Brain, behavior, & immunity - health最新文献

{"title":"Lyme disease associated neurological and musculoskeletal symptoms: A systematic review and meta-analysis","authors":"Ganesh Bushi ,&nbsp;Ashok Kumar Balaraman ,&nbsp;Shilpa Gaidhane ,&nbsp;Suhas Ballal ,&nbsp;Sanjay Kumar ,&nbsp;Mahakshit Bhat ,&nbsp;Shilpa Sharma ,&nbsp;M Ravi Kumar ,&nbsp;Aashna Sinha ,&nbsp;Mahalaqua Nazli Khatib ,&nbsp;Nishant Rai ,&nbsp;Sanjit Sah ,&nbsp;Ambanna Yappalparvi ,&nbsp;Shailesh Kumar Samal ,&nbsp;Doddolla Lingamaiah ,&nbsp;Muhammed Shabil","doi":"10.1016/j.bbih.2024.100931","DOIUrl":"10.1016/j.bbih.2024.100931","url":null,"abstract":"<div><h3>Background and objective</h3><div>Lyme disease, caused by <em>Borrelia burgdorferi</em>, presents major health challenges worldwide, leading to serious neurological and musculoskeletal issues that impact patients' lives and healthcare systems. This systematic review and meta-analysis aim to determine the prevalence and link between Lyme disease and these complications, aiming to enhance clinical and public health approaches.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed, EMBASE, and Web of Science up until April 01, 2024, to find studies reporting the prevalence and severity of neurological and musculoskeletal complications associated with Lyme disease. Screening and data extraction were conducted using Nested Knowledge software. Two independent reviewers performed the quality assessment using the Newcastle-Ottawa Scale. Meta-analyses were performed using R software v4.3, employing a random-effects model.</div></div><div><h3>Results</h3><div>Out of 3576 records, 17 studies were included, involving 3932 participants. These studies revealed significant prevalence of musculoskeletal symptoms (21.1%) and neurological disabilities (18%) among Lyme disease patients. The analysis showed a notable increase in risk for both complications in individuals with Lyme disease, with pooled Risk Ratios (RR) of 1.82 for musculoskeletal symptoms and 1.64 for neurological disabilities, indicating a significantly higher risk compared to control groups. Although heterogeneity across the studies was high, sensitivity analysis confirmed the consistency of our findings. Additionally, there was evidence of publication bias.</div></div><div><h3>Conclusion</h3><div>The study reveals significant neurological and musculoskeletal complications in Lyme disease patients, emphasizing the importance of early diagnosis, comprehensive treatment, and supportive care. The noted heterogeneity and potential publication bias highlight the need for transparent research and further study on long-term outcomes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100931"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indications for an antidepressive effect of thymosin alpha-1 in a small open-label proof of concept study in common variable immune deficiency patients with depression","authors":"Daniël G. Aynekulu Mersha ,&nbsp;Sarah E. Fromme ,&nbsp;Frank van Boven ,&nbsp;Gara Arteaga-Henríquez ,&nbsp;Annemarie Wijkhuijs ,&nbsp;Marianne van der Ent ,&nbsp;Raf Berghmans ,&nbsp;Bernard T. Baune ,&nbsp;Hemmo A. Drexhage ,&nbsp;Virgil Dalm","doi":"10.1016/j.bbih.2024.100934","DOIUrl":"10.1016/j.bbih.2024.100934","url":null,"abstract":"<div><h3>Background</h3><div>A considerable proportion (21%) of patients with common variable immunodeficiency (CVID) suffers from depression. These subjects are characterized by reduced naïve T cells and a premature T cell senescence similar to that of patients with major depressive disorder (MDD). It is known that T cells are essential for limbic system development/function. Treatment with thymosin α1 (Tα1) is capable to increase the thymus output of naïve T cells.</div></div><div><h3>Objective</h3><div>To treat CVID patients with a comorbid depressive episode with Tα1 to increase naïve T cells and thereby improve mood.</div></div><div><h3>Design</h3><div>A small open-label, proof of concept trial. Five depressed CVID patients (Hamilton Depression Rating Scale, HDRS &gt;12) could be treated with Tα1 (8 weeks, 1.6 mg daily subcutaneously, 1st week, thereafter 1.6 mg twice weekly). At the start, at 8 weeks and 8 weeks after the last injection, the HDRS was recorded and blood samples drawn for measuring naïve and memory T cells, Th17 and Treg cells, hsCRP, IL-6 and IL-7. Outcomes were compared to those of a contrast group (42 MDD patients, same severity but treated as usual (TAU)).</div></div><div><h3>Results</h3><div>In all 5 depressed CVID patients HDRS decreased during Tα1 treatment (with average 52%, TAU decreased scores with 36% in MDD patients). All 5 CVID patients showed an increase in naïve/memory CD4⁺ and CD8⁺ T cell ratios, and in 4 of the 5 patients with detectable IL-6 levels reductions were recorded. TAU did not show such immune improvements. In the 8-week wash-out, depression recurred in the 2 most severe patients, while continued to improve in the others. Immune effects were not sustained in the wash-out.</div></div><div><h3>Conclusion</h3><div>This preliminary small study suggests thymus hormone treatment to have antidepressive and related immune correcting effects. Data urge for larger placebo-controlled trials.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100934"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What is the relationship between exposure to environmental pollutants and severe mental disorders? A systematic review on shared biological pathways","authors":"Pierluigi Catapano,&nbsp;Mario Luciano,&nbsp;Salvatore Cipolla,&nbsp;Daniela D'Amico,&nbsp;Alessandra Cirino,&nbsp;Maria Chiara Della Corte,&nbsp;Gaia Sampogna,&nbsp;Andrea Fiorillo","doi":"10.1016/j.bbih.2024.100922","DOIUrl":"10.1016/j.bbih.2024.100922","url":null,"abstract":"<div><div>Severe mental disorders are multi-dimensional constructs, resulting from the interaction of genetic, biological, psychosocial, and environmental factors. Among the latter, pollution and climate change are frequently being considered in the etiopathogenesis of severe mental disorders. This systematic review aims to investigate the biological mechanisms behind the relationship between environmental pollutants, climate change, and mental disorders. An extensive literature search was performed on PubMed, Scopus, and APA PsycInfo databases according to the PRISMA guidelines. Articles were considered eligible if they involved humans or animals examining the association between exposure to environmental pollutants and if the resulting biological mechanisms that may have an impact on mental health and may support or even cause severe mental disorders (SMD) are assessed. For this reason, only studies dealing with biomarkers or biological pathways were taken into account. The 47 papers included in the review were divided into two groups: those conducted on human participants (15 studies) and those utilizing animal models (31 studies); one study included both humans and animals. Studies carried out with humans, which are mainly focused on measuring the impact of particulate matter (PM_2.5 and PM₁₀) exposure on mental health, showed an increased risk of depression or psychotic relapses through the inflammation and oxidative stress pathways, or through the alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Animal models showed the potential impact of pollution on brain functioning through increased inflammatory responses, oxidative stress, HPA axis disruption, hippocampal damage, and neurotransmitters dysregulation. Our findings show that environmental pollutants have an impact on human mental health through different biological pathways. The biological mechanisms by which environmental pollution and climate change influence the onset and exacerbation of severe mental disorders are complex and include gene expression, inflammation, oxidative stress, and anatomical brain changes. A better understanding of those pathways is important for the progress of knowledge on the pathophysiology of severe mental disorders according to the one health model, that promotes a collaborative, multisectoral, and transdisciplinary approach across various levels to optimize health outcomes by recognizing the interconnectedness of humans, animals, plants, and their shared environment.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100922"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Should we consider microbiota-based interventions as a novel therapeutic strategy for schizophrenia? A systematic review and meta-analysis","authors":"Lucas Hassib ,&nbsp;Alexandre Kanashiro ,&nbsp;João Francisco Cordeiro Pedrazzi ,&nbsp;Bárbara Ferreira Vercesi ,&nbsp;Sayuri Higa ,&nbsp;Íris Arruda ,&nbsp;Yago Soares ,&nbsp;Adriana de Jesus de Souza ,&nbsp;Alceu Afonso Jordão ,&nbsp;Francisco Silveira Guimarães ,&nbsp;Frederico Rogério Ferreira","doi":"10.1016/j.bbih.2024.100923","DOIUrl":"10.1016/j.bbih.2024.100923","url":null,"abstract":"<div><div>Schizophrenia is a chronic psychiatric disorder characterized by a variety of symptoms broadly categorized into positive, negative, and cognitive domains. Its etiology is multifactorial, involving a complex interplay of genetic, neurobiological, and environmental factors, and its neurobiology is associated with abnormalities in different neurotransmitter systems. Due to this multifactorial etiology and neurobiology, leading to a wide heterogeneity of symptoms and clinical presentations, current antipsychotic treatments face challenges, underscoring the need for novel therapeutic approaches. Recent studies have revealed differences in the gut microbiome of individuals with schizophrenia compared to healthy controls, establishing an intricate link between this disorder and gastrointestinal health, and suggesting that microbiota-targeted interventions could help alleviate clinical symptoms. Therefore, this meta-analysis investigates whether gut microbiota manipulation can ameliorate psychotic outcomes in patients with schizophrenia receiving pharmacological treatment. Nine studies (n = 417 participants) were selected from 81 records, comprising seven randomized controlled trials and two open-label studies, all with a low risk of bias, included in this systematic review and meta-analysis. The overall combined effect size indicated significant symptom improvement following microbiota treatment (Hedges' g = 0.48, 95% CI = 0.09 to 0.88, p = 0.004, I² = 62.35%). However, according to Hedges' g criteria, the effect size was small (approaching moderate), and study heterogeneity was moderate based on I² criteria. This review also discusses clinical and preclinical studies to elucidate the neural, immune, and metabolic pathways by which microbiota manipulation, particularly with <em>Lactobacillus</em> and <em>Bifidobacterium</em> genera, may exert beneficial effects on schizophrenia symptoms via the gut-brain axis. Finally, we address the main confounding factors identified in our systematic review, highlight key limitations, and offer recommendations to guide future high-quality trials with larger participant cohorts to explore microbiome-based therapies as a primary or adjunctive treatment for schizophrenia.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100923"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional brain correlates of the neutrophil- and monocyte-to-lymphocyte ratio in neuropsychiatric disorders","authors":"Roger McIntosh","doi":"10.1016/j.bbih.2024.100940","DOIUrl":"10.1016/j.bbih.2024.100940","url":null,"abstract":"<div><div>Skews in the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) increasingly demonstrate prognostic capability in a range of acute and chronic mental health conditions. There has been a recent uptick in structural and functional magnetic responance imaging data corroborating the role of NLR and MLR in a cluster of neuropsychiatric disorders that are characterized by cognitive, affective, and psychomotor dysfunction. Moreover, these deficits are mostly evident in setting of acute and chronic disease comorbidity implicating aging and immunosenescent processes in the manifestation of these geriatric syndromes. The studies reviewed in this special edition implicate neutrophil and monocyte expansion relative to lymphocytopenia in the sequelae of depression, cognitive and functional decline, as well as provide support from a range of neuroimaging techniques that identify brain alteartions concommitant with expansion of the NLR or MLR and the sequelae of depression, dementia, and functional decline.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100940"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of inflammatory biomarkers in trigeminal neuralgia","authors":"Shenglong Lai,&nbsp;Haiyang Li,&nbsp;Yazhou Xing,&nbsp;Du Wu,&nbsp;Lin Wang,&nbsp;Qinghua Liang","doi":"10.1016/j.bbih.2024.100930","DOIUrl":"10.1016/j.bbih.2024.100930","url":null,"abstract":"<div><h3>Background</h3><div>Trigeminal neuralgia (TN) is a severe facial pain disorder with complex etiology. Inflammation has been suggested as a contributing factor to TN pathogenesis. This study investigates the causal relationship between inflammatory biomarkers, including 41 circulating inflammatory cytokines, C-reactive protein (CRP), and procalcitonin (PCT), and TN using Mendelian randomization (MR) analysis.</div></div><div><h3>Methods</h3><div>A two-sample MR approach was employed using genome-wide association study (GWAS) data from 8293 Finnish individuals for inflammatory cytokines and data from the FinnGen database for TN. Instrumental variables (IVs) were selected based on genome-wide significance and clumping thresholds to avoid linkage disequilibrium. Inverse variance weighting (IVW) was used as the primary method, complemented by MR Egger regression, weighted median, simple mode, and weighted mode methods. Additionally, Bayesian Weighted MR (BWMR) and Multivariable MR (MVMR) were utilized to validate the findings and explore potential confounders.</div></div><div><h3>Results</h3><div>The present MR analysis identified significant causal associations for three inflammatory cytokines with TN. Stem cell growth factor beta (SCGF-β) (OR = 1.362, 95% CI = 1.049–1.770, p = 0.021) and Interleukin-4 (IL-4) (OR = 1.533, 95% CI = 1.014–2.316, p = 0.043) were positively associated with TN, while Interleukin-16 (IL-16) (OR = 0.720, 95% CI = 0.563–0.921, p = 0.009) had a protective effect. CRP levels were also linked to TN risk (OR = 0.751, 95% CI = 0.593–0.951, p = 0.017). No significant causal effect of PCT on TN was observed. Sensitivity analyses confirmed the robustness of these findings, showing no evidence of horizontal pleiotropy or heterogeneity.</div></div><div><h3>Conclusion</h3><div>This study highlights specific inflammatory biomarkers that may play pivotal roles in TN pathogenesis. SCGF-β and IL-4 are potential therapeutic targets due to their facilitative effects on TN, while IL-16 could offer protective benefits. CRP's association with TN further supports the involvement of systemic inflammation in this condition. These findings provide novel insights into TN's inflammatory mechanisms, suggesting new avenues for targeted interventions.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100930"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimmune axis: Linking environmental factors to pancreatic β-cell dysfunction in Diabetes","authors":"Luz Andreone","doi":"10.1016/j.bbih.2024.100926","DOIUrl":"10.1016/j.bbih.2024.100926","url":null,"abstract":"<div><div>Pancreatic β-cells are specialized in secreting insulin in response to circulating nutrients, mainly glucose.</div><div>Diabetes is one of the most prevalent endocrine-metabolic diseases characterized by an imbalance in glucose homeostasis, which result mainly from lack of insulin production (type 1 diabetes) or insufficient insulin and peripheral insulin resistance (type 2 diabetes), both influenced by genetic and environmental components. Pancreatic β-cell dysfunction and islet inflammation are common characteristics of both types of the disease. Pancreatic islets are a highly innervated tissue whose function can be influenced by the brain, either directly through the autonomic nervous system or indirectly via neuroendocrine mechanisms. In addition, it is well-established that there is a fine-tuned communication between the immune and neuroendocrine tissues in maintaining endocrine pancreas homeostasis.</div><div>Various psycho-social, physico-chemical and lifestyle environmental factors have been associated with diabetes risk. In this review, I briefly comment on certain aspects of the psycho-neuro-immune interactions that link environmental factors and the endocrine pancreas, leading to metabolic health or diabetes<strong>.</strong></div><div>Interdisciplinary research, embracing new and broader perspectives, should be conducted to explore strategies for preventing or slowing down the constant increase in diabetes worldwide.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100926"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium","authors":"Paul Denver ,&nbsp;Lucas Tortorelli ,&nbsp;Karen Hov ,&nbsp;Jens Petter Berg ,&nbsp;Lasse M. Giil ,&nbsp;Arshed Nazmi ,&nbsp;Ana Lopez-Rodriguez ,&nbsp;Daire Healy ,&nbsp;Carol Murray ,&nbsp;Robyn Barry ,&nbsp;Leiv Otto Watne ,&nbsp;Colm Cunningham","doi":"10.1016/j.bbih.2024.100920","DOIUrl":"10.1016/j.bbih.2024.100920","url":null,"abstract":"<div><div>Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, directly impairing brain function. It is not known whether these molecules reach higher brain levels when the blood cerebrospinal fluid barrier (BCSFB) is impaired. Here, in human hip-fracture patients, we tested the influence of BCSFB integrity on CSF levels of chemokines and assessed their association with delirium. CSF levels of IP-10, eotaxin, eotaxin 3 and TARC showed weak to moderate correlations with BCSFB permeability, as measured by the Q_albumin ratio, while MCP1, IL-8, MIP1α and MIP1β showed no significant correlation. Chemokines were not associated with delirium in univariate analysis or when stratified on dementia status, but exploratory analyses showed that elevated Eotaxin (CCL11) and MIP1α (CCL3) were associated with prevalent delirium. Modelling acute systemic inflammation, we used bacterial LPS (250 μg/kg) or sterile laparotomy surgery in mice to demonstrate <em>de novo</em> synthesis of chemokines at the choroid plexus (CP) and microvasculature. Gene expression data showed CP-enriched expression of <em>Il1b, Tnfa, Cxcl1</em> and <em>Ccl3</em> in both models and immunohistochemistry showed cytokine and chemokine synthesis in CP stromal (IL-1β, CCL2/MCP1) or epithelial cells (CXCL10/IP-10) cells and at the microvasculature. Larger studies are required to confirm these human findings on chemokine associations with BCSFB permeability and prevalent delirium. Preclinical studies are warranted to determine whether chemokines might play a role in the pathophysiology of delirium.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100920"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep immunophenotyping of circulating immune cells in major depressive disorder patients reveals immune correlates of clinical course and treatment response","authors":"Fabiola Stolfi ,&nbsp;Claudio Brasso ,&nbsp;Davide Raineri ,&nbsp;Virginia Landra ,&nbsp;Camilla Barbero Mazzucca ,&nbsp;Ali Ghazanfar ,&nbsp;Lorenza Scotti ,&nbsp;Riccardo Sinella ,&nbsp;Vincenzo Villari ,&nbsp;Giuseppe Cappellano ,&nbsp;Paola Rocca ,&nbsp;Annalisa Chiocchetti","doi":"10.1016/j.bbih.2024.100942","DOIUrl":"10.1016/j.bbih.2024.100942","url":null,"abstract":"<div><div>Major Depressive Disorder (MDD) is a widespread psychiatric condition impacting social and occupational functioning, making it a leading cause of disability. The diagnosis of MDD remains clinical, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, as biomarkers have not yet been validated for diagnostic purposes or as predictors of treatment response. Traditional treatment strategies often follow a one-size-fits-all approach obtaining suboptimal outcomes for many patients who fail to experience response or recovery. Several studies have reported an association between MDD and immune system dysregulation, but few have focused on the deep characterization of circulating cells, during the acute phase of MDD. This work aimed at immunophenotyping peripheral blood cells in the relapse phase of the disorder, to identify relevant cell populations for clinical monitoring of patients. Multiparametric analysis was performed on the peripheral blood of 60 MDD patients using flow cytometry to identify lymphocytes (naïve/effector, memory, regulatory) and myeloid cells (dendritic cells, monocytes). We studied the associations between immunophenotype and depressive symptoms, social and working functioning, and subjective quality of life during the acute phase and after three months of treatment. Multivariate analysis showed that CD4⁺ terminally differentiated effector memory (TEMRA) were associated with more depressive symptoms with a particular emphasis on anhedonic features and worse social and working functioning and quality of life. CD8⁺ TEMRA were associated with those depressive symptoms related to hopelessness. Conversely, ICOS + Tregs were associated with low-intensity suicidal ideation, suggestive of a protective role. Baseline T CD4⁺ effector memory (EM) was a negative predictor of reduction of depressive symptoms after three months of treatment, whilst plasmacytoid dendritic cells (pDC) were predicting reduction of hopelessness. These results confirm the involvement of the immune system in MDD and demonstrate the existence of immunological signatures associated with the severity of major depressive episodes and treatment response that could guide clinical monitoring and future personalized therapies.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100942"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated social defeat in male mice induced unique RNA profiles in projection neurons from the amygdala to the hippocampus","authors":"Rebecca G. Biltz ,&nbsp;Wenyuan Yin ,&nbsp;Ethan J. Goodman ,&nbsp;Lynde M. Wangler ,&nbsp;Amara C. Davis ,&nbsp;Braedan T. Oliver ,&nbsp;Jonathan P. Godbout ,&nbsp;John F. Sheridan","doi":"10.1016/j.bbih.2024.100908","DOIUrl":"10.1016/j.bbih.2024.100908","url":null,"abstract":"<div><div>Chronic stress increases the incidence of psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Repeated Social Defeat (RSD) in mice recapitulates several key physiological, immune, and behavioral changes evident after chronic stress in humans. For instance, neurons in the prefrontal cortex, amygdala, and hippocampus are involved in the interpretation of and response to fear and threatful stimuli after RSD. Therefore, the purpose of this study was to determine how stress influenced the RNA profile of hippocampal neurons and neurons that project into the hippocampus from threat appraisal centers. Here, RSD increased anxiety-like behavior in the elevated plus maze and reduced hippocampal-dependent novel object location memory in male mice. Next, pan-neuronal (Baf53 b-Cre) RiboTag mice were generated to capture ribosomal bound mRNA (i.e., active translation) activated by RSD in the hippocampus. RNAseq revealed that there were 1694 differentially expressed genes (DEGs) in hippocampal neurons after RSD. These DEGs were associated with an increase in oxidative stress, synaptic long-term potentiation, and neuroinflammatory signaling. To further examine region-specific neural circuitry associated with fear and anxiety, a retrograde-adeno-associated-virus (AAV2rg) expressing Cre-recombinase was injected into the hippocampus of male RiboTag mice. This induced expression of a hemagglutinin epitope in neurons that project into the hippocampus. These AAV2rg-RiboTag mice were subjected to RSD and ribosomal-bound mRNA was collected from the amygdala for RNA-sequencing. RSD induced 677 DEGs from amygdala projections. Amygdala neurons that project into the hippocampus had RNA profiles associated with increased synaptogenesis, interleukin-1 signaling, nitric oxide, and reactive oxygen species production. Using a similar approach, there were 1132 DEGs in neurons that project from the prefrontal cortex. These prefrontal cortex neurons had RNA profiles associated with increased synaptogenesis, integrin signaling, and dopamine feedback signaling after RSD. Collectively, there were unique RNA profiles of stress-influenced projection neurons and these profiles were associated with hippocampal-dependent behavioral and cognitive deficits.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100908"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}