Attempted suicide and oxytocin-related gene polymorphisms

Parris, Michelle S.; Grunebaum, Michael F.; Galfalvy, Hanga; Andronikashvili, Ana; Burke, Ainsley K.; Yin, Honglei; Min, Eli; Huang, Yung‐yu; Mann, J. John

doi:10.1016/j.jad.2018.05.022

Cited by 48 publications

(36 citation statements)

References 60 publications

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“…This finding suggests that results from our previous work, in which we found increased risk for social anxiety and depression over time among rs3796863 A-allele carriers who experienced greater interpersonal stress, may have been specific to individuals with higher levels of neuroticism, who were oversampled (Tabak et al, 2016). These results also follow the pattern shown by McQuaid et al (2016) who found higher levels of depression and suicidal ideation among individuals with the rs3796863 AA genotype compared to C-allele carriers (but see Parris et al, 2018;Handley et al, 2019). Results also suggest that accounting for neuroticism in future studies of CD38 genetic variation may help to explain discrepant associations of the rs3796863 A-allele with outcomes such as greater empathy and altruism (Liu et al, 2017), reduced risk of autism spectrum disorders (Munesue et al, 2010), but also higher levels of depression and suicidal ideation (McQuaid et al, 2016).…”

Section: Discussionsupporting

confidence: 83%

Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity

et al. 2020

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CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e., neuroticism) and promising biomarker (i.e., amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression.

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Section: Discussionsupporting

confidence: 83%

Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity

et al. 2020

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“…The interaction effect of the two OXTR SNPs, rs1488467 and rs4564970, with alcohol consumption on trait anger was reported for the Finnish sample of men and women [ 28 ]. The A allele at rs53576 of the OXTR gene was associated with prior suicide attempts, and neither abuse history nor attachment style moderated this relationship [ 29 ]. Data on Chinese Han adolescent highlight the compound effect of stressful life events on aggression and provided evidence of the relationship between the oxytocin system and aggressive behavior [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Oxytocin receptor gene polymorphism (rs53576) and digit ratio associates with aggression: comparison in seven ethnic groups

Butovskaya

Rostovtseva

Butovskaya

et al. 2020

J Physiol Anthropol

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Background The specific role of the oxytocin receptor ( OXTR ) gene polymorphisms in emotional support seeking, related to social norms and culturally normative behavior, has been discussed in several studies. Evidence on the association between aggression and OXTR polymorphisms has also been reported. The goal of the current study was to analyze the effect of the OXTR rs53576 polymorphism, prenatal testosterone effect (second-to-fourth digit ratio, or 2D:4D), and culture on aggression assessed with the Buss-Perry Aggression Questionnaire (BPAQ). Methods The data were collected in Russia and Tanzania and included seven ethnic groups of European, Asian, and African origin. The total sample included 1705 adults (837 males, 868 females). All the subjects were evaluated with the BPAQ. As a measure of prenatal androgenization, the second and fourth digits were measured directly from hand, and the digit ratios were calculated. All the participants provided buccal samples, from which genomic DNA was extracted, and the OXTR gene rs53576 polymorphism was genotyped. Statistical analysis was performed using SPSS version 23.0; the alpha level for all analyses was set at 0.05. Results The ethnic group factor was the most significant predictor of ratings on BPAQ (medium effect size for physical aggression, anger and hostility scales, and low for verbal aggression). To study the effect of sex, the OXTR polymorphism, and prenatal androgenization, we conducted the z -score transformation for BPAQ scales and 2D:4D for each ethnic group and pooled these data into new z -score variables. According to the GLM analysis after leveling the effects of culture (z-transformation), all four scales of BPAQ demonstrated association with sex (main effects), with men scoring higher on physical and verbal aggression and women scoring higher on anger and hostility. Anger and hostility scales were also associated with OXTR polymorphism and 2D:4D of the right hand. The lowest levels of anger and hostility were observed in individuals with the AA genotype, especially in men. Conclusions Our data suggest that both oxytocin ( OXTR gene polymorphism) and fetal testosterone (2D:4D) may significantly affect emotional (anger) and cognitive (hostility) aggression in humans, given the leveling the role of culture.

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“…Since oxytocin was shown to regulate different social behaviors including social recognition, affiliation and response to threat ( Meyer-Lindenberg et al., 2011 ; Skuse and Gallagher, 2009 ) via regulation of HPA axis and attenuate amygdala's response to stress ( Bernhard et al., 2016 ), the OXTR gene became explored with respect to depressive mood, stress reactivity, antisocial behavior, emotional loneliness ( Inoue et al., 2010 ; Kang et al., 2017 ; Kawamura et al., 2010 ; LoParo et al., 2016 ; Lucht et al., 2009 ; Thompson et al., 2011 ). Congruent with a suggestion that variations in the OXTR gene may differentially affect oxytocin regulation moderated by the effect of family environment, several studies clarified the effect of gene-by-environment interactions based on the OXTR gene variants in clinical samples ( Asherin et al., 2019 ; Choi et al., 2019 ; Elwood et al., 2019 ; Park et al., 2019 ; Parris et al., 2018 ). However, no findings of OXTR -by-environment effect on depressive-like behavior in non-clinical cohort were published to date.…”

Section: Introductionmentioning

confidence: 99%

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

Казанцева

Davydova

Enikeeva

et al. 2020

Heliyon

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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.

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Attempted suicide and oxytocin-related gene polymorphisms

Cited by 48 publications

References 60 publications

Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity

Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity

Oxytocin receptor gene polymorphism (rs53576) and digit ratio associates with aggression: comparison in seven ethnic groups

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

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