[Anhedonia in mood disorders and somatic diseases: results of exploratory Mendelian randomization analysis]. / Angedoniya pri rasstroistvakh nastroeniya i somaticheskikh zabolevaniyakh: rezul'taty razvedochnogo Mendelevskogo randomizatsionnogo analiza.

OBJECTIVE: To conduct an exploratory Mendelian randomization analysis of the causal relationships of anhedonia with a wide range of psychiatric and somatic phenotypes based on the genetic data of participants in a population study. MATERIAL AND METHODS: This cross-sectional study included 4520 participants, of which 50.4% (n=2280) were female. The mean age was 36.8 (S.D.=9.8) years. Participants were pheno-nailed based on the DSM-5 criteria for anhedonia in the framework of depression. An episode of anhedonia exceeding 2 weeks during life was reported by 57.6% (n=2604) of participants. A genome-wide association study (GWAS) of the anhedonia phenotype was performed, as well as a Mendelian randomization analysis using summary statistics of large-scale GWASs on psychiatric and somatic phenotypes. RESULTS: The GWAS on anhedonia did not reveal the variants with genome-wide significant association (p<10-8). The most significant (p=9.71×10-7) was the variant rs296009 (chr5:168513184) in an intron of the slit guidance ligand 3 (SLIT3) gene. Using Mendelian randomization, nominally significant (p<0.05) causal associations of anhedonia with 24 phenotypes were identified, which can be divided into 5 main groups: psychiatric/neurological diseases, inflammatory diseases of the digestive system, respiratory diseases, oncological diseases and metabolic disorders. The most significant causal effects of anhedonia were found for breast cancer (p=0.0004, OR=0.9986, 95% confidence interval (CI) (0.9978-0.999)), minimal depression phenotype (p=0.009, OR=1.004, 95% CI (1.001-1.007)), as well as for apolipoprotein A (p=0.01, OR=0.973, 95% CI (0.952-0.993)) and respiratory diseases (p=0.01, OR=0.9988, 95% CI (0.9980-0.9997)). CONCLUSION: The polygenic nature of anhedonia may cause the risks of comorbidity of this phenotype with a wide range of somatic diseases, as well as may be associated with mood disorders.

[Association of depression and anxiety with somatic diseases: negative lifestyle factors impact]. / Svyaz' depressii i trevogi s somaticheskimi zabolevaniyami: rol' negativnykh vneshnikh faktorov.

OBJECTIVE: To assess the associations of various depression and anxiety phenotypes with manifestations of different somatic disorders and negative lifestyle factors. MATERIAL AND METHODS: The study involved 5116 people. In the online questionnaire, participants provided information about age, sex, height and weight, as well as a history of smoking, alcohol use, physical activity and diagnoses/symptoms of various physical diseases. Self-questions based on the DSM-5 criteria and the online version of the HADS were used to screen for phenotypes of affective and anxiety disorders in a population sample. RESULTS: An association of both subclinical and clinical depressive symptoms on HADS-D was noted for respondents with weight gain (OR 1.43; CI: 1.29-1.58, p<0.05 and OR 1,CI: 1.05-1.52, p<0.05, respectively), increased BMI (OR 1.36; CI: 1.24-1.48, p<0.05 OR 1.27; CI: 1.09-1.47, p<0.05 respectively), and decreased physical activity (OR 1.67; CI: 1.35-2.07, p<0.05 and OR 2.35; CI: 1.59-3.57, p<0.05, respectively) at the time of testing. The phenotypes of depression, anxiety disorders, and bipolar disorder by DSM criteria were associated with a history of smoking. (OR 1.37; CI: 1.18-1.62, p<0.001; OR 1.36; CI: 1.24-1.48, p<0.05 and OR 1.59; CI: 1.26-2.01, p<0.001, respectively). For higher BMI the association was reported only for the bipolar depression phenotype (OR 1.16; CI: 1.04-1.29, p<0.05), and with a decrease in physical activity - for the phenotypes of major depression and anxiety disorders (OR 1.27; CI: 1.07-1.52, p<0.05 and OR 1.61; CI: 1.31-1.99, p<0.001, respectively). A significant association with various somatic disorders was noted for all phenotype variants, but to the greatest extent for those based on DSM criteria. CONCLUSIONS: The study confirmed the association of negative external factors and various somatic disorders with depression. These associations were noted for various phenotypes of anxiety and depression, both in severity and structure, and may be due to complex mechanisms that have shared biological and environmental mechanisms.

[The association of serum folate levels with schizophrenia symptoms]. / Assotsiatsiya urovnya folatov syvorotki krovi s klinicheskimi simptomami shizofrenii.

OBJECTIVE: To evaluate the association of serum folate levels with schizophrenia and its clinical characteristics in patients from a Russian sample. MATERIAL AND METHODS: Ninety-three patients with schizophrenia and 60 healthy volunteers were examined. Determination of serum folate levels was performed by chemiluminescent immunoassay on microparticles (Architect, Abbott Lab SA). Symptoms of schizophrenia were assessed with the Positive and Negative Syndrome Scale, the Calgary Schizophrenia Depression Scale, the Snight-Hamilton Anhedonia Scale, the Brief Assessment of Cognition in Schizophrenia, the Personal and Social Performance Scale, the Scale for Therapy Side-Effects assessment, Simpson-Angus scales, abnormal involuntary movements scale, Barnes akathisia rating scale. Statistical analysis was performed using the Statistica 6.0. Since the data distribution was different from normal, non-parametric criteria were used. RESULTS: Patients had significantly lower folate levels than healthy controls (p=0.00053), mainly in women (p=0.0025). At the same time, in all the subgroups (including healthy ones), the vast majority of the participants had folate levels below the median (9.95 ng/ml) and in the lower quartile of the reference values. In patients, folate levels are inversely correlated with the severity of most negative symptoms and directly correlated with all measures of cognitive functions. Patients with folate levels below the reference values differed from other patients by a greater severity of the total score of negative symptoms (p=0.023), Marder's factors of negative symptoms (p=0.046) and disorganized thinking (p=0.033), a greater severity of general side effects of therapy (p=0.021) and all measures of cognitive functions except for verbal memory. Smoking has a significant effect on serum folate levels in all participants (p=0.016). There was also an inverse association of folate levels with the selectivity of antipsychotics (p=0.035), and more severe folate deficiency in inpatients than outpatients (p=0.0063). CONCLUSION: The results obtained in the Russian sample on the association of folate deficiency with schizophrenia and a wide range of clinical indicators, including those affecting the prognosis of schizophrenia, indicate the high relevance of further study of this topic and the introduction of approaches to augmentation of antipsychotic therapy for schizophrenia with folates.

[Validation of a DSM-5-based screening test using digital phenotyping in the Russian population]. / Validatsiya skriningovogo testa, osnovannogo na kriteriyakh DSM-5, metodom tsifrovogo fenotipirovaniya na rossiiskoi populyatsii.

OBJECTIVE: To evaluate the validity of a depression and anxiety screening test based on DSM-5 diagnostic criteria to identify cases of these conditions simultaneously assessed with the validated Hospital Anxiety and Depression Scale (HADS) in a population sample by digital phenotyping. MATERIAL AND METHODS: This cross-validation study included 5.116 respondents (mean age 36.9 (9.8)), of which 49.4% (2526) were women. The depression and anxiety screening test was done in electronic form and based on the DSM-5 diagnostic criteria for major depressive disorder and generalized anxiety disorder. The validated HADS scale was used as a standard test. The categories of depression (HADS-D) and anxiety (HADS-A) phenotypes were formed with a cutoff of ≥8 points and ≥11 points. The main parameters of the validity of the screening test were calculated, including accuracy (Ac), sensitivity (Sn) and specificity (Sp) with their 95% confidence intervals [CI]. RESULTS: The prevalence of current depression and anxiety according to the screening test was 7.8% (400) and 12.5% (639), respectively. The prevalence of lifetime depression was 25.9% (1327). For the HADS-D depression subscale with cut-offs of ≥11 and ≥8 points, the prevalence of depression was 3.4% (174) and 15% (766), respectively. For the HADS-A anxiety subscale with cut-offs of ≥11 and ≥8 points, the prevalence of anxiety was 8.9% (456) and 31.8% (1628), respectively. For HADS-D and HADS-A with a cutoff of ≥11 points, the parameters of current depression were Ac=92%, Sn=47% (CI 95% [39-54]), Sp=94% (CI 95% [93-94]), lifetime depression - Ac=75%, Sn=63% (CI 95% [56-70]), Sp=75% (CI 95% [74-77]) and current anxiety - Ac=88%, Sn=54% (CI 95% [50-59]) and Sp=92% (CI 95% [90-92]). For HADS-D and HADS-A with a cutoff of ≥8 points, the parameters of current depression were Ac=86%, Sn=30% (CI 95% [27-33]), Sp=96% (CI 95% [95-97]), lifetime depression - Ac=74%, Sn=51% (CI 95% [48-55]), Sp=75% 79% (CI 95% [77-80]) and current anxiety - Ac=75%, Sn=31% (CI 95% [29-33]), Sp=96% (95% CI [95-97]). CONCLUSION: The high Ac and Sp of this test allows it to be used for screening purposes to identify (but not exclude) cases of depression and anxiety in the population. However, further studies are needed to validate the screening test using a diagnostic interview with a physician.