Sudden Cardiac Death in Schizophrenia During Hospitalization: An Autopsy-Based Study

Zhang²,

et al. 2023

Front. Neurol.

Self Cite

Epilepsy is a common neurological disorder that is associated with increased morbidity and mortality. Sudden unexpected death in epilepsy (SUDEP) is one of the most common causes for epilepsy-related deaths and its characteristics remain largely unknown, particularly from a forensic autopsy perspective. The present study aimed to investigate the neurological, cardiac, and pulmonary findings for a total of 388 SUDEP decedents, encompassing three cases from our forensic center during 2011–2020 and 385 literature-reported autopsy cases. In the cases mentioned in this study, two of them presented with only mild cardiac abnormalities, such as focal myocarditis and mild coronary atherosclerosis of the left anterior coronary artery. The third one was negative of any pathological findings. After pooling together these SUDEP cases, we found that neurological changes (n = 218 cases, 56.2%) were the most common postmortem findings associated with SUDEP, with cerebral edema/congestion (n = 60 cases, 15.5%) and old traumatic brain injury (n = 58 cases, 14.9%) being the major findings. Interstitial fibrosis, myocyte disarray/hypertrophy, and mild coronary artery atherosclerosis were the most common findings related to primary cardiac pathology, documented in 49 (12.6%), 18 (4.6%), and 15 (3.9%) cases, respectively. Non-specific pulmonary edema was the major finding in the lungs. This is an autopsy-based study that reports the scenario of postmortem findings for SUDEP cases. Our study paves the way for understanding the pathogenesis of SUDEP and the interpretation of death.

Section: Methodsmentioning

confidence: 98%

Sudden unexpected death in epilepsy: Investigation of autopsy-based studies

Zhang²,

et al. 2023

Front. Neurol.

Self Cite

“…Being affected by SCZ predicts a shorter lifespan, by 10–15 years compared to the general population ( Kirkpatrick et al, 2008 ), with a mortality rate that is ∼10 times higher than in age-matched controls ( Lindqvist et al, 2015 ). An autopsy-based study showed that 77.8% of admitted decadents died of sudden cardiac death such as myocarditis, cardiomyopathy, coronary artery atherosclerosis, and pulmonary thromboembolism ( Chen et al, 2022 ). However, other causes of death were also mentioned, including respiratory inflammation and hepatic steatosis ( Chen et al, 2022 ), as well as antipsychotic type such as risperidone and flupentixol owing to their blocking effects of cardiac potassium channel encrypted by the human Ether-à-go-go-related gene (hERG) ( van Noord et al, 2011 ; Chen et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…An autopsy-based study showed that 77.8% of admitted decadents died of sudden cardiac death such as myocarditis, cardiomyopathy, coronary artery atherosclerosis, and pulmonary thromboembolism ( Chen et al, 2022 ). However, other causes of death were also mentioned, including respiratory inflammation and hepatic steatosis ( Chen et al, 2022 ), as well as antipsychotic type such as risperidone and flupentixol owing to their blocking effects of cardiac potassium channel encrypted by the human Ether-à-go-go-related gene (hERG) ( van Noord et al, 2011 ; Chen et al, 2020 ). One pathomechanistic reason identified between the increased death rates, and cardiovascular dysfunctions, was suggested to include the presence of altered levels of the immune-active gut-bacterial derived metabolite, trimethylamine N -oxide (TMAO), notably involved in the exacerbation of neuropsychiatric diseases characterized by vascular senescence, reduced capacity to regenerate hematopoietic system, and accelerated aging ( Zeisel and Warrier, 2017 ; Ke et al, 2018 ; Li et al, 2018 ; Chen et al, 2019 ; Brunt et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia

Ben-Azu

VanderZwaag

et al. 2023

Front. Cell. Neurosci.

Brain aging, which involves a progressive loss of neuronal functions, has been reported to be premature in probands affected by schizophrenia (SCZ). Evidence shows that SCZ and accelerated aging are linked to changes in epigenetic clocks. Recent cross-sectional magnetic resonance imaging analyses have uncovered reduced brain reserves and connectivity in patients with SCZ compared to typically aging individuals. These data may indicate early abnormalities of neuronal function following cyto-architectural alterations in SCZ. The current mechanistic knowledge on brain aging, epigenetic changes, and their neuropsychiatric disease association remains incomplete. With this review, we explore and summarize evidence that the dynamics of gut-resident bacteria can modulate molecular brain function and contribute to age-related neurodegenerative disorders. It is known that environmental factors such as mode of birth, dietary habits, stress, pollution, and infections can modulate the microbiota system to regulate intrinsic neuronal activity and brain reserves through the vagus nerve and enteric nervous system. Microbiota-derived molecules can trigger continuous activation of the microglial sensome, groups of receptors and proteins that permit microglia to remodel the brain neurochemistry based on complex environmental activities. This remodeling causes aberrant brain plasticity as early as fetal developmental stages, and after the onset of first-episode psychosis. In the central nervous system, microglia, the resident immune surveillance cells, are involved in neurogenesis, phagocytosis of synapses and neurological dysfunction. Here, we review recent emerging experimental and clinical evidence regarding the gut-brain microglia axis involvement in SCZ pathology and etiology, the hypothesis of brain reserve and accelerated aging induced by dietary habits, stress, pollution, infections, and other factors. We also include in our review the possibilities and consequences of gut dysbiosis activities on microglial function and dysfunction, together with the effects of antipsychotics on the gut microbiome: therapeutic and adverse effects, role of fecal microbiota transplant and psychobiotics on microglial sensomes, brain reserves and SCZ-derived accelerated aging. We end the review with suggestions that may be applicable to the clinical setting. For example, we propose that psychobiotics might contribute to antipsychotic-induced therapeutic benefits or adverse effects, as well as reduce the aging process through the gut-brain microglia axis. Overall, we hope that this review will help increase the understanding of SCZ pathogenesis as related to chronobiology and the gut microbiome, as well as reveal new concepts that will serve as novel treatment targets for SCZ.

“…Embora seja bem reconhecido que os indivíduos com esse transtorno morrem prematuramente em comparação com a população em geral, (2 a 3 vezes maior chance de morte), as razões para a diferença de expectativa de vida estimada entre 15 a 20 anos não são claras, mas alguns autores citam relação com morte não natural, incluindo suicídios, acidentes, violência e abuso de substâncias. Um número considerável de pacientes morre de causas naturais, como doença cardiovascular (DCV), câncer, diabetes e doenças pulmonares (CAO; MENG; LI;MA et al, 2020;WANG et al, 2022;CORRELL;CROATTO;SCHNEIDER et al, 2022;.Estudos populacionais, incluindo estudos de gêmeos e familiares, indicam que a esquizofrenia é altamente hereditária e envolve a interação sinérgica de múltiplos genes e fatores ambientais (PEREZ-COSTAS; MELENDEZ-FERRO; ROBERTS, 2010). De acordo com alguns autores, tal doença, com forte componente genético, possui uma herdabilidade de aproximadamente 80 a 85% (BRENNAND; SIMONE; JOU;CAO;MENG;MA et al, 2020;GREENE;KEALY;HUMPHRIES;GONG et al, 2018;,desagradáveise onerosos em vários sentidos, como a ocorrência de dormência emocional, distúrbios do movimento e distúrbios funcionais de diversos órgãos, que podem levar ao desenvolvimento de síndrome metabólica, diabetes e DCV.…”

unclassified

“…Em contrapartida, segundoAndrade (2015), Bleuler em 1911, em suas observações reconheceu que a esquizofrenia não acometia apenas jovens, e sim indivíduos até 54 anos de idade, e mulheres cinco anos mais tarde(ANDRADE, 2015). Os sintomas da esquizofrenia podem ser divididos em três categorias: positivos (alucinações, delírios, hostilidade e SHYUE; HSU;LEE, 2018;WANG et al, 2022;FREEDMAN, 2003;LODGE;GRACE, 2011; MEDNOVA et al, Fonte:…”

unclassified

Efeitos do antipsicótico olanzapina na reatividade in vitro da aorta torácica de ratos

Prandi¹

AgradecimentoA Deus, por acalmar meu coração e me manter conectada ao universo.Ao meu marido Oswaldo José Gola (in memoriam), que sempre motivou minha jornada como colaboradora da ciência.Aos meus pais Alzira R. Prandi (in memoriam) e Orany José Prandi pelos ensinamentos e amor.Às minhas irmãs Elaine e Roselaine pelo amor, carinho e ajuda, e principalmente minha amada irmã Joselaine que, por sua existência e amor nunca soltou das minhas mãos nos momentos que me deparava com meu próprio abismo.Aos meus filhos, Melmoara, Jade e Ianco, que me ajudaram e tiveram paciência nos momentos mais difíceis durante esse processo.Ao meu neto António, que só pelo fato de existir, me faz amar mais a vida.Ao meu orientador professor Paulo Roberto Barbosa Evora, pelo carinho e dedicação durante esses anos de pesquisa.À professora Andréa Carla Celotto pela força, ensinamento e ajuda, acrescentando conhecimentos a cada nova etapa dessa pesquisa. Aos amigos que fiz aqui e levarei para vida toda, Jéssyca, Carlos, Cecília, Claudinha e Tauana, que foram fundamentais nos momentos de alegria e tristeza, me acalentando e ajudando a clarear o caminho. Ao mestre Willian Márcio da Silva por me mostrar sempre o caminho das pedras. À minha amiga Marielen Ronconi por ajudar a lembrar de mim mesma quando eu me esquecia. À secretária do Departamento de Cirurgia e Anatomia da FMRP Juliana Pischiottin da Silva Moraes, que sempre me orientou com clareza, atenção e dedicação. À amiga Vanessa S. Nakagi, uma amiga que levo para vida. Conte sempre comigo. Ao biotério Central da FMRP, principalmente ao Renaldo, nos proporcionando os ratos necessários para desenvolver essa pesquisa. Estávamos no ápice da pandemia Covid-19.À profissional e amiga Agnes Afrodite S. Albuquerque Fagundes, técnica do laboratório de Cirurgia Cardiovascular. Só tenho a agradecer de todo coração pela amizade, entrega e dedicação. Sem você nada aconteceria, dominou toda técnica necessária para que o funcionamento de todos instrumentos e materiais mantivessem sincronicidade.Agradeço aos animais, ratos hannover, pois sem eles essa pesquisa não seria possível.