Genetic Contributions to Attachment Stability Over Time: the Roles of CRHR1 Polymorphisms.

Corticotropin-releasing hormone receptor 1 (CRHR1), a hormone receptor essential to the activation of HPA axis and the subsequent release of cortisol, plays critical roles in emotional and behavioral responses relevant to attachment. However, the specific roles of CRHR1 polymorphisms in attachment remain unclear. To further clarify these genetic effects, this research conducted a three-wave study to investigate whether the CRHR1 polymorphisms (i.e., rs110402 and rs242924) are associated with the stability and variability of attachment by using a sample of freshmen (N = 604; Mage = 18.57 years, SD = 1.90; 68.8% girls). The results showed that rs110402 and rs242924 were associated with the stability of closeness-dependence. The G alleles of the both polymorphisms were found not to be related to lower attachment stability. However, these polymorphisms were not associated with the variability of attachment. Overall, these findings provide evidence for the contribution of CRHR1 to attachment stability.

Genetic architecture of well-being: cumulative effect of serotonergic polymorphisms.

Serotonin influences mental health and well-being. To understand the influences of genetic variations in serotonin pathway on well-being, we examined the effects of seven serotonergic polymorphisms on subjective well-being (i.e. affective balance and global life satisfaction) and psychological well-being (i.e. optimal psychological functions in the face of existential challenges) in a larger sample. Results indicated that the cumulative genetic score, but single genetic effects of serotonergic polymorphisms, was related to individual differences in well-being. Specifically, individuals with a greater cumulative genetic score, which is related to a low risk of depression, tended to exhibit high levels of subjective well-being and psychological well-being. These findings suggest that the overall serotoninergic genetic profile, rather than a specific genetic polymorphism, could greatly influence the individual differences in well-being.

Bright side of the MAOA-uVNTR on trait and situational forgiveness.

The stress-and-coping theory of forgiveness posits that forgiveness and aggression are alternative ways of coping with stress of interpersonal offences. Inspired by the link between aggression and MAOA-uVNTR (a genetic variant involving in catabolism of monoamines), we investigated the relationship between this variant and forgiveness with two studies. Study 1 examined the relationship between the MAOA-uVNTR and trait forgiveness in students, and study 2 examined the effect of this variant on third-party forgiveness in response to situational offences in male inmates. The results showed that the MAOA-H (a high activity allele) was associated with higher trait forgiveness in male students and greater third-party forgiveness to accidentally committed harm and attempted but failed harm in male inmates than the MAOA-L. These findings highlight the bright side of MAOA-uVNTR on trait and situational forgiveness.

The interplay between parental care and OPRM1 in reward responsiveness.

The Reinforcement Sensitivity Theory (RST) explains a variety of reward-motivated behaviors as the result of the activation of biologically-based systems. Inspired by the influences of parental bonding and opioid peptide on reward system, we investigated the contributions of parental bonding and mu-opioid receptor gene (OPRM1) towards motivation systems (i.e., the BAS, BIS-anxiety, and FFFS-fear). Results indicated that (1) parental care was negatively related to FFFS-fear, but parental overprotection was positively related to both FFFS-fear and BIS-anxiety; (2) parental care significantly interacted with OPRM1 rs1799971 in reward responsiveness with diathesis-stress model. Poor parental care reduced reward responsiveness among individuals with the G allele, but not those with the AA genotype. These findings from this study demonstrate a new gene-environment interactive mechanism of the RST.

The OXTR rs53576 impacts moral permissibility of attempted but failed harms in populations of students and prisoners.

Previous research has highlighted the roles of oxytocin in empathy and altruistic behaviors. Based on these findings, recent studies have examined the association between the oxytocin receptor gene (OXTR) and outcome-based moral judgment with sacrificial dilemmas (e.g. runaway trolley case). However, little is known about the relationships between OXTR polymorphisms and intent-based moral judgment of harms (e.g. attempted but failed harm or intentionally committed harm). This study investigated the association between the OXTR rs53576 and intent-based moral judgment in college students (N = 544) and prisoners (N = 540). Results indicated that both students and prisoners with the GG genotype of OXTR rs53576 rated attempted but failed harm as less permissible than those with the AA and AG genotypes. These findings highlight the role of the OXTR gene in intent-based moral judgment.

Intranasal oxytocin administration but not peripheral oxytocin regulates behaviors of attachment insecurity: A meta-analysis.

In light of the roles of oxytocin (OT) in social bonding and interpersonal relationship, studies have examined the roles of OT in human attachment, but by and large previous findings are inconsistent. Here, we conducted - meta-analyses to estimate the associations between peripheral OT level (e.g., blood and salivary OT) and attachment (i.e., attachment dimensions and behaviors of attachment insecurity) and examine the effects of intranasal OT administration on behaviors of attachment insecurity. The analyses indicated that: (1) Peripheral OT level was not significantly associated with attachment dimensions (e.g., attachment anxiety and attachment avoidance) and behaviors of attachment insecurity; (2) intranasal OT administration significantly reduced behaviors of attachment insecurity of neutral contexts, particularly behaviors of attachment avoidance. The findings suggest that intranasal OT administration is an available approach for reducing behaviors of attachment insecurity of interpersonal situations with ambiguous social cues, which implicates suggestions for therapeutic treatments of attachment-related dysfunctions.

OXTR moderates adverse childhood experiences on depressive symptoms among incarcerated males.

OBJECTIVES: This study examined the moderation of an oxytocin receptor (OXTR) gene in the link between childhood adversity and depressive symptoms among incarcerated males. METHODS: Questionnaires about adverse childhood experiences and depressive symptoms, as well as genomic DNA from blood were collected among 608 incarcerated males (Mage = 32.4 years, SD = 9.41, 18-74 years). Moderation analysis was applied to examine the interaction between adverse childhood experiences (including abuse, neglect, and household dysfunction) and the OXTR polymorphisms (rs2254298, rs53576) in predicting depressive symptoms. RESULTS: Incarcerated males had relatively higher prevalence of childhood adversity (70.2%) and depressive symptoms (49.8%). Higher childhood adversity was associated with increased depressive symptoms, and the effect was more pronounced in the GG homozygotes of OXTR rs2254298 (b = 0.406, p < .001), as compared with the AA/AG carriers (b = 0.236, p < .001). By contrast, the OXTR rs53576 did not interact with childhood adversity in predicting depressive symptoms. CONCLUSIONS: Chinese incarcerated males with the GG genotype of OXTR rs2254298 have higher vulnerability in the effect of childhood adversity on depressive symptoms.

The BDNF Val66Met polymorphism impacts victim's moral emotions following interpersonal transgression.

Immoral behaviors make individuals abominate and punish transgressors. Inspired by the associations between the Val66Met polymorphism of brain-derived neurotropic factor (BDNF) gene and emotional responses following negative events, we investigated whether this polymorphism was also associated moral emotions such as punishment and forgiveness following interpersonal transgression. To do so, we categorized 340 individuals according to the BDNF Val66Met and assessed moral emotions by using 12 hypothetic scenarios in different conditions of intention and interpersonal consequence. The results indicated that this polymorphism was significantly associated with moral aversion and punishment towards transgressors. Victims with the Val/Val genotype expressed less aversion and punishment than the Met carriers, regardless of intention and interpersonal consequence. Moreover, this polymorphism was associated with forgiveness. Victims with the Val/Val genotype expressed more forgiveness than the Met carriers. Taken together, these findings highlight the importance of the BDNF Val66Met to moral emotions.

The OXTR polymorphisms are not associated with attachment dimensions: A three-approach study.

Inspired by the roles of oxytocin in social behaviors, scientists have devoted considerable efforts to examine the association between the oxytocin receptor gene (OXTR) and human attachment, a personality of seek and receiving comfort from intimate figures. However, there are still a lot of controversies on the association. To clarify the relationship, this research integrated three studies: (1) A cross-sectional study indicated that the OXTR polymorphisms (i.e., rs53576 and rs2254298) were not significantly associated with attachment dimensions in a college student sample (N = 1193); (2) A three-wave study showed that the polymorphisms were not associated with the individual differences and changes of attachment dimensions in a freshmen sample (N = 657); and (3) Meta-analysis indicated that attachment dimensions were not associated with the polymorphisms of rs53576 (Anxiety: 14 samples, N = 5053; Avoidance: ten samples, N = 4273) and rs2254298 (Anxiety: ten samples, N = 3670; Avoidance: ten samples, N = 3698). Taken together, these findings provide strong evidence that the OXTR polymorphisms are not related to attachment dimensions.

The rs6311 of serotonin receptor 2A (5-HT2A) gene is associated with alexithymia and mental health.

BACKGROUNDS: Alexithymia, difficulties in identifying and describing one's own feelings, is related to substantial clinical practice. Inspired by the links between serotonin functions and affective disorders, this study investigated associations of the serotonin receptor 2A (5-HT2A) gene with alexithymia and mental health. METHODS: We differentiated subjects according to two functional polymorphisms (i.e., rs6311 and rs6313) of 5-HT2A gene and scored alexithymia and mental health of college students with the Toronto Alexithymia Scale (TAS-20) and the Symptom Check List-90 (SCL-90), respectively. RESULTS: The analyses basing on sample 1 (N = 566) and sample 2 (N = 602) indicated that the G allele of rs6311 was related to higher score on the TAS-20 as compared to the AA genotype. The analysis with 467 individuals from sample 2 indicated that the rs6311 was associated with mental health, and this association was mediated by alexithymia. LIMITATIONS: The potential confounding variables such as depression and anxiety were neglected in the analyses. CONCLUSIONS: These findings demonstrate the contribution of the 5-HT2A to alexithymia, and highlight the link between alexithymia and mental health at genetic level.

Revisiting the relationships of 2D:4D with androgen receptor (AR) gene and current testosterone levels: Replication study and meta-analyses.

The relationships of digit ratio (2D:4D) with the length of AR (CAG)n, and testosterone levels from saliva and blood have been extensively debated over the years. This research including three studies further clarifies such controversies. To do so, we re-examined the relationships between the length of AR (CAG)n, 2D:4D, and current testosterone levels, through replication study and meta-analysis for each study. The results indicate: (a) the length of AR (CAG)n is not significantly associated with 2D:4D; (b) current testosterone levels are not significantly associated with the ratio; and (c) the length is not significantly associated with testosterone levels. Thus, AR (CAG)n and current testosterone levels are not significantly related to 2D:4D at individual level.

The 5-HTTLPR polymorphism impacts moral permissibility of impersonal harmful behaviors.

Inspired by the roles of serotonin in an emotional aversion to harmful actions, we examined to what extent serotonin transporter gene (5-HTT)-linked polymorphic region (5-HTTLPR), a proxy for measuring serotonin function, underpinned the individual differences in moral judgment through cross-sectional analysis and two-wave comparison. The cross-sectional analysis with a larger cohort (N = 1197) showed that the SS carriers of the 5-HTTLPR polymorphism, corresponding to the low ratio of serotonin recycling from the synaptic cleft, rated impersonal harmful actions (e.g. flipping a switch to divert a train to hit one person instead of five people) as more permissible as compared with the L-allele carriers. The two-wave comparison with a subsample from the larger cohort (N = 563) indicated that the association between 5-HTTLPR polymorphism and moral permissibility of impersonal harmful actions was stable from wave 1 to wave 2. Thus, these findings highlight the importance of the 5-HTTLPR polymorphism to harmful moral behaviors.

5-HTTLPR and COMT Val158Met are not associated with alexithymia: New evidence and meta-analyses.

BACKGROUNDS: Alexithymia refers to the difficulties in identifying and describing one's own emotions, lacking of imagination, and an externally oriented thinking style. Studies up to date have examined the associations of 5-HTTLPR and COMT Val158Met polymorphisms with alexithymia. However, the previous findings were mixed. METHODS: We replicated the associations by scoring on alexithymia with the 20-item Toronto Alexithymia Scale and genotyping the polymorphisms of 5-HTTLPR and COMT Val158Met in a large population of college students (N = 1698). Moreover, we also meta-analyzed the associations with five samples (N = 7517) for the 5-HTTLPR and with five samples (N = 2186) for the COMT Val158Met. RESULTS: Neither the replicated study nor the meta-analyses indicated the 5-HTTLPR and COMT Val158Met were associated with alexithymia. CONCLUSIONS: The findings suggest that the 5-HTTLPR and COMT Val158Met polymorphisms are not associated with alexithymia. However, genetic-environmental studies with different ethnicity and psychopathology should be carried in future.

OXTR rs53576 polymorphism impacts interpersonal adaptability: Dispositional forgiveness as a mediator.

Polymorphisms in the oxytocin receptor (OXTR) gene have been shown to be related to individual differences in social skills that are important for building and maintaining social relationships, such as the capability to efficiently process social information and regulate emotions. However, what remains unclear is the potential roles of OXTR polymorphisms in interpersonal adaptability, namely the ability to cope with the situational demands of interpersonal interactions. In this study, we examined the roles of OXTR rs53576 polymorphism in interpersonal adaptability, empathic perception, and dispositional forgiveness in a cohort of 573 college freshmen. The results indicated that the scores on interpersonal adaptability and dispositional forgiveness, apart from empathic perception, increased as functions of the number of G alleles of OXTR rs53576. Moreover, dispositional forgiveness, but not empathic perception, mediated the association between OXTR rs53576 and interpersonal adaptability. The findings highlight the influences of the OXTR gene on adaptive interpersonal interactions, especially when individuals face changing social situations.

Independent self-construal mediates the association between CYP19A1 gene variant and subjective well-being.

Testosterone and estrogen are involved in self-related behavioral dispositions and experiences of subjective well-being. In this study, we investigated to what extent the aromatase (CYP19A1) gene, which encodes an enzyme in converting testosterone into estrogen, contributes to subjective well-being and in another self-related disposition: independent and interdependent self-construal. In study 1, a meta-analysis showed that the GG genotype of CYP19A1 (a G/A substitution at Val80, rs700518) was associated with higher testosterone and lower estradiol. In study 2, an empirical study of individuals with the GG (n=115), AG (n=286) and AA (n=193) genotypes indicated that individuals with the GG genotype exhibited higher independent self-construal and higher subjective well-being. The association between the GG genotype of CYP19A1 Val80 and subjective well-being was mediated by the independent self-construal. Our findings reinforce the idea that personality traits such as independent self-construal explain the link between genetic variant and subjective well-being.

A field study of the association between CD38 gene and altruistic behavior: Empathic response as a mediator.

Inspired by the enhancement effects of oxytocin on empathic responses and altruistic behaviors, we conducted a field study with a real fundraising event and investigated to what extent oxytocin pathway genes (CD38 and OXTR) modulate individual differences in charitable donation. Participants were informed that a teacher in their university was diagnosed with uremia and could not afford the cost of medication. They were given the opportunity to donate any amount of money and report their empathic responses to the misfortune of the teacher. We found a significant association between CD38 rs3796863 and the amount of donation both before and after controlling for gender, age, subjective socioeconomic status, religious belief, and social desirability. Individuals with the genotypes (AA/AC) leading to higher oxytocin levels reported stronger empathic responses and donated more money than individuals with the CC genotype. Moreover, empathic response mediated the gene-altruism association. However, we observed no significant associations between the three polymorphisms of OXTR (rs53576, rs2254298, and rs1042778) and the amount of donation. This study demonstrates the importance of CD38 as a source of individual differences in altruistic behavior and highlights the role of empathic response in bridging the link between the oxytocin pathway gene and altruism.

Identifying new susceptibility genes on dopaminergic and serotonergic pathways for the framing effect in decision-making.

The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing. Using genome-wide association data and the gene-based principal components regression method, we examined genetic variations of 26 genes on the pathways in 1317 Chinese Han participants. Consistent with previous studies, we found that the genetic variations of the SLC6A4 gene and the COMT gene were associated with the framing effect. More importantly, we demonstrated that the genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which is involved in the synthesis of both dopamine and serotonin, contributed to individual differences in the susceptibility to framing. Our findings shed light on the understanding of the genetic basis of affective decision-making.

The association between well-being and the COMT gene: Dispositional gratitude and forgiveness as mediators.

BACKROUND: Previous studies have demonstrated the contributions of genetic variants and positive psychological traits (e.g. gratitude and forgiveness) to well-being. However, little is known about how genes interact with positive traits to affect well-being. METHODS: To investigate to what extent the COMT Val158Met polymorphism modulates well-being and to what extent dispositional gratitude and forgiveness mediate the individual differences in well-being, 445 participants were recruited and required to complete a battery of questionnaires. RESULTS: We found that individuals with a smaller number of the Met alleles reported greater well-being, less depressive symptoms, and greater tendencies for gratitude and forgiveness. Moreover, dispositional gratitude and forgiveness mediated the genotype effects on well-being and depressive symptoms. These results remained significant after controlling for non-genetic factors (socioeconomic status, religious beliefs, romantic relationship status, parenting style). LIMITATION: The sample size limits the generalizability of results. CONCLUSION: This study demonstrates the contribution of the COMT Val158Met polymorphism to individual differences in well-being and suggests a potential psychobiological pathway from dopaminergic and noradrenergic systems to happiness.

The CAG polymorphism in androgen receptor (AR) gene impacts the moral permissibility of harmful behavior in females.

The moral permissibility of harm is strikingly varied among individuals. In light of the connection between testosterone levels and utilitarian moral judgment, this study examined to what extent a CAG polymorphism in the androgen receptor gene, a genetic polymorphism with the ability to regulate testosterone function, contributes to individual differences in moral judgment. Four hundred and thirty-nine Chinese Han participants completed permissibility ratings of harm in moral dilemmas and moral transgression scenarios. Results showed a significant association between the CAG polymorphism and moral permissibility of harm in females. Females with more copies of the S allele, which is associated with higher availability of testosterone, were more likely to judge harmful utilitarian acts and unintentionally harmful acts as permissible, while these effects were absent in males. The findings provide the first evidence for a link between the androgen receptor gene and moral judgment and highlight the role of androgens in moral foundations.

Revisiting the impact of OXTR rs53576 on empathy: A population-based study and a meta-analysis.

Oxytocin in the brain is related to empathy, which refers to the ability to understand and share others' internal states or responses. Previous studies have investigated the impact of OXTR rs53576, the most intensively examined polymorphism in the oxytocin receptor (OXTR) gene, on individual differences in empathy. However, these studies produced inconsistent results. In the current study, we reexamined the association of OXTR rs53576 with empathy in a relatively large population (N=1830) and also evaluated the association by a comprehensive meta-analysis (N=6631, 13 independent samples). The replication study indicated that OXTR rs53576 was indeed associated with individual differences in empathy. Individuals with a greater number of G alleles showed better empathic ability, particularly in fantasizing other's feelings and actions. The meta-analysis not only confirmed this association, but also indicated that the impact of this polymorphism was significant in both Europeans and Asians. These findings provide convincing evidence for the impact of OXTR rs53576 on empathy, highlighting the importance of OXTR gene in individuals' social cognition.