International review of neurobiology最新文献

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric impairments caused by Huntingtin (HTT) gene mutations, resulting in the mutant huntingtin (mHTT) protein. Both innate and adaptive immunities play crucial roles in the pathogenesis of HD. In this chapter, we explore the vital role of the gut microbiota in HD, emphasizing its impact on the immune response and brain health via the gut-brain axis. Dysbiosis influences immune responses and HD pathogenesis through microbial metabolites such as short-chain fatty acids (SCFAs) and pathogen-associated molecular patterns (PAMPs). We discuss advanced mathematical models, telemedicine, and biosensors for tracking HD progression and detecting gut dysbiosis. Nutritional interventions to restore microbiota balance and using artificial intelligence and machine learning to predict disease prognosis and personalized treatments have been highlighted. Based on their unique immune profiles and gut microbiota, personalized medicine has been proposed as a promising strategy for effective HD treatment.

Schizophrenia is a chronic and thoughtful psychological disorder that affects a person's thinking, feelings, and behaviours. Multi-factorial genetic, environmental, and neurological variables cause it. Recently, more research focused on the human microbiome, which alters the immune system and develops adverse health effects on the human body. The study discusses a possible relationship between the oropharyngeal microbiome and schizophrenia. According to recent studies, the oropharyngeal microbiome may alter the immune system in the human body and cause various psychiatric disorders, including schizophrenia. The oropharyngeal microbiome can cause schizophrenia either by affecting the genes, chromosomes, and immune system in the human body. Additionally, it examines the combined mechanism of how the oropharyngeal microbiome's alterations lead to genetic abnormalities and immune dysregulation in schizophrenia. By combining the various approaches, this chapter offers a comprehensive view of the oropharyngeal microbiome's role in schizophrenia and suggests that microbial alterations could serve as biomarkers or therapeutic targets for the disorder.

One of the major issues modern medicine faces is the increasing use of antibiotics in reaction to the increased incidence of infectious agents. The current trend of antibiotic overuse contributes to microbial dysbiosis. Recent studies have hypothesized that antibiotic exposure during pregnancy, which alters the composition of the microbiome, might increase the likelihood of attention deficit hyperactivity disorder (ADHD). In addition to the ongoing discussion about the potential links between antibiotic usage, microbiome dysbiosis, and ADHD, there is a rising interest in integrating AI and ML into healthcare practices. Diagnosis, treatment plans, and prognoses are all enhanced by these technological advancements. Remote monitors or telemedicine monitoring are among the management techniques described in this chapter for effectively managing illnesses. Also discussed are ways to halt the progression of diseases by preventative measures that use biosensor technology and dietary approaches. Personalized treatment programs, disease progression stages, and prognosis evaluations are all made possible with the use of artificial intelligence and machine learning. By using these technologies to provide individualized therapy, healthcare practitioners may get a better understanding of ADHD and perhaps improve patient outcomes.

To design therapeutic trials and select the most appropriate substance and dose for an indication, a detailed understanding of clinical pharmacology is crucial. In recent years, several studies have explored the human pharmacology of different psychedelics and 3,4-methylendioxymethylamphetamin (MDMA). This chapter summarizes pharmacological characteristics of the serotonergic psychedelics psilocybin, lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT), 5-methoxy-DMT (5-MeO-DMT), and MDMA. We summarize their mechanisms of action, pharmacokinetics, pharmacodynamics, metabolism, and safety, with a focus on human data from modern clinical trials. Additionally, we provide recommendations for dosing, dose adjustment, and interactions with other medications. We show that the different serotonergic psychedelics produce overall comparable acute subjective and somatic effects primarily through interactions with 5-HT_2A receptors. However, the exact mechanisms of their potential therapeutic benefits in patients remain to be elucidated. Moreover, classic psychedelics differ substantially in their pharmacokinetics and metabolism, resulting mainly in different durations of action, which may influence their suitability for specific therapeutic uses and indications. In contrast, MDMA has a psychopharmacological profile that is distinct from serotonergic psychedelics, characterized by acute stimulant-like and empathogenic effects. In terms of pharmacokinetic-pharmacodynamic relationships, acute effects of the psychedelics mirror their plasma-concentration-time curves, whereas acute effects of MDMA are shorter-lasting than its presence in the body. Thus, MDMA, but not the psychedelics, exhibits marked acute pharmacological tolerance. A good understanding of the pharmacology of classic psychedelics and MDMA forms the basis for their clinical use and the design of clinical therapeutic trials.

Molecular brain imaging by positron emission tomography (PET) and single photon emission computer-tomography (SPECT) entails the mapping of the cerebral distribution of radiopharmaceuticals that track physiological processes such as blood perfusion and glucose metabolism, or the abundance in brain of specific molecular targets such as neuroreceptors. PET and SPECT emerged as useful in vivo research technologies in the 1980s, finding early application in the study of psychostimulant drugs. The past decade has seen growing use of molecular imaging methods in the study of psychedelic action, although the published literature remains comparatively small. The preponderance of publications cited in this review are SPECT studies of cerebral perfusion and PET studies of metabolism and neuroreceptors, the latter mainly focusing on the 5-hydroxytryptamine (serotonin) 5-HT_2A receptors, which are largely responsible for the psychedelic action of classical psychedelic substances. There is some documentation of interactions of psychedelics at dopamine D_2/3receptors in the striatum, but many other plausible molecular targets of psychedelic action await investigation by molecular brain imaging. The emerging role of psychedelics as treatments for neurological and psychiatric disorders calls for a broader and systematic investigation of their effects on brain function.

Research on psychiatric disorders faces the challenge that symptoms of psychopathology are by their nature elusive. Functional symptoms, hallucinations, delusions, and passivity phenomena involve private changes in experience which are often unpredictable in nature, co-morbid, confounded, and heterogeneous. Hypnosis and experimental suggestion provide a potential means of overcoming these limitations. By eliciting precise, transient alterations in experience under controlled conditions, symptom models created by suggestion in hypnosis allow researchers to probe mechanisms that are otherwise difficult to study, such as disruptions in self-monitoring, agency, and belief evaluation. This chapter reviews the historical and contemporary development of hypnotic symptom modelling, evaluates the methodological debates concerning suggestibility, demand characteristics, and phenomenological characterisation, and considers applications ranging from hallucinations and delusional misidentification to functional neurological symptoms. We conclude that while suggested symptoms do not replicate clinical disorders in full, they provide useful experimental analogues that can bridge laboratory and clinic, refine cognitive theories, and highlight potential therapeutic strategies. Moreover, by linking mechanistic insights from modelling to therapeutic practice, clinical hypnosis and suggestion can potentially alleviate distress in clinical contexts.

Gut microbiota not only affects the function of the gastrointestinal tract but also the function of other organs, including the brain. The microbiota-gut-brain axis reflects the constant bidirectional communication between the central nervous system and the gastrointestinal tract. Gut microbiota metabolites can cross brain barriers, the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSF) and influence neuropsychiatric disorders, including depression. In recent years, the communication between the microbiome and brain in depression has been extensively studied in humans and animal models. In this chapter, we summarise the current literature on the role of gut microbiota in depression, focusing in particular on brain barriers and bidirectional gut-brain communication.

Classic psychedelics have been used by various cultures for millennia for healing and religious purposes. The modern era of psychedelic science began with the first empirical experiments by Dr. Arthur Heffter in 1898 to determine just what they are when he discovered the active alkaloid in the peyote cactus responsible for its intoxicating effects and named it mescaline. As with many aspects of society there has been a dramatic and often contentious relationship between 'western' society and psychedelics. In the early to mid-20th century, they were seen as valuable medicines with great potential for healing, and as scientific tools for understanding in the nascent field of neuroscience. As the counterculture of the 1960s embraced psychedelics as elements of youthful protest, governments around the world labeled them as dangerous, with no medical value. That ultimately led to severe legal penalties for their possession and essentially halted any significant scientific advances. No clinical studies were carried out for nearly 20 years, with very few preclinical studies performed by only a handful of researchers. As the political climate changed, clinical trials were once again allowed, culminating in several high profile published studies on the efficacy of psychedelics to treat psychiatric disorders. Around that time a paradigm shift in the acceptance of psychedelics as medicines to benefit society began to occur, spurring the rapid growth of the ecosystem surrounding psychedelics research. This review presents an overview of the last 125 years of psychedelic science, with key events and findings along the way highlighted leading to a greater understanding of their pharmacology, chemistry, and therapeutic potential.