Individual Burden of Illness Index in Bipolar Disorder Remission: A Cross-Sectional Study.

BACKGROUND: A population-based method for estimating disease burden is commonly used. Nevertheless, these measurements do not entirely capture the comprehensive burden of illness on an individual patient. To address the problem, the Individual Burden of Illness Index (IBI index) Index was created and validated, specifically for major depressive disorder. The IBI represents the overall influence of the condition, encompassing distress from symptom intensity, functional impairment, and the patient's quality of life. AIM: The aim of the study was to approve and validate the IBI index for the integral assessment of disease burden in patients with bipolar disorder (BD) in remission. METHODS: The cross-sectional study was conducted in the outpatient psychiatric services in Saint Petersburg, Russia, from April through October 2020. Eighty-five patients aged 18 to 45 (mean age 36.6±5.7 years) with BD (type I - 75%, n=64; type II - 25%, n=21) in remission were examined. The study procedure included a structured clinical interview and the use of clinical scales: the World Health Organization's Quality of Life Questionnaire, Hamilton Rating Scale for Depression (HDRS), Young Mania Rating Scale (YMRS), and Personal and the Social Performance Scale. RESULTS: The principal component analysis in accordance with the adjusted one showed that the burden of illness in patients with BD in remission is directly related to the severity of residual depressive symptoms, reflected in the HDRS score: as the HDRS score increases (0.27, p <0.001), residual mania (-0.14, p <0.001), social functioning (-0.06, p <0.001), and quality of life (-0.04, p <0.001) decrease. In contrast, when there are remaining residual mania symptoms, as indicated by the YMRS score, the result tends to be a lower burden, better social functioning, and enhanced quality of life. CONCLUSION: The study has demonstrated through statistical means a successful adaptation and validation of the previously calculated IBI index for patients with BD in remission. Residual affective symptoms were shown to have different impacts on the social functioning of patients with BD in remission, indicating the need for a timely assessment and targeted therapy of these symptoms in such patients.

Mental health, minority stress and discrimination against transgender people: a cross-sectional survey in Russia.

Mental health needs of transgender people in Russia remain unmet and stigmatised as in many other countries around the globe. The aim of this study was to assess the stressors and perceived need for mental health care among transgender people in Russia. A structured online survey was conducted in November 2019. A total of 588 transgender adults (mean age: 24.0 ± 6.7) was included in the final analysis. An overwhelming majority of respondents (95.1%) reported stress in their lives. Financial burden (73.5%), relationships with relatives (59.4%), and intimate relationships (37.9%) were among the most frequently reported sources of stress. Most of respondents (71.8%) indicated that the psychological distress they perceived interfered with their ability to lead a fulfilling social life. More than half of the respondents (52.4%) had visited a mental health professional prior to their gender transition. Virtually half of them (49%) reported problems related to seeking mental healthcare attributed to stigma. Over one third (37.8%) reported taking non-prescription or off-label medications to improve their well-being or mood. Our study confirmed high rates of psychiatric problems in this vulnerable group and problems in help-seeking. The article also discusses the challenges of providing psychiatric care to transgender people in Russia.

Altered Sphingolipid Hydrolase Activities and Alpha-Synuclein Level in Late-Onset Schizophrenia.

Recent data described that patients with lysosomal storage disorders (LSDs) may have clinical schizophrenia (SCZ) features. Disruption of lipid metabolism in SCZ pathogenesis was found. Clinical features of schizophrenia (SCZ) have been demonstrated in patients with several lysosomal storage disorders (LSDs). Taking into account the critical role of lysosomal function for neuronal cells' lysosomal dysfunction could be proposed in SCZ pathogenesis. The current study analyzed lysosomal enzyme activities and the alpha-synuclein level in the blood of patients with late-onset SCZ. In total, 52 SCZ patients with late-onset SCZ, 180 sporadic Parkinson's disease (sPD) patients, and 176 controls were recruited. The enzymatic activity of enzymes associated with mucopolysaccharidosis (alpha-L-Iduronidase (IDUA)), glycogenosis (acid alpha-glucosidase (GAA)) and sphingolipidosis (galactosylceramidase (GALC), glucocerebrosidase (GCase), alpha-galactosidase (GLA), acid sphingomyelinase (ASMase)) and concentration of lysosphingolipids (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), and lysosphingomyelin (LysoSM)) were measured using LC-MS/MS. The alpha-synuclein level was estimated in magnetically separated CD45+ blood cells using the enzyme-linked immunosorbent assay (ELISA). Additionally, NGS analysis of 11 LSDs genes was conducted in 21 early-onset SCZ patients and 23 controls using the gene panel PGRNseq-NDD. Decreased ASMase, increased GLA activities, and increased HexSpn, LysoGb3, and LysoSM concentrations along with an accumulation of the alpha-synuclein level were observed in late-onset SCZ patients in comparison to the controls (p < 0.05). Four rare deleterious variants among LSDs genes causing mucopolysaccharidosis type I (IDUA (rs532731688, rs74385837) and type III (HGSNAT (rs766835582)) and sphingolipidosis (metachromatic leukodystrophy (ARSA (rs201251634)) were identified in five patients from the group of early-onset SCZ patients but not in the controls. Our findings supported the role of sphingolipid metabolism in SCZ pathogenesis. Aberrant enzyme activities and compounds of sphingolipids associated with ceramide metabolism may lead to accumulation of alpha-synuclein and may be critical in SCZ pathogenesis.

Genetic Predisposition to Schizophrenia and Depressive Disorder Comorbidity.

Background: Patients with schizophrenia have an increased risk of depressive disorders compared to the general population. The comorbidity between schizophrenia and depression suggests a potential coincidence of the pathophysiology and/or genetic predictors of these mental disorders. The aim of this study was to review the potential genetic predictors of schizophrenia and depression comorbidity. Materials and Methods: We carried out research and analysis of publications in the databases PubMed, Springer, Wiley Online Library, Taylor & Francis Online, Science Direct, and eLIBRARY.RU using keywords and their combinations. The search depth was the last 10 years (2010-2020). Full-text original articles, reviews, meta-analyses, and clinical observations were analyzed. A total of 459 articles were found, of which 45 articles corresponding to the purpose of this study were analyzed in this topic review. Results: Overlap in the symptoms and genetic predictors between these disorders suggests that a common etiological mechanism may underlie the presentation of comorbid depression in schizophrenia. The molecular mechanisms linking schizophrenia and depression are polygenic. The most studied candidate genes are GRIN1, GPM6A, SEPTIN4, TPH1, TPH2, CACNA1C, CACNB2, and BCL9.Conclusion: Planning and conducting genome-wide and associative genetic studies of the comorbid conditions under consideration in psychiatry is important for the development of biological and clinical predictors and a personalized therapy strategy for schizophrenia. However, it should be recognized that the problems of predictive and personalized psychiatry in the diagnosis and treatment of schizophrenia and comorbid disorders are far from being resolved.

Association of a Single-Nucleotide Variant rs11100494 of the NPY5R Gene with Antipsychotic-Induced Metabolic Disorders.

BACKGROUND: The usage of antipsychotics (APs) is the most robust and scientifically based approach in the treatment of schizophrenia spectrum disorders (SSDs). The efficiency of APs is based on a range of target receptors of the central nervous system (CNS): serotoninergic, dopaminergic, adrenergic, histaminergic and cholinergic. Metabolic disorders are the most severe adverse drug reactions (ADRs) and lead to cardiovascular diseases with a high rate of mortality in patients with SSDs. Neuropeptide Y receptor Y5 (NPY5R) is known in the chain of interaction to target receptors for APs, agouti-related peptide receptors and proopiomelanocortin receptors. We studied the association of the single-nucleotide variants (SNVs) rs11100494 and rs6837793 of the NPY5R gene, and rs16147, rs5573, rs5574 of the NPY gene, with metabolic disorders in Russian patients with SSDs. METHODS: We examined 99 patients with SSDs (mean age-24.56 years old). The mean duration of APs monotherapy was 8 weeks. The biochemical blood test included levels of glucose, cholesterol, lipoproteins, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein and albumin. Anthropometry included weight, height, waist circumference and hip circumference. We used real-time PCR to study the carriage of major and minor alleles of the SNV rs11100494 (1164C>A) of the NPY5R gene (chromosome localization-4q32.2). Group 1 comprised 25 patients with SSDs taking APs with a change in body weight of more than 6% since the start of APs therapy. Group 2 comprised 74 patients with SSDs taking APs with a change in body weight of less than 6% since the start of APs therapy. RESULTS: We show the significance of genetic risk factors (carriage of major allele C of SNV rs11100494 of the NPY5R gene) for the development of AP-induced weight gain in Russian patients with SSDs. The allele C predisposes to AP-induced weight gain (OR = 33.48 [95% CI: 12.62; 88.82], p-value < 0.001). Additionally, the results of our study demonstrate that first-generation APs (FGAs) are more likely to cause an increase in serum transaminase levels but are less likely to increase body weight. Second-generation APs (SGAs) are more likely to cause weight gain and changes in serum glucose levels. CONCLUSION: Our study shows the predictive role of the allele C of SNV rs11100494 of the NPY5R gene in the development of AP-induced weight gain. However, we did not find a significant association between biochemical markers and this SNV in Russian patients with SSDs.

Anxiety and Depression Among Transgender People: Findings from a Cross-Sectional Online Survey in Russia.

Purpose: As we still do not know enough about the mental health concerns of gender minority people in Russia, there is a need to initiate research on these issues. We aimed to examine the frequency of anxiety and depression symptoms in a Russian sample of transgender people. Methods: The study consisted of a structured online survey and was conducted throughout November 2019. The Hospital Anxiety and Depression Scale was used for online screening of anxiety and depression symptoms. A total of 588 transgender adults living in all Federal Districts of Russia (mean age 24.0 ± standard deviation 6.7) was included in the final analysis. Results: It was found that 45.1% (n = 265) and 24.0% (n = 141) of transgender people had clinically significant levels of anxiety and depression, respectively. No statistically significant differences in the prevalence of anxiety and depression were found among those who identified as a transgender man, a transgender woman, or other transgender identities. The anxiety and depression mean scores in the sample were statistically significantly higher than in the general Russian population (p < 0.001). No statistically significant differences were found in the level of depression and anxiety symptoms among respondents in Moscow, St. Petersburg, and other Russian cities. Conclusions: We found high rates of clinical symptoms of depression and anxiety among transgender people, consistent with international research. The study highlights the need for further research on the psychological well-being and mental health of transgender people, and the availability of psychiatric care to transgender people living in Russia.

The combined effect of CYP2D6 and DRD2 Taq1A polymorphisms on the antipsychotics daily doses and hospital stay duration in schizophrenia inpatients (observational naturalistic study).

BACKGROUND: To assess the correlation between the antipsychotics (AP) mean daily doses, hospital stay duration and CYP2D6, DRD2 polymorphisms in naturalistic study. SUBJECTS AND METHODS: CYP2D6 polymorphisms *3, *4, *5, *6, *1XN and DRD2/ANKK1 Taq1A polymorphisms were genotyped in a cohort of 226 Caucasian schizophrenic inpatients. AP daily doses, hospital stay duration and AP treatment duration were taken from medical records. To compare mean daily doses of AP among CYP2D6 PMs, EMs, UMs and DRD2/ANKK1 Taq1A carriers the actual AP doses were converted to chlorpromazine (CPZ) equivalents and DDD (defined daily dose). RESULTS: Significant correlation (p=0.004) between CYP2D6 metabolic activity and AP mean daily doses was observed only among DRD2/ANKK1 Taq1A polymorphic allele carriers: 250.53 (95%CI: 154.90-346.17), 473.82 (95%CI: 426.99-520.64) 602.77 (95%CI: 469.65-735.88) CPZ equivalents in PMs, EMs and UMs, consequently. PMs with DRD2/ANKK1 Taq1A CT genotype received significantly lower doses of AP comparing to CC genotype (p=0.02). Mean hospital stay duration of PMs+UMs was significantly higher comparing to EMs (66.4 days (95% CI: 56.9-75.8) vs 50.2 days (95%CI: 45.5-54.7); p=0.047). CONCLUSIONS: In a cohort of schizophrenia inpatients CYP2D6 metabolic activity affects mean AP daily dose only in the presence of DRD2 Taq1A polymorphic allele. CYP2D6 metabolic activity correlates independently from DRD2 Taq1A polymorphism with hospital stay duration. Subpopulation of schizophrenia inpatients with altered CYP2D6 activity (PMs and UMs) carriers of Taq1A polymorphisms needs special attention of clinicians in aligning of AP treatment.