International review of neurobiology最新文献

Depressive disorders continue to pose a major clinical challenge worldwide, particularly given the high prevalence and increasing number of treatment-resistant cases. Over the past decade, advances in research have elucidated the antidepressant potential of psilocybin and other 5-HT₂A receptor agonists in patients with major depressive disorder (MDD) and treatment-resistant depression (TRD). Phase I and II clinical trials have consistently demonstrated that even a single administration can yield rapid and sustained symptom reduction. These effects compare favourably with conventional pharmacotherapies such as SSRIs and ketamine. The distinctive pharmacological profile and robust safety data associated with serotonergic psychedelics make them particularly promising candidates, especially for patients who do not respond to standard treatments. Nonetheless, several challenges impede their integration into routine clinical practice, including the resource-intensive nature of psychedelic-assisted therapy, which demands specialized training and controlled settings. Despite those limitations, some countries including Australia, Switzerland or Canada are paving the way by allowing the use of psilocybin in TRD cases. This chapter reviews the antidepressant potential of psilocybin, DMT, ayahuasca and 5-MeO-DMT based on modern clinical trial data, comparing effect sizes of psychedelics to conventional treatments like SSRIs and ketamine, and provides a brief overview of their potential neurobiological mechanisms.

Psychedelics are primarily recognized for their profound behavioral effects, leading most research on psychedelics and their primary target, the 5-HT_2A receptor, to focus on brain activity. However, these receptors are not only found within the brain and are present in nearly every tissue and cell type throughout the body, playing a significant role alongside serotonin in modulating various processes, including immune function. Serotonin acting at 5-HT_2A receptors generally promotes inflammation. Levels are elevated at sites of inflammation and through 5-HT_2A receptor activation lead to events including increased cytokine production, eosinophil recruitment, T-cell activation, and mast cell degranulation. Some psychedelics, but not all, have been found to have powerful anti-inflammatory and immunomodulatory effects through activation of 5-HT2A receptors in preclinical experimental systems and models of human inflammatory diseases. Human studies examining anti-inflammatory effects of psychedelics are limited but suggestive that psychedelics may represent a new strategy to treat inflammatory diseases. In this review we will present an overview of serotonergic modulation of immune function, the role of 5-HT2A receptors in these processes, and a summary of key findings with psychedelics with regards to anti-inflammatory efficacy.

In recent years, viral infections have been increasingly identified as major players in neuromuscular pathologies. This chapter presents an overview of the evidence and future directions for virus-induced neuromuscular disorders. Information is integrated on the global burden of these diseases related to epidemiology, clinical features, diagnosis, treatment, and preventive strategies was integrated. Responsible viruses include enteroviruses, flaviviruses, herpesviruses, and emerging pathogens such as SARS-CoV-2. It represents a broad spectrum of neuromuscular disorders, including Guillain-Barré syndrome, viral myositis, and critical illness neuropathy/myopathy. The book chapter discusses different diagnostic approaches, therapy strategies, and rehabilitation methods, in addition to early intervention and preventive measures. This has led to new insights into novel therapies, unmet research needs, and future perspectives on viral neuromuscular disorders. This chapter demonstrates that supporting both clinical care and patient management with clinical research entails a profound understanding of the difficult interactions between the viruses concerned and the neuromuscular system.

Bacterial meningitis is a severe infection that can lead to neuroinflammation, posing risks to the central nervous system (CNS). This inflammation, if uncontrolled, can cause long-term neurological damage, cognitive decline, and neuron injury. Management strategies include telemedicine and remote monitoring, enabling continuous observation and timely adjustments in treatment. Early detection through biosensor technology is vital, offering healthcare providers insights for proactive intervention before critical issues arise. Nutritional support, particularly hydration, is also emphasized to strengthen immune response and potentially delay disease progression. The chapter highlights the transformative potential of Artificial Intelligence (AI) and machine learning in disease management, from prognostic assessments to creating personalized treatment plans. By integrating AI-driven insights with advanced monitoring and preventive approaches, healthcare providers can mitigate the impact of bacterial meningitis, enhancing patient outcomes and recovery potential.

This chapter explores the intriguing and complex relationship between the human microbiome and Bipolar Disorder (BD). The microbiome, notably the gut microbiota, has been increasingly recognised as a key performer in brain health and disease. This is due to its role in the gut-brain axis, a bidirectional communication between the gastrointestinal tract and the central nervous system. Disruptions in the gut microbiota due to factors such as diet, and stress, may influence this axis and potentially trigger or exacerbate psychiatric conditions. Hence, we investigate into the present interpretation of the microbiome's role in mental health, concentrating on its impact on mood regulation and cognitive function. Consequently, we also explore the possible mechanisms through which microbiome disruption may pay to the behavioural changes observed in BD. Further exploration understand the complex interplay between the microbiome and BD and translate these findings into effective therapeutic plans.

Nearly 90 % of generalized myasthenia gravis (MG) patients have IgG1 or IgG3 antibodies against the acetylcholine receptor (AChR). Acetylcholine receptor antibodies induce neuromuscular transmission defect by various potential mechanisms including internalisation of AChR, receptor blockade and by activation of the classical complement pathway. Membrane attack complex (MAC) which is the final end product of complement activation leads to architectural destruction of the neuromuscular junction (NMJ). Several experimental models (EAMG) have shown evidence for complement in the pathogenesis of MG, with demonstration of prevention or reversal of the disease using complement inhibitory therapies. Various molecules that target the complement system have been developed to treat myasthenia gravis. Most of the currently studied molecules inhibit complement protein 5 (C5), which prevents the formation of MAC and subsequent NMJ destruction. The currently studied anti-complement therapies for MG include eculizumab, zilucoplan, ravulizumab, pozelimab, cemdisiran, gefurilimab, danicopan and few others in the pipeline. Many of these have also been shown to have long term benefit in different sub-groups of patients with MG. Given the risk of Gram-negative septicaemia (especially by meningococcus), patients would need vaccination prior to initiation of treatment and in some countries prophylactic antibiotics during treatment is recommended, although no major safety signatures have been noted in the studies so far. Future studies identifying specific biomarkers might help clinicians select the most appropriate patients who are more likely to respond to complement inhibitory therapies.

The role of non-pharmacological management in MG is currently underdeveloped and underutilized. Exercise training has been shown to be both feasible and beneficial in improving function and strength in individuals with MG. Observational studies indicate that physical activity is associated with reduced perceived fatigue. Barriers to exercise persist in MG, and should be addressed by healthcare professionals. Maintaining or increasing muscle strength and endurance as well as cardiorespiratory fitness should be prioritized regardless of current level of function. In the general population, exercise has the potential to reduce anxiety and depression although studies in MG are still lacking. Exercise programs should be individualized and progressive, with a clear emphasis on reducing sedentary behavior. Current research has primarily focused on individuals with mild-moderate MG. Further studies are needed to understand the potential impact of exercise training on enhancing pharmacological therapies and the potential role of exercise in immunomodulation in MG. This chapter reviews the existing literature on exercise in MG.

Treatment options for patients with myasthenia gravis (MG) are rapidly increasing. Seven new MG therapies across 2 novel classes have been approved by the FDA to treat MG; a robust treatment pipeline spans at least 7 novel therapeutic classes. International MG Consensus Guidance define successful treatments as those that result in minimal disease manifestations or remission with no more than minimal adverse events (AE). The MG community has a number of disease specific outcome measures to evaluate treatment response and patient quality of life. Treatment efficacy only represents one important way to assess treatment value; side effects, burden of therapy, and cost all reduce treatment value. Indeed, patients and clinicians both rate treatment safety as a key consideration when choosing among treatment options. Despite this concern, we have not established the best way to measure side effect burden in MG clinical trials or clinics. To date, the MG community has been focused on the negative side effects associated with corticosteroids, despite well documented, unique side effect profiles that are associated with both traditional and new generation non-steroid MG treatments, some of which can be serious and life threatening. Careful measurement of side effect burden and comparison of this burden among MG therapies will be critical as we attempt to optimize treatment for our patients. This chapter focuses on the importance of measuring MG treatment side effect burden and three measures that may facilitate measuring this burden in future comparative effectiveness trials and in the clinic.

Hypnosis research flourishes when competing theoretical models make testable predictions about significant psychological, physiological and clinical outcomes. Neurocomputational theories are currently unifying theory and research in these diverse domains and are poised to enter the field of hypnosis. Here we explore three current attempts to employ Bayesian predictive coding models to understand the mechanisms used to generate responses to hypnotic suggestions. Predictive coding is shown to be a framework able to generate multiple theorical explanations with testable predictions and distinct consequences for the growth of knowledge and clinical practice. Current theories of dissociated control, absorption and response expectancy can be modelled within this unifying framework. The unique Bayesian mechanism of Active Inference plays a central role in each of the accounts compared and testable neurophysiological predictions are drawn from each model. This provides a foundation for future research programs and successful grant funding to drive the next wave in the understanding of hypnotic suggestion, hypnotic responses and closely related social and clinical phenomena.

Human neuroimaging with functional Magnetic Resonance Imaging has been a key feature of the current wave of psychedelic research, in both healthy and clinical populations. The available data has suggested that classic psychedelics (psilocybin, LSD, DMT) have a characteristic effect of acutely and profoundly disrupting the normal pattern of resting-state connectivity in the human brain, and that this effect may be closely related to both the characteristic subjective phenomenology of psychedelics, and their more clinically-relevant longer-term effects on emotional brain systems. This chapter briefly outlines the basic methodological background of fMRI, and then provides an overview of the current state of knowledge of psychedelic drug action as revealed by task and resting-state fMRI, in both non-clinical and clinical cohorts. Current limitations of the field are largely addressable by ongoing and future work, particularly in terms of providing additional datasets, increased standardisation of data acquisition and analysis procedures, potential multi-modal imaging studies, and more open data-sharing. Neuroimaging with fMRI remains a central platform of modern psychedelic research, with implications for our mechanistic understanding of psychedelics, as well as a strong influence on the clinical development of psychedelic-based treatments.