Pub Date : 2026-01-26DOI: 10.1016/j.bbih.2026.101186
Ella McLoughlin , Daniele Magistro , Roberto Vagnetti , George M. Slavich , James E. Turner , Rachel Arnold , Lee J. Moore , John Hough
Many young adults experience mental ill-health which is increasing over time. From a theoretical perspective, the accumulation of stressors experienced over the lifespan may be an important factor in influencing the mental health and well-being of young adults. Although continued exposure to stressors can negatively impact aspects of immunity, researchers have yet to examine how lifetime stressor exposure (i.e., frequency and severity) influences mental ill-health and well-being, and how these states subsequently affected immune cell mobilisation in response to a laboratory-based social stressor in young adults. Eighty-six participants (Mage = 23.31 years, SD = 4.94) completed an online questionnaire which assessed their exposure to lifetime stressors, symptoms of depression and anxiety, and levels of well-being. Next, participants completed the Trier Social Stress Test while immunological (i.e., lymphocytes, monocytes and neutrophils) data were collected immediately pre and post the test. Results revealed that the more frequent and severe stressors experienced during early life rendered individuals more susceptible to stressors during adulthood, which positively influenced symptoms of depression and subsequent anxiety. These aspects then deterred well-being, which negatively affected immune cell mobilisation to the acute stressor. The results highlight the potential importance of assessing lifetime stressor exposure for researchers and clinicians aiming to study the social-environmental drivers of poor immune and clinical health.
{"title":"A network analysis of lifetime stressor exposure, mental health, well-being, and immune cell mobilisation to acute stressors in young adults","authors":"Ella McLoughlin , Daniele Magistro , Roberto Vagnetti , George M. Slavich , James E. Turner , Rachel Arnold , Lee J. Moore , John Hough","doi":"10.1016/j.bbih.2026.101186","DOIUrl":"10.1016/j.bbih.2026.101186","url":null,"abstract":"<div><div>Many young adults experience mental ill-health which is increasing over time. From a theoretical perspective, the accumulation of stressors experienced over the lifespan may be an important factor in influencing the mental health and well-being of young adults. Although continued exposure to stressors can negatively impact aspects of immunity, researchers have yet to examine how lifetime stressor exposure (i.e., frequency and severity) influences mental ill-health and well-being, and how these states subsequently affected immune cell mobilisation in response to a laboratory-based social stressor in young adults. Eighty-six participants (<em>M</em><sub><em>age</em></sub> = 23.31 years, <em>SD</em> = 4.94) completed an online questionnaire which assessed their exposure to lifetime stressors, symptoms of depression and anxiety, and levels of well-being. Next, participants completed the Trier Social Stress Test while immunological (i.e., lymphocytes, monocytes and neutrophils) data were collected immediately pre and post the test. Results revealed that the more frequent and severe stressors experienced during early life rendered individuals more susceptible to stressors during adulthood, which positively influenced symptoms of depression and subsequent anxiety. These aspects then deterred well-being, which negatively affected immune cell mobilisation to the acute stressor. The results highlight the potential importance of assessing lifetime stressor exposure for researchers and clinicians aiming to study the social-environmental drivers of poor immune and clinical health.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101186"},"PeriodicalIF":3.5,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-20DOI: 10.1016/j.bbih.2026.101183
Esteban Santacruz-Martínez, Eva Soto-Tinoco, Ruud M. Buijs
Immune challenges elicit significant physiological responses which are coordinated by the central nervous system. Among these is the sympathetic system-mediated anti-inflammatory reflex, which suppresses the TNF response. The sympathetic system has two main effector pathways: direct organ-targeted noradrenergic innervation and hormonal secretion from the adrenal gland. Experiments supporting the sympathetic nature of the anti-inflammatory reflex are based on observations that both β-blockers and splanchnic nerve transection increase the TNF response, yet these not only interfere with direct noradrenergic signaling but also negatively impact adrenal gland function. Meanwhile, endotoxin administration causes hyperglycemia; however, the role of the sympathetic nervous system in this process remains unclear. Additionally, most experimental approaches exploring sympathetic responses are conducted in anesthetized animals, where the sympathetic response is changed. Therefore, we examined the effect of i.v. LPS administration in stress-free intact animals. Inhibiting prostaglandin synthesis with indomethacin and blocking β-adrenergic receptors with propranolol caused increased TNF levels and prevented LPS-induced hyperglycemia, without affecting the Corticosterone response. Adrenal de-medullated animals (AdMX) receiving LPS lacked a hyperglycemic response and had higher circulating TNF levels. Intravenous adrenaline, but not noradrenaline administration in AdMX, recovered hyperglycemia and reduced TNF responses after LPS. Prostaglandin administration induced hyperglycemia in Sham but not in AdMX animals, showing that prostaglandins require the adrenal to promote acute biological effects in vivo. These findings demonstrate a critical role for the adrenal medulla and adrenaline in the efferent arm of the anti-inflammatory reflex, inhibiting TNF secretion and promoting hyperglycemia, thus fueling the body's defenses during an acute immune challenge.
{"title":"Endotoxin-induced inflammation promotes, via the adrenomedullary system, a hyperglycemic and anti-inflammatory reflex","authors":"Esteban Santacruz-Martínez, Eva Soto-Tinoco, Ruud M. Buijs","doi":"10.1016/j.bbih.2026.101183","DOIUrl":"10.1016/j.bbih.2026.101183","url":null,"abstract":"<div><div>Immune challenges elicit significant physiological responses which are coordinated by the central nervous system. Among these is the sympathetic system-mediated anti-inflammatory reflex, which suppresses the TNF response. The sympathetic system has two main effector pathways: direct organ-targeted noradrenergic innervation and hormonal secretion from the adrenal gland. Experiments supporting the sympathetic nature of the anti-inflammatory reflex are based on observations that both β-blockers and splanchnic nerve transection increase the TNF response, yet these not only interfere with direct noradrenergic signaling but also negatively impact adrenal gland function. Meanwhile, endotoxin administration causes hyperglycemia; however, the role of the sympathetic nervous system in this process remains unclear. Additionally, most experimental approaches exploring sympathetic responses are conducted in anesthetized animals, where the sympathetic response is changed. Therefore, we examined the effect of i.v. LPS administration in stress-free intact animals. Inhibiting prostaglandin synthesis with indomethacin and blocking β-adrenergic receptors with propranolol caused increased TNF levels and prevented LPS-induced hyperglycemia, without affecting the Corticosterone response. Adrenal de-medullated animals (AdMX) receiving LPS lacked a hyperglycemic response and had higher circulating TNF levels. Intravenous adrenaline, but not noradrenaline administration in AdMX, recovered hyperglycemia and reduced TNF responses after LPS. Prostaglandin administration induced hyperglycemia in Sham but not in AdMX animals, showing that prostaglandins require the adrenal to promote acute biological effects <em>in vivo</em>. These findings demonstrate a critical role for the adrenal medulla and adrenaline in the efferent arm of the anti-inflammatory reflex, inhibiting TNF secretion and promoting hyperglycemia, thus fueling the body's defenses during an acute immune challenge.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101183"},"PeriodicalIF":3.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-19DOI: 10.1016/j.bbih.2026.101178
Yash Patel , Anita Woo , Sammy Shun Wai Shi , Eric Kim , Jean Shin , Yohan Yee , Jason P. Lerch , Brian J. Nieman , Tomas Paus , Zdenka Pausova
Neuroinflammation is increasingly implicated in post-infectious brain atrophy and cognitive impairment, as well as the etiology of neurodegenerative and psychiatric disorders. Here, we employed an established mouse model of neuroinflammation (systemic lipopolysaccharide [LPS]) and studied its macrostructural, microstructural, and cellular effects on the mouse brain. We combined whole-brain two-photon microscopy, multiparametric magnetic resonance imaging, and in silico transcriptomics. We demonstrate that LPS increases microglial soma size, a marker of microglial proinflammatory transformation, throughout the brain. LPS also induces in vivo volumetric increases of multiple brain regions, but not of the cerebral cortex. These in vivo increases are no longer observed ex vivo (post-fixation), suggesting they may be due to brain edema. Moreover, LPS induces microstructural alterations, as indicated by ex vivo reductions in fractional anisotropy and magnetization transfer ratio, which were most pronounced in the cerebral cortex. These reductions had the largest effect size in regions with higher expression of genes specific to parvalbumin inhibitory neurons and excitatory layer 4/5 intratelencephalic neurons, which were enriched in genes encoding synapse components. Thus, these results suggest that LPS-induced neuroinflammation may lead to brain edema, which spares the cerebral cortex, and microstructural alterations, which impact the cerebral cortex and may involve specific subtypes of inhibitory and excitatory neurons and their synapses.
{"title":"Macrostructural, microstructural, and cellular effects of neuroinflammation on the mouse brain","authors":"Yash Patel , Anita Woo , Sammy Shun Wai Shi , Eric Kim , Jean Shin , Yohan Yee , Jason P. Lerch , Brian J. Nieman , Tomas Paus , Zdenka Pausova","doi":"10.1016/j.bbih.2026.101178","DOIUrl":"10.1016/j.bbih.2026.101178","url":null,"abstract":"<div><div>Neuroinflammation is increasingly implicated in post-infectious brain atrophy and cognitive impairment, as well as the etiology of neurodegenerative and psychiatric disorders. Here, we employed an established mouse model of neuroinflammation (systemic lipopolysaccharide [LPS]) and studied its macrostructural, microstructural, and cellular effects on the mouse brain. We combined whole-brain two-photon microscopy, multiparametric magnetic resonance imaging, and <em>in silico</em> transcriptomics. We demonstrate that LPS increases microglial soma size, a marker of microglial proinflammatory transformation, throughout the brain. LPS also induces <em>in vivo</em> volumetric increases of multiple brain regions, but not of the cerebral cortex. These <em>in vivo</em> increases are no longer observed <em>ex vivo</em> (post-fixation), suggesting they may be due to brain edema. Moreover, LPS induces microstructural alterations, as indicated by <em>ex vivo</em> reductions in fractional anisotropy and magnetization transfer ratio, which were most pronounced in the cerebral cortex. These reductions had the largest effect size in regions with higher expression of genes specific to parvalbumin inhibitory neurons and excitatory layer 4/5 intratelencephalic neurons, which were enriched in genes encoding synapse components. Thus, these results suggest that LPS-induced neuroinflammation may lead to brain edema, which spares the cerebral cortex, and microstructural alterations, which impact the cerebral cortex and may involve specific subtypes of inhibitory and excitatory neurons and their synapses.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101178"},"PeriodicalIF":3.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acute respiratory infections (ARIs) are among the most common infectious diseases encountered in clinical practice, with approximately 70–80 % of cases attributed to viral pathogens. Among these, seasonal influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistently pose public health threats due to their high genetic variability, strong transmissibility and significant pathogenicity. Recently, accumulating evidence has suggested that these viruses can not only cause typical respiratory symptoms but also affect the central nervous system (CNS) through neuroinvasion and inflammation, thereby increasing the risk of developing or exacerbating mood disorders such as anxiety and depression. This makes them significant complications affecting patient prognosis and public health resources.
This comorbidity between infection and mood disorders exhibits a complex bidirectional relationship. Beyond viral CNS involvement, individuals with mood disorders appear to be more susceptible to IAV and SARS-CoV-2 infections and may be at greater risk of developing severe illness. This comorbidity not only significantly impairs quality of life and clinical outcomes but also places a substantial burden on healthcare systems and public health infrastructure.
Therefore, this review aims to summarize the clinical characteristics of IAV and SARS-CoV-2 infections comorbid with mood disorders. Based on existing evidence, we innovatively distinguish two mechanism pathways: an externally driven pathway dominated by psychological stress (acute stress), and an internal biological pathway represented by immune dysregulation and gut microbiota imbalance. This classification will provide a theoretical framework and research direction for accurately identifying acute stress responses and persistent neuropathology, as well as for future basic research and targeted intervention strategies.
{"title":"Association between influenza A virus and SARS-CoV-2 infections and mood disorders","authors":"Yanling Xiang , Wanqi Wang , Jinyi Zhu , Zexing Chen , Wanyi Huang","doi":"10.1016/j.bbih.2026.101182","DOIUrl":"10.1016/j.bbih.2026.101182","url":null,"abstract":"<div><div>Acute respiratory infections (ARIs) are among the most common infectious diseases encountered in clinical practice, with approximately 70–80 % of cases attributed to viral pathogens. Among these, seasonal influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistently pose public health threats due to their high genetic variability, strong transmissibility and significant pathogenicity. Recently, accumulating evidence has suggested that these viruses can not only cause typical respiratory symptoms but also affect the central nervous system (CNS) through neuroinvasion and inflammation, thereby increasing the risk of developing or exacerbating mood disorders such as anxiety and depression. This makes them significant complications affecting patient prognosis and public health resources.</div><div>This comorbidity between infection and mood disorders exhibits a complex bidirectional relationship. Beyond viral CNS involvement, individuals with mood disorders appear to be more susceptible to IAV and SARS-CoV-2 infections and may be at greater risk of developing severe illness. This comorbidity not only significantly impairs quality of life and clinical outcomes but also places a substantial burden on healthcare systems and public health infrastructure.</div><div>Therefore, this review aims to summarize the clinical characteristics of IAV and SARS-CoV-2 infections comorbid with mood disorders. Based on existing evidence, we innovatively distinguish two mechanism pathways: an externally driven pathway dominated by psychological stress (acute stress), and an internal biological pathway represented by immune dysregulation and gut microbiota imbalance. This classification will provide a theoretical framework and research direction for accurately identifying acute stress responses and persistent neuropathology, as well as for future basic research and targeted intervention strategies.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101182"},"PeriodicalIF":3.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.bbih.2026.101169
Shaimaa Mosad Elrefaay , Aric A. Prather , Steven W. Cole , Elissa Epel , Kord Kober
The purpose of this exploratory analysis is to identify pathways common to both DNA methylation and gene expression linked to high perceived stress and evaluate protein-protein interactions of the genes in these pathways. To do this, we selected a sample of premenopausal healthy women stratified for being high (n = 31) and low stress (n = 32) from a large study who had available biospecimens. We used two meta-analysis approaches (strict and inclusive) to identify the pathways supported across the molecular data types, both methylation and gene expression. To delineate potential interactions among the pathways and functional roles of genes linked to the high stress group through epigenomic and transcriptomic analyses, we assessed protein-protein interaction (PPI) network connectivity utilizing the Search Tool for the Retrieval of Interacting Genes (STRING). We identified 17 KEGG pathways that were significant (p-value <0.05) and are implicated in immune response and inflammation, cellular transduction and structure, neurotransmission, and disease. The PPI network exhibits significant interconnectedness among genes, with many gene members of multiple pathways, indicating direct interactions among these pathways. Our findings help target novel stress-related biological pathways for monitoring - for timely intervention, prevention, and tailored treatment approaches. Further replicative studies in wider, diverse populations are necessary to validate the observed functional network pathways and to quantify the specificity of these pathways for duration or magnitude of perceived psychological stress.
{"title":"Novel epigenetic and transcriptomic profiles of immune, inflammatory, and cellular transduction pathways are associated with chronic perceived stress in midlife women","authors":"Shaimaa Mosad Elrefaay , Aric A. Prather , Steven W. Cole , Elissa Epel , Kord Kober","doi":"10.1016/j.bbih.2026.101169","DOIUrl":"10.1016/j.bbih.2026.101169","url":null,"abstract":"<div><div>The purpose of this exploratory analysis is to identify pathways common to both DNA methylation and gene expression linked to high perceived stress and evaluate protein-protein interactions of the genes in these pathways. To do this, we selected a sample of premenopausal healthy women stratified for being high (n = 31) and low stress (n = 32) from a large study who had available biospecimens. We used two meta-analysis approaches (strict and inclusive) to identify the pathways supported across the molecular data types, both methylation and gene expression. To delineate potential interactions among the pathways and functional roles of genes linked to the high stress group through epigenomic and transcriptomic analyses, we assessed protein-protein interaction (PPI) network connectivity utilizing the Search Tool for the Retrieval of Interacting Genes (STRING). We identified 17 KEGG pathways that were significant (p-value <0.05) and are implicated in immune response and inflammation, cellular transduction and structure, neurotransmission, and disease. The PPI network exhibits significant interconnectedness among genes, with many gene members of multiple pathways, indicating direct interactions among these pathways. Our findings help target novel stress-related biological pathways for monitoring - for timely intervention, prevention, and tailored treatment approaches. Further replicative studies in wider, diverse populations are necessary to validate the observed functional network pathways and to quantify the specificity of these pathways for duration or magnitude of perceived psychological stress.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101169"},"PeriodicalIF":3.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.bbih.2026.101179
Lucia M. Li , Eleftheria Kodosaki , Chloe J.Y. Xu , Amanda Heslegrave , Henrik Zetterberg , Neil S.N. Graham , Karl A. Zimmerman , Elena Garbero , Federico Moro , Sandra Magnoni , Guido Bertolini , David J. Loane , David J. Sharp
Traumatic Brain Injury (TBI) triggers an acute systemic inflammatory response, which may impact outcomes. This response may interact with pre-existing factors linked to inflammation, such as age, to influence outcomes. Previous studies have typically measured few cytokines, but high-dimensional proteomic approaches can sensitively detect a broad range of inflammatory markers, to better characterise post-TBI inflammation.
We analysed plasma from BIO-AX-TBI study participants (n = 37 acute moderate–severe TBI (Mayo Criteria), n = 22 acute non-TBI trauma (NTT), n = 28 non-injured controls (CON)) using the Alamar NULISA™ panel (>200 inflammatory markers). The NTT group enabled differentiation of TBI-specific versus general injury-related responses. Inflammatory markers were correlated with plasma NFL, GFAP, total tau, UCH-L1 (Simoa®), S100B (Millipore), and subacute (10 days–6 weeks) 3T MRI measures of lesion volume and white matter injury.
Differential expression analysis identified four markers elevated specifically in TBI (VSNL1, IL1RN/IL-1Ra, GFAP, IKBKG), while other derangements reflected non-specific injury responses. Higher VSNL1 correlated with greater lesion volume (rs = 0.53) and higher IL1RN/IL-1Ra with greater white matter injury (rs = −0.66, both FDR-adjusted p < 0.05). IL33, part of the non-specific injury response was higher in participants with good (GOS-E 5–8) versus poor (GOS-E 1–4) outcomes (W = 47, FDR-adjusted p = 0.0024). Using an Elastic Net model trained on healthy controls, we show that “inflammation age” exceeded chronological age in TBI, particularly in younger participants.
In summary, acute post-TBI inflammation includes both TBI-specific and non-specific components, linked to structural brain injury and functional outcome. Age modulates the inflammatory response. VSNL1, IL1RN/IL-1Ra, and IL33 are potential mediators of post-TBI pathophysiology.
{"title":"Systemic inflammation and its associations in acute moderate-severe Traumatic Brain Injury: a cross-sectional study","authors":"Lucia M. Li , Eleftheria Kodosaki , Chloe J.Y. Xu , Amanda Heslegrave , Henrik Zetterberg , Neil S.N. Graham , Karl A. Zimmerman , Elena Garbero , Federico Moro , Sandra Magnoni , Guido Bertolini , David J. Loane , David J. Sharp","doi":"10.1016/j.bbih.2026.101179","DOIUrl":"10.1016/j.bbih.2026.101179","url":null,"abstract":"<div><div>Traumatic Brain Injury (TBI) triggers an acute systemic inflammatory response, which may impact outcomes. This response may interact with pre-existing factors linked to inflammation, such as age, to influence outcomes. Previous studies have typically measured few cytokines, but high-dimensional proteomic approaches can sensitively detect a broad range of inflammatory markers, to better characterise post-TBI inflammation.</div><div>We analysed plasma from BIO-AX-TBI study participants (n = 37 acute moderate–severe TBI (Mayo Criteria), n = 22 acute non-TBI trauma (NTT), n = 28 non-injured controls (CON)) using the Alamar NULISA™ panel (>200 inflammatory markers). The NTT group enabled differentiation of TBI-specific versus general injury-related responses. Inflammatory markers were correlated with plasma NFL, GFAP, total tau, UCH-L1 (Simoa®), S100B (Millipore), and subacute (10 days–6 weeks) 3T MRI measures of lesion volume and white matter injury.</div><div>Differential expression analysis identified four markers elevated specifically in TBI (VSNL1, IL1RN/IL-1Ra, GFAP, IKBKG), while other derangements reflected non-specific injury responses. Higher VSNL1 correlated with greater lesion volume (r<sub>s</sub> = 0.53) and higher IL1RN/IL-1Ra with greater white matter injury (r<sub>s</sub> = −0.66, both FDR-adjusted p < 0.05). IL33, part of the non-specific injury response was higher in participants with good (GOS-E 5–8) versus poor (GOS-E 1–4) outcomes (W = 47, FDR-adjusted p = 0.0024). Using an Elastic Net model trained on healthy controls, we show that “inflammation age” exceeded chronological age in TBI, particularly in younger participants.</div><div>In summary, acute post-TBI inflammation includes both TBI-specific and non-specific components, linked to structural brain injury and functional outcome. Age modulates the inflammatory response. VSNL1, IL1RN/IL-1Ra, and IL33 are potential mediators of post-TBI pathophysiology.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101179"},"PeriodicalIF":3.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><h3>Background</h3><div>Impaired smell/taste sensation (dysosmia/dysgeusia) are common manifestations of coronavirus disease 2019 (COVID-19). Scattered peripheral chemoreceptors and directly innervating central nerves from the brain to the receptors are responsible systems for perception in the human body. The shared neurotransmitter serotonin (5-HT) and neuroimmune modulators of the kynurenine (Kyn) pathway (KP) are metabolites derived from tryptophan (Trp). The synthesis of KP metabolites is initiated by the rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can activate Trp metabolism. Therefore, we investigated whether serum metabolites of Trp and IDO/TDO activity could serve as biomarkers for assessing smell/taste impairment (dysosmia/dysgeusia) in patients during the acute phase of COVID-19.</div></div><div><h3>Methods</h3><div>We conducted a retrospective case-control study. Among patients admitted with acute COVID-19 to our hospital between September 13, 2021, and September 30, 2023, those whose chief complaints included dysosmia/dysgeusia at admission were identified. These symptoms were confirmed by the attending physician for COVID-19. Patients were stratified based on the presence or absence of dysosmia and/or dysgeusia.</div><div>In both patient groups, serum concentrations of Trp, 5-HT, Kyn, kynurenic acid (KYNA), and quinolinic acid (QUIN) were measured using enzyme-linked immunosorbent assay. IDO/TDO activity was expressed as Kyn–Trp ratio (KTR). The relationships between these biomarkers and dysosmia/dysgeusia, as well as other clinical parameters and outcomes, were evaluated.</div></div><div><h3>Results</h3><div>Of 520 patients admitted with COVID-19, 95 met the inclusion and exclusion criteria. Among them, 26 patients with dysosmia/dysgeusia (group A) and 26 patients without these symptoms (group B) were analyzed. No significant intergroup difference was observed in the average timepoint at blood sampling after COVID-19 onset (post-day from onset: pdo) (4.69 ± 2.51 days in group A <em>vs</em>. 3.62 ± 2.22 in group B). Group A showed significantly lower Trp levels [median 9.70 μg/mL (range 4.59–13.89) <em>vs</em>. 10.40 (7.52–13.34), <em>p</em> = 0.031], and higher KTR [61.34 (40.47–384.2) <em>vs</em>. 53.52 (26.13–86.64), <em>p</em> < 0.037] and QUIN levels [574.39 nM (100.39–11909) <em>vs</em>. 443.65 (83.09–998.3), <em>p</em> < 0.0169]. No significant differences were observed in 5-HT or KYNA levels between groups. Almost all cases of dysosmia involved anosmia/hyposmia and were significantly correlated with non-vaccination status with mRNA vaccine (<em>p</em> = 0.017). In contrast, dysgeusia exhibited heterogeneous manifestations, primarily ageusia or hypogeusia, followed by hypersensitivity to salty taste, and was not correlated with vaccination status.</div></div><div><h3>Conclusion</h3><div>Clinically, serum K
{"title":"Quinolinic acid as trigger/biomarker of dysosmia/dysgeusia in patients with acute coronavirus disease 2019: A retrospective case-control study","authors":"Jun Tsukiji , Shiro Koizume , Tomoko Takahashi , Shuji Murakami , Hiroyuki Takahashi , Sachiyo Mitsunaga , Sho Nakamura , Hiroto Narimatsu , Yohei Miyagi","doi":"10.1016/j.bbih.2026.101175","DOIUrl":"10.1016/j.bbih.2026.101175","url":null,"abstract":"<div><h3>Background</h3><div>Impaired smell/taste sensation (dysosmia/dysgeusia) are common manifestations of coronavirus disease 2019 (COVID-19). Scattered peripheral chemoreceptors and directly innervating central nerves from the brain to the receptors are responsible systems for perception in the human body. The shared neurotransmitter serotonin (5-HT) and neuroimmune modulators of the kynurenine (Kyn) pathway (KP) are metabolites derived from tryptophan (Trp). The synthesis of KP metabolites is initiated by the rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can activate Trp metabolism. Therefore, we investigated whether serum metabolites of Trp and IDO/TDO activity could serve as biomarkers for assessing smell/taste impairment (dysosmia/dysgeusia) in patients during the acute phase of COVID-19.</div></div><div><h3>Methods</h3><div>We conducted a retrospective case-control study. Among patients admitted with acute COVID-19 to our hospital between September 13, 2021, and September 30, 2023, those whose chief complaints included dysosmia/dysgeusia at admission were identified. These symptoms were confirmed by the attending physician for COVID-19. Patients were stratified based on the presence or absence of dysosmia and/or dysgeusia.</div><div>In both patient groups, serum concentrations of Trp, 5-HT, Kyn, kynurenic acid (KYNA), and quinolinic acid (QUIN) were measured using enzyme-linked immunosorbent assay. IDO/TDO activity was expressed as Kyn–Trp ratio (KTR). The relationships between these biomarkers and dysosmia/dysgeusia, as well as other clinical parameters and outcomes, were evaluated.</div></div><div><h3>Results</h3><div>Of 520 patients admitted with COVID-19, 95 met the inclusion and exclusion criteria. Among them, 26 patients with dysosmia/dysgeusia (group A) and 26 patients without these symptoms (group B) were analyzed. No significant intergroup difference was observed in the average timepoint at blood sampling after COVID-19 onset (post-day from onset: pdo) (4.69 ± 2.51 days in group A <em>vs</em>. 3.62 ± 2.22 in group B). Group A showed significantly lower Trp levels [median 9.70 μg/mL (range 4.59–13.89) <em>vs</em>. 10.40 (7.52–13.34), <em>p</em> = 0.031], and higher KTR [61.34 (40.47–384.2) <em>vs</em>. 53.52 (26.13–86.64), <em>p</em> < 0.037] and QUIN levels [574.39 nM (100.39–11909) <em>vs</em>. 443.65 (83.09–998.3), <em>p</em> < 0.0169]. No significant differences were observed in 5-HT or KYNA levels between groups. Almost all cases of dysosmia involved anosmia/hyposmia and were significantly correlated with non-vaccination status with mRNA vaccine (<em>p</em> = 0.017). In contrast, dysgeusia exhibited heterogeneous manifestations, primarily ageusia or hypogeusia, followed by hypersensitivity to salty taste, and was not correlated with vaccination status.</div></div><div><h3>Conclusion</h3><div>Clinically, serum K","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101175"},"PeriodicalIF":3.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/j.bbih.2026.101177
Qing Xu , Yanlin Han , Shuzhan Gao , Siyi Wang , Yanyan Lu , Kuan-Pin Su , Xijia Xu
Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune inflammatory demyelinating conditions primarily affecting the optic nerves and spinal cord. While NMOSD pathogenesis is mediated by aquaporin-4 antibody (AQP4-IgG) autoimmunity, increasing evidence suggests significant comorbidity with affective symptoms. The neuropathological mechanisms underlying this comorbidity, however, remain incompletely understood. We reported two cases of female patients with concurrent NMOSD and mood disorders that illustrate a shared neuroinflammatory etiology. Case 1, a 26-year-old female, presented with a decade-long history of mood instability, diagnosed as bipolar disorder (BD) mixed episode, which coincided with her NMOSD diagnosis. Case 2, a 25-year-old female, initially presented with major depressive disorder (MDD) but was subsequently diagnosed with NMOSD following the acute onset of neurological symptoms. Both patients were, serum AQP4-IgG positive and exhibited demyelinating changes in the frontal lobe. Following immunosuppressive and psychiatric treatment, both patients experienced marked improvement in neurological function, suicidality, and affective symptoms. These case reports suggest a bidirectional relationship between NMOSD and mood disorders, likely mediated by AQP4-IgG-driven neuroinflammatory responses. AQP4-IgG screening may serve as a critical tool to distinguish organic mood disorder from primary psychiatric conditions, particularly in patients with atypical neurological symptoms.
{"title":"AQP4-IgG and mood disorders: Case series of neuromyelitis optica spectrum disorder","authors":"Qing Xu , Yanlin Han , Shuzhan Gao , Siyi Wang , Yanyan Lu , Kuan-Pin Su , Xijia Xu","doi":"10.1016/j.bbih.2026.101177","DOIUrl":"10.1016/j.bbih.2026.101177","url":null,"abstract":"<div><div>Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune inflammatory demyelinating conditions primarily affecting the optic nerves and spinal cord. While NMOSD pathogenesis is mediated by aquaporin-4 antibody (AQP4-IgG) autoimmunity, increasing evidence suggests significant comorbidity with affective symptoms. The neuropathological mechanisms underlying this comorbidity, however, remain incompletely understood. We reported two cases of female patients with concurrent NMOSD and mood disorders that illustrate a shared neuroinflammatory etiology. Case 1, a 26-year-old female, presented with a decade-long history of mood instability, diagnosed as bipolar disorder (BD) mixed episode, which coincided with her NMOSD diagnosis. Case 2, a 25-year-old female, initially presented with major depressive disorder (MDD) but was subsequently diagnosed with NMOSD following the acute onset of neurological symptoms. Both patients were, serum AQP4-IgG positive and exhibited demyelinating changes in the frontal lobe. Following immunosuppressive and psychiatric treatment, both patients experienced marked improvement in neurological function, suicidality, and affective symptoms. These case reports suggest a bidirectional relationship between NMOSD and mood disorders, likely mediated by AQP4-IgG-driven neuroinflammatory responses. AQP4-IgG screening may serve as a critical tool to distinguish organic mood disorder from primary psychiatric conditions, particularly in patients with atypical neurological symptoms.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101177"},"PeriodicalIF":3.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/j.bbih.2026.101176
Qingying Zheng , Guoyuan Huang , Qian Liu , Weiguang Ni , Ying Zhao
Background
Mind-body exercises (MBEs), including Tai Chi (TC), Qigong (QG), Yoga (YG), and Mindfulness-Based Stress Reduction (MBSR), show promise in neuropsychiatric rehabilitation by modulating neuroinflammation. This study systematically examines the effects of MBEs on neuroinflammation-related biomarkers in neuropsychiatric disorders, aiming to identify optimal modalities, dosages, and key moderators.
Methods
Databases were systematically searched for eligible RCTs from inception until February 2025. Data were analyzed using R packages (“meta,” “multinma,” “MBNMAdose,” “GEMTC,” “BUGSnet,” “ggplot2”) to assess the effects of MBEs on TNF-α, IL-6, IL-1β, IL-10, CRP, and BDNF in adults with neuropsychiatric disorders.
Results
Twenty-nine RCTs involving 2253 participants were included. MBEs significantly reduced IL-6 [standardized mean difference (SMD) = −0.47] and IL-1β [SMD = −0.90], while increasing BDNF [SMD = 1.08] and IL-10 [SMD = 0.87]. Effects on TNF-α [SMD = −0.33] and CRP [SMD = −0.12] showed a non-significant trend toward benefit. Dosages between 600 and 1000 MET-min/week yielded the most pronounced anti-inflammatory effects. Network meta-analysis ranked TC and MBSR as the most effective for reducing proinflammatory cytokines, while QG showed the greatest benefits for neurotrophic outcomes. Participant characteristics (age, population, clinical conditions) and MBE parameters (duration, frequency, session length) significantly moderated neuroprotective effects.
Conclusion
MBEs effectively reduce proinflammatory cytokines (IL-1β, IL-6) and enhance anti-inflammatory cytokine (IL-10) and neurotrophic factor (BDNF) in neuropsychiatric disorders. The optimal dosage ranges from 600 to 1000 MET-min/week. Given the impact of participant characteristics and MBE parameters, personalized prescriptions may enhance clinical outcomes and long-term neuroprotective effects.
{"title":"Optimal doses of mind-body exercise on neuroinflammation in individuals with neuropsychiatric disorders: A systematic review and dose-response meta-analysis","authors":"Qingying Zheng , Guoyuan Huang , Qian Liu , Weiguang Ni , Ying Zhao","doi":"10.1016/j.bbih.2026.101176","DOIUrl":"10.1016/j.bbih.2026.101176","url":null,"abstract":"<div><h3>Background</h3><div>Mind-body exercises (MBEs), including Tai Chi (TC), Qigong (QG), Yoga (YG), and Mindfulness-Based Stress Reduction (MBSR), show promise in neuropsychiatric rehabilitation by modulating neuroinflammation. This study systematically examines the effects of MBEs on neuroinflammation-related biomarkers in neuropsychiatric disorders, aiming to identify optimal modalities, dosages, and key moderators.</div></div><div><h3>Methods</h3><div>Databases were systematically searched for eligible RCTs from inception until February 2025. Data were analyzed using R packages (“<em>meta</em>,” “<em>multinma</em>,” “<em>MBNMAdose</em>,” “<em>GEMTC</em>,” “<em>BUGSnet</em>,” “<em>ggplot2</em>”) to assess the effects of MBEs on TNF-α, IL-6, IL-1β, IL-10, CRP, and BDNF in adults with neuropsychiatric disorders.</div></div><div><h3>Results</h3><div>Twenty-nine RCTs involving 2253 participants were included. MBEs significantly reduced IL-6 [standardized mean difference (SMD) = −0.47] and IL-1β [SMD = −0.90], while increasing BDNF [SMD = 1.08] and IL-10 [SMD = 0.87]. Effects on TNF-α [SMD = −0.33] and CRP [SMD = −0.12] showed a non-significant trend toward benefit. Dosages between 600 and 1000 MET-min/week yielded the most pronounced anti-inflammatory effects. Network meta-analysis ranked TC and MBSR as the most effective for reducing proinflammatory cytokines, while QG showed the greatest benefits for neurotrophic outcomes. Participant characteristics (age, population, clinical conditions) and MBE parameters (duration, frequency, session length) significantly moderated neuroprotective effects.</div></div><div><h3>Conclusion</h3><div>MBEs effectively reduce proinflammatory cytokines (IL-1β, IL-6) and enhance anti-inflammatory cytokine (IL-10) and neurotrophic factor (BDNF) in neuropsychiatric disorders. The optimal dosage ranges from 600 to 1000 MET-min/week. Given the impact of participant characteristics and MBE parameters, personalized prescriptions may enhance clinical outcomes and long-term neuroprotective effects.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101176"},"PeriodicalIF":3.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1016/j.bbih.2026.101172
A. Papageorgiou , D. Chatzistefanidis , M. Nikolakea , N.-R. Karela , M. Gkrampovari , K. Lantavos , D. Bartzi , L. Traikov , S. Markoula
Acute ischemic stroke is one of the leading causes of mortality and morbidity worldwide. The underlying inflammation process following the ischemic event arises as an important factor of great therapeutic interest. Recent research has showcased the roles of B- and T-lymphocytes in the acute post-stroke period, with various types of lymphocytes affecting differently the clinical outcome of the patient. Herein, we reviewed the literature and discussed the functional role of various subpopulations of lymphocytes in recovery and repair of the ischemic tissue as well as their influence on the final outcome of the patient. Additionally, we searched the literature regarding current knowledge on various drugs possibly affecting neuroinflammation or exhibiting a neuroprotective role in the acute post-stroke period.
{"title":"“The emerging role of lymphocytes in post-stroke inflammation: A treatable target and review of current pharmacological evidence in humans\"","authors":"A. Papageorgiou , D. Chatzistefanidis , M. Nikolakea , N.-R. Karela , M. Gkrampovari , K. Lantavos , D. Bartzi , L. Traikov , S. Markoula","doi":"10.1016/j.bbih.2026.101172","DOIUrl":"10.1016/j.bbih.2026.101172","url":null,"abstract":"<div><div>Acute ischemic stroke is one of the leading causes of mortality and morbidity worldwide. The underlying inflammation process following the ischemic event arises as an important factor of great therapeutic interest. Recent research has showcased the roles of B- and T-lymphocytes in the acute post-stroke period, with various types of lymphocytes affecting differently the clinical outcome of the patient. Herein, we reviewed the literature and discussed the functional role of various subpopulations of lymphocytes in recovery and repair of the ischemic tissue as well as their influence on the final outcome of the patient. Additionally, we searched the literature regarding current knowledge on various drugs possibly affecting neuroinflammation or exhibiting a neuroprotective role in the acute post-stroke period.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101172"},"PeriodicalIF":3.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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