Antipsychotics (APs) are a class of psychotrophic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of other psychotic disorders. Biotransformation is a major mechanism for APs elimination. Most APs undergo biotransformation, or metabolism, after they enter the body. There are three phases of APs metabolism. Cytochrome P450 (CYP) monooxygenase (mixed function oxidase) plays a central role in the most APs biotransformation. CYP’s functional activity depends on gene-drug and drug-drug interaction and influences on occurrence of adverse drug reactions (ADRs). So, it is extremely important for a practicing psychiatrist to know the oxidation pathway of APs, since most of them are metabolized in the liver and this is important both to prevent ADRs and to avoid unwanted drug-drug interactions, which will undoubtedly increase the effectiveness and safety of AP therapy.

In connection with the widespread use of anticonvulsants (antiepileptic drugs – AEDs) in psychiatric and neurological practice and the need for their long-term use to treat a wide range of mental disorders and neurological diseases, the question of their safety profile, including the assessment of the risk of developing life-threatening conditions and adverse reactions (ADRs), becomes relevant. In this regard, from the position of personalized medicine, it is critical to develop an interdisciplinary approach with the participation of doctors of various specialties and a new strategy of a personalized approach to predicting AED-induced prolongation of the QT interval as one of the most prognostically unfavorable cardiological ADRs (including sudden death syndrome – SDS). We searched for full-text publications for the period from 2011 to 2021 databases using the following keywords and its combination. We have found and systematized monogenic and multifactorial forms of long QT syndrome (LQTS) and candidate genes that slow down AEDs metabolism in the liver. Identification of risk alleles of single nucleotide variants (SNVs) of the candidate genes predisposing to the development of AED-induced LQTS and SDS will make it possible to adjust the choice and dosage of these drugs and prevent the development of ADRs, which will improve the quality of life of patients and prevent SDS in the patients with psychiatric and neurological disorders.

The intervertebral discs degeneration (IDD) is one of the leading structural substrates, causing chronic low back pain (LBP). LBP is a common neurological disorder but the LPB genetic predictors have not been sufficiently studied. Fibril collagens are important components of the nucleus pulposus, the anulus fibrosus and the vertebral endplate. Collagen type I is most studied as a structural component of the nucleus pulposus and the anulus fibrosus of the intervertebral disc. Single nucleotide variants (SNVs) of genes encoding alpha-1 and alpha-2 chains of collagen type I are associated with IDD, but the results of genetical studies are not translated into action. (1) The purpose of the study is the analysis of associative genetic and genome-wide studies of the COL1 gene family role in the development of IDD and LBP. The study of the COL1A1 gene’s SNVs association of with the IDD is important for the perspective of personalized neurology. A personalized approach can help to identify patients at high risk of the IDD developing and its complications, including intervertebral disc herniation and spinal stenoses in young and working age patients. On the other hand, the role of nutritional support for patients, carriers of the SNV risk alleles in the COL1A1 gene, including collagen hydrolysates and oxyproline preparations has not been sufficiently studied.

We searched for full-text publications in Russian and English in the E-Library, PubMed, Springer, Clinical keys, Google Scholar databases, using keywords and combined word searches (amyotrophic lateral sclerosis - ALS, motor neuron disease, epidemiology, incidence, prevalence), for 2015 – 2020. In addition, the review included earlier publications of historical interest. Despite our comprehensive searches of these commonly used databases and search terms, it cannot be excluded that some publications may have been missed. A total of 74 publications were analyzed, reflecting epidemiological studies of ALS in 168 countries. The incidence of ALS worldwide varies from 0.4 per 100,000 per year (Ecuador) to 9.45 per 100,000 per year (Japan, Oshima region). Prevalence - from 0.1 per 100,000 population (Somalia) to 42.1 per 100,000 population (Canada). This data depends on many factors, including the quality of the diagnosis and the health care system.

The antipsychotic-induced metabolic disorders (AIMD) are common side effects during the treatment of schizophrenia. Single nucleotide polymorphisms in the genes associated with AIMD, in particular in the leptin and neuropeptide Y genes were explored. The aim of this study was to develop a real-time PCR technique for SNP allele discrimination and allele frequency estimation in the Russian population. A total of 9 real-time PCR tests for rs7799039, rs1137101, rs8179183, rs16147, rs6837793, rs11100494, rs1414334, rs3813929 and rs518147 SNPs were developed and examined using 106 DNA samples. The revealed allele frequencies did not show any statistically significant differences with ones for the Caucasian population from Ensembl data base. Thus, our results are in accordance with the allele frequencies for the studied populations and allow using published data on the risk alleles for the development of new diagnostics PCR kits for the complex diagnostics of AIMD.

Background: Suicidal behaviour is the leading cause of mortality from external causes at all ages worldwide. More than a million people commit completed suicide each year. According to the World Health Organisation, 25-50% of suicide victims suffered from alcohol and other substance use disorders, 22% of all suicide deaths were attributable to alcohol use (WHO, 2014). Several papers have suggested potential associations of insomnia and increased suicide risk in patients with alcoholism. We hypothesise that mutations in melatonin receptor genes may be associated with suicide risk in patients with alcoholism.

Methods. The Insomnia Severity Index (ISI) was used as a tool to assess the presence and severity of insomnia. The Columbia Suicide Severity Rating Scale (C-SSRS) was used as a method to examine suicidal behavior. Genotyping of MTNR1A (rs34532313), MTNR1B (rs10830963) genes was performed using real-time polymerase chain reaction (RT-PCR). A comparative genetic study of two groups of patients was carried out: the first group, patients with alcohol dependence syndrome (F10.2); the second group, patients with alcohol dependence syndrome (F10.2) and insomnia, which persisted 7-14 days after starting alcohol withdrawal therapy.

Results. Suicidal thoughts and a history of auto-aggressive behaviour were more common in subjects with insomnia in the post-withdrawal period. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were more likely to have suicidal thoughts and a history of suicide attempts in a genetic study of patients with insomnia.

Conclusions. Our study found that the TT genotype of the MTNR1A gene (rs34532313) is a genetic marker of suicidal behaviour risk in patients with insomnia in the post-withdrawal period. However, the same pattern was not observed in patients without insomnia.

Schizophrenia is a common and socially significant mental disorder that requires long-term use of antipsychotics (APs). Long-term use of APs increases the risk of developing adverse drug reactions (ADRs) and/or therapeutic resistance in some patients. This may be due to a genetically determined impairment of APs metabolism by cytochrome P450 enzymes. Pharmacogenetic testing (PGx) is a method to identify a group of patients with a high risk of developing AP-induced ADRs. Our experience of using PGx to search for low-functional and non-functional single nucleotide variants (SNVs) / polymorphisms of the CYP1A2, CYP2C9, CYP3A4, CYP3A5 and CYP2D6) genes encoding cytochrome P450 enzymes involved in APs metabolism demonstrates the importance of this new personalized approach to the choice of APs and its dosing in patients with pharmacogenetic profile poor metabolizer. The main purpose of the case report is to present the experience of using PGx in a 28-year-old patient with treatment-resistant schizophrenia and a medical history of AP-induced ADRs.

Schizophrenia is a common and socially significant mental disorder that requires long-term use of antipsychotics (APs). Long-term use of APs increases the risk of developing adverse drug reactions (ADRs) and/or therapeutic resistance in some patients. This may be due to a genetically determined impairment of APs metabolism by cytochrome P450 enzymes and of Aps transport across the blood-brain barrier (BBB) and the cell membrane of APs target neurons in the brain. Pharmacogenetic testing (PGx) is a method to identify a group of patients with a high risk of developing AP-induced ADRs. The aim of the case report is to present the experience of using PGx in a 36-year-old patient with treatment-resistant schizophrenia and a medical history of AP-induced ADRs.

Schizophrenia is a common and socially significant mental disorder requiring long-term use of antipsychotics (APs). Long-term use of APs increases the risk of developing adverse drug reactions (ADRs) and / or treatment resistance in some patients. This may be due to a genetically determined impairment of APs transport across the blood-brain barrier (BBB) and the membrane of APs target neurons in the brain. Pharmacogenetic testing (PGx) is a method to identify a group of patients with a high risk of developing AP-induced ADRs. Foreign panels for PGx do not include non-functional variants of genes encoding APs transporter proteins. However, our experience ofusing PGx to search for low-functional and non-functional single-nucleotide variants (SNVs)/polymorphisms of three genes (ABCB1, ABCG2, ABCC1) encoding APs transporter proteins demonstrates the importance of this new personalized approach to the choice of APs and its dosing in patients with a slow transporter PGx profile. The main purpose of the work is to present the experience of using pharmaco-genetic testing (PGx) in a 32-year-old patient with treatment-resistant schizophrenia and a medical history of AP-induced ADRs.