Brain, behavior, & immunity - health最新文献

{"title":"Biological sex, microglial signaling pathways, and radiation exposure shape cortical proteomic profiles and behavior in mice","authors":"Alexandra O. Strohm ,&nbsp;Sadie Oldfield ,&nbsp;Eric Hernady ,&nbsp;Carl J. Johnston ,&nbsp;Brian Marples ,&nbsp;M. Kerry O'Banion ,&nbsp;Ania K. Majewska","doi":"10.1016/j.bbih.2024.100911","DOIUrl":"10.1016/j.bbih.2024.100911","url":null,"abstract":"<div><div>Patients receiving cranial radiation therapy experience tissue damage and cognitive deficits that severely decrease their quality of life. Experiments in rodent models show that these adverse neurological effects are in part due to functional changes in microglia, the resident immune cells of the central nervous system. Increasing evidence suggests that experimental manipulation of microglial signaling can regulate radiation-induced changes in the brain and behavior. Furthermore, many studies show sex-dependent neurological effects of radiation exposure. Despite this, few studies have used both males and females to explore how sex and microglial function interact to influence radiation effects on the brain. Here, we used a system levels approach to examine how deficiencies in purinergic and fractalkine signaling, two important microglial signaling pathways, impact brain proteomic and behavioral profiles in irradiated and control male and female mice. We performed a comprehensive analysis of the cortical proteomes from irradiated and control C57BL/6J, P2Y12−/−, and CX3CR1−/− mice of both sexes using multiple bioinformatics methods. We identified distinct proteins and biological processes, as well as behavioral profiles, regulated by sex, genotype, radiation exposure, and their interactions. Disrupting microglial signaling, had the greatest impact on proteomic expression, with CX3CR1−/− mice showing the most distinct proteomic profile characterized by upregulation of CX3CL1. Surprisingly, radiation exposure caused relatively smaller proteomic changes in glial and synaptic proteins, including Rgs10, Crybb1, C1qa, and Hexb. While we observed some radiation effects on locomotor behavior, biological sex as well as loss of P2Y12 and CX3CR1 signaling had a stronger influence on locomotor outcomes in our model. Lastly, loss of P2Y12 and CX3CR1 strongly regulated exploratory behaviors. Overall, our findings provide novel insights into the molecular pathways and proteins that are linked to P2Y12 and CX3CR1 signaling, biological sex, radiation exposure, and their interactions.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100911"},"PeriodicalIF":3.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745588","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":"Prenatal inflammation and trauma symptoms in Latina mothers: The role of discrimination and growing up in an ethnic minoritized context","authors":"Rebeca Alvarado-Harris ,&nbsp;Krista Perreira ,&nbsp;Cheryl L. Woods-Giscombe ,&nbsp;William Roger Mills‐Koonce ,&nbsp;Hudson P. Santos Jr.","doi":"10.1016/j.bbih.2024.100914","DOIUrl":"10.1016/j.bbih.2024.100914","url":null,"abstract":"<div><h3>Background</h3><div>The race-based traumatic stress model proposes that discrimination elicits trauma-related symptoms. Cumulative discriminatory experiences and subsequent trauma symptoms may lead to prenatal inflammation, with far reaching consequences for the health of a mother and her child.</div></div><div><h3>Methods</h3><div>Latina mothers, primarily of Mexican and Central American heritage (<em>n</em> = 150), completed the Everyday Discrimination Scale and the Traumatic Avoidance subscale of the Inventory of Depression and Anxiety Symptoms-II during pregnancy (24–32 weeks). Plasma levels of cytokines were measured with multiplex assays, which were aggregated into a pro-inflammatory cytokine profile (IL-1β, TNF-α, IFN-γ, and IL-8) after a Confirmatory Factor Analysis supported this approach.</div></div><div><h3>Results</h3><div>Latina mothers who grew up in the US reported more discrimination, more traumatic avoidance symptoms, and had a more elevated cytokine profile than those who immigrated after childhood. Based on a two-mediator sequential model, discrimination and traumatic avoidance symptoms sequentially provided mechanistic support for the higher levels of cytokines observed in mothers who grew up in the US. Additionally, mothers who experienced trauma symptoms in response to discrimination had an elevated cytokine profile, whereas those who did not had a suppressed cytokine profile.</div></div><div><h3>Conclusion</h3><div>This is among the first studies to examine the association between trauma symptoms, discrimination, and inflammation during pregnancy. In so doing, it elucidates critical pathways by which discrimination may be differentially biologically embedded across immigrant generations. Emotional responses to and chronicity of discrimination may be critical factors for understanding how experiences of discrimination may influence the maternal inflammatory milieu.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100914"},"PeriodicalIF":3.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721042","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":"Inflammation biomarkers and neurobehavioral performance in rural adolescents","authors":"Beemnet Amdemicael ,&nbsp;Kun Yang ,&nbsp;Briana N.C. Chronister ,&nbsp;Caroline Mackey ,&nbsp;Xin Tu ,&nbsp;Sheila Gahagan ,&nbsp;Danilo Martinez ,&nbsp;Harvey Checkoway ,&nbsp;David R. Jacobs Jr. ,&nbsp;Jose Suarez-Torres ,&nbsp;Suzi Hong ,&nbsp;Jose R. Suarez-Lopez","doi":"10.1016/j.bbih.2024.100912","DOIUrl":"10.1016/j.bbih.2024.100912","url":null,"abstract":"<div><h3>Background</h3><div>Systemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador.</div></div><div><h3>Methods</h3><div>We examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least squares regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes.</div></div><div><h3>Results</h3><div>Higher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by −0.465 units (95% CI: −0.80, −0.13) and −0.418 units (−0.72, −0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by −0.112 units (−0.19, −0.03). A greater inflammatory composite variable from seven markers was associated with lower scores in language (β = −0.11, p = 0.043), visuospatial processing (β = −0.15, p = 0.086), and social perception (β = −0.22, p = 0.005) domains.</div></div><div><h3>Conclusions</h3><div>Higher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100912"},"PeriodicalIF":3.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756648","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":"Attachment State of Mind and complex traumatization in patients with Functional Motor Disorder (Motor Conversion Disorder)","authors":"Cristina Civilotti ,&nbsp;Veronica Nisticò ,&nbsp;Roberta Tedesco ,&nbsp;Sofia Cuoco ,&nbsp;Rossella Bisogno ,&nbsp;Paolo Barone ,&nbsp;Alessia Celeghin ,&nbsp;Giulia Di Fini ,&nbsp;Gabriella Gandino ,&nbsp;Roberto Erro ,&nbsp;Benedetta Demartini","doi":"10.1016/j.bbih.2024.100913","DOIUrl":"10.1016/j.bbih.2024.100913","url":null,"abstract":"<div><h3>Introduction</h3><div>Functional Motor Disorder (FMD) is characterized by motor neurological symptoms that cannot be explained by typical neurological diseases or other medical conditions. The role of psychological factors in the development, severity, and persistence of FMD remains unclear. We investigated the Attachment State of Mind (SoM) in FMD patients using the Adult Attachment Interview (AAI) and retrospectively examined the quality of their traumatic experiences, if any.</div></div><div><h3>Methods</h3><div>Thirty FMD patients and thirty healthy controls (HC) underwent the AAI and were classified according to both the three-way classification (Free/Secure, Dismissing or Entangled SoM) and the four-way classification (Unresolved SoM, indicating unelaborated traumatic events). Frequency and quality of adverse childhood experiences before the age of 14 were assessed via the Complex Trauma Questionnaire (ComplexTQ).</div></div><div><h3>Results</h3><div>Among HC, 53.3% exhibited a Free/Secure SoM, while 73.3% of FMD patients displayed an Insecure SoM (Entangled or, primarily, Dismissing). Individuals with Insecure SoM were three times more likely to manifest FMD. Unresolved Trauma was present in 26.7% of HC and 46.7% of FMD patients, with Unresolved Trauma leading to a fourfold increase in the likelihood of manifesting FMD. FMD patients reported significantly higher neglect from both parents, physical abuse from the mother, and parental loss compared to HC.</div></div><div><h3>Discussion</h3><div>Using a gold-standard instrument for evaluating Attachment SoM, we found that FMD patients had a significantly higher prevalence of Insecure SoM and childhood traumatic unresolved events compared to HC, supporting previous literature assessing FMD Attachment Styles through self-report questionnaires. We discuss the potential pathophysiological, neurobiological, and therapeutic implications of our findings.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100913"},"PeriodicalIF":3.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699386","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":"Exercise-induced anxiety impairs local and systemic inflammatory response and glucose metabolism in C57BL/6J mice","authors":"I. Gálvez ,&nbsp;M.C. Navarro ,&nbsp;S. Torres-Piles ,&nbsp;L. Martín-Cordero ,&nbsp;M.D. Hinchado ,&nbsp;E. Ortega","doi":"10.1016/j.bbih.2024.100910","DOIUrl":"10.1016/j.bbih.2024.100910","url":null,"abstract":"<div><h3>Introduction</h3><div>The complex physiological and psychological responses to regular exercise are yet to be fully elucidated. Exercise strongly modulates the immune system, inducing a plethora of dynamic responses involving the innate immune cell function and inflammatory processes that contribute to both potential health benefits and harmful side effects. Indeed, the relationship between physical exercise, stress, immunity, and metabolism serves as a paramount model of neuroimmunoendocrine interaction. Thus, the objective of this study was to conduct a comprehensive analysis of both systemic and local immunophysiological responses together with behavioral responses to a protocol of anxiety-inducing exercise.</div></div><div><h3>Material and methods</h3><div>C57BL/6J mice were randomly allocated into sedentary or exercised groups, where the anxiety-inducing exercise protocol was based on a 14-day consecutive program of swimming in water at 38 °C. Anxiety-like behavior was corroborated through the elevated plus maze test. Systemic biomarkers of the stress response were assessed using ELISA technique and the expression of systemic inflammatory cytokines with Bio-Plex system. Phagocytic/microbicide activity, the expression of M1/M2 phenotype markers (CD11c, iNOS, CD206, ARG-1) and cytokines of the inflammatory response (MCP-1, IL-8, IL-6, TNF-α, TGF-β, IL-10) of peritoneal macrophages were determined via flow cytometry. Adipose tissue macrophage infiltration was studied through fluorescence immunohistochemistry.</div></div><div><h3>Results</h3><div>Anxiety-like behavior, elevated circulating glucose concentrations, systemic stress and inflammatory responses, together with increased oxidative stress and inflammatory profile of peritoneal macrophages, and macrophage infiltration in white adipose tissue were observed in exercised animals.</div></div><div><h3>Conclusions</h3><div>A protocol of exercise that induces anxiety is associated with a neuroimmunoendocrine dysregulation affecting the feedback between the inflammatory and the stress responses, together with detrimental metabolic effects in glucose modulation. Systemic inflammatory alterations are accompanied by detrimental inflammatory responses in tissue macrophage populations. Altogether, these results show that exercise associated with anxiety, stress, pro-inflammatory responses, and hyperglycaemia represents a model of ‘dangerous exercise’.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100910"},"PeriodicalIF":3.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745589","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":"Immune cells and the trajectories of depression, anxiety, and cognitive function among people with amyotrophic lateral sclerosis","authors":"Yihan Hu ,&nbsp;Elie Deeba ,&nbsp;Ulf Kläppe ,&nbsp;Linn Öijerstedt ,&nbsp;John Andersson ,&nbsp;Nicolas Ruffin ,&nbsp;Fredrik Piehl ,&nbsp;Caroline Ingre ,&nbsp;Fang Fang ,&nbsp;Christina Seitz","doi":"10.1016/j.bbih.2024.100907","DOIUrl":"10.1016/j.bbih.2024.100907","url":null,"abstract":"<div><h3>Background</h3><div>Amyotrophic lateral sclerosis (ALS) represents a complex syndrome characterized by motor, psychiatric, and cognitive symptoms, where associations between cellular immune features and non-motor manifestations remain unknown.</div></div><div><h3>Methods</h3><div>In this cohort study, we enrolled 250 incident people with ALS (pwALS) assessed with the Hospital Anxiety and Depression Scale, and 226 pwALS with the Montreal Cognitive Assessment, including 218 overlapping pwALS. All individuals were diagnosed between January 2015 and January 2023 in Stockholm, Sweden. We applied joint latent class models to delineate distinct trajectories of anxiety, depression, and cognition, incorporating survival outcomes. A majority of the pwALS had data on leukocyte counts and flow cytometric analyses using a comprehensive T cell panel. We then used immune cell subtypes measured at diagnosis to predict trajectories of these outcomes following ALS diagnosis.</div></div><div><h3>Results</h3><div>We identified two distinct trajectories for anxiety, depression, and cognitive function following ALS diagnosis. PwALS with longer survival displayed more stable trajectories, while those with shorter survival showed decreasing anxiety symptom, increasing depressive symptom, and declining cognitive function. Higher count of leukocytes at the time of ALS diagnosis tended to associate with anxiety and depression trajectories related to shorter survival. Among T cell subpopulations, several CD8⁺ T cell subsets were associated with a stable trajectory of depressive symptom, and, in turn, better survival.</div></div><div><h3>Conclusion</h3><div>ALS-associated psychiatric and cognitive trajectories vary significantly between pwALS with different prognosis. Certain T cell subsets measured at diagnosis might be indicative of depression trajectories post-diagnosis.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100907"},"PeriodicalIF":3.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699473","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":"Associations of plasma SMOC1 and soluble IL6RA levels with the progression from mild cognitive impairment to dementia","authors":"Xavier Morató ,&nbsp;Raquel Puerta ,&nbsp;Amanda Cano ,&nbsp;Adelina Orellana ,&nbsp;Itziar de Rojas ,&nbsp;María Capdevila ,&nbsp;Laura Montrreal ,&nbsp;Maitée Rosende-Roca ,&nbsp;Pablo García-González ,&nbsp;Claudia Olivé ,&nbsp;Fernando García-Gutiérrez ,&nbsp;Josep Blázquez ,&nbsp;Andrea Miguel ,&nbsp;Raúl Núñez-Llaves ,&nbsp;Vanesa Pytel ,&nbsp;Montserrat Alegret ,&nbsp;María Victoria Fernández ,&nbsp;Marta Marquié ,&nbsp;Sergi Valero ,&nbsp;Jose Enrique Cavazos ,&nbsp;Agustín Ruiz","doi":"10.1016/j.bbih.2024.100899","DOIUrl":"10.1016/j.bbih.2024.100899","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Despite the central role attributed to neuroinflammation in the etiology and pathobiology of Alzheimer's disease (AD), the direct link between levels of inflammatory mediators in blood and cerebrospinal fluid (CSF) compartments, as well as their potential implications for AD diagnosis and progression, remains inconclusive. Moreover, there is debate on whether inflammation has a protective or detrimental effect on disease onset and progression. Indeed, distinct immunological mechanisms may govern protective and damaging effects at early and late stages, respectively.&lt;/div&gt;&lt;div&gt;This study aims to (i) identify inflammatory mediators demonstrating robust correlations between peripheral and central nervous system (CNS) compartments by means of plasma and CSF analysis, respectively, and (ii) assess their potential significance in the context of AD and disease progression from mild cognitive impairment (MCI) to dementia. To achieve this, we have examined the inflammatory profile of a well-defined subcohort comprising 485 individuals from the Ace Alzheimer Center Barcelona (ACE). Employing a hierarchical clustering approach, we thoroughly evaluated the intercompartmental correlations of 63 distinct inflammation mediators, quantified in paired CSF and plasma samples, using advanced SOMAscan technology. Of the array of mediators investigated, only six mediators (CRP, IL1RAP, ILRL1, IL6RA, PDGFRB, and YKL-40) exhibited robust correlations between the central and peripheral compartments (proximity scores &lt;400). To strengthen the validity of our findings, these identified mediators were subsequently validated in a second subcohort of individuals from ACE (n = 873). The observed plasma correlations across the entire cohort consistently have a Spearman rho value above 0.51 (n = 1,360, p &lt; 1.77E-93).&lt;/div&gt;&lt;div&gt;Of the high CSF-plasma correlated proteins, only soluble IL6RA (sIL6RA) displayed a statistically significant association with the conversion from MCI to dementia. This association remained robust even after applying a stringent Bonferroni correction (Cox proportional hazard ratio [HR] = 1.936 per standard deviation; p = 0.0018). This association retained its significance when accounting for various factors, including CSF amyloid (Aβ42) and Thr181-phosphorylated tau (p-tau) levels, age, sex, baseline Mini-Mental State Examination (MMSE) score, and potential sampling biases identified through principal component analysis (PCA) modeling. Furthermore, our study confirmed the association of both plasma and CSF levels of SPARC-related modular calcium-binding protein 1 (SMOC1) with amyloid and tau accumulation, indicating their role as early surrogate biomarkers for AD pathology. Despite the lack of a statistically significant correlation between SMOC1 levels in CSF and plasma, both acted as independent biomarkers of disease progression (HR &gt; 1.3, p &lt; 0.002).&lt;/div&gt;&lt;div&gt;In conclusion, our study unveils that sIL6RA and SMOC1 are associated wi","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100899"},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699387","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":"Examining vaccination-related adverse events in frequent neurodegenerative diseases","authors":"Shabnam Sodagari ,&nbsp;Nassim Sodagari","doi":"10.1016/j.bbih.2024.100902","DOIUrl":"10.1016/j.bbih.2024.100902","url":null,"abstract":"<div><div>This study investigates adverse events following vaccination in patients with four neurodegenerative diseases: Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease, Multiple Sclerosis (MS), and Parkinson's disease. We applied advanced data processing techniques to analyze symptom patterns and severity scores across these disease groups. Patients were identified through filtering, and symptom clusters were extracted to group similar symptoms into distinct clusters, and severity scores were computed based on hospitalization and death reports. A chi-squared test was performed to assess the statistical significance of adverse event distributions among the diseases for different vaccines. The results reveal that ALS patients exhibit severe respiratory symptoms post-vaccination, while Alzheimer's patients report significant respiratory and gastrointestinal issues. MS patients commonly experience general symptoms such as fatigue, while Parkinson's patients face exacerbated motor symptoms. Notably, our analysis showed no significant difference in adverse event reporting rates between COVID-19 and pneumococcal vaccines across these disease groups. This research provides new insights into disease-specific responses to vaccines, emphasizing the importance of personalized monitoring and treatment strategies to mitigate risks and improve clinical outcomes in these vulnerable populations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100902"},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745587","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":"Genetic association of the kynurenine pathway to suicidal behavior","authors":"Rabah Tamimou ,&nbsp;Christine Montout ,&nbsp;Thibault Mura ,&nbsp;Ismael Conejero ,&nbsp;Alexandre Evrard ,&nbsp;Philippe Courtet ,&nbsp;Pablo Bonilla-Escribano ,&nbsp;Carlos Riaza ,&nbsp;Concepción Vaquero-Lorenzo ,&nbsp;Enrique Baca-Garcia ,&nbsp;Fabrice Jollant ,&nbsp;Serge Lumbroso ,&nbsp;Kevin Mouzat ,&nbsp;Jorge Lopez-Castroman","doi":"10.1016/j.bbih.2024.100903","DOIUrl":"10.1016/j.bbih.2024.100903","url":null,"abstract":"<div><div>Suicidal behavior has been associated with dysfunctions in the kynurenine pathway, including alterations in the levels of neuroprotective and neurotoxic metabolites. Changes in the catalytic activity of enzymes within the pathway may contribute significantly. Variations in the genes encoding enzymes within the pathway can significantly affect their catalytic activity, playing a crucial role in the process. To explore this possibility, we hypothesized that these genetic variations would occur more frequently in patients with a history of suicidal behavior compared to non-suicidal individuals. Thus, we investigated the relationship between a history of suicide attempts and five single nucleotide polymorphisms (SNPs) within genes involved in the kynurenine pathway: <em>IDO1</em> (rs7820268), <em>IDO2</em> (rs10109853), <em>KMO</em> (rs1053230), <em>KAT1</em> (rs10988134), and <em>ACSMD</em> (rs2121337). Our sample comprised 849 subjects: 325 individuals who had attempted suicide in their lifetime (SAs), 99 individuals with a history of major depression disorder but no previous suicide attempts (non-SAs), and 425 non-psychiatric controls (CTRL). We performed SNP association analyses using codominant, dominant, and recessive models. Adjustment for sex and multiple comparisons was applied. After adjustment, the analysis revealed that SAs showed a significantly higher frequency of T alleles and TT genotypes of the rs1053230 SNP compared to CTRL across nearly all models. Furthermore, in the recessive model, non-SAs displayed a higher prevalence of the TT genotype of the rs10109853 SNP compared to CTRL.</div><div>The rs1053230 and rs10109853 SNPs could play a role in the previously observed metabolic dysregulation among SAs and non-SAs, respectively. To validate our findings, it is crucial to conduct functional analyses to investigate the impact of rs10109853 and rs1053230 SNPs on the expression and/or catalytic activity of the corresponding enzymes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100903"},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699388","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":"Skin-brain dialogue in auto-inflammatory diseases: A new route to biomarkers?","authors":"S. Matar ,&nbsp;S. Aractingi ,&nbsp;R. Gaillard ,&nbsp;A.-C. Petit","doi":"10.1016/j.bbih.2024.100906","DOIUrl":"10.1016/j.bbih.2024.100906","url":null,"abstract":"<div><div>Autoinflammatory diseases (AID) are rare systemic inflammatory disorders due to monogenic or polygenic dysfunction of innate immunity. They affect many organs including the brain and the skin. The spectrum of these diseases has been rapidly expanding recently due to newly developed diagnostic tools. The neuro-immuno-endocrine-cutaneous interactions play an important role in the pathophysiology of these diseases. The skin-brain interplay is not fully investigated in AID and evidence supporting bidirectional communication is examined. This article provides an overview of the current state of the art in the pathophysiology of AID with cutaneous and psychiatric manifestations. Elucidating the neuro-immuno-endocrine-cutaneous dysregulation underlying pathophysiology of AID is promising for determining future biomarkers and therapeutic options.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100906"},"PeriodicalIF":3.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663788","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}