[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.

[Family history of mood disorders may weaken the link between adverse childhood experience and suicidality in patients with depression]. / Svyaz' semeinoi otyagoshchennosti rasstroistvami nastroeniya s neblagopriyatnym detskim opytom i suitsidal'nost'yu u patsientov s depressiei.

OBJECTIVE: To study the impact of family history of mood disorders (FHMD), comprising genetic factors associated with depression, on the association between adverse childhood experience (ACE) and suicidality in depression. MATERIAL AND METHODS: This multicenter cross-sectional study included 200 in- and outpatients (64% (n=128) women, mean age - (M (SD)) 36.21 (15.09) yrs.) with depression. Self-reports about FHMD and lifetime suicide attempts were obtained in clinical interview. The lifetime intensity of suicidal ideas and behavior was assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), ACE - by the Adverse Childhood Experience International Questionnaire (ACE-IQ). RESULTS: FHMD did not affect the prevalence of ACE, suicide attempts and C-SSRS scores. We found that FHMD weakens the link between ACE and the risk of suicide attempt. The emotional neglect itself increased the risk of suicide attempt (p=0.001, OR=4.428, CI 95% [1.797-10.911]), but reduced it in patients with FHMD (p=0.03, OR=0.128, CI 95% [0.018-0.893]). GLM analysis revealed that FHMD significantly affected the association between suicidal ideas and domestic violence (p=0.045) and between suicidal behavior and emotional neglect (p=0.015) and abuse (p=0.044). CONCLUSION: FHMD may weaken the link between ACE and suicidality in patients with depression. Suicidality in these patients may be underlined by mechanisms not involved in the response to ACE although more studies are needed.

[Modern approaches to the genetics of depression: scopes and limitations]. / Sovremennye podkhody k izucheniyu genetiki depressii: vozmozhnosti i ogranicheniya.

Recent findings in candidate genes for depression showed significant replication failures and thus appeared irrelevant. Much of the earlier studies' limitations can be overcome by the strategy of genome-wide association studies (GWAS), which aims to identify associations between different genomic variants and phenotypic traits without pathophysiological hypotheses application. With the use of such studies, it seems possible to calculate polygenic risk scores (PRS) as a promising approach for predicting depression risk. The aim of this review is to analyze modern approaches of genetic research used to assess the risk of depression in a population.