Personalized Psychiatry and Neurology

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Vol 1, Issue 2 (2021)


1 269

Pharmacogenetics in addiction psychiatry is a relatively young and quickly growing area of science. Indeed, associations of treatment outcomes with some genetics polymorphisms have been demonstrated for virtually all evidence based pharmacotherapies for addictive disorders in retrospective data analysis of candidate genes. For alcohol use disorder associations of genetic polymorphisms with treatment outcomes and side effects were shown for naltrexone, acamprosate, topiramate, pregabalin, ondansetron, disulfiram, selective serotonin reuptake inhibitors, and baclofen. For nicotine use disorders the same was demonstrated for varenicline, bupropione, and nicotine replacement therapy. For opioid use disorders – for all opioid agonists (methadone, buprenorphine) and antagonists (naltrexone). However, in two recent prospective studies of associations of single nucleotide polymorphisms with treatment outcomes reveled in retrospective data analysis had not been confirmed. So apparently, further studies in this promising area of medicine are needed. Pharmacogenetic approach will help to develop personalized and individually tailored pharmacotherapies for addictive disorders. Gene therapy is another new and very promising approach to treatment of alcohol and drug dependencies. In particular, it was shown that microRNA might substantially decrease synthesis of aldehyde-dehydrogenase – an enzyme essential for alcohol catabolism - that makes drinking aversive. Another possible gene therapy is injection of RNA coding a special subtype of dopamine receptors in the brain that lead to the increase of the number of dopamine receptors in the membranes of the neurons and brings about a significant reduction of alcohol consumption by alcohol dependent rats. To conclude, pharmacogenetics and gene therapy might significantly increase efficacy of treatment of addictive disorders and in its turn reduce negative consequences they cause to society!


2-20 570

Due to the high prevalence of the disease, its genetic and clinical heterogeneity, the need for lifelong therapy and the emergence of new views on the pathogenesis and course of JME, it is necessary to provide primary care physicians (general practitioners, district therapists, neurologists) with up-to-date systematized information about the most common form of genetic generalized epilepsy (Herpin-Janz syndrome). JME is a genetically determined disease of the brain, accompanied by a triad of seizures (absences, myoclonia, generalized tonic-clonic seizures), and developing mainly in adolescence and young age. In recent years, monogenic and multifactorial forms of JME have been identified, but questions about the genetics of JME are far from being resolved. JME is characterized by the preservation of intelligence, life expectancy with adequate therapy does not differ from the average population, but the frequency of failures of pharmaco-induced remission is high when taking anticonvulsants is canceled. This explains the need for lifelong pharmacotherapy, individual selection of anticonvulsants. About 30% of patients with JME have non-psychotic mental disorders, disorders of the sleep and wake cycle, which in turn leads to an aggravation of epileptic seizures mainly in the first half of the day. This review presents an analysis of full-text publications in Russian and English over the past five years in the databases eLibrary, PubMed, Web of Science, OxfordPress, Springer, and Clinicalkeys. In addition, the review includes earlier publications of historical significance.


21-45 596

The purpose of this review is to analyze approaches to the treatment of depressive and negative disorders in schizophrenia in terms of their level of efficacy and safety. Materials and Methods: A search was conducted for full-text articles published over the last 10 years in PubMed, Springer, Wiley Online Library, Taylor & Francis Online, APA PsycInfo, CORE, Science Direct, and eLIBRARY.RU databases. Several articles published previously to this period were also included into the review due to their high scientific value. Results: Our review suggests that antidepressants (ADs) are effective medications and they can be prescribed to correct depressive disorders and negative symptoms in patients with schizophrenia when used in combination with antipsychotics (АPs). However, when administering ADs and АPs combinations, it is important to consider the safety profile of these combinations as well as their tolerance. Negative symptoms of schizophrenia, including those induced by a number of АP, are less amenable to correction by АDs monotherapy, which requires a long period of АPs (on average - 8 weeks), which can be limited in the real life of the patient outside the hospital. Current approaches to the therapy of depressive disorders in patients suffering from schizophrenia vary from country to country. However, most of АDs used in clinical psychiatric practice are widely used in the comorbid state under consideration. Conclusion: The efficacy and safety of АDs of the different classes considered in this review depends on their mechanisms of action, duration of admission, type of АPs taken, and specific clinical situation (acute depressive disorder, major depressive episode, or chronic depressive episode). Most promising in clinical practice are serotonin–norepinephrine reuptake inhibitors (SNRIs) and dual ADs. The use of tricyclic antidepressants (TCAs) is limited due to a higher risk of adverse drug reactions (ADRs). The use of most selective serotonin reuptake inhibitors (SSRIs) is limited due to the risk of aggravation of hallucinations (this risk being higher for patients with visual hallucinations, and lower for those with auditory hallucinations) and\or iatrogenic psychosis. These ADRs may probably occur in patients suffering from schizophrenia due to their ideal "poor metabolizer" pharmacogenetic profile, since most of the drugs considered in this review have hepatic metabolism.

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Anticonvulsant-induced osteoporosis (AIO) and associated pain syndromes and patient disabilities are an important interdisciplinary medical problem generated by various molecular, genetic and pathophysiological mechanisms. AIO are the most important pathological processes associated with chronic pain in adults with epilepsy. Standard approaches to their prevention and treatment do not always solve the problem of the progression of the pathological process and chronicity of AIO. This is the reason for the search for new personalized strategies for the prevention and treatment of AIO. Vitamin D metabolism, expression and specificity of vitamin D receptors (VDRs) may play a key role in the development of AIO and chronic back pain in patients with epilepsy. The aim of the study was to review publications on changes in the vitamin D system in patients with AIO. We searched for articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar. The search was carried out by key-words and their combinations. The role of vitamin D and VDR in the development of AIO and the chronicity of back pain has been demonstrated mainly in animal models and humans. Associative genetic studies have shown that single nucleotide variants (SNVs) of the VDR gene encoding VDR may be associated with the development of osteoporosis of the spine (including those associated with the intake of an anticonvulsants). The prospects for the use of vitamin D preparations for modulating the effect of anticonvulsants used to treat epilepsy are discussed. Genetic association studies of VDR gene SNVs are important for understanding the genetic predictors of AIO and chronic back pain in patients with epilepsy, as well as for developing new personalized pharmacotherapy strategies.

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Ascorbic acid (vitamin C) is a vital nutrient that belongs to the group of antioxidants. Vitamin C plays an important role in the functioning of the central (CNS) and peripheral nervous system (PNS), including maturation and differentiation of neurons, formation of myelin, synthesis of catecholamines, modulation of neurotransmission and antioxidant protection. Neurological diseases and mental disorders are characterized by increased generation of free radicals. At the same time, the highest concentrations of vitamin C are found in the brain and neuroendocrine tissues. It is believed that vitamin C can affect the age of debut and the course of many neurological diseases and mental disorders. However, its potential therapeutic role continues to be studied. The efficacy and safety of vitamin C is likely influenced by the pharmacogenetic profile of the patient, including the carriage of single-nucleotide variants (SNVS), candidate genes associated with vitamin C metabolism in the human body in normal and neuropsychic disorders. The purpose of this thematic review is to update current knowledge about the role of vitamin C pharmacogenetics in the efficacy and safety of its use in neurological diseases (amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Huntington's disease, Alzheimer's disease, etc.) and mental disorders (depression, anxiety, schizophrenia, etc.). Special attention is paid to the possibility of translating the results of pharmacogenetic studies into real clinical practice in neurology and psychiatry.

83-94 433

It is generally recognized that an elite athlete's status is a multifactorial phenotype depending on many environmental and genetic factors. Variations in the sequence of nucleotides in deoxyribonucleic acid (DNA), in particular, single-nucleotide variants (SNVs) act as key internal factors associated with achieving high results in sports. The determination of specific individuals' genetic characteristics allows us to identify athletes who have the greatest genetically determined potential for certain sports that require speed, strength or endurance manifestation. Of course, peculiarities of the structure and function of skeletal muscles are among the most important characteristics in sports results context, in sports associated with the development of power / strength or endurance phenotypes. The composition and function of skeletal muscles are controlled by many different genes, and their SNVs can serve as strength or endurance athletes' status biomarkers. (1) Background: to conduct a thematic review of candidate genes studies and their single-nucleotide variants (SNVs) associated with the functioning of skeletal muscles in athletes. (2) Methods: A search for articles for the period from 2010 to 2020 was conducted in the databases SCOPUS, Web of Science, Google Calendar, Clinical keys, PubMed, e-LIBRARY using keywords and their combinations; (3) Conclusions: The identification of genetic biomarkers associated with muscular system regulation can help neurologists, sports doctors and coaches in developing personalized strategies for selecting children, adolescents and young adults for endurance, strength and speed sports (for example, running short, medium or long distances). Such a personalized approach will increase sports performance and reduce the risk of sports injuries of the musculoskeletal system.


95-105 286

Juvenile myoclonic epilepsy (JME) is reported as a clinically and genetically heterogeneous disease with a high risk of inheritance. The aim of the study was to establish phenotype features and genetic risk factors for juvenile myoclonic epilepsy to advance existing approaches of prevention, treatment, and observation of patients with JME. Methods: anamnestic; clinical; neurophysiological (EEG); neuroradiological (MRI), neuropsychological; laboratory (DNA-diagnostics). JME starts with absences more frequently in females as compared to males (32.0% vs. 15.4%), and with GTCS and myoclonic in males as compared to females (46.2% and 36.5% vs. 36.0% and 31.2%, respectively). The 1st phenotype of JME was more frequently encountered in male individuals in comparison with female ones (55.8% vs. 34.7%), and the 2nd phenotype was more frequently encountered in female individuals in comparison with male ones (16.9% vs. 5.8%). Homozygous carriage of the T allele of the GJD2 gene (rs3743123) was associated with the development of JME in the study population, OR = 2.66 (95% CI 1.24 to 5.74). 41.5% of patients with JME have a slow metabolizer pharmacogenetic status, which is a risk factor for pseudo-pharmacoresistance and the development of adverse drug reactions.

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Currently, a search for a solution to the problem of drug-resistant epilepsy is being actively pursued. Along with personalized (including targeted) drug methods, personalized nondrug methods of treating drug-resistant epilepsy are being actively developed. Our previous studies have shown that the developed author's technique with an individual selection of the wrist tapping (WT) leads to an increase in the activity of the frontotemporal cortex, mainly of the right hemisphere, involved in emotional control, and a decrease in the fear of recurrence of focal epileptic seizures (FS) or transformation of FS into bilateral tonic-clonic seizures (BTCS). In addition, WT leads to a decrease in intrahemispheric coherence in the frontotemporal regions of the left hemisphere, which is a biomarker for reducing the risk of generalized epileptic activity.

111-116 366

Alcohol withdrawal is the most threatening condition encountered in patients with alcohol use disorder. Our study aimed to investigate the association of alcohol withdrawal severity with polymorphic variants in melatonin receptor genes. Methods. The clinical study was carried out on the basis of the Republican Narcological Dispensary №1 in Ufa and the Republican Narcological Dispensary №2 in Sterlitamak. Genetic analysis was performed at the Department of Personalised Psychiatry and Neurology at the V.M. Bekhterev Research Centre, Saint Petersburg. The final sample consisted of 307 subjects. Results. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were found to have less hypertension during alcohol withdrawal than carriers of the other genotypes. In comparison, carriers of the GG genotype of the MTNR1B gene (rs10830963) experienced more symptoms than other genotypes: paroxysmal sweating, visual hallucinations, anxiety, and overall CIWA-Ar score. Conclusions. Thus, it can be concluded that the TT genotype of MTNR1A gene (rs34532313) is associated with a lower risk of hypertension during alcohol withdrawal compared to carriers of other gene genotypes. The GG genotype of MTNR1B gene (rs10830963) is associated with severe withdrawal. In general, it can be concluded that melatonin receptors are involved in the pathogenesis of alcohol withdrawal and the severe of some of its symptoms.


117-125 391

(1) Background: to reveal the prevalence of non-motor disorders in Parkinson’s disease (PD), we analyzed both Russian and international studies on the issue of PD-associated non-motor disorders in Caucasian patients; (2) Methods: We have carried out a search for full-text Englishand Russian-language articles published during the last ten years (from 2010 to 2020) in PubMed, Scopus, Web of Science, Springer, Clinical case, and E-library databases using multiple versions of keywords and their combinations. (3) Results: General prevalence of PD-associated non-motor disorders proved to be high. At the same time, we did not find significant differences between the prevalence of cognitive, affective, or behavioral disorders in PD patients. However, depression was found to be more common in PD patients in the Russian Federation; (4) Conclusions: According to the results of our review, cognitive and affective disorders in PD represent the issues of major concern.



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ISSN 2712-9179 (Online)