Pub Date : 2025-12-19DOI: 10.1016/j.bbih.2025.101164
Sizhi Wu , Yiwen Lv , Peng Pang , Huachong Xu , Li Deng , Wei Ma , Xiaoyin Chen
Background
Climate factors exert a profound influence on human emotional well-being and physical health. Exposure to a humid heat environment is known to precipitate anxiety-like behaviors and exacerbate the clinical manifestations of influenza; concurrently, mounting evidence has demonstrated a bidirectional regulation between the gut microbiota and human health, suggesting a potential link between environmental stress and microbial homeostasis.
Methods
In this study, C57BL/6J male mice were subjected to a humid heat environment for 3 weeks prior to infection with the influenza A virus. Microbiota composition, metabolites, and intestinal mucosal immunity were comprehensively measured. Furthermore, behavioral phenotypes and neurotransmitter levels were assessed to explore their potential correlations with gut dysbiosis.
Results
Exposure to a humid heat environment aggravated pulmonary and intestinal tissue damage while reshaping the gut microbiota composition and metabolome. This environmental stress precipitated severe pathological injury and robust inflammatory in the intestinal mucosa, characterized by a multifold upregulation of Th1/Th2-related cytokines and the suppressed expression of Ocln, ZO-1, pIgR, and SIgA. Further experiments revealed that the humid heat environment exacerbated neurological deficits in influenza A virus-infected mice, accompanied by a significant reduction in neurotransmitter levels. Conclusions: These data demonstrate that exposure to a humid heat environment exacerbates influenza infection severity through the dysregulation of the intestinal homeostasis and the neuroendocrine system, revealing the potential mechanisms underlying the digestive and nervous system symptoms observed in influenza patients.
{"title":"Distinct actions of the humid heat environment on host gut microbiota, intestinal mucosal immunity, neuroendocrinology in influenza A virus-infected mouse","authors":"Sizhi Wu , Yiwen Lv , Peng Pang , Huachong Xu , Li Deng , Wei Ma , Xiaoyin Chen","doi":"10.1016/j.bbih.2025.101164","DOIUrl":"10.1016/j.bbih.2025.101164","url":null,"abstract":"<div><h3>Background</h3><div>Climate factors exert a profound influence on human emotional well-being and physical health. Exposure to a humid heat environment is known to precipitate anxiety-like behaviors and exacerbate the clinical manifestations of influenza; concurrently, mounting evidence has demonstrated a bidirectional regulation between the gut microbiota and human health, suggesting a potential link between environmental stress and microbial homeostasis.</div></div><div><h3>Methods</h3><div>In this study, C57BL/6J male mice were subjected to a humid heat environment for 3 weeks prior to infection with the influenza A virus. Microbiota composition, metabolites, and intestinal mucosal immunity were comprehensively measured. Furthermore, behavioral phenotypes and neurotransmitter levels were assessed to explore their potential correlations with gut dysbiosis.</div></div><div><h3>Results</h3><div>Exposure to a humid heat environment aggravated pulmonary and intestinal tissue damage while reshaping the gut microbiota composition and metabolome. This environmental stress precipitated severe pathological injury and robust inflammatory in the intestinal mucosa, characterized by a multifold upregulation of Th1/Th2-related cytokines and the suppressed expression of <em>Ocln</em>, <em>ZO-1</em>, <em>pIgR</em>, and <em>SIgA</em>. Further experiments revealed that the humid heat environment exacerbated neurological deficits in influenza A virus-infected mice, accompanied by a significant reduction in neurotransmitter levels. <strong>Conclusions</strong>: These data demonstrate that exposure to a humid heat environment exacerbates influenza infection severity through the dysregulation of the intestinal homeostasis and the neuroendocrine system, revealing the potential mechanisms underlying the digestive and nervous system symptoms observed in influenza patients.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101164"},"PeriodicalIF":3.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939223","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 : 2025-12-18DOI: 10.1016/j.bbih.2025.101163
Faith Dickerson , Emily Katsafanas , Andrea Origoni , Kelly Rowe , Sabahat Khan , Fahad Mukhtar , Shuojja Yang , Victor W. Splan , Robert Yolken
Matrix metalloproteinases (MMPs) are a diverse set of enzymes associated with tissue remodeling as well as inflammation and tissue destruction. MMP-9 is of interest since it has been associated with psychiatric disorders including major depressive disorder (MDD). Suicide attempts are a major complication of MDD. However, the association between MMP-9 levels and suicide attempts has not been extensively studied in persons with MDD. Sensitive enzyme immunoassays were employed to measure the levels of MMP-9 in blood samples from 186 persons with MDD receiving hospital care, 92 with a suicide attempt within the previous 30 days and 94 without a recent attempt, as well as 79 persons without a psychiatric disorder. Lifetime suicide attempt history in the MDD group was also recorded. Mixed effects models were employed to compare the MMP-9 levels among the groups adjusted for demographic and clinical variables. Wald tests were used to calculate pairwise comparisons. Employing these models, we found that individuals with MDD and a recent suicide attempt had higher levels of MMP-9 than individuals with MDD without a recent suicide attempt as well as individuals without a psychiatric disorder. There was not a significant difference in MMP-9 levels between the non-psychiatric group and individuals with MDD without a recent suicide attempt, regardless of whether they had a lifetime suicide attempt. Therapeutic modalities to modulate MMP-9 activity are currently being developed. The measurement of MMP-9 might be used to inform future clinical trials of these modalities for the prevention of suicide behaviors in high-risk individuals.
{"title":"Levels of matrix metalloproteinase 9 (MMP-9) are elevated in persons with major depressive disorder who have had a recent suicide attempt","authors":"Faith Dickerson , Emily Katsafanas , Andrea Origoni , Kelly Rowe , Sabahat Khan , Fahad Mukhtar , Shuojja Yang , Victor W. Splan , Robert Yolken","doi":"10.1016/j.bbih.2025.101163","DOIUrl":"10.1016/j.bbih.2025.101163","url":null,"abstract":"<div><div>Matrix metalloproteinases (MMPs) are a diverse set of enzymes associated with tissue remodeling as well as inflammation and tissue destruction. MMP-9 is of interest since it has been associated with psychiatric disorders including major depressive disorder (MDD). Suicide attempts are a major complication of MDD. However, the association between MMP-9 levels and suicide attempts has not been extensively studied in persons with MDD. Sensitive enzyme immunoassays were employed to measure the levels of MMP-9 in blood samples from 186 persons with MDD receiving hospital care, 92 with a suicide attempt within the previous 30 days and 94 without a recent attempt, as well as 79 persons without a psychiatric disorder. Lifetime suicide attempt history in the MDD group was also recorded. Mixed effects models were employed to compare the MMP-9 levels among the groups adjusted for demographic and clinical variables. Wald tests were used to calculate pairwise comparisons. Employing these models, we found that individuals with MDD and a recent suicide attempt had higher levels of MMP-9 than individuals with MDD without a recent suicide attempt as well as individuals without a psychiatric disorder. There was not a significant difference in MMP-9 levels between the non-psychiatric group and individuals with MDD without a recent suicide attempt, regardless of whether they had a lifetime suicide attempt. Therapeutic modalities to modulate MMP-9 activity are currently being developed. The measurement of MMP-9 might be used to inform future clinical trials of these modalities for the prevention of suicide behaviors in high-risk individuals.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101163"},"PeriodicalIF":3.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939224","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 : 2025-12-18DOI: 10.1016/j.bbih.2025.101161
Weiye Chen, Ian N. Johnston
A subset of cancer patients and survivors experience cognitive decline during and after chemotherapy, a condition known as chemotherapy-induced cognitive impairment (CICI). Among the most affected domains are executive functions (EFs) - a set of higher-order cognitive processes essential for goal-directed behaviour, including working memory, behavioural flexibility, and inhibition. Emerging evidence suggests that these domains are differentially susceptible to chemotherapy drugs, implicating the selective disruption of distinct neural circuits and neurochemical pathways. To better understand the underlying mechanisms, we conducted a systematic review of rodent models of CICI, focusing on neurobiological alterations associated with chemotherapy and their relationship to EF deficits. A comprehensive search across PubMed, Web of Science, Scopus, and PsycINFO identified 67 eligible papers. Across studies, working memory and problem-solving impairments were most frequently examined and showed the greatest overlap across multiple mechanistic categories, including oxidative stress, mitochondrial dysfunction, neuroimmune dysregulation, impaired plasticity, and altered white matter integrity. Behavioural flexibility was most often linked to disrupted neurogenesis and metabolic imbalance, whereas attention and inhibition showed variable associations with neurotransmission and synaptic markers. Considerable heterogeneity within mechanistic categories reflected interactions among treatment regimen, animal sex, strain, and timing of assessment. Future studies should integrate molecular, cellular, and systems-level analyses within longitudinal and sex-balanced designs to clarify causal mechanisms and guide targeted interventions for preserving cognitive health in cancer survivors.
一部分癌症患者和幸存者在化疗期间和之后经历认知能力下降，这种情况被称为化疗诱导的认知障碍（CICI）。其中受影响最大的领域是执行功能（EFs），这是一组对目标导向行为至关重要的高阶认知过程，包括工作记忆、行为灵活性和抑制。新出现的证据表明，这些区域对化疗药物的敏感性不同，这意味着不同的神经回路和神经化学途径的选择性破坏。为了更好地了解潜在的机制，我们对CICI的啮齿动物模型进行了系统的回顾，重点关注与化疗相关的神经生物学改变及其与EF缺陷的关系。在PubMed， Web of Science， Scopus和PsycINFO上进行全面搜索，确定了67篇符合条件的论文。在所有研究中，工作记忆和解决问题的障碍是最常被检查的，并且在多个机制类别中显示出最大的重叠，包括氧化应激、线粒体功能障碍、神经免疫失调、可塑性受损和白质完整性改变。行为灵活性通常与神经发生紊乱和代谢失衡有关，而注意力和抑制则与神经传递和突触标志物有不同的关联。机制分类中相当大的异质性反映了治疗方案、动物性别、品系和评估时间之间的相互作用。未来的研究应该在纵向和性别平衡设计中整合分子、细胞和系统水平的分析，以阐明因果机制，并指导有针对性的干预措施，以保持癌症幸存者的认知健康。
{"title":"A systematic review of the neurobiological mechanisms of chemotherapy-induced deficits in executive functions","authors":"Weiye Chen, Ian N. Johnston","doi":"10.1016/j.bbih.2025.101161","DOIUrl":"10.1016/j.bbih.2025.101161","url":null,"abstract":"<div><div>A subset of cancer patients and survivors experience cognitive decline during and after chemotherapy, a condition known as chemotherapy-induced cognitive impairment (CICI). Among the most affected domains are executive functions (EFs) - a set of higher-order cognitive processes essential for goal-directed behaviour, including working memory, behavioural flexibility, and inhibition. Emerging evidence suggests that these domains are differentially susceptible to chemotherapy drugs, implicating the selective disruption of distinct neural circuits and neurochemical pathways. To better understand the underlying mechanisms, we conducted a systematic review of rodent models of CICI, focusing on neurobiological alterations associated with chemotherapy and their relationship to EF deficits. A comprehensive search across PubMed, Web of Science, Scopus, and PsycINFO identified 67 eligible papers. Across studies, working memory and problem-solving impairments were most frequently examined and showed the greatest overlap across multiple mechanistic categories, including oxidative stress, mitochondrial dysfunction, neuroimmune dysregulation, impaired plasticity, and altered white matter integrity. Behavioural flexibility was most often linked to disrupted neurogenesis and metabolic imbalance, whereas attention and inhibition showed variable associations with neurotransmission and synaptic markers. Considerable heterogeneity within mechanistic categories reflected interactions among treatment regimen, animal sex, strain, and timing of assessment. Future studies should integrate molecular, cellular, and systems-level analyses within longitudinal and sex-balanced designs to clarify causal mechanisms and guide targeted interventions for preserving cognitive health in cancer survivors.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101161"},"PeriodicalIF":3.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939122","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 : 2025-12-11DOI: 10.1016/j.bbih.2025.101158
Monica T. Jones , Rachael A. Cronin , Mathew D. Marques , Matthias Weigl , Nicolas Rohleder , Linda Becker , Helena C. Kaltenegger , Bradley J. Wright
Objective
Chronic low-grade inflammation may help explain the relationship between stress, well-being, and disease, but the pathway and temporal order have not yet been tested prospectively. To understand the pathways between perceived stress, well-being, C-reactive protein, and hair cortisol, we investigated the temporal ordering of these variables in a sample of hospital employees.
Methods
Random-intercepts cross-lagged panel models were conducted using three 6-monthly waves of data collected from new employees at a German hospital (N = 296, 77.7 % female, M age = 28.59) in a prospective cohort study. Self-reported data on perceived stress and well-being, hair strands for hair cortisol concentration, and capillary blood samples for C-reactive protein were collected for analysis.
Results
While our study did not support a causal relationship between changes in stress levels and later changes in either hair cortisol or low-grade inflammation, we provide evidence to suggest that increases in perceived stress led to later decreases in well-being. In contrast, changes in well-being did not predict changes in perceived stress levels.
Conclusion
This is the first prospective repeated-measure study to examine the temporal associations between stress, well-being, hair cortisol concentrations, and chronic low-grade inflammation. Our analyses suggest that perceived stress in this sample precedes changes in well-being, highlighting the importance of prevention and early intervention.
{"title":"Perceived stress precedes declines in Well-being: A prospective study of stress, well-being, hair cortisol, and low-grade inflammation in hospital employees","authors":"Monica T. Jones , Rachael A. Cronin , Mathew D. Marques , Matthias Weigl , Nicolas Rohleder , Linda Becker , Helena C. Kaltenegger , Bradley J. Wright","doi":"10.1016/j.bbih.2025.101158","DOIUrl":"10.1016/j.bbih.2025.101158","url":null,"abstract":"<div><h3>Objective</h3><div>Chronic low-grade inflammation may help explain the relationship between stress, well-being, and disease, but the pathway and temporal order have not yet been tested prospectively. To understand the pathways between perceived stress, well-being, C-reactive protein, and hair cortisol, we investigated the temporal ordering of these variables in a sample of hospital employees.</div></div><div><h3>Methods</h3><div>Random-intercepts cross-lagged panel models were conducted using three 6-monthly waves of data collected from new employees at a German hospital (<em>N</em> = 296, 77.7 % female, M age = 28.59) in a prospective cohort study. Self-reported data on perceived stress and well-being, hair strands for hair cortisol concentration, and capillary blood samples for C-reactive protein were collected for analysis.</div></div><div><h3>Results</h3><div>While our study did not support a causal relationship between changes in stress levels and later changes in either hair cortisol or low-grade inflammation, we provide evidence to suggest that increases in perceived stress led to later decreases in well-being. In contrast, changes in well-being did not predict changes in perceived stress levels.</div></div><div><h3>Conclusion</h3><div>This is the first prospective repeated-measure study to examine the temporal associations between stress, well-being, hair cortisol concentrations, and chronic low-grade inflammation. Our analyses suggest that perceived stress in this sample precedes changes in well-being, highlighting the importance of prevention and early intervention.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101158"},"PeriodicalIF":3.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798680","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 : 2025-12-05DOI: 10.1016/j.bbih.2025.101154
Hesed Virto-Farfan , Carlos Virto , Gustavo E. Tafet
Introduction
The Pururauka protocol is an accelerated intermittent theta burst stimulation (iTBS) paradigm designed to rapidly reduce depressive symptoms and suicidal ideation in individuals with severe major depressive episodes. This study evaluated its clinical effects in patients presenting with insufficient response to at least two prior pharmacological treatments, current suicidal ideation, and more than two previous suicide attempts.
Methods
Thirty-six adults with non-psychotic major depressive disorder (ICD-11) and HAM-D-17 scores >20 received a five-day accelerated iTBS intervention (180,000 pulses total) targeting the left dorsolateral prefrontal cortex. Depressive symptoms were assessed using the HAM-D and MADRS at baseline, daily during treatment, and at 1-, 3-, and 6-month follow-ups. Suicidal ideation was evaluated with HAM-D item 3 across the same time points. Satisfaction was measured with a visual analogue scale (VAS). Safety assessments included EEG screening and neuropsychiatric evaluations. Ethical approval was obtained from the Andean University of Cusco Ethics Committee (INFORME 023-2024-CIEI-UAC).
Results
Mean HAM-D scores decreased from 38.89 at baseline to 13.61 at day 5 and 12.36 at six months (p < 0.001). Suicidal ideation resolved in most participants by day 3 and remained minimal or absent during follow-up. MADRS scores showed similar patterns, with 68 % of participants presenting no depressive symptoms immediately after treatment. No serious adverse events occurred, and satisfaction scores remained high throughout the protocol.
Conclusion
The Pururauka accelerated iTBS protocol was associated with rapid and sustained reductions in depressive symptoms and suicidal ideation in individuals with severe depressive episodes and insufficient response to previous medications. These preliminary findings warrant confirmation in future randomized controlled trials.
{"title":"Accelerated Theta Burst Stimulation Transcranial Magnetic Stimulation (iTBS-TMS) Pururauka program for severe depressive episode and suicide ideation","authors":"Hesed Virto-Farfan , Carlos Virto , Gustavo E. Tafet","doi":"10.1016/j.bbih.2025.101154","DOIUrl":"10.1016/j.bbih.2025.101154","url":null,"abstract":"<div><h3>Introduction</h3><div>The <em>Pururauka</em> protocol is an accelerated intermittent theta burst stimulation (iTBS) paradigm designed to rapidly reduce depressive symptoms and suicidal ideation in individuals with severe major depressive episodes. This study evaluated its clinical effects in patients presenting with insufficient response to at least two prior pharmacological treatments, current suicidal ideation, and more than two previous suicide attempts.</div></div><div><h3>Methods</h3><div>Thirty-six adults with non-psychotic major depressive disorder (ICD-11) and HAM-D-17 scores >20 received a five-day accelerated iTBS intervention (180,000 pulses total) targeting the left dorsolateral prefrontal cortex. Depressive symptoms were assessed using the HAM-D and MADRS at baseline, daily during treatment, and at 1-, 3-, and 6-month follow-ups. Suicidal ideation was evaluated with HAM-D item 3 across the same time points. Satisfaction was measured with a visual analogue scale (VAS). Safety assessments included EEG screening and neuropsychiatric evaluations. Ethical approval was obtained from the Andean University of Cusco Ethics Committee (INFORME 023-2024-CIEI-UAC).</div></div><div><h3>Results</h3><div>Mean HAM-D scores decreased from 38.89 at baseline to 13.61 at day 5 and 12.36 at six months (p < 0.001). Suicidal ideation resolved in most participants by day 3 and remained minimal or absent during follow-up. MADRS scores showed similar patterns, with 68 % of participants presenting no depressive symptoms immediately after treatment. No serious adverse events occurred, and satisfaction scores remained high throughout the protocol.</div></div><div><h3>Conclusion</h3><div>The <em>Pururauka</em> accelerated iTBS protocol was associated with rapid and sustained reductions in depressive symptoms and suicidal ideation in individuals with severe depressive episodes and insufficient response to previous medications. These preliminary findings warrant confirmation in future randomized controlled trials.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101154"},"PeriodicalIF":3.5,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712146","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 : 2025-12-03DOI: 10.1016/j.bbih.2025.101143
Lennart Seizer , Johanna Löchner , Tobias J. Renner
The interaction between the immune system and the central nervous system has been implicated in the development of psychiatric disorders in adult patients. However, comprehensive data regarding pediatric psychiatry are still lacking. This study aims to describe the distributions of various markers of immune system activity in a large clinical sample of children and adolescents and summarize the immunological profiles associated with different psychiatric disorders. We analyzed blood samples from 1543 patients aged 6–18 years (62 % female), admitted to the Child and Adolescent Psychiatry at the University Hospital of Tübingen between 2014 and 2024. Immune markers such as C-reactive protein and various cell counts and ratios were measured and regressed on psychiatric diagnoses according to the ICD-10 classification. Our findings revealed several distinct immunological profiles linked to specific psychiatric conditions in youth, such as higher CRP levels in patients with severe stress and adjustment disorders. The study underscores the potential role that immune system aberrations may play in mental health disorders and highlights the importance of investigating this link in this age group. However, some inconsistencies with the existing literature were found, such as the lack of association between depression and immune activity, which calls for further research to elucidate these relationships. Future studies should include longitudinal designs to better understand the causal pathways and potential for immune-targeted therapies in pediatric psychiatry.
{"title":"Peripheral immune system activity in young psychiatry patients","authors":"Lennart Seizer , Johanna Löchner , Tobias J. Renner","doi":"10.1016/j.bbih.2025.101143","DOIUrl":"10.1016/j.bbih.2025.101143","url":null,"abstract":"<div><div>The interaction between the immune system and the central nervous system has been implicated in the development of psychiatric disorders in adult patients. However, comprehensive data regarding pediatric psychiatry are still lacking. This study aims to describe the distributions of various markers of immune system activity in a large clinical sample of children and adolescents and summarize the immunological profiles associated with different psychiatric disorders. We analyzed blood samples from 1543 patients aged 6–18 years (62 % female), admitted to the Child and Adolescent Psychiatry at the University Hospital of Tübingen between 2014 and 2024. Immune markers such as C-reactive protein and various cell counts and ratios were measured and regressed on psychiatric diagnoses according to the ICD-10 classification. Our findings revealed several distinct immunological profiles linked to specific psychiatric conditions in youth, such as higher CRP levels in patients with severe stress and adjustment disorders. The study underscores the potential role that immune system aberrations may play in mental health disorders and highlights the importance of investigating this link in this age group. However, some inconsistencies with the existing literature were found, such as the lack of association between depression and immune activity, which calls for further research to elucidate these relationships. Future studies should include longitudinal designs to better understand the causal pathways and potential for immune-targeted therapies in pediatric psychiatry.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101143"},"PeriodicalIF":3.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941060","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}
Psychological distress (depression, anxiety, stress) is common in inflammatory bowel disease (IBD) and is linked to poorer outcomes, yet behavioural pathways and economic consequences remain unclear. This study tested a gut-brain-behaviour-outcome (GBBO) framework, testing: 1) reciprocal links between distress and disease activity; 2) whether health behaviours mediate distress-disease activity relationships; 3) if distress and self-reported disease activity (SRDA) predict adverse disease outcomes, controlling for inflammation and 4) whether disease activity mediates relationships between distress and adverse outcomes.
Methods
IBD patients (n = 157) reported distress, health behaviours, SRDA, healthcare use and disease-related outcomes at 3 waves at 6-month intervals. Faecal calprotectin (FCP) was assayed at baseline and 6 months. Analyses were conducted using structural equation modelling and mixed-effects models.
Results
Baseline distress predicted higher SRDA six months later (β = 0.16, p=.03) but did not predict FCP; reverse pathways were nonsignificant. Impaired sleep quality mediated 55 % of the effect of distress on future SRDA (β = 0.09, p=.04). Other behaviours were nonsignificant. Controlling for FCP, distress and SRDA independently predicted secondary healthcare usage (primary/secondary care) and disease-related outcomes (flare frequency/severity, absenteeism and productivity loss). FCP was positively related to flare frequency/severity and allied health practitioner visits only. Mediation analysis showed that SRDA partially mediated absenteeism.
Conclusions
Psychological distress exacerbates symptoms and economic cost. Poor sleep partially mediates the relationship between distress and SRDA, but not inflammation. Psychological interventions that focus on improving sleep could be cost-effective ways to improve mental health and symptom burden, with downstream impact on healthcare utilisation and productivity losses.
{"title":"Psychological distress predicts disease activity in inflammatory bowel disease: Results from the mind-body IBD longitudinal study","authors":"Natasha Seaton , Joanna L. Hudson , Valeria Mondelli , Leah Raymond , Pooja Schmill , Ailsa Hart , Rona Moss-Morris","doi":"10.1016/j.bbih.2025.101147","DOIUrl":"10.1016/j.bbih.2025.101147","url":null,"abstract":"<div><h3>Background & aims</h3><div>Psychological distress (depression, anxiety, stress) is common in inflammatory bowel disease (IBD) and is linked to poorer outcomes, yet behavioural pathways and economic consequences remain unclear. This study tested a gut-brain-behaviour-outcome (GBBO) framework, testing: 1) reciprocal links between distress and disease activity; 2) whether health behaviours mediate distress-disease activity relationships; 3) if distress and self-reported disease activity (SRDA) predict adverse disease outcomes, controlling for inflammation and 4) whether disease activity mediates relationships between distress and adverse outcomes.</div></div><div><h3>Methods</h3><div>IBD patients (n = 157) reported distress, health behaviours, SRDA, healthcare use and disease-related outcomes at 3 waves at 6-month intervals. Faecal calprotectin (FCP) was assayed at baseline and 6 months. Analyses were conducted using structural equation modelling and mixed-effects models.</div></div><div><h3>Results</h3><div>Baseline distress predicted higher SRDA six months later (β = 0.16, <em>p=.</em>03) but did not predict FCP; reverse pathways were nonsignificant. Impaired sleep quality mediated 55 % of the effect of distress on future SRDA (β = 0.09, <em>p=.</em>04). Other behaviours were nonsignificant. Controlling for FCP, distress and SRDA independently predicted secondary healthcare usage (primary/secondary care) and disease-related outcomes (flare frequency/severity, absenteeism and productivity loss). FCP was positively related to flare frequency/severity and allied health practitioner visits only. Mediation analysis showed that SRDA partially mediated absenteeism.</div></div><div><h3>Conclusions</h3><div>Psychological distress exacerbates symptoms and economic cost. Poor sleep partially mediates the relationship between distress and SRDA, but not inflammation. Psychological interventions that focus on improving sleep could be cost-effective ways to improve mental health and symptom burden, with downstream impact on healthcare utilisation and productivity losses.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101147"},"PeriodicalIF":3.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746985","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 : 2025-12-01DOI: 10.1016/j.bbih.2025.101146
Alicia J. Smith , Stacey Kigar , Quentin Dercon , Mary-Ellen Lynall , Konstantinos Ioannidis , Muzaffer Kaser , Caitlin Hitchcock , Tim Dalgleish , Camilla L. Nord
<div><h3>Background</h3><div>Psychiatric disorders are increasingly conceptualised as heterogeneous categories with transdiagnostic underlying mechanisms that cut across multiple diagnoses and vary within a single diagnosis. Inflammation induced by psychosocial stress is one particularly potent example: previous research suggests that inflammatory profiles may correspond to symptom subgroups rather than traditional diagnostic categories. However, robust identification of transdiagnostic symptoms linked to specific inflammatory profiles remains rare. In this study, we examined the relationship between inflammatory profiles (at baseline and after a stress induction) and transdiagnostic symptom dimensions in females, who show higher prevalence of stress-related disorders such as anxiety and depression.</div></div><div><h3>Methods</h3><div>A modest but relatively homogenous healthy female sample, between the ages of 18 and 35, was recruited (N = 26). We obtained venous blood samples, at baseline and after a combined physiological and social stress induction, to measure full blood counts, plasma cytokines and peripheral blood mononuclear cells (PBMCs; for cell stimulation and intracellular flow cytometry analysis). Participants completed a battery of psychiatric self-report questions, from which we modelled three transdiagnostic factor scores. Finally, we used Bayesian regressions to evaluate the predictive contribution of transdiagnostic factors to inflammatory markers (at baseline and stress-induced), as well as to the principal components of inflammatory measures (derived from a principal component analysis (PCA) of the inflammatory data).</div></div><div><h3>Results</h3><div>We identified specific relationships between inflammatory profiles and transdiagnostic symptom dimensions. Higher scores on a ‘social withdrawal’ factor were associated with greater baseline neutrophil (95 % highest density interval (HDI) = [0.06, 1.32]; BF<sub>10</sub> = 2.92) and monocyte counts (95 % HDI = [0.29, 1.46]; BF<sub>10</sub> = 19.08), whereas higher ‘anxious-depression’ scores were associated with a lower baseline monocyte count (95 % HDI = [-0.96, −0.02]; BF<sub>10</sub> = 1.81) and a greater inflammatory response to stress (e.g., change in neutrophil scores from pre-to post stress induction: (95 % HDI = [0.18, 2.14]); BF<sub>10</sub> = 5.66). We also found evidence for an association between the ‘social withdrawal’ factor and an immune principal component most strongly weighted by monocytes, basophils, and IL-6 (95 % HDI = [-1.14, −0.01]; BF<sub>10</sub> = 1.88).</div></div><div><h3>Conclusions</h3><div>We find preliminary evidence that different transdiagnostic psychiatric symptom dimensions map onto specific inflammatory profiles, both at baseline and after a stress induction. This represents a proof-of-principle for the use of data-driven and hypothesis-driven approaches to identify and link transdiagnostic factors with inflammatory changes, which may be of
{"title":"Inflammatory profiles of transdiagnostic symptom dimensions in healthy females","authors":"Alicia J. Smith , Stacey Kigar , Quentin Dercon , Mary-Ellen Lynall , Konstantinos Ioannidis , Muzaffer Kaser , Caitlin Hitchcock , Tim Dalgleish , Camilla L. Nord","doi":"10.1016/j.bbih.2025.101146","DOIUrl":"10.1016/j.bbih.2025.101146","url":null,"abstract":"<div><h3>Background</h3><div>Psychiatric disorders are increasingly conceptualised as heterogeneous categories with transdiagnostic underlying mechanisms that cut across multiple diagnoses and vary within a single diagnosis. Inflammation induced by psychosocial stress is one particularly potent example: previous research suggests that inflammatory profiles may correspond to symptom subgroups rather than traditional diagnostic categories. However, robust identification of transdiagnostic symptoms linked to specific inflammatory profiles remains rare. In this study, we examined the relationship between inflammatory profiles (at baseline and after a stress induction) and transdiagnostic symptom dimensions in females, who show higher prevalence of stress-related disorders such as anxiety and depression.</div></div><div><h3>Methods</h3><div>A modest but relatively homogenous healthy female sample, between the ages of 18 and 35, was recruited (N = 26). We obtained venous blood samples, at baseline and after a combined physiological and social stress induction, to measure full blood counts, plasma cytokines and peripheral blood mononuclear cells (PBMCs; for cell stimulation and intracellular flow cytometry analysis). Participants completed a battery of psychiatric self-report questions, from which we modelled three transdiagnostic factor scores. Finally, we used Bayesian regressions to evaluate the predictive contribution of transdiagnostic factors to inflammatory markers (at baseline and stress-induced), as well as to the principal components of inflammatory measures (derived from a principal component analysis (PCA) of the inflammatory data).</div></div><div><h3>Results</h3><div>We identified specific relationships between inflammatory profiles and transdiagnostic symptom dimensions. Higher scores on a ‘social withdrawal’ factor were associated with greater baseline neutrophil (95 % highest density interval (HDI) = [0.06, 1.32]; BF<sub>10</sub> = 2.92) and monocyte counts (95 % HDI = [0.29, 1.46]; BF<sub>10</sub> = 19.08), whereas higher ‘anxious-depression’ scores were associated with a lower baseline monocyte count (95 % HDI = [-0.96, −0.02]; BF<sub>10</sub> = 1.81) and a greater inflammatory response to stress (e.g., change in neutrophil scores from pre-to post stress induction: (95 % HDI = [0.18, 2.14]); BF<sub>10</sub> = 5.66). We also found evidence for an association between the ‘social withdrawal’ factor and an immune principal component most strongly weighted by monocytes, basophils, and IL-6 (95 % HDI = [-1.14, −0.01]; BF<sub>10</sub> = 1.88).</div></div><div><h3>Conclusions</h3><div>We find preliminary evidence that different transdiagnostic psychiatric symptom dimensions map onto specific inflammatory profiles, both at baseline and after a stress induction. This represents a proof-of-principle for the use of data-driven and hypothesis-driven approaches to identify and link transdiagnostic factors with inflammatory changes, which may be of ","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101146"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684162","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 : 2025-12-01DOI: 10.1016/j.bbih.2025.101145
Heidemarie K. Laurent , Sherryl H. Goodman , Douglas A. Granger , Penina M. Backer
Well-regulated coordination of a multi-system stress response is particularly consequential for intergenerational health during pregnancy, when maternal stress systems typically adapt to protect the fetus. However, little is known about patterns of combined immune/inflammatory mediator (IM) and hypothalamic-pituitary-adrenal (HPA) axis responding to acute stress in human pregnancy, let alone variations associated with maternal health risks. In this study we aimed to define normative perinatal stress response coordination and potential risk profiles by testing relations among pregnant women's salivary IM's and cortisol in response to psychosocial stress, as well as both concurrent affective distress symptomatology and lifetime diagnoses of affective disorders. A community sample of pregnant women (n = 158) participating in the first timepoint of a longitudinal study completed the Trier Social Stress Task and contributed five saliva samples assayed for cortisol; pro-inflammatory cytokines IL1β, IL6, TNFα; and CRP. They self-reported symptoms reflecting common (general distress) and distinct (anhedonic depression, anxious arousal) components of affective distress, and were interviewed about mental health history with a structured clinical interview. Multilevel modeling of IM and cortisol trajectories revealed IM and cortisol responses were positively coordinated on average, but varied across women. Greater affective distress predicted higher/increasing IM stress responses that diverged from cortisol recovery; history of mood disorder specifically related to increasing post-stress IM's, while current general distress related to non-coordination/divergence of IM from cortisol response. These findings highlight a novel stress response pathway characterizing both previous and current affective distress that may help efforts to ameliorate intergenerational impacts of perinatal stress.
{"title":"Coordination of inflammatory and adrenocortical stress response during pregnancy and variation by mental health","authors":"Heidemarie K. Laurent , Sherryl H. Goodman , Douglas A. Granger , Penina M. Backer","doi":"10.1016/j.bbih.2025.101145","DOIUrl":"10.1016/j.bbih.2025.101145","url":null,"abstract":"<div><div>Well-regulated coordination of a multi-system stress response is particularly consequential for intergenerational health during pregnancy, when maternal stress systems typically adapt to protect the fetus. However, little is known about patterns of combined immune/inflammatory mediator (IM) and hypothalamic-pituitary-adrenal (HPA) axis responding to acute stress in human pregnancy, let alone variations associated with maternal health risks. In this study we aimed to define normative perinatal stress response coordination and potential risk profiles by testing relations among pregnant women's salivary IM's and cortisol in response to psychosocial stress, as well as both concurrent affective distress symptomatology and lifetime diagnoses of affective disorders. A community sample of pregnant women (<em>n</em> = 158) participating in the first timepoint of a longitudinal study completed the Trier Social Stress Task and contributed five saliva samples assayed for cortisol; pro-inflammatory cytokines IL1β, IL6, TNFα; and CRP. They self-reported symptoms reflecting common (general distress) and distinct (anhedonic depression, anxious arousal) components of affective distress, and were interviewed about mental health history with a structured clinical interview. Multilevel modeling of IM and cortisol trajectories revealed IM and cortisol responses were positively coordinated on average, but varied across women. Greater affective distress predicted higher/increasing IM stress responses that diverged from cortisol recovery; history of mood disorder specifically related to increasing post-stress IM's, while current general distress related to non-coordination/divergence of IM from cortisol response. These findings highlight a novel stress response pathway characterizing both previous and current affective distress that may help efforts to ameliorate intergenerational impacts of perinatal stress.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101145"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618114","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 : 2025-12-01DOI: 10.1016/j.bbih.2025.101153
Cherie L. Marvel , Alison W. Rebman , Kylie H. Alm , Pegah Touradji , Arnold Bakker , Prianca A. Nadkarni , Deeya Bhattacharya , Owen P. Morgan , Amy Mistri , Christopher C. Sandino , Jonathan A. Ecker , Erica A. Kozero , Arun Venkatesan , Abhay Moghekar , Ashar A. Keeys , John N. Aucott
In Lyme disease (LD), 10–20 % of patients develop persistent symptoms following antibiotic treatment (i.e., post-treatment Lyme disease (PTLD)), which often includes neurological symptoms. This study tested the hypothesis that physiological brain changes occur early in LD and influence outcomes.
Task-based functional MRI (fMRI) and health surveys were administered to patients with acute LD (n = 20) after treatment and six months later. Demographically matched healthy controls (HC; n = 19) were also assessed six months apart. The LD group was categorized at six months into those who had returned to health (RTH, n = 11) or reported persistent symptoms (sPTLD, n = 9). FMRI data from both LD subgroups were compared to each other and HC at both time points. FMRI-guided regions of interest (ROI) values were compared to health surveys.
Baseline brain activity in RTH was elevated in fronto-parietal regions relative to sPTLD (p < .0025) and HC (p < .001). Notably, 64 % of activation clusters in RTH were in white matter, confirmed by segmentation analysis. FMRI-guided ROI values from RTH vs. HC correlated with higher health survey scores. At 6-months, few group differences remained. By contrast, sPTLD vs. HC fMRI comparisons yielded few activation differences at either time point or correlations with health survey scores.
Robust brain activity in early LD was associated with future RTH. By contrast, the absence of early brain activity was associated with persistent symptoms, suggesting that failure to mount an early response contributes to PTLD. Understanding how brain activity relates to recovery in LD can aid prognosis and guide treatment.
在莱姆病（LD）中，10 - 20%的患者在抗生素治疗后出现持续症状（即治疗后莱姆病（PTLD）），通常包括神经系统症状。本研究验证了脑生理变化发生在LD早期并影响预后的假设。对20例急性LD患者（n = 20）在治疗后和6个月后进行任务型功能磁共振成像（fMRI）和健康调查。人口统计学匹配的健康对照（HC, n = 19）也相隔6个月进行评估。LD组在6个月时被分为恢复健康（RTH, n = 11）和报告持续症状（sPTLD, n = 9）。两个LD亚组的FMRI数据相互比较，并在两个时间点对HC进行比较。将fmri引导的感兴趣区域（ROI）值与健康调查进行比较。与sPTLD和HC相比，RTH的额顶叶区基线脑活动升高（p < .001）。值得注意的是，通过分割分析，RTH中64%的激活簇位于白质中。fmri引导下RTH与HC的ROI值与较高的健康调查得分相关。6个月时，几乎没有组间差异。相比之下，sPTLD与HC的fMRI比较在任何时间点或与健康调查分数的相关性上都没有什么激活差异。LD早期活跃的大脑活动与未来的RTH相关。相比之下，早期大脑活动的缺乏与持续症状有关，这表明未能形成早期反应有助于PTLD的发生。了解脑活动与LD恢复的关系有助于预后和指导治疗。
{"title":"Early brain changes in Lyme disease are associated with clinical outcomes","authors":"Cherie L. Marvel , Alison W. Rebman , Kylie H. Alm , Pegah Touradji , Arnold Bakker , Prianca A. Nadkarni , Deeya Bhattacharya , Owen P. Morgan , Amy Mistri , Christopher C. Sandino , Jonathan A. Ecker , Erica A. Kozero , Arun Venkatesan , Abhay Moghekar , Ashar A. Keeys , John N. Aucott","doi":"10.1016/j.bbih.2025.101153","DOIUrl":"10.1016/j.bbih.2025.101153","url":null,"abstract":"<div><div>In Lyme disease (LD), 10–20 % of patients develop persistent symptoms following antibiotic treatment (i.e., post-treatment Lyme disease (PTLD)), which often includes neurological symptoms. This study tested the hypothesis that physiological brain changes occur early in LD and influence outcomes.</div><div>Task-based functional MRI (fMRI) and health surveys were administered to patients with acute LD (n = 20) after treatment and six months later. Demographically matched healthy controls (HC; n = 19) were also assessed six months apart. The LD group was categorized at six months into those who had returned to health (RTH, n = 11) or reported persistent symptoms (sPTLD, n = 9). FMRI data from both LD subgroups were compared to each other and HC at both time points. FMRI-guided regions of interest (ROI) values were compared to health surveys.</div><div>Baseline brain activity in RTH was elevated in fronto-parietal regions relative to sPTLD (p < .0025) and HC (p < .001). Notably, 64 % of activation clusters in RTH were in white matter, confirmed by segmentation analysis. FMRI-guided ROI values from RTH vs. HC correlated with higher health survey scores. At 6-months, few group differences remained. By contrast, sPTLD vs. HC fMRI comparisons yielded few activation differences at either time point or correlations with health survey scores.</div><div>Robust brain activity in early LD was associated with future RTH. By contrast, the absence of early brain activity was associated with persistent symptoms, suggesting that failure to mount an early response contributes to PTLD. Understanding how brain activity relates to recovery in LD can aid prognosis and guide treatment.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101153"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684160","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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