Various aspects of folate and tetrahydrobiopterin (BH4) metabolism disturbances have been detected in patients with schizophrenia.Data were obtained that disturbances in the pterins (folates and BH4) ...metabolism can be associated with oxidative stress and inflammation, but has not yet been confirmed in clinical studies in schizophrenia. Within the framework of this study, a correlation and factor analysis of biochemical markersof pterin metabolism, inflammation and redox imbalance in patients with schizophrenia was performed in order to test the hypothesis of the single etiopathogenetic node, including the studied biochemical processes. Methods: 125 patients with schizophrenia and 95 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, B12, homocysteine, C-reactive protein, interleukin-6, reduced glutathione levels in the blood serum; activity of superoxide dismutase and catalase - in erythrocytes; malondialdehyde - in blood plasma. All patients underwent an examination using standardized psychopathology rating scales. Spearman rank coefficient (ρ) with Benjamini-Hochberg correction was used for the correlation analysis. The principal components analysis (PCA) was used as a factor analysis. Results: Significant correlations were found within groups of pterin metabolism, inflammatory markers and redox-imbalance, and also between separate inflammation, oxidative stress and markers of pterin metabolism. The performed factor analysis made it possible to distinguish two components: 1 — pterin metabolism, 2 — oxidativeinflammatory markers. Despite the weak statistical associations and, possibly, functional relationships between pterin metabolism and oxidative/inflammation markers, each of the components has its own clinical correlates and, probably, a separate contribution to the pathology of schizophrenia.
•Weak correlations between pterin metabolism, inflammation and redox markers were revealed.•It may indicate functional relationships between studied 3 groups of biomarkers.•Factor analysis identified pterin metabolism and oxidative-inflammatory components.•Each of distinguished components has its own clinical correlates.•Hypothetically, each component has its own contribution to schizophrenia pathology.
It was reported that the levels of tetrahydrobiopterin (BH4) are reduced in schizophrenia. However, mechanisms of BH4 deficiency in schizophrenia had not been studied precisely. Objective: the search ...of the association between BH4 deficiency in schizophrenia and a range of biochemical and clinical parameters for the evaluation of the possible mechanisms of BH4 loss and its role in the development of the symptoms. Methods: 93 patients with schizophrenia and 60 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, cobalamin (B12), homocysteine, C-reactive protein (CRP), reduced glutathione (GSH) levels in the blood serum.Patients underwent standardized psychopathological examination. Results: In patients, the levels of BH4 and folate were lower (p = 0.001 and p = 0.054, respectively), and the levels of homocysteine were higher (p = 0.012) compared to the control group. BH4 levels directly moderately correlated with folate (ρ = 0.43; p = 0.0029) and B12 levels (ρ = 0.43; p = 0.0020) and inversely moderately correlated with homocysteine levels (ρ = −0.54; p = 0.00015) in patients. Cluster analysis identified schizophrenia biotype characterized by a deficiency of BH4, folate, B12, and hyperhomocysteinemia. The clinical characteristics of this biotype were not specific. CRP and GSH were higher in patients compared to controls, but their association with serum BH4 was not confirmed.
Genetic polymorphisms associated with impaired one-carbon metabolism (1-CM) can be a risk factor not only for somatic and neurological diseases, but also for affective disorders (AD).
Objective
: to ...compare the frequency of genetic polymorphisms
MTHFR, MTR, MTRR
associated with 1-CM disorders among patients with AD, their blood relatives and healthy individuals.
Patients and methods
. This cross-sectional study of the frequency of genetic polymorphisms (
MTHFR, MTR, MTRR
) associated with 1-CM included patients with AD (n=24), their blood relatives (n=40), as well as a group of healthy individuals (n=35). All study participants underwent a structured diagnostic interview, as well as genetic analysis using real-time polymerase chain reaction.
Results and discussion
. Patients with AD were statistically more likely to carry the minor allele C of the 1298A>C polymorphism of the
MTHFR
gene and the minor allele G of the 2756A>G polymorphism of the
MTR
gene compared to the group of healthy individuals. The minor allele T of the 677C>T polymorphism of the
MTHFR
gene was associated with longer depressive episodes, as well as with the presence of concomitant cardiovascular diseases in blood relatives of patients with AD.
Conclusion
. Genetic polymorphisms associated with 1-CM may contribute to familial aggregation of AD and somatic diseases. Further highquality family studies using molecular genetic methods are needed.
The introduction of information technologies is inextricably linked with improving the quality and accessibility of medical care, as well as reducing the cost of medical services. Digital ...phenotyping is one of the clinical tools in the field of information technology that allows you to evaluate a person’s phenotype using various personal information devices, such as a smartphone, tablet, smartwatch, various sensors and other computer tools. The advantage of digital phenotyping is the ability to receive information about the patient’s condition in real time, without inpatient and outpatient monitoring and even without the active participation of the patient himself. This fact significantly expands the possibilities of screening and diagnosis of mental disorders, and also helps to track the risks of relapses and take timely measures to prevent an exacerbation of the disease. Information technologies have great prospects for use for scientific purposes — they provide an opportunity to conduct research online that does not require visiting research centers, while at the same time reducing the time and costs of ongoing clinical trials. However, the use of digital phenotyping for scientific and clinical purposes has a number of limitations. For further improvement of digital phenotyping in order to screen psychopathology and subsequent assessment of the condition of patients, it is necessary to develop new psychometric tools used in electronic form and devoid of the shortcomings of questionnaires that are currently being used. This critical review provides data on the current opportunities and problems of digital phenotyping, as well as the prospects for its development.
The need to use large cohorts to identify genetic risk loci for mental disorders has led to the dilemma of phenotyping quality. This dilemma is particularly relevant to mental disorders common in the ...population, such as depression (prevalence throughout life up to 16.2%). On the one hand, there is the very resource-consuming method of acquiring data on patients by physicians applying diagnostic criteria for one of the classifications of mental disorders (DSM-5/ICD-10). On the other hand, there is the popular method of minimal phenotyping using patient registers, with self-assessments by respondents on the symptoms, diagnoses, and treatment of depression. There is currently no ideal method for phenotyping this disorder as a result of the understandable focus of all diagnostic methods only on its clinical symptoms. Active use of minimal phenotyping in genome-wide association studies (GWAS) has led to significant increases in both the clinical and genetic heterogeneity of depression. On the other hand, an important limitation to the use of DSM-5/ICD-10 is the high cost of phenotyping due to the involvement of medical specialists. Thus, the most rational approach is to use electronic diagnostic questionnaires based on DSM-5/ICD-10 criteria. This approach will accelerate increases in the power of studies but retain all the internal contradictions typical of the official diagnostic classifications (phenotype heterogeneity, lack of objective diagnostic criteria, the categorial approach, etc.). This increases the critical role of psychiatric epidemiology both in developing standardized tools for operationalized diagnostic criteria and in running future GWAS research by introducing new phenotypic subtypes of depression and its dimensions.
The COVID-19 pandemic imposed not only serious threats to the physical health of the population, but also provoked a wide range of psychological problems. The study was aimed to define the structure ...of anxiety in the population during the epidemic period, as well as to identify the most vulnerable social groups (including individuals with affective disorders) which were most in need of psychological and/or psychiatric help. The online survey of 1957 Russian-speaking respondents aged over 18 was carried out from March 30 to April 5, 2020. The anxiety distress level was verified using the Psychological Stress Measure (PSM-25), the stigmatization of individuals experiencing respiratory symptoms was assessed using the modified Perceived Devaluation-Discrimination Questionnaire (PDD; Cronbach's α = 0.707). In 99.8% of respondents, the combination of various concerns associated with COVID-19 was observed, the mean psychological stress score was increased to moderate level (score 104.9 ± 34.4), and the stigmatization score exceeded the whole sample median value (19.5±3.4; Me = 17). About 35% of respondents had concerns associated with anxiety distress (Cohen’s d = 0.16–0.39): these were the "risk of social isolation" and the "possible lack of medication for daily use". The following groups of respondents were the most susceptible to the stress: people with affective disorders, young people (aged ≤20), unemployed persons, single persons, people with no formal education, and women. Thus, the broad sectors of the population need correction of anxiety distress associated with the COVID-19 pandemic. Therefore, the measures’ implementation should be targeted, and in terms of coverage and content oriented to the identified vulnerable social groups.
CD40 receptor is expressed on B lymphocytes and other professional antigen–presenting cells. The binding of CD40 to its ligand CD154 on the surface of T helper cells plays an important role in the ...activation of B lymphocytes required for production of antibodies, in particular, against autoantigens. Association of several single nucleotide polymorphisms (SNPs) located in the non–coding areas of human
CD40
locus with the elevated risk of autoimmune diseases has been demonstrated. The most studied of these SNPs is rs4810485 located in the first intron of the
CD40
gene. Expression of the
CD40
gene in B lymphocytes of donors homozygous for the common allelic variant of this polymorphism (G) is higher than in B cells from donors carrying the minor (T) variant. We investigated the enhancer activity of this fragment of the
CD40
locus in human B cell lines and showed that it is independent on the rs4810485 alleles. However, the minor allelic variants of the rs4810485–linked SNPs rs548231435 and rs115662534 were associated with a significant decrease in the activity of the
CD40
promoter due to the impairments in the binding of EBF1 and STAT1 transcription factors, respectively.
Depression is one of the leading causes of reduced quality of life and social functioning in patients. The prophylaxis of depression is a priority in preventive medicine. Achievement of prophylaxis ...requires the opportunity to detect the risk group within the population. i.e., individuals at high genetic risk of developing depression. This review describes the methodology and design of a project to develop a genetic test system based on a polygenic risk score (PRS) for developing depression taking account of the multiple ethnicity and multicultural nature of the Russian population. The study should yield the first data on the genetic architecture of depression (by the GWAS method) and produce polygenic risk scores (PRS) for developing depression. Development of a genetic test system based on studies of the Russian population in conditions of constantly decreasing costs of genetic studies will provide for an effective transition to the development of preventive medicine in mental health.
Affective disorders (recurrent depressive disorder and bipolar affective disorder) are multifactorial and polygenic diseases, which suggests the involvement of multiple neurobiological mechanisms. ...The phenotype of affective disorders is a heterogeneous group of clinically similar psychopathological symptoms, which also makes it difficult to detect potential biomarkers and new therapeutic targets. To study families at high risk of developing affective disorders using both clinical and molecular genetic approaches can help to study the neurobiological basis of depressive conditions, as well as to identify endophenotypes of affective disorders. The most important criterion for an endophenotype is its heritability, which can be proved only within the framework of the family design of the study. Comprehensive clinical and molecular genetic studies based on family design have the best prospects.
Despite the emergence of new antidepressants with different mechanisms of action, a large number of problems in antidepressant therapy remain. Considering the known antimicrobial activity of ...antidepressants, the role of the microbiota in the thymoanaleptic activity of these drugs is of high interest. In recent years, important data have been obtained on the role of the gut microbiota in the regulation of behavior and the pathophysiology of a number of mental disorders, including depression. Of particular interest is the assessment of the normal intestinal microbiota role in the course of the therapeutic process. The emerging bi-directional interactions between drugs and microorganisms may be critical for personalized drug selection and future drug development. However, at the present time, this problem remains poorly understood. The proposed manuscript articulates the main directions that are of clinical importance and can become an object for further study in this area.The research results indicate that the effect of antidepressants on the microbiota is a promising area, the study of which could provide many important findings for clinical practice. This type of therapeutic manipulation can provide an opportunity for intervention in order to potentiate the activity of antidepressants or to minimize side effects. The problem with this method of intervention is enormous complexity, when manipulations can have both positive and negative effects simultaneously, depending on different strains of microorganisms influencing different therapeutic effects. More research is needed to understand what changes occur in the microbiome with acute and chronic administration of specific antidepressants. Perhaps this will contribute to the development of microbiomodulatory tactics for individualized interventions.
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