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Schizophrenia (Sch) is a severe and widespread mental disorder. Antipsychotics (APs) of the first and new generations as the first-line treatment of Sch are not effective in about a third of cases and are also unable to treat negative symptoms and cognitive deficits of schizophrenics. This explains the search for new therapeutic strategies for a disease-modifying therapy for treatment-resistant Sch (TRS). Biological compounds are of great interest to researchers and clinicians, among which D-Serine (D-Ser) and D-Aspartate (D-Asp) are among the promising ones. The Sch glutamate theory suggests that neurotransmission dysfunction caused by glutamate N-methyl-D-aspartate receptors (NMDARs) may represent a primary deficiency in this mental disorder and play an important role in the development of TRS. D-Ser and D-Asp are direct NMDAR agonists and may be involved in modulating the functional activity of dopaminergic neurons. This narrative review demonstrates both the biological role of D-Ser and D-Asp in the normal functioning of the central nervous system (CNS) and in the pathogenesis of Sch and TRS. Particular attention is paid to D-Ser and D-Asp as promising components of a nutritive disease-modifying therapy for TRS. [ABSTRACT FROM AUTHOR]

Among neurological adverse reactions in patients with schizophrenia treated with antipsychotics (APs), drug-induced parkinsonism (DIP) is the most common motility disorder caused by drugs affecting dopamine receptors. One of the causes of DIP is the disruption of neurotransmitter interactions that regulate the signaling pathways of the dopaminergic, cholinergic, GABAergic, adenosinergic, endocannabinoid, and other neurotransmitter systems. Presently, the development mechanisms remain poorly understood despite the presence of the considered theories of DIP pathogenesis. [ABSTRACT FROM AUTHOR]

Presented clinical observation of anti-NMDA-receptor encephalitis, which was first described in 2007, is rare and to date has not been sufficiently studied. The disease often manifests with psychopathological symptoms and catatonia, so patients are transferred into a mental healthcare institution and often require intensive care and resuscitation, due to the development of life-threatening respiratory and hemodynamic disorders. Diagnosis is based on detection of autoantibodies to the NR1- and NR2 subunits of the glutamate NMDA receptor in blood serum and cerebrospinal fluid. Pathogenesis-based therapy includes the administration of glucocorticoids and intravenous immunoglobulins, plasmapheresis, as well as the introduction of monoclonal antibodies in also used, and in severe cases, cytostatics are prescribed. The widespread comorbidity of anti-NMDA receptor encephalitis with ovarian neoplasms in women (up to 60%) requires appropriate diagnosis and early removal of ovarian neoplasms when they are detected. With timely diagnosis and adequate treatment strategies, the outcome of this rare disorder is usually positive.

Objective: To evaluate the modifiable daily behavior patterns associated with increased anxiety indicators in the general population in response to the COVID-19 pandemic., Material and Methods: The study examined the characteristics of the Russian population ( n= 7777) of the international multicenter project COMET-G. In particular, variables were targeted to describe deviations in the behavior of adults during the period of application of measures of social isolation in connection with the pandemic, and revealing a relationship with the total score on the Spielberger State Anxiety Scale (STAI-S). Among these variables, experts selected those that could potentially be subject to change in the short term, that is, act as manageable or modifiable risk factors for the development of anxiety. The selected variables were analyzed in a statistical PLS-model to identify indicators that make the most significant contribution to the increase in the total anxiety score., Results: Our statistical model explained 48.4% of the variability in the STAI-S anxiety total scores related to changes in daily life habits. In particular, doom-scrolling/doom-surfing about the spread of the virus and the COVID-19 pandemic, changes in sleep patterns and usual daily life activities due to social isolation measures presented as factors significantly contributing to the increase of state anxiety., Conclusion: Given the manageable or modifiable risk factors that we have identified, public awareness and therapeutic recommendations, pointing to the need to (I) control the amount of time spent in the internet and monitor their internet-based content consumption, (II) regulate sleep-wake patterns, (III) maintain daily habits and household activities, may reduce the likelihood of developing anxiety disorders in the context of the impact of a global chronic stress due to the COVID-19 pandemic and associated social isolation measures.

Selective and progressive death of neurons is a characteristic feature of the process of neurodegeneration and leads to corresponding neuronal dysfunctions. Neurodegenerative diseases represent a heterogeneous group of clinically distinct disorders with similar molecular mechanisms of pathogenesis. They are based on the processes of abnormal aggregation of proteins, the formation of fibrillary insoluble structures and their deposition in the form of histopathological inclusions in the tissues of the nervous system. Disturbance of homeostatic functions that regulate neuronal ion and energy metabolism, biosynthesis and degradation of proteins and nucleotides, chronic hypoxia and the penetration of toxic and inflammatory substances into the brain from the bloodstream not only cause metabolic changes associated with age and disorders in the sleep-wake cycle, but also contribute to the development of neurodegenerative diseases. In animal studies, clearance pathways have been identified in which solutes and specific tracers are excreted perivascular into the meningeal lymphatics. The glymphatic pathway promotes the removal of metabolites, including Aβ amyloid and tau protein, from the parenchymal extracellular space of the brain. The glymphatic system is discussed to be more efficient during natural sleep, and fluid dynamics through this pathway exhibit daily fluctuations and are under circadian control. This review systematizes the key aspects and scientific data of recent studies on the role of the glymphatic pathway and astroglial AQP-4 as its main determinant in maintaining homeostatic fluid circulation in the brain in normal and pathological conditions, in particular in relation to the regulatory role of the sleep-wake cycle and in development of neurodegeneration.

Orphan diseases have a prevalence ranging one patient per 10.000 population in the Russian Federation to one per 1500-2000 individuals in Australia and the USA. Many orphan diseases lead to a severe decrease in quality of life and high mortality. In this article, we discuss the problem of early diagnosis in orphan diseases in the Russian Federation, which has lagged behind global trends towards improved recognition and treatment of orphan diseases. We identify the need for improved focus at the level of national healthcare, while discussing relevant issues arising from the international experience. We review national and regional health programs and healthcare practices of Australia, Germany, Denmark, China, Norway, Slovenia, UK, and the United States, with a focus on screening and diagnosis of orphan disease. We also present a review on the state of affairs in the Russian Federation. Orphan diseases are amenable to current molecular-genetic and other diagnostic technologies, including targeted, whole exome and whole genome sequencing (targeted NGS, WES, WGS) using next generation sequencing technologies (next generation sequencing, NGS) and tandem mass spectrometry (TMS, MS/MS). We conclude with a call for major measures aimed at improving the diagnosis of orphan diseases, in particular through the expansion of the neonatal screening program, the creation of a network of orphan disease referral centers, and centralized management of patients registers.