Pub Date : 2025-07-14DOI: 10.1038/s41582-025-01116-4
Michael Maes, Abbas F. Almulla, Zili You, Yingqian Zhang
This Review examines the role of neuroimmune imbalances and their relationship with metabolism and oxidative stress in the development and progression of major depressive disorder (MDD) and suicidal behaviours. We provide a concise overview of the neuroinflammatory environment and indicators of neuronal injury in the central nervous system of individuals with MDD. Furthermore, we explore the evidence for perturbations in both the peripheral and central immune system, T cell activation versus T regulatory cell depletion, intracellular signalling networks including nuclear factor-κB, lipid metabolism and neuroprotection. Last, we examine the mechanisms by which psychological stressors, translocation of Gram-negative bacteria, viral infections such as SARS-CoV-2 and metabolic syndrome can contribute to neuroimmune imbalances and, consequently, the acute phase of MDD. In this Review, the authors describe perturbations in neuroimmune, metabolic and oxidative pathways in major depressive disorder and explore how imbalances in each of these pathways can contribute to the acute phase of the disease.
{"title":"Neuroimmune, metabolic and oxidative stress pathways in major depressive disorder","authors":"Michael Maes, Abbas F. Almulla, Zili You, Yingqian Zhang","doi":"10.1038/s41582-025-01116-4","DOIUrl":"10.1038/s41582-025-01116-4","url":null,"abstract":"This Review examines the role of neuroimmune imbalances and their relationship with metabolism and oxidative stress in the development and progression of major depressive disorder (MDD) and suicidal behaviours. We provide a concise overview of the neuroinflammatory environment and indicators of neuronal injury in the central nervous system of individuals with MDD. Furthermore, we explore the evidence for perturbations in both the peripheral and central immune system, T cell activation versus T regulatory cell depletion, intracellular signalling networks including nuclear factor-κB, lipid metabolism and neuroprotection. Last, we examine the mechanisms by which psychological stressors, translocation of Gram-negative bacteria, viral infections such as SARS-CoV-2 and metabolic syndrome can contribute to neuroimmune imbalances and, consequently, the acute phase of MDD. In this Review, the authors describe perturbations in neuroimmune, metabolic and oxidative pathways in major depressive disorder and explore how imbalances in each of these pathways can contribute to the acute phase of the disease.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 9","pages":"473-489"},"PeriodicalIF":33.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-11DOI: 10.1038/s41582-025-01104-8
Chinedu T. Udeh-Momoh, Celeste A. de Jager Loots, Tamlyn J. Watermeyer, Udunna C. Anazodo, Catherine Ajalo, Edna N. Bosire, Ameenah Sorefan, Christine Musyimi, Chido Rwafa, Njideka Okubadejo, Miia Kivipelto
Global dementia cases are rising, particularly in low- and middle-income countries with limited health-care access and scarce resources, calling for preventive strategies that align with local capital and cultural practices. The Africa-FINGERS project, an adaptation of the Finnish FINGER trial, pioneers a culturally relevant, multidomain approach to dementia risk reduction for African settings. This Perspective article explores the efficacy of multimodal lifestyle interventions in reducing risks associated with cognitive decline, addressing the unique challenges involved and examining opportunities for implementing such programmes in Africa. Drawing on preliminary insights from ongoing implementation efforts in Africa and lessons from the World Wide FINGERS global network, we describe a standardized, evidence-based precision brain health model that aims to dynamically and equitably optimize protective factors for brain health in Africa. This model is tailored to accommodate the diverse cultural, socioeconomic and logistical contexts of Africa, emphasizing culturally adapted, scalable and resource-sensitive solutions for sustainable implementation. Building on the successful execution of regional lifestyle-based interventions for other non-communicable diseases, we highlight the potential of the Africa-FINGERS programme to improve brain health and mitigate dementia risks across diverse global settings. This Perspective article explores the efficacy of multimodal lifestyle interventions to tackle the rising incidence of dementia in low- and middle-income countries. The authors discuss a contextual adaptation of the Finnish FINGER trial, Africa-FINGERS, which is pioneering a culturally relevant, multidomain approach to dementia risk reduction for African settings.
{"title":"Translating lifestyle interventions for optimal brain health in Africa","authors":"Chinedu T. Udeh-Momoh, Celeste A. de Jager Loots, Tamlyn J. Watermeyer, Udunna C. Anazodo, Catherine Ajalo, Edna N. Bosire, Ameenah Sorefan, Christine Musyimi, Chido Rwafa, Njideka Okubadejo, Miia Kivipelto","doi":"10.1038/s41582-025-01104-8","DOIUrl":"10.1038/s41582-025-01104-8","url":null,"abstract":"Global dementia cases are rising, particularly in low- and middle-income countries with limited health-care access and scarce resources, calling for preventive strategies that align with local capital and cultural practices. The Africa-FINGERS project, an adaptation of the Finnish FINGER trial, pioneers a culturally relevant, multidomain approach to dementia risk reduction for African settings. This Perspective article explores the efficacy of multimodal lifestyle interventions in reducing risks associated with cognitive decline, addressing the unique challenges involved and examining opportunities for implementing such programmes in Africa. Drawing on preliminary insights from ongoing implementation efforts in Africa and lessons from the World Wide FINGERS global network, we describe a standardized, evidence-based precision brain health model that aims to dynamically and equitably optimize protective factors for brain health in Africa. This model is tailored to accommodate the diverse cultural, socioeconomic and logistical contexts of Africa, emphasizing culturally adapted, scalable and resource-sensitive solutions for sustainable implementation. Building on the successful execution of regional lifestyle-based interventions for other non-communicable diseases, we highlight the potential of the Africa-FINGERS programme to improve brain health and mitigate dementia risks across diverse global settings. This Perspective article explores the efficacy of multimodal lifestyle interventions to tackle the rising incidence of dementia in low- and middle-income countries. The authors discuss a contextual adaptation of the Finnish FINGER trial, Africa-FINGERS, which is pioneering a culturally relevant, multidomain approach to dementia risk reduction for African settings.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 8","pages":"449-460"},"PeriodicalIF":33.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-11DOI: 10.1038/s41582-025-01121-7
Paul M. Brennan, Graham M. Teasdale
A consensus recommendation has been made for a new classification system for traumatic brain injury. The new system adds complexity that might not benefit clinical decision making compared with the gold-standard Glasgow Coma Scale. Brennan and Teasdale compare a newly proposed classification system for traumatic brain injury with the gold-standard Glasgow Coma Scale.
{"title":"Challenges of combining multimodal data in assessment of people with traumatic brain injury","authors":"Paul M. Brennan, Graham M. Teasdale","doi":"10.1038/s41582-025-01121-7","DOIUrl":"10.1038/s41582-025-01121-7","url":null,"abstract":"A consensus recommendation has been made for a new classification system for traumatic brain injury. The new system adds complexity that might not benefit clinical decision making compared with the gold-standard Glasgow Coma Scale. Brennan and Teasdale compare a newly proposed classification system for traumatic brain injury with the gold-standard Glasgow Coma Scale.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 9","pages":"469-470"},"PeriodicalIF":33.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-08DOI: 10.1038/s41582-025-01122-6
Heather Wood
A voice-synthesis neuroprosthesis based on a brain–computer interface has restored instantaneous, natural-sounding speech to a man with amyotrophic lateral sclerosis.
一种基于脑机接口的语音合成神经假体使一名肌萎缩侧索硬化症患者恢复了即时、自然的语言。
{"title":"Brain–computer interface restores naturalistic speech to a man with ALS","authors":"Heather Wood","doi":"10.1038/s41582-025-01122-6","DOIUrl":"10.1038/s41582-025-01122-6","url":null,"abstract":"A voice-synthesis neuroprosthesis based on a brain–computer interface has restored instantaneous, natural-sounding speech to a man with amyotrophic lateral sclerosis.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 8","pages":"409-409"},"PeriodicalIF":33.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-25DOI: 10.1038/s41582-025-01112-8
Philipp Karschnia, Jörg Dietrich
Genetically engineered chimeric antigen receptor (CAR) T cells have emerged as a powerful treatment option in patients with B cell malignancies, but neurological adverse effects are common and hamper the success of such therapies. Immune effector cell-associated neurotoxicity syndrome encompasses a wide range of acute neurological adverse effects, including encephalopathy with alterations in cognition and behaviour, language, motor function and coordination. In patients treated with CAR T cells for CNS malignancies, a more localized on-tumour, on-target neurotoxicity syndrome termed tumour inflammation-associated neurotoxicity can develop acutely, resulting in localized oedema with mass effect or in electrophysiological dysfunction with neurological symptoms. Following B cell maturation antigen-targeting CAR T cell therapies, delayed neurological complications, including cranial nerve palsies and a unique delayed-onset parkinsonism syndrome, are increasingly recognized. Management of neurological complications includes symptomatic treatments such as antiepileptic drugs or cerebrospinal fluid diversion, temporary immunosuppression with corticosteroids, various cytokine-targeting agents, and other distinct approaches depending on the nature of the toxicity. As our understanding of the mechanisms that contribute to the various neurological adverse effects of CAR T cell and other T cell-engaging therapies increases, novel treatment strategies to alleviate symptoms, as well as innovative CAR designs, promise to improve the safety and neurotoxicity of these powerful immunotherapies. Chimeric antigen receptor (CAR) T cells provide an effective treatment option for advanced haematological malignancies, but neurological adverse effects of CAR T cell therapies are common. This article reviews current knowledge regarding the mechanisms that contribute to neurological toxicities following CAR T cell therapy and highlights current and emerging management strategies.
{"title":"Neurological complications of CAR T cell therapy for cancers","authors":"Philipp Karschnia, Jörg Dietrich","doi":"10.1038/s41582-025-01112-8","DOIUrl":"10.1038/s41582-025-01112-8","url":null,"abstract":"Genetically engineered chimeric antigen receptor (CAR) T cells have emerged as a powerful treatment option in patients with B cell malignancies, but neurological adverse effects are common and hamper the success of such therapies. Immune effector cell-associated neurotoxicity syndrome encompasses a wide range of acute neurological adverse effects, including encephalopathy with alterations in cognition and behaviour, language, motor function and coordination. In patients treated with CAR T cells for CNS malignancies, a more localized on-tumour, on-target neurotoxicity syndrome termed tumour inflammation-associated neurotoxicity can develop acutely, resulting in localized oedema with mass effect or in electrophysiological dysfunction with neurological symptoms. Following B cell maturation antigen-targeting CAR T cell therapies, delayed neurological complications, including cranial nerve palsies and a unique delayed-onset parkinsonism syndrome, are increasingly recognized. Management of neurological complications includes symptomatic treatments such as antiepileptic drugs or cerebrospinal fluid diversion, temporary immunosuppression with corticosteroids, various cytokine-targeting agents, and other distinct approaches depending on the nature of the toxicity. As our understanding of the mechanisms that contribute to the various neurological adverse effects of CAR T cell and other T cell-engaging therapies increases, novel treatment strategies to alleviate symptoms, as well as innovative CAR designs, promise to improve the safety and neurotoxicity of these powerful immunotherapies. Chimeric antigen receptor (CAR) T cells provide an effective treatment option for advanced haematological malignancies, but neurological adverse effects of CAR T cell therapies are common. This article reviews current knowledge regarding the mechanisms that contribute to neurological toxicities following CAR T cell therapy and highlights current and emerging management strategies.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 8","pages":"422-431"},"PeriodicalIF":33.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-24DOI: 10.1038/s41582-025-01114-6
Georg Starke, Marcello Ienca
Artificial intelligence and neurotechnology promise to transform neurological care, but their acceptance will depend on public trust. Such trust must be earned and maintained through responsible development, transparent reporting, public engagement and ethical oversight. Without these foundations, even highly beneficial technologies may fail to gain legitimacy or uptake.
{"title":"AI, neurotechnology and society — a question of trust","authors":"Georg Starke, Marcello Ienca","doi":"10.1038/s41582-025-01114-6","DOIUrl":"10.1038/s41582-025-01114-6","url":null,"abstract":"Artificial intelligence and neurotechnology promise to transform neurological care, but their acceptance will depend on public trust. Such trust must be earned and maintained through responsible development, transparent reporting, public engagement and ethical oversight. Without these foundations, even highly beneficial technologies may fail to gain legitimacy or uptake.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 8","pages":"407-408"},"PeriodicalIF":33.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-21DOI: 10.1038/s41582-025-01106-6
Ambra Stefani, Diego A. Golombek
Aspects of modern society, such as artificial lighting and rigid schedules, create ‘social jetlag’ — a mismatch between biological chronotypes and societal demands. This circadian misalignment particularly affects evening chronotypes, leading to sleep deprivation, mental health issues and physical disorders. Flexible schedules and environmental modifications could restore natural sleep patterns and improve well-being.
{"title":"Influence of sleep and chronotypes: are we adapted to today’s society?","authors":"Ambra Stefani, Diego A. Golombek","doi":"10.1038/s41582-025-01106-6","DOIUrl":"10.1038/s41582-025-01106-6","url":null,"abstract":"Aspects of modern society, such as artificial lighting and rigid schedules, create ‘social jetlag’ — a mismatch between biological chronotypes and societal demands. This circadian misalignment particularly affects evening chronotypes, leading to sleep deprivation, mental health issues and physical disorders. Flexible schedules and environmental modifications could restore natural sleep patterns and improve well-being.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 8","pages":"405-406"},"PeriodicalIF":33.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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