Valproate-Induced Metabolic Syndrome.

Valproic acid (VPA) and its salts (sodium calcium magnesium and orotic) are psychotropic drugs that are widely used in neurology and psychiatry. The long-term use of VPA increases the risk of developing adverse drug reactions (ADRs), among which metabolic syndrome (MetS) plays a special role. MetS belongs to a cluster of metabolic conditions such as abdominal obesity, high blood pressure, high blood glucose, high serum triglycerides, and low serum high-density lipoprotein. Valproate-induced MetS (VPA-MetS) is a common ADR that needs an updated multidisciplinary approach to its prevention and diagnosis. In this review, we consider the results of studies of blood (serum and plasma) and the urinary biomarkers of VPA-MetS. These metabolic biomarkers may provide the key to the development of a new multidisciplinary personalized strategy for the prevention and diagnosis of VPA-MetS in patients with neurological diseases, psychiatric disorders, and addiction diseases.

Genetic Predictors of Antipsychotic Efflux Impairment via Blood-Brain Barrier: Role of Transport Proteins.

Antipsychotic (AP)-induced adverse drug reactions (ADRs) are a current problem of biological and clinical psychiatry. Despite the development of new generations of APs, the problem of AP-induced ADRs has not been solved and continues to be actively studied. One of the important mechanisms for the development of AP-induced ADRs is a genetically-determined impairment of AP efflux across the blood-brain barrier (BBB). We present a narrative review of publications in databases (PubMed, Springer, Scopus, Web of Science E-Library) and online resources: The Human Protein Atlas; GeneCards: The Human Gene Database; US National Library of Medicine; SNPedia; OMIM Online Mendelian Inheritance in Man; The PharmGKB. The role of 15 transport proteins involved in the efflux of drugs and other xenobiotics across cell membranes (P-gp, TAP1, TAP2, MDR3, BSEP, MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8, MRP9, BCRP) was analyzed. The important role of three transporter proteins (P-gp, BCRP, MRP1) in the efflux of APs through the BBB was shown, as well as the association of the functional activity and expression of these transport proteins with low-functional and non-functional single nucleotide variants (SNVs)/polymorphisms of the ABCB1, ABCG2, ABCC1 genes, encoding these transport proteins, respectively, in patients with schizophrenia spectrum disorders (SSDs). The authors propose a new pharmacogenetic panel "Transporter protein (PT)-Antipsychotic (AP) Pharmacogenetic test (PGx)" (PTAP-PGx), which allows the evaluation of the cumulative contribution of the studied genetic biomarkers of the impairment of AP efflux through the BBB. The authors also propose a riskometer for PTAP-PGx and a decision-making algorithm for psychiatrists. Conclusions: Understanding the role of the transportation of impaired APs across the BBB and the use of genetic biomarkers for its disruption may make it possible to reduce the frequency and severity of AP-induced ADRs, since this risk can be partially modified by the personalized selection of APs and their dosing rates, taking into account the genetic predisposition of the patient with SSD.

Machine learning techniques in diagnostics and prediction of the clinical features of schizophrenia: a narrative review.

BACKGROUND: Schizophrenia is a severe psychiatric disorder associated with a significant negative impact. Early diagnosis and treatment of schizophrenia has a favorable effect on the clinical outcome and patients quality of life. In this context, machine learning techniques open up new opportunities for a more accurate diagnosis and prediction of the clinical features of this illness. AIM: This literature review is aimed to search for information on the use of machine learning techniques in the prediction and diagnosis of schizophrenia and the determination of its clinical features. METHODS: The Google Scholar, PubMed, and eLIBRARY.ru databases were used to search for relevant data. The review included articles that had been published not earlier than January 1, 2010, and not later than March 31, 2023. Combinations of the following keywords were applied for search queries: machine learning, deep learning, schizophrenia, neural network, predictors, artificial intelligence, diagnostics, suicide, depressive, insomnia, and cognitive. Original articles regardless of their design were included in the review. Descriptive analysis was used to summarize the retrieved data. RESULTS: Machine learning techniques are widely used in the functional assessment of patients with schizophrenia. They are used for interpretation of MRI, EEG, and actigraphy findings. Also, models created using machine learning algorithms can analyze speech, behavior, and the creativity of people and these data can be used for the diagnosis of psychiatric disorders. It has been found that different machine learning-based models can help specialists predict and diagnose schizophrenia based on medical history and genetic data, as well as epigenetic information. Machine learning techniques can also be used to build effective models that can help specialists diagnose and predict clinical manifestations and complications of schizophrenia, such as insomnia, depressive symptoms, suicide risk, aggressive behavior, and changes in cognitive functions over time. CONCLUSION: Machine learning techniques play an important role in psychiatry, as they have been used in models that help specialists in the diagnosis of schizophrenia and determination of its clinical features. The use of machine learning algorithms is one of the most promising direction in psychiatry, and it can significantly improve the effectiveness of the diagnosis and treatment of schizophrenia.