"Healing pain without cells: how stem cell secretions could transform osteoarthritis treatment","authors":"Steve Oh Kah Weng","doi":"10.1016/j.bbi.2026.106475","DOIUrl":"10.1016/j.bbi.2026.106475","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106475"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112254","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":"Targeting α7nAChR-driven brain endothelial pyroptosis mitigates HIV-1 gp120-induced blood–brain barrier breakdown","authors":"Jinhu Zou ,&nbsp;Xuefeng Gao ,&nbsp;Jie Chen ,&nbsp;Bingliang Zhou ,&nbsp;Xiangshun Meng ,&nbsp;Jingyu Chen ,&nbsp;Pengwei Huang ,&nbsp;Hong Cao","doi":"10.1016/j.bbi.2026.106478","DOIUrl":"10.1016/j.bbi.2026.106478","url":null,"abstract":"<div><div>HIV-1-associated neurocognitive disorder (HAND) persists in over 40% of people with HIV despite effective antiretroviral therapy, underscoring the absence of targeted interventions. Disruption of the blood–brain barrier (BBB) is a hallmark of HAND, yet the mechanisms that link viral proteins to endothelial injury remain insufficiently understood. This study demonstrates that the HIV-1 envelope glycoprotein gp120 induces pyroptosis of brain microvascular endothelial cells (BMECs), thereby compromising BBB integrity. This process is mediated by the α7 nicotinic acetylcholine receptor (α7nAChR)-dependent activation of the ROS/NF-κB/NLRP3 inflammasome axis. Unexpectedly, α7nAChR, typically regarded as anti-inflammatory, exhibits a paradoxical pathogenic role under HIV-1 gp120 exposure, driving inflammatory endothelial cell death rather than protection. Importantly, this detrimental pathway is effectively inhibited by two clinically approved drugs, memantine and metformin, through suppression of α7nAChR. These findings uncover endothelial pyroptosis as a previously unrecognized mechanism of gp120-induced BBB disruption, redefine the functional role of α7nAChR in HAND pathogenesis, and highlight a promising therapeutic strategy through drug repurposing. By revealing a targetable pathway with direct clinical applicability, this work provides mechanistic insights and translational opportunities for preserving BBB function in HIV-associated neuropathology.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106478"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131158","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":"Bright light therapy influences glymphatic system function in individuals with subthreshold depression: a randomized clinical trial","authors":"Pan Chen ,&nbsp;Guanmao Chen ,&nbsp;Zixuan Guo ,&nbsp;Ruoyi Chen ,&nbsp;Xinyue Tang ,&nbsp;Zibin Yang ,&nbsp;Wenhao Ma ,&nbsp;Chao Chen ,&nbsp;Shilin Sun ,&nbsp;Yuan Zhang ,&nbsp;Hui Zhong ,&nbsp;Shu Zhang ,&nbsp;Zhangzhang Qi ,&nbsp;Wenjie Fang ,&nbsp;Lijun Jiang ,&nbsp;Zhinan Yin ,&nbsp;Li Huang ,&nbsp;Junxian Ma ,&nbsp;Qian Tao ,&nbsp;Ying Wang","doi":"10.1016/j.bbi.2026.106484","DOIUrl":"10.1016/j.bbi.2026.106484","url":null,"abstract":"<div><div>Glymphatic system dysfunction is a potential early biomarker for neuropsychiatric disorders. This study aimed to evaluate the effects of bright light therapy (BLT) on the glymphatic system in individuals with subthreshold depression (StD) and its connections to brain activity, inflammatory cytokines, and depressive symptoms. A randomized placebo-controlled trial assigned adults with StD (N = 110) to 8 weeks of morning BLT (5000 lx, 30 min/day; n = 57) or placebo (inactive device; n = 53). Depression severity (primary outcome, including anhedonia), glymphatic markers (diffusion tensor image analysis along the perivascular space [DTI-ALPS] index, free water [FW], perivascular space volume), regional homogeneity (ReHo; functional MRI), and serum pro-inflammatory cytokines were assessed at baseline and post-treatment. Compared to placebo, BLT significantly relieved depressive symptoms, increased DTI-ALPS index, and decreased FW from baseline to post-treatment. BLT also increased ReHo in the left superior frontal gyrus (SFG) and decreased levels of interleukin-9 and tumor necrosis factor-β. Changes in the DTI-ALPS index correlated with ameliorated depressive symptoms, increased ReHo in the SFG, and decreased inflammatory cytokine levels. Additionally, the pairwise interaction effects between glymphatic markers, ReHo values, and serum levels of pro-inflammatory cytokines were independent predictors of improvements in depressive symptoms, particularly anhedonia. BLT may influence glymphatic function in StD, with enhanced glymphatic function correlated with reduced inflammation, enhanced prefrontal cortex activity, and symptom amelioration.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106484"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164259","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":"Sex-dependent protective effects of a ketogenic diet following prenatal stress exposure: Evidence from adolescent rats","authors":"Veronica Begni ,&nbsp;Alessia Marchesin ,&nbsp;Rodrigo Orso ,&nbsp;Kerstin Camile Creutzberg ,&nbsp;Federica Precetti ,&nbsp;Annamaria Cattaneo ,&nbsp;Marco Andrea Riva","doi":"10.1016/j.bbi.2026.106301","DOIUrl":"10.1016/j.bbi.2026.106301","url":null,"abstract":"<div><div>Exposure to stress during gestation (prenatal stress, PNS) disrupts neurodevelopmental trajectories and increases vulnerability to neuropsychiatric disorders, through dysregulation of different molecular pathways. PNS-induced alterations frequently emerge during adolescence, a highly dynamic maturational period, highlighting a critical window in which therapeutic interventions may modify pathological outcomes. Here, we investigated whether a post-weaning ketogenic diet (KD) could modulate PNS-induced behavioral and molecular alterations in adolescent Sprague–Dawley rats. At weaning offspring from dams exposed to repeated restraint stress during gestation were assigned to a control diet (CD) or KD. Behavioral testing was conducted during adolescence, and prefrontal cortex (PFC) was analyzed for excitatory/inhibitory markers, redox regulators, and inflammatory mediators. PNS induced sociability deficits that were ameliorated by KD. A two-step cluster analysis identified ∼50–55 % of PNS offspring as “vulnerable,” whereas KD reduced this proportion to 22 % in males and 12 % in females. At the molecular level, KD exerted sex-dependent effects in the PFC: in males, it enhanced inhibitory interneuron markers and reduced pro-inflammatory transcripts while altering NRF2/KEAP1 redox signaling; in females, it increased NRF2 and partially restored GCLC1, while PNS selectively disrupted inhibitory and excitatory markers. Together, these findings demonstrate that post-weaning KD rescues PNS-induced social deficits and reshapes PFC molecular profiles, engaging sex-specific mechanisms of resilience. In summary, diet-based interventions during adolescence may represent a promising strategy to counteract developmental stress-related vulnerability.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106301"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early rebalancing of neuroinflammatory cascades lastingly rescues prefrontal deficits in a 22q11.2ds model","authors":"Anne Günther ,&nbsp;Mattia Chini ,&nbsp;Sebastian H. Bitzenhofer ,&nbsp;Annette Marquardt ,&nbsp;Ileana L. Hanganu-Opatz","doi":"10.1016/j.bbi.2026.106470","DOIUrl":"10.1016/j.bbi.2026.106470","url":null,"abstract":"<div><div>Cognitive deficits, a characteristic feature of neuropsychiatric disorders, reflect perturbed activity in neuronal networks. Increasing evidence has linked neuroinflammation to impaired neuronal activity and resulting cognitive dysfunction, yet the underlying cellular mechanisms and developmental dynamics remain largely unclear. Here, we address this knowledge gap by investigating the <em>Df(16)A</em> mouse model of human 22q11.2 microdeletions, a prevalent chromosomal abnormality associated with an increased incidence of neuropsychiatric disorders. During early postnatal development, <em>Df(16)A</em>^+/− mice show an imbalance of inflammatory signaling markers accompanied by increased microglial density in the superficial layers of the prefrontal cortex. Consequently, spine densities of pyramidal neurons were decreased, resulting in disrupted patterns of prefrontal neuronal activity during development and poor performance in a set-shifting task at juvenile age. Early treatment with minocycline, an anti-inflammatory drug, lastingly rescued these deficits in <em>Df(16)A</em>^+/− mice, rebalancing signaling cascades and restoring neural activity as well as cognitive performance. These findings identify the early rebalancing of inflammatory signaling cascades as a promising therapeutic strategy for mitigating pathophysiological trajectories associated with the 22q11.2 deletion syndrome.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106470"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100104","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":"Longitudinal associations between depression, substance use, and immune activation and inflammation: A secondary analysis of men who have sex with men living with HIV in Brazil (HPTN 063)","authors":"Emily M. Cherenack ,&nbsp;Michaela E. Larson ,&nbsp;Margaret E. Roach ,&nbsp;Daniel J. Feaster ,&nbsp;Ruth Khalili Friedman ,&nbsp;Steven A. Safren ,&nbsp;Adam W. Carrico","doi":"10.1016/j.bbi.2026.106300","DOIUrl":"10.1016/j.bbi.2026.106300","url":null,"abstract":"<div><h3>Background</h3><div>Limited research has examined the longitudinal interplay of depression, substance use, and immune dysregulation among men with HIV.</div></div><div><h3>Methods</h3><div>We analyzed longitudinal data from 100 men who have sex with men (MSM) living with HIV enrolled in the HPTN 063 cohort (2011–2013) in Brazil. Depressive symptom severity, alcohol use severity, and recent illicit stimulant use were assessed quarterly over 12 months. Soluble markers of immune activation (sCD14) and inflammation (IL-6) were measured at baseline and at a 12-month visit.</div></div><div><h3>Results</h3><div>Depressive symptom severity and alcohol use severity showed substantial within-person variability across time, whereas stimulant use remained relatively stable. These psychosocial factors were weakly intercorrelated. Controlling for baseline IL-6, the odds of having detectable IL-6 at 12 months increased by 2 % for each point increase in the proportion of visits with elevated depression, 7 % for each point increase in mean depressive severity across visits, 5 % for each point increase in depressive severity at nine months, and 6 % for each point increase in depressive severity at 12 months. Effects persisted after controlling for baseline HIV viral load. Controlling for baseline sCD14, estimated 12-month sCD14 increased 8 ng/mL for each point increase in 12-month depressive severity and 20 ng/mL for each point increase in 12-month alcohol use severity. The alcohol–sCD14 association was attenuated when adjusting for HIV viral load. Neither baseline IL-6 nor sCD14 strongly predicted future depressive symptoms or substance use.</div></div><div><h3>Conclusions</h3><div>Depressive symptoms predicted future inflammation and current immune activation. Research should examine if interventions to treat depression can improve immune functioning.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106300"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036705","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}