Genetic Associations of Anhedonia: Insights into Overlap of Mental and Somatic Disorders.

BACKGROUND: Anhedonia is characterized by a reduced ability to anticipate, experience, and/or learn about pleasure. This phenomenon has a transdiagnostic nature and is one of the key symptoms of mood disorders, schizophrenia, addictions, and somatic conditions. AIM: To evaluate the genetic architecture of anhedonia and its overlap with other mental disorders and somatic conditions. METHODS: We performed a genome-wide association study of anhedonia on a sample of 4,520 individuals from a Russian non-clinical population. Using the available summary statistics, we calculated polygenic risk scores (PRS) to investigate the genetic relationship between anhedonia and other psychiatric or somatic phenotypes. RESULTS: No variants with a genome-wide significant association were identified. PRS for major depression, bipolar disorder, and schizophrenia were significantly associated with anhedonia. Conversely, no significant associations were found between PRS for anxiety and anhedonia, which aligns well with existing clinical evidence. None of the PRS for somatic phenotypes attained a significance level after correction for multiple comparisons. A nominal significance for the anhedonia association was determined for omega-3 fatty acids, type 2 diabetes mellitus, and Crohn's disease. CONCLUSION: Anhedonia has a complex polygenic architecture, and its presence in somatic diseases or normal conditions may be due to a genetic predisposition to mood disorders or schizophrenia.

Antimicrobial activity of antidepressants on normal gut microbiota: Results of the in vitro study.

Currently, there is little published data on the effects of antidepressants on normal gut microbiota and the consequences of such effects on treatment outcomes. The aim of the study: was to evaluate the growth kinetics of normal human gut microorganisms with antidepressants most common in routine clinical practice. Materials and methods: Research objects were species of microorganisms representing normal gut microbiota: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Candida albicans ATCC 24433, Bifidobacterium 791, Enterococcus faecalis ATCC 29212, Lactobacillus rhamnosus ATCC 53103. All microorganisms were cultivated in Schaedler broth (HiMedia) under aerobic/anaerobic conditions. The active substances of all studied antidepressants (fluvoxamine, fluoxetine, escitalopram, duloxetine, venlafaxine, mirtazapine) were extracted from ground preparations by dimethyl sulfoxide and centrifuged. Each solution of antidepressants was added to a Schaedler broth containing a certain microorganism's strain and diluted to final concentrations-200 µg/ml, 500 µg/ml, and 700 µg/ml. For a quantitative assessment of the effect, the specific growth rates (µ, h-1) of microorganisms were calculated as the slope of the initial part of the growth curve in coordinates (lnA, t). To evaluate the antidepressant effects on representatives of the normal microbiota in vitro, the following parameters were chosen: specific growth rate and IC50. Results: All antidepressants had an inhibitory effect on the growth of all studied microorganisms. Fluvoxamine and venlafaxine had the least effect on the growth activity of all studied microorganisms. Fluoxetine showed a pronounced effect on growth activity against E. coli, E. feacalis, S. aureus, and the least effect against C. albicans. Escitalopram had a greater effect on the growth rate of E. coli, E. feacalis, B. bifidum, L. rhamnosus, and C. albicans, which puts it among the leaders in terms of its effect on the growth activity of the microorganisms we studied. Mirtazapine, according to the results of our experiment, showed the greatest activity against L. rhamnosus and C. albicans. Conclusions: Our results confirm the effects of antidepressants on the growth activity of the normal gut microbiota individual strains. Further study of the antimicrobial activity of antidepressants may become one of the new directions for optimizing the personalized therapy of patients with depression.

Prevalence of eating disorders in patients with bipolar disorder: a scoping review of the literature.

BACKGROUND: Eating disorder (ED) and bipolar disorder (BD) exhibit certain phenomenological similarities rooted in eating behavior and emotional regulation. However, despite the growing body of research on the comorbidity of ED and BD, scientific data on the concurrent course of these disorders has remained poorly systematized. AIM: To conduct a scoping review of published data on the prevalence of various types of ED among patients with BD types I and II in the context of the sex and clinical features of the concurrent course of these disorders. METHODS: The analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. The search was conducted in the MEDLINE electronic database. Studies were included if they were focused samples of patients diagnosed with BD and ED, and the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions (DSM-IV, DSM-5), or International Statistical Classification of Diseases and Related Health Problems, tenth Revision (ICD-10), were used for the verification of the ED and BD diagnoses. The descriptive analysis method was used to summarize the review findings. RESULTS: A total of 41 studies were selected for the review. Lifetime ED in patients with BD ranged from 2.2% to 31.1%, and the prevalence rates of BD among patients with ED varied from 11.3% to 68.1%. ED nominally had a higher prevalence among individuals with BD type II and females. Additionally, the presence of ED in patients with BD was associated with earlier onset of mood disorder, a higher number of depressive episodes, higher levels of atypical depressive symptoms, suicide attempts, as well as a higher frequency of comorbid obsessive-compulsive and anxiety disorders, addictions, and various metabolic disorders. CONCLUSION: Despite the high degree of volatility in the results, the prevalence rates of a concurrent course of ED and BD are rather high. For this reason, screening for ED in patients with BD and vice versa holds significant value in the accurate diagnosis and selection of the most effective therapy. The patterns of comorbidity among different types of ED and BD, depending on gender, need further exploration in future research.

Determinants of Stress Levels and Behavioral Reactions in Individuals With Affective or Anxiety Disorders During the COVID-19 Pandemic in Russia.

Introduction: Individuals with affective and anxiety disorders are among those most vulnerable to the negative effects of the COVID-19 pandemic. Aim: This study aims to analyze the determinants of stress levels and protective behavioral strategies associated with the COVID-19 pandemic in Russian-speaking people with affective or anxiety disorders (AADs). Materials and Methods: In this cross-sectional online survey, the psychological distress and behavioral patterns of respondents with self-reported AAD (n = 1,375) and without disorders (n = 4,278) were evaluated during three periods of restrictive measures in Russia (March-May 2020). Distress levels were verified using the Psychological Stress Measure (PSM-25). Results: Stress levels among respondents with AAD were higher at all study periods than for those with no mental disorder (Cohen's d 0.8-1.6). The stress level increased (Cohen's d = 0.4) in adolescents (16-18 years) with AAD and remained the same in those without disorders; in youths (19-24 years) with and without disorders, an increase (Cohen's d = 0.3) and a decrease (Cohen's d = 0.3) in the stress were observed, correspondingly; the stress in adults (25-44 years) with disorders did not change and decreased in those without disorders (Cohen's d = 0.4). Individuals with bipolar disorders demonstrated lower stress than individuals with depressive (Cohen's d = 0.15) and anxiety disorders (Cohen's d = 0.27). Respondents with depressive and bipolar disorders employed fewer protective measures simultaneously and were less likely to search for information about COVID-19. Conclusion: The presence of affective or anxiety disorders is associated with a more acute response to the COVID-19 pandemic. Apparently, the type of mental disorder influenced stress levels and protective behavior patterns.

Mental State of Inpatients With COVID-19: A Computational Psychiatry Approach.

Background: The overload of healthcare systems around the world and the danger of infection have limited the ability of researchers to obtain sufficient and reliable data on psychopathology in hospitalized patients with coronavirus disease 2019 (COVID-19). The relationship between severe acute respiratory syndrome with the coronavirus 2 (SARS-CoV-2) infection and specific mental disturbances remains poorly understood. Aim: To reveal the possibility of identifying the typology and frequency of psychiatric syndromes associated with acute COVID-19 using cluster analysis of discrete psychopathological phenomena. Materials and Methods: Descriptive data on the mental state of 55 inpatients with COVID-19 were obtained by young-career physicians. Classification of observed clinical phenomena was performed with k-means cluster analysis of variables coded from the main psychopathological symptoms. Dispersion analysis with p level 0.05 was used to reveal the clusters differences in demography, parameters of inflammation, and respiration function collected on the basis of the original medical records. Results: Three resulting clusters of patients were identified: (1) persons with anxiety; disorders of fluency and tempo of thinking, mood, attention, and motor-volitional sphere; reduced insight; and pessimistic plans for the future (n = 11); (2) persons without psychopathology (n = 37); and (3) persons with disorientation; disorders of memory, attention, fluency, and tempo of thinking; and reduced insight (n = 7). The development of a certain type of impaired mental state was specifically associated with the following: age, lung lesions according to computed tomography, saturation, respiratory rate, C-reactive protein level, and platelet count. Conclusion: Anxiety and/or mood disturbances with psychomotor retardation as well as symptoms of impaired consciousness, memory, and insight may be considered as neuropsychiatric manifestations of COVID-19 and should be used for clinical risk assessment.

Association of antioxidant deficiency and the level of products of protein and lipid peroxidation in patients with the first episode of schizophrenia.

Schizophrenia is considered a multifactorial disease, where one of the pathogenetic links is oxidative stress; however, the results of studies are often contradictory, largely due to significant heterogeneity among study methods. The present study was undertaken to compare the levels of oxidative stress markers in the peripheral blood of patients with a first episode of schizophrenia (FES) and in healthy volunteers (HV). The study included 50 patients with FES and 37 HV. Blood samples were collected for spectrophotometric assessment of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), aldehyde-2,4-dinitrophenylhydrazone (ADNPH), and ketone-2,4-dinitrophenylhydrazone (KDNPH) in blood plasma. Results showed that in patients with FES compared with HV, a significant decrease in CAT activity and an increase in oxidative modification of proteins (OMP) were found. In both groups, a significant increase in the level of MDA with age was revealed. In patients, the GSH plasma level was inversely proportional to the ADNPH level, and SOD activity was directly proportional to the KDNPH level. In volunteers there was no such correlation; however, there was a direct correlation between CAT activity and the levels of OMP and MDA. In both groups, a moderate direct correlation between peroxidation products was observed. The results confirm that a redox imbalance (a deficiency of antioxidants, in particular CAT, and excess OMP) may be a pathogenetic link in schizophrenia, which is manifested already at an early stage of the disease.

GWAS of depression in 4,520 individuals from the Russian population highlights the role of MAGI2 (S-SCAM) in the gut-brain axis.

We present the results of the depression Genome-wide association studies study performed on a cohort of Russian-descent individuals, which identified a novel association at chromosome 7q21 locus. Gene prioritization analysis based on already known depression risk genes indicated MAGI2 (S-SCAM) as the most probable gene from the locus and potential susceptibility gene for the disease. Brain and gut expression patterns were the main features highlighting functional relatedness of MAGI2 to the previously known depression risk genes. Local genetic covariance analysis, analysis of gene expression, provided initial suggestive evidence of hospital anxiety and depression scale and diagnostic and statistical manual of mental disorders scales having a different relationship with gut-brain axis disturbance. It should be noted, that while several independent methods successfully in silico validate the role of MAGI2, we were unable to replicate genetic association for the leading variant in the MAGI2 locus, therefore the role of rs521851 in depression should be interpreted with caution.

Association of Anxiety and Depression with Objective and Subjective Cognitive Decline in Outpatient Healthcare Consumers with COVID-19: А Cross-Sectional Study.

BACKGROUND: In addition to the neurological complications affecting people infected with COVID-19, cognitive impairment symptoms and symptoms of anxiety and depression remain a frequent cause of complaints. The specificity of cognitive impairment in patients with COVID-19 is still poorly understood. AIM: An exploratory study of factors that may be associated with cognitive decline during the COVID-19 pandemic. METHODS: The cross-sectional multicentre observational study was conducted in a polyclinic unit in Saint Petersburg and in the regions of the North-Western Federal Region. During the study, socio-demographic parameters and information about the somatic condition of patients who applied for primary health care was collected. Emotional and cognitive state were investigated using the Hospital Anxiety and Depression Scale (HADS) and Montreal Cognitive Assessment (MoCA). Mathematical and statistical data processing was carried out using SPSS and RStudio statistical programs. RESULTS: The study included 515 participants, 60% (n=310) of which were women. The sample was divided into those who did (28.5%, n=147) and did not (71.4%, n=368) complain of cognitive decline. Patients with complaints of cognitive decline were significantly older, had lower levels of education and higher levels of depression and anxiety according to HADS (p <0.05). Patients with complaints of cognitive decline underwent the MoCA test (24.3%, n=125). The median MoCA test scores were within the normal range (Median=27, Q1=25, Q3=28), and cognitive decline (MoCA less than 26 points) was detected in 40% (n=50) of patients with complaints of cognitive decline. No significant correlations were found between the MoCA scores and the levels of anxiety and depression according to the HADS (p >0.05). Patients with mild severity of the COVID-19 course were more successful with MoCA subtests than patients with moderate and severe courses. CONCLUSION: We found no linear association between objective cognitive deficit and the affective state of respondents. Patients' subjective complaints about cognitive dysfunction were mostly caused by their emotional state than an objective decrease of their cognitive functions. Therefore, in case of subjective complaints on cognitive decline, it is necessary to assess not only the cognitive but also the affective state of the patient. The severity of the COVID-19 course affects the functions of the cognitive sphere, including attention, regulatory functions and speech fluency. Mild and moderate severity of the COVID-19 correlates with clinically determined depression. The absence of this relationship with the severe course of the disease is probably explained by the significant somatic decompensation of patients.

Behavioral and Emotional Reactions of the Russian Population to the Beginning of the COVID-19 Pandemic: An On-Line Survey Results.

BACKGROUND: The study aimed to identify the patterns of adaptive and behavioral strategies in different population groups, also to evaluate their association with the infection prevention strategies and the distress during the COVID-19 pandemic. METHODS: The data were obtained from the on-line survey of 1958 respondents (mean age 31±12 years) from March 30, 2020 to April 5, 2020. 578 respondents reported a history of affective disorders; 884 respondents - a history of somatic disease. The level of anxiety distress was evaluated with the Psychological Stress Measure (PSM-25). The analysis of variance was used for statistics. p<0.05 was considered significant. The effect sizes (ES) were evaluated according to Cohen's d and Cramer's V criteria. RESULTS: The average PSM-25 score corresponded to moderate stress intensity. An increased level of psychological stress was associated with the young age of the respondents, the history of affective disorders and somatic diseases, the compliance with self-isolation, the practice of social distancing, and the use of sanitizer. Concerns about the availability of protective equipment were specifically associated with the self-isolation compliance (ES=0.1); the combination of concerns about the contagiousness of the virus (ES=0.12) and the inaccessibility of daily medications (ES=0.11) - with the principles of social distance. Moreover, the concerns about the lack of specific treatment, the danger to one's own life, the contagiousness of the virus, and the lack of protective equipment were associated with the protective behavior resulting in increased hand hygiene. The history of affective disorders was rarely associated with wearing masks and gloves, but more often - with the use of self-isolation strategies. CONCLUSIONS: The psychological reactions of the population during the COVID-19 pandemic are specifically associated with adaptive behavior in the process of anti-epidemic measures. Respondents with affective disorders experienced specific patterns of anxiety about coronavirus infection in combination with high rates of psychological stress.

Inherited Metabolic Diseases as a Multisystem Model of Mental Disorders Research

Abstract Recent biological and genetic research data confirm shared pathological mechanisms of inherited metabolic diseases and mental disorders. We suggest that for further research a model of synergistic heterozygosity can become a convenient tool. In that case the use of inherited metabolic disorders as a multisystem research model can provide both significant theoretical and practical results. At the initial stage of this hypothesis evaluation, it seems efficient to screen for mental symptoms the families of patients with inherited metabolic disorders.

Stress and Stigmatization in Health-Care Workers during the COVID-19 Pandemic.

BACKGROUND: The health-care workers showed the highest risks of the adverse psychological reactions from the COVID-19 pandemic. AIM: This study aimed to evaluate the structure and severity of psychological distress and stigmatization in different categories of health-care workers during the COVID-19 pandemic. MATERIALS AND METHODS: This study included two phases of online survey in 1800 Russian-speaking health-care workers (March 30 - April 5 and May 4 - May 10, 2020). The Psychological Stress Scale (PSM-25) and modified Perceived Devaluation-Discrimination scale (Cronbach's α = 0.74) were used. Dispersion analysis was performed with P = 0.05, Cohen's d, and Cramer's V calculated (effect size [ES]). RESULTS: The psychological stress levels decreased in the second phase (ES = 0.13), while the stigma levels (ES = 0.33) increased. Physicians experienced more stress compared with nurses and paramedical personnel (ES = 0.34; 0.64), but were less likely to stigmatize SARS-CoV-2-infected individuals (ES = 0.43; 0.41). The increasing probability of contact with infected individuals was associated with higher levels of psychological stress (probable contact ES = 0.48; definite contact ES=0.97). The highest rates of contacts with COVID-19 patients were reported by physicians (χ2 = 123.0; P = 0.00, Cramer's V = 0.2), the youngest (ES = 0.5), and less experienced medical workers (ES = 0.33). CONCLUSION: Direct contact with coronavirus infection is associated with a significant increase in stress among medical personnel. The pandemic compromises the psychological well-being of the youngest and highly qualified specialists. However, the stigmatizing reactions are not directly associated with the risks of infection and are most prevalent among nurses and paramedical personnel.

Opening up new horizons for psychiatric genetics in the Russian Federation: moving toward a national consortium.

We provide an overview of the recent achievements in psychiatric genetics research in the Russian Federation and present genotype-phenotype, population, epigenetic, cytogenetic, functional, ENIGMA, and pharmacogenetic studies, with an emphasis on genome-wide association studies. The genetic backgrounds of mental illnesses in the polyethnic and multicultural population of the Russian Federation are still understudied. Furthermore, genetic, genomic, and pharmacogenetic data from the Russian Federation are not adequately represented in the international scientific literature, are currently not available for meta-analyses and have never been compared with data from other populations. Most of these problems cannot be solved by individual centers working in isolation but warrant a truly collaborative effort that brings together all the major psychiatric genetic research centers in the Russian Federation in a national consortium. For this reason, we have established the Russian National Consortium for Psychiatric Genetics (RNCPG) with the aim to strengthen the power and rigor of psychiatric genetics research in the Russian Federation and enhance the international compatibility of this research.The consortium is set up as an open organization that will facilitate collaborations on complex biomedical research projects in human mental health in the Russian Federation and abroad. These projects will include genotyping, sequencing, transcriptome and epigenome analysis, metabolomics, and a wide array of other state-of-the-art analyses. Here, we discuss the challenges we face and the approaches we will take to unlock the huge potential that the Russian Federation holds for the worldwide psychiatric genetics community.