Naturalistic comparison of clomethiazole and Diazepam treatment in alcohol withdrawal: effects on oxidative stress, inflammatory cytokines and hepatic biomarkers.

Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3-5 days. Hence, our hypothesis was not confirmed during this observation period.

Possible temporal relationship between SARS-CoV-2 infection and anti-NMDA receptor encephalitis: a meta-analysis.

The global impact of SARS-CoV-2 infection has raised concerns about secondary diseases beyond acute illness. This review explores the significance and potential underlying mechanisms of how SARS-CoV-2 infection might elicit an immune response targeting N-methyl-D-aspartate (NMDA) receptors, and its implications for autoimmune-driven neuropsychiatric manifestations. We identified 19 published case reports of NMDA receptor encephalitis associated with SARS-CoV-2 infection or vaccination by a systematic literature search. The significance of these reports was limited since it is not clear if a coincidental or causal relationship exists between SARS-CoV-2 infection or vaccination and manifestation of NMDA receptor encephalitis. The included studies were hampered by difficulties in establishing if these patients had pre-existing NMDA receptor antibodies which entered the brain by infection- or vaccination-associated transient blood-brain barrier leakage. In addition, four cases had comorbid ovarian teratoma, which is a known trigger for development of NMDA receptor encephalitis. Considering that billions of people have contracted COVID-19 or have been vaccinated against this virus, the publication of only 19 case reports with a possible link to NMDA receptor encephalitis, indicates that it is rare. In conclusion, these findings do not support the case that SARS-CoV-2 infection or vaccination led to an increase of existing or de novo encephalitis mediated by an autoimmune response targeting NMDA receptor function. Nevertheless, this work underscores the importance of ongoing vigilance in monitoring viral outbreaks and their potential impact on the central nervous system through basic, epidemiological and translational research.

Maximizing Analytical Performance in Biomolecular Discovery with LC-MS: Focus on Psychiatric Disorders.

In this review, we discuss the cutting-edge developments in mass spectrometry proteomics and metabolomics that have brought improvements for the identification of new disease-based biomarkers. A special focus is placed on psychiatric disorders, for example, schizophrenia, because they are considered to be not a single disease entity but rather a spectrum of disorders with many overlapping symptoms. This review includes descriptions of various types of commonly used mass spectrometry platforms for biomarker research, as well as complementary techniques to maximize data coverage, reduce sample heterogeneity, and work around potentially confounding factors. Finally, we summarize the different statistical methods that can be used for improving data quality to aid in reliability and interpretation of proteomics findings, as well as to enhance their translatability into clinical use and generalizability to new data sets.

Soluble terminal complement complex blood levels are elevated in schizophrenia.

The role of the complement system in schizophrenia (Sz) is inconclusive due to heterogeneity of the disease and study designs. Here, we assessed the levels of complement activation products and functionality of the classical pathway in acutely ill unmedicated Sz patients at baseline and after 6 weeks of treatment versus matched controls. The study included analyses of the terminal complement complex (sTCC) and C5a in plasma from 96 patients and 96 controls by enzyme-linked immunosorbent assay. Sub-group analysis of serum was conducted for measurement of C4 component and activity of the classical pathway (28 and 24 cases per cohort, respectively). We found no differences in levels of C5a, C4 and classical pathway function in patients versus controls. Plasma sTCC was significantly higher in patients [486 (392-659) ng/mL, n = 96] compared to controls [389 (304-612) ng/mL, n = 96] (p = 0.027, δ = 0.185), but not associated with clinical symptom ratings or treatment. The differences in sTCC between Sz and controls were confirmed using an Aligned Rank Transformation model considering the covariates age and sex (p = 0.040). Additional analysis showed that sTCC was significantly associated with C-reactive protein (CRP; p = 0.006). These findings suggest that sTCC plays a role in Sz as a trait marker of non-specific chronic immune activation, as previously described for CRP. Future longitudinal analyses with more sampling time points from early recognition centres for psychoses may be helpful to better understand the temporal dynamics of innate immune system changes during psychosis development.

Digital technology and mental health during the COVID-19 pandemic: a narrative review with a focus on depression, anxiety, stress, and trauma.

The sudden appearance and devastating effects of the COVID-19 pandemic resulted in the need for multiple adaptive changes in societies, business operations and healthcare systems across the world. This review describes the development and increased use of digital technologies such as chat bots, electronic diaries, online questionnaires and even video gameplay to maintain effective treatment standards for individuals with mental health conditions such as depression, anxiety and post-traumatic stress syndrome. We describe how these approaches have been applied to help meet the challenges of the pandemic in delivering mental healthcare solutions. The main focus of this narrative review is on describing how these digital platforms have been used in diagnostics, patient monitoring and as a treatment option for the general public, as well as for frontline medical staff suffering with mental health issues.

Testes sanguíneos de biomarcadores para diagnóstico e tratamento de desordens mentais: foco em esquizofrenia / Biomarker blood tests for diagnosis and management of mental disorders: focus on schizophrenia

A descoberta e a aplicação clínica de biomarcadores para desordens mentais são confrontadas com muitos desafios. Em geral, os atuais métodos de descoberta e validação de biomarcadores não produziram os resultados que foram inicialmente aguardados depois da finalização do Projeto Genoma Humano. Isso se deve principalmente à falta de processos padronizados conectando a descoberta de marcadores com tecnologias para a validação e a tradução para uma plataforma que ofereça precisão e fácil uso em clínica. Como consequência, a maior parte dos psiquiatras e praticantes em geral são relutantes em aceitar que testes de biomarcadores pode suplementar ou substituir os métodos de diagnóstico utilizados baseados em entrevista. Apesar disso, agências regulatórias concordam agora que melhoras nos correntes métodos são essenciais. Além disso, essas agências estipularam que biomarcadores são importantes para o desenvolvimento de futuras drogas e iniciaram esforços no sentido de modernizar métodos e técnicas para suportar esses esforços. Aqui revisamos os desafios encontrados por essa tentativa do ponto de vista de psiquiatras, praticantes em geral, agências reguladoras e cientistas de biomarcadores. Também descrevemos o desenvolvimento de um novo teste sanguíneo molecular para esquizofrenia como um primeiro passo a esse objetivo

The discovery and clinical application of biomarkers for mental disorders is faced with many challenges. In general, the current methods for discovery and validation of biomarkers have not produced the results which were first anticipated after completion of the human genome project. This is mostly due to the lack of a standardized pipeline connecting marker discovery with technologies for validation and translation to a platform that offers accuracy and ease of use in a clinical setting. As a consequence, most psychiatrists and general practitioners are still reluctant to accept that biomarker tests can supplement or replace the long standing interview-based methods for diagnosis. Despite this, the regulatory agencies now agree that improvements over the current methods are essential. Furthermore, these agencies stipulate that biomarkers are important for future drug development and have initiated efforts to modernize methods and techniques to support these efforts. Here, we review the challenges faced by this endeavour from the point of view of psychiatrists, general practitioners, the regulatory agencies and biomarker scientists. We also describe the development of a novel molecular blood-test for schizophrenia as a first promising step towards achieving this goal

Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia / The effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in subjects with schizophrenia

Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA). Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica

Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition

Explorando o componente inflamatório da esquizofrenia / Targeting the inflammatory component of schizophrenia

A esquizofrenia é uma doença heterogênea caracterizada por um conjunto de manifestações clínicas. Um grande número de estudos ao longo dos últimos 20 anos apontou para anormalidades no sistema imune em pacientes que sofrem dessa condição. Em adição, tem sido mostrado que a psicose e a disfunção cognitiva associadas com a esquizofrenia estão ligadas a doenças autoimunes. Aqui, revisamos a evidência que sugere que um status pró-inflamatório do sistema imune induz sintomas psicopatológicos e pode estar envolvido na fisiopatologia dessa principal doença mental. Também propomos que futuros estudos pré-clínicos e clínicos deveriam levar em conta tais causas predefinidas e o status do componente inflamatório. Estratificação de pacientes e estratégias de medicina personalizadas baseadas no direcionamento ao componente inflamatório da doença poderiam ajudar na redução de sintomas e da progressão da doença. Por fim, isso poderia levar a novos conceitos na identificação de alvos moleculares em esquizofrenia e estratégias de descoberta de drogas

Schizophrenia is a heterogeneous disease characterised by an array of clinical manifestations. A large number of studies over the last 20 years have pointed towards immune system abnormalities in patients suffering from this condition. In addition, the psychosis and cognitive dysfunction associated with schizophrenia have been shown to be linked with autoimmune diseases. Here, we review the evidence, which suggests that a pro-inflammatory status of the immune system induces psychopathologic symptoms and may be involved in the pathophysiology of this major mental illness. We also propose that future preclinical and clinical studies should take such pre-defined causes and the dynamic status of the inflammatory component into account. Patient stratification and personalised medicine strategies based on targeting the inflammatory component of the disease could help in alleviation of symptoms and slowing disease progression. Ultimately, this could also lead to novel concepts in schizophrenia target/molecular identification and drug discovery strategies

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento / Translational neuropsychiatry of genetic and neurodevelopmental animal models of schizophrenia

Sintomas psiquiátricos são subjetivos por natureza e tendem a se sobrepor entre diferentes desordens. Sendo assim, a criação de modelos de uma desordem neuropsiquiátrica encontra desafios pela falta de conhecimento dos fundamentos da fisiopatologia e diagnósticos precisos. Modelos animais são usados para testar hipóteses de etiologia e para representar a condição humana tão próximo quanto possível para aumentar nosso entendimento da doença e avaliar novos alvos para a descoberta de drogas. Nesta revisão, modelos animais genéticos e de neurodesenvolvimento de esquizofrenia são discutidos com respeito a achados comportamentais e neurofisiológicos e sua associação com a condição clínica. Somente modelos animais específicos de esquizofrenia podem, em último caso, levar a novas abordagens diagnósticas e descoberta de drogas. Argumentamos que biomarcadores moleculares são importantes para aumentar a tradução de animais a humanos, já que faltam a especificidade e a fidelidade necessárias às leituras comportamentais para avaliar sintomas psiquiátricos humanos

Psychiatric symptoms are subjective by nature and tend to overlap between different disorders. The modelling of a neuropsychiatric disorder therefore faces challenges because of missing knowledge of the fundamental pathophysiology and a lack of accurate diagnostics. Animal models are used to test hypotheses of aetiology and to represent the human condition as close as possible to increase our understanding of the disease and to evaluate new targets for drug discovery. In this review, genetic and neurodevelopmental animal models of schizophrenia are discussed with respect to behavioural and neurophysiological findings and their association with the clinical condition. Only specific animal models of schizophrenia may ultimately lead to novel diagnostic approaches and drug discovery. We argue that molecular biomarkers are important to improve animal to human translation since behavioural readouts lack the necessary specificity and reliability to assess human psychiatric symptoms