AVPR1A main effect and OXTR-by-environment interplay in individual differences in depression level

Abstract

Background Multiple studies of depression indicated a significant role of gene-by-environment interactions; however, they are mainly limited to the examination of modulating effect of recent stressful life events. Other environmental factors occurring at different stages of ante- and postnatal development may affect the association between multiple genes and depression. The study aimed to analyze the main and haplotype-based effect of serotonergic system and HPA-axis gene polymorphisms on depression and to detect gene-by-environment interaction models explaining individual variance in depression in mentally healthy young adults from Russia. Methods Depression score was assessed using Beck Depression Inventory (BDI) in 623 healthy individuals (81% women; 17-25 years) of Caucasian origin (Russians, Tatars, Udmurts) from Russia. The main- and gene-based effects of 12 SNPs in SLC6A4 (5-HTTLPR, rs1042173), HTR2A (rs7322347), OXTR (rs7632287, rs2254298, rs13316193, rs53576, rs2228485, rs237911), AVPR1A (rs3803107, rs1042615), and AVPR1B (rs33911258) genes, and gene-by-environment interactions were tested with linear regression models (PLINK v.1.9) adjusted for multiple comparisons. Results We observed ethnicity-specific main effect of the AVPR1A rs3803107 (P = 0.003; P FDR = 0.047) and gene-based effect of the OXTR gene (Р = 0.005; P perm = 0.034) on BDI-measured depression, and modifying effect of paternal care on OXTR rs53576 (P = 0.004; P FDR = 0.012) and birth order on OXTR rs237911 (P = 0.006; P FDR = 0.018) association with depression level. Limitations A hypothesis driven candidate gene approach, which examined a limited number of genetic variants in a moderately large sample, was used. Conclusions Our preliminary findings indicate that familial environment may play a permissive role modulating the manifestation of OXTR -based depression variance in mentally healthy subjects.

Oxytocin receptor polymorphism influences characterization of harm avoidance by moderating susceptibility to affectionless control parenting

“…Taken together, these results suggest that OXTR polymorphism does not affect the personality traits directly, but it might influence the characterization of harm avoidance by moderating susceptibility to AC parenting. These results are in line with those of earlier studies which suggest that the A allele is sensitive to negative parental environments such as maternal depression and low paternal care during childhood, which are related to increased susceptibility to depressive symptoms and behavioral problems (Choi et al., 2019 ; Kazantseva et al., 2020 ; Thompson et al., 2014 ). This report is the first of a study that specifically examines interaction effects between OXTR polymorphism and the environment on personality.…”

“…Therefore, associations of this polymorphism with personality must be re‐examined. Furthermore, the results of recent studies particularly addressing the gene–environment interactions suggest that A allele carriers of the polymorphism are sensitive to childhood negative environments, leading to increased depressive symptoms (Kazantseva et al., 2020 ; Thompson et al., 2014 ) and behavioral problems (Choi et al., 2019 ). Nevertheless, no report has described a study examining effects of interaction between this polymorphism and environments on personality traits.…”

The role of the KIBRA and APOE genes in developing spatial abilities in humans

“…All enrolled individuals filled the inventory consisting of questions on ethnicity by three generations together with several social parameters such as the specificity of child-parent relationship (a style of parental rearing, maltreatment in childhood, rearing in a full/incomplete family), family income level, maternal and paternal age at individual's birth, place of residence in childhood, sibship size and birth order, bilingual rearing, the presence of chronic disorders and smoking. Place of residence in childhood (urban/rural residency) was determined on the basis of its population size according to (Kazantseva et al, 2020a): demographic locations with population size under 50,000 individuals were determined as a rural residency. All the volunteers filled informed consents for the participation in the study.…”

Individual Differences in Relative Telomere Length in Mentally Healthy Subjects: The Effect of TERT Gene Polymorphism and Urban Residency

“…In addition, all the subjects filled out a questionnaire to obtain the data on ethnic background up to three generations and specificity of rearing and parent–childhood relations, including the episodes of childhood maltreatment, rearing in a complete/incomplete family, family income, maternal age at delivery, place of residence (urban/rural), number of children in a family, and individual weight at birth (weight under 2500 g was considered as low). The place of residence (urban/rural residency) was determined on the basis of the population of the locality: demographic units with a population less than 50 000 people were assigned to rural areas [ 21 ]. On the basis of the survey, we formed the database consisting of information on birth order and sibship size (number of children in a family), rearing style (according to the Parental Bonding Inventory), and rearing in a bilingual family for individuals of Tatar and Udmurt origin.…”

“…The accumulation of age-dependent reactive oxygen species and free radicals in the cells, which is associated with the effects of stress factors, inflammatory reactions, and unhealthy lifestyle (smoking, excessive alcohol intake, low physical activity), results in shortening of telomeres [ 2 , 18 ]. Considering a possible effect of the aforementioned environmental factors on the emotional state [ 20 , 21 ] and cellular aging of the body, the study of a large array of sociodemographic characteristics in the context of their effect on telomere length is of relevance.…”