mRNA-based therapy represents one of the most promising directions in modern biomedicine and is actively being investigated for the treatment of neurodegenerative diseases. In contrast to traditional gene therapy approaches based on DNA vectors, mRNA does not integrate into the host genome and does not require entry into the nucleus, thereby reducing the risk of mutagenesis and improving the safety profile of the method. This review provides an overview of the advantages and limitations of mRNA-based therapeutic approaches for neurodegenerative diseases. Key features of mRNA platforms are discussed, including the possibility of programmable expression of therapeutic proteins, the high flexibility of nucleotide sequence modification, and the relative simplicity of scalable production. Particular attention is given to mRNA delivery systems, especially lipid nanoparticles, which protect mRNA molecules from degradation and enhance the efficiency of intracellular delivery. The major limitations of this technology are also addressed, including the difficulty of crossing the blood-brain barrier, the low stability of mRNA, its potential immunogenicity, and the requirement for repeated administrations in the treatment of chronic diseases. In addition, current experimental strategies for the application of mRNA therapy are described, including protein replacement approaches, delivery of neuroprotective factors, and genome editing technologies. Overall, mRNA therapy holds considerable potential for the treatment of neurodegenerative disorders, however, its broad clinical implementation will require further improvements in delivery systems and enhanced stability of mRNA molecules.

Research over the last decade has shown that schizophrenia spectrum disorders (SSDs) cannot be viewed exclusively as a neurotransmitter pathology. A significant proportion of patients, especially those in the acute phase and with treatment resistance, exhibit signs of low-grade inflammation (LGI), which is associated with cardiovascular comorbidity, including the risk of venous thromboembolism (VTE). The role of antipsychotics (APs), which are the mainstay of SSDs therapy, in the development of VTE remains controversial. On one hand, preclinical in vitro and in vivo studies demonstrate an antiplatelet effect of APs. This effect is mediated through blockade of adenosine diphosphate (P2Y1 and P2Y2) and serotonin (5-HT2A) receptors, and inhibition of thromboxane A2. On the other hand, clinical in vivo studies indicate the persistence or even increase of procoagulant platelet activity and LGI, which significantly elevates the risk of VTE in patients with SSDs during long-term AP treatment. Materials and Methods: In this narrative review, we analyzed and summarized the results of preclinical and clinical studies on biomarkers of AP-induced platelet activation, as well as their prognostic role in assessing VTE risk in patients with SSDs. Results: As a result, the knowledge of psychiatrists regarding the potential negative impact on platelet hemostasis has been updated for firstand new-generation APs. It has been shown that asenapine and amisulpride carry the highest risk of developing AP-induced VTE. Haloperidol and droperidol have a dose-dependent risk of VTE. An increased risk of AP-induced pathological bleeding is observed with the use of quetiapine, thioridazine, thiothixene, and flupentixol. Conclusion: The diverse effects of APs on platelet hemostasis have been demonstrated. This underscores the need for a differentiated approach to selecting APs and the complexity of predicting the additive effect during AP polytherapy. Dynamic monitoring of hematological biomarkers (platelet and inflammatory) is important for reducing the risk of developing VTE in patients with SSDs.

Pharmacogenetic testing (PGx) of polymorphisms that alter the expression of genes asso- ciated with the distribution and response to antipsychotics (APs) can replace the "trial and error" method in AP dosage adjustment and reduce the risk of AP-induced adverse drug reactions (ADRs). This narrative review demonstrates the growing commercial interest in the pharmacogenomics and pharmaco-economics of PGх. However, the significant heterogeneity of pharmacogenetic panels and the lack of unified interpretation standards substantially hinder the implementation of PGх as an advanced tool in personalized psychiatry. The conducted review demonstrates not only techno- logical and commercial progress in the field of PGх for APs but also a complex of interrelated problems that require resolution for the successful translation of this method from the realms of scientific research and commercial services into the routine clinical practice. Although the develop- ment of PGх for identifying at risk patient groups aligns with Russia's new healthcare development strategy, numerous barriers impede its implementation into psychiatric practice. One such barrier is the lack of data on the convergence of pharmacogenomics and pharmacoeconomics of APs. Re- moving this barrier can facilitate the development and real-world clinical implementation of diagnostic pharmacogenetic test systems as a key to a new era of personalized, cost-effective, and safe therapy for mental disorders.

Alcohol withdrawal syndrome (AWS) complicated by seizures requires rapid symptom control while avoiding excessive sedation and other dose-related adverse drug reactions. This pilot randomized controlled trial evaluated whether pharmacogenetically guided optimization of pharmacotherapy could improve early clinical dynamics and tolerability in this high-risk inpatient population. Fifty inpatients with alcohol withdrawal state with convulsions (ICD-10 F10.31) were randomized 1:1 to pharmacogenetically guided treatment or control care. Pharmacogenetic testing was performed at admission in all patients; treating physicians in the intervention group received the true PGx report, whereas control physicians received a neutral report of identical format indicating wild-type genotypes and standard dosing. The primary endpoint was the area under the CIWA-Ar curve over 72 hours. Mean AUC CIWA-Ar was lower in the pharmacogenetic group than in controls (790 ± 175 vs 905 ± 185 score-hours; p = 0.032), with consistent non-parametric sensitivity analysis. Repeated-measures modelling showed a significant group-by-time interaction, with adjusted differences at 48 and 72 hours. The pharmacogenetic group also showed shorter time to stabilization, lower rescue medication burden, shorter hospitalization, lower UKU scores, and fewer clinically significant adverse events. These preliminary findings suggest that pharmacogenetically guided prescribing may improve tolerability and early withdrawal dynamics, but require confirmation in larger multicentre studies.

Schizophrenia (SCZ) is a severe mental disorder which exact pathogenesis remains unknown. The disorder has been linked to disturbances in lipid metabolism and lysosomal function. A link between this disorder and Parkinson's disease (PD) is suggested. Pathogenic mutations in the GBA1 gene, which lead to dysfunction of the lysosomal enzyme glucocerebrosidase, are a highrisk factor of PD. Meanwhile, mutations in the LRRK2 gene are the most common cause of hereditary forms of PD and may indirectly affect the activity of this enzyme. GBA1and LRRK2related PD are the most prevalent forms of the disease known today. Materials and Methods: In this study, we used PCR-RFLP and real-time PCR allelic discrimination to assess the frequency of mutations in the LRRK2 (G2019S) and GBA1 (N370S, L444P, E326K) genes among 161 SCZ patients and 434 control individuals residing in the Northwestern region of Russia. Results: The study found no association between the investigated mutations and the risk of SCZ. Among SCZ patients, no carriers of the N370S mutation in the GBA1 gene or the G2019S mutation in the LRRK2 gene were identified. The frequency of GBA1 mutations (L444P+N370S+E326K) among SCZ patients was found to be 3.2%. Conclusions: Thus, this study demonstrated that mutations in the GBA1 gene are not associated with the risk of SCZ.