The genomic impact of kindness to self vs. others: A randomized controlled trial.

OBJECTIVE: Prosocial behavior has been linked to improved physical health, but the biological mechanisms involved remain unclear. This study tested whether a 4-week kindness intervention could reduce expression of a stress-related immune response gene signature known as the Conserved Transcriptional Response to Adversity (CTRA). METHODS: In a diverse sample of community adults (N = 182), study participants were randomly assigned to perform 3 kind acts for other people, to perform 3 kind acts for themselves, or to list daily activities (control), on one day per week over 4 weeks. CTRA gene expression was measured by RNA sequencing of dried blood spots (DBS) collected at baseline and 5 weeks later (1 week after completing study assignments). Participants' descriptions of their kind acts were coded for protocol adherence and act content. RESULTS: Participants who were randomized to perform kind acts for others showed significant reductions in CTRA gene expression relative to controls. Participants who were randomized to perform kind acts for themselves also showed significant reductions in CTRA gene expression relative to controls, but this pattern emerged only for those who failed to perform the requested self-kind acts (protocol non-adherent). Those who fully adhered to the self-kindness protocol showed no change in CTRA gene expression and did not differ from controls. Act content analyses implicated self-stress-reducing behavior in the paradoxical effects of self-kindness and the physical presence of others in the effects of prosocial behavior. CONCLUSIONS: Prosocial engagement-doing something kind for others rather than oneself-reduces CTRA gene expression. The nature of kind acts and their intended recipient plays a key role in shaping the genomic impact of kindness.

Lack of association of common polymorphisms linked to empathic behavior with self-reported trait empathy in healthy volunteers.

BACKGROUND: In a previously specified sample of 421 healthy subjects, we found associations of a common oxytocin receptor (OXTR) polymorphism with self-reported trait empathy. In this study, we used this sample to explore polymorphisms in other genes which have been frequently linked to empathic behavior for associations with self-reported trait empathy: CD38 (CD38), involved in oxytocin secretion, the serotonin transporter (SLC6A4), the Catechol-O-Methyltransferase (COMT) and the corticotropin releasing hormone receptor 1 (CRHR1). METHODS: We genotyped our sample for the following common polymorphisms: rs3796863 in the CD38 gene, 5-HTTLPR in the SLC6A4 gene, rs4680 in the COMT gene and rs242924 in the CRHR1 gene. Dispositional empathy was tested using Davis' Interpersonal Reactivity Index (IRI). We used a Bonferroni corrected alpha level of p = 0.002 to adjust for multiple comparisons. RESULTS: None of the genotypes were associated with any of the IRI scales for the complete sample (n = 421) or for the sub-groups of male (n = 213) and female (n = 190) participants. Our sample of 421 participants achieved 95% power to detect effects greater than r = ±0.18. For smaller effects, however, false negatives could not be rejected with equal confidence as false positives. CONCLUSIONS: We conclude that an association between the four polymorphisms with trait empathy measured by the IRI may not be present. We propose that the associations that have been found in other studies can be largely explained by differences in empathy-related constructs and measurements.

Childhood Adversity, Socioeconomic Instability, Oxytocin-Receptor-Gene Methylation, and Romantic-Relationship Support Among Young African American Men.

Men's emerging adult romantic relationships forecast downstream relationship behavior, including commitment and quality. Accumulating evidence implicates methylation of the oxytocin-receptor-gene (OXTR) system in regulating relationship behavior. We tested hypotheses regarding the links between (a) childhood adversity and (b) socioeconomic instability in emerging adulthood on supportive romantic relationships via their associations with OXTR methylation. Hypotheses were tested using path analysis with data from 309 participants in the African American Men's Project. Consistent with our hypotheses, results showed that OXTR methylation proximally predicted changes in relationship support during a 1.5-year period. Childhood adversity was not directly associated with OXTR methylation but, rather, with contemporaneous socioeconomic instability, which in turn predicted elevated OXTR methylation. Findings suggest that early adversity is indirectly associated with OXTR methylation by links with downstream socioeconomic instability. Findings must be considered provisional, however, because preregistered replications are needed to establish more firmly the relations among these variables.

Genome-wide meta-analysis of cognitive empathy: heritability, and correlates with sex, neuropsychiatric conditions and cognition.

We conducted a genome-wide meta-analysis of cognitive empathy using the 'Reading the Mind in the Eyes' Test (Eyes Test) in 88,056 research volunteers of European Ancestry (44,574 females and 43,482 males) from 23andMe Inc., and an additional 1497 research volunteers of European Ancestry (891 females and 606 males) from the Brisbane Longitudinal Twin Study. We confirmed a female advantage on the Eyes Test (Cohen's d=0.21, P<2.2 × 10-16), and identified a locus in 3p26.1 that is associated with scores on the Eyes Test in females (rs7641347, Pmeta=1.58 × 10-8). Common single nucleotide polymorphisms explained 5.8% (95% CI: 4.5%-7.2%; P=1.00 × 10-17) of the total trait variance in both sexes, and we identified a twin heritability of 28% (95% CI: 13%-42%). Finally, we identified significant genetic correlation between the Eyes Test and anorexia nervosa, openness (NEO-Five Factor Inventory), and different measures of educational attainment and cognitive aptitude.

Genome Editing for Involuntary Moral Enhancement.

During the previous years, voluntary moral bioenhancement (VMBE) has been contrasted to compulsory moral bioenhancement (CMBE). In this paper a third possible type of moral bioenhancement is discussed: genome editing for moral enhancement of the unborn that is neither voluntary nor compulsory, but involuntary. Involuntary moral bioenhancement (IMBE) might engineer people who will be more moral than they otherwise would have been. The possibilities of genome editing aimed at moral enhancement of our offspring is assessed. It is argued that genome editing might have the potential to engineer our offspring in three domains: to be more empathetic, to be less violently aggressive, and to have a higher potential for complex moral reflection. Genome editing is discussed in these three domains, and a proposal made that a combination of VMBE and IMBE might be the best option humans have to become better.

Female orgasm and the emergence of prosocial empathy: An evo-devo perspective.

In human females, direct or indirect stimulation of the clitoris plays a central role in reaching orgasm. A majority of women report that penetrative coitus alone is insufficient for triggering orgasm, puzzling researchers who expect orgasm to be an outcome of procreative intercourse. In the present paper, we turn our attention to the evolutionary role that such unreliability of orgasm at coitus might have played in human evolution. We emphasize that we do not thereby attempt an explanation of its origin, but its potential evolutionary effect. The present proposal suggests that the variable female orgasm, the position of the clitoris remote from the vagina, and the mismatch of the male refractory period with the female capacity for multiple orgasms, may have contributed to the evolution of human prosocial qualities.

Distinct transcriptional and metabolic profiles associated with empathy in Buddhist priests: a pilot study.

BACKGROUND: Growing evidence suggests that spiritual/religious involvement may have beneficial effects on both psychological and physical functions. However, the biological basis for this relationship remains unclear. This study explored the role of spiritual/religious involvement across a wide range of biological markers, including transcripts and metabolites, associated with the psychological aspects of empathy in Buddhist priests. METHODS: Ten professional Buddhist priests and 10 age-matched non-priest controls were recruited. The participants provided peripheral blood samples for the analysis of gene expression and metabolic profiles. The participants also completed validated questionnaires measuring empathy, the Health-Promoting Lifestyle Profile-II (HPLP-II), and a brief-type self-administered diet history questionnaire (BDHQ). RESULTS: The microarray analyses revealed that the distinct transcripts in the Buddhist priests included up-regulated genes related to type I interferon (IFN) innate anti-viral responses (i.e., MX1, RSAD2, IFIT1, IFIT3, IFI27, IFI44L, and HERC5), and the genes C17orf97 (ligand of arginyltranseferase 1; ATE1), hemoglobin γA (HBG1), keratin-associated protein (KRTAP10-12), and sialic acid Ig-like lectin 14 (SIGLEC14) were down-regulated at baseline. The metabolomics analysis revealed that the metabolites, including 3-aminoisobutylic acid (BAIBA), choline, several essential amino acids (e.g., methionine, phenylalanine), and amino acid derivatives (e.g., 2-aminoadipic acid, asymmetric dimethyl-arginine (ADMA), symmetric dimethyl-arginine (SMDA)), were elevated in the Buddhist priests. By contrast, there was no significant difference of healthy lifestyle behaviors and daily nutrient intakes between the priests and the controls in this study. With regard to the psychological aspects, the Buddhist priests showed significantly higher empathy compared with the control. Spearman's rank correlation analysis showed that empathy aspects in the priests were significantly correlated with the certain transcripts and metabolites. CONCLUSIONS: We performed in vivo phenotyping using transcriptomics, metabolomics, and psychological analyses and found an association between empathy and the phenotype of Buddhist priests in this pilot study. The up-regulation of the anti-viral type I IFN responsive genes and distinct metabolites in the plasma may represent systemic biological adaptations with a unique signature underlying spiritual/religious practices for Buddhists.

Adult Empathy: Possible Gender Differences in Gene-Environment Architecture for Cognitive and Emotional Components in a Large Italian Twin Sample.

Empathy plays a central role in prosocial behavior and human cooperation. Very few twin researchers have investigated innate and environmental effects in adult empathy, and twin research on gender differences in these effects is sparse. The goal of this study was to examine innate and environmental influences on three components of an empathy scale frequently used with adults - the expression of cognitive (CE), emotional (EE), and social skills (SS) empathy - and to explore gender differences in the influences. Study participants were ~1,700 twins (18-65 years) enrolled in the Italian Twin Registry. Empathy was assessed with the Italian version of the Empathy Quotient (EQ), for which the three-factor structure (i.e., CE, EE, and SS) was confirmed. Twin correlations in monozygotic and dizygotic pairs, and males and females were estimated for the total EQ and subscale scores, and univariate genetic model fitting was carried out. Women's empathy (i.e., total EQ as well as CE and EE subdimensions) was predominantly driven by genetic factors and individual experiences, whereas for males, no genetic contribution or important shared and individual environmental effects emerged. Although of large magnitude, the gender differences did not reach statistical significance. Age did not moderate empathy heritability in adulthood. Only for the SS subscale were genetic and environmental proportions of variance similar for men and women. This study suggests possible gender-specific innate and environmental influences on empathy and its cognitive and emotional components that need to be confirmed in future studies.

The Inventory of Callous-Unemotional Traits (ICU) in Children: Reliability and Heritability.

Callous-unemotional (CU) traits comprise the core symptoms of psychopathy, yet no study has estimated the heritability of CU traits in a community sample of children using an instrument designed solely to assess CU traits. The current study uses data from 339 twin pairs aged 9-14 to examine the reliability and heritability of the parent-report Inventory of Callous-unemotional Traits (ICU) at two assessments approximately 3 weeks apart. Time-specific measurement error was taken into account to obtain a more accurate estimate of the heritability reflecting the latent liability to CU traits. Test-retest reliability was 0.84 and heritability at visit 1 was 39%. The heritability of the latent liability to CU traits was 47%. This latent liability contributed 79% of the variance in ICU score at visit 1 and visit 2. This is the first study to account for measurement error while examining the heritability of CU traits, furthering our understanding of psychopathy in children.

Oxytocin Receptor (OXTR) Single Nucleotide Polymorphisms Indirectly Predict Prosocial Behavior Through Perspective Taking and Empathic Concern.

Engaging in prosocial behavior can provide positive outcomes for self and others. Prosocial tendencies contribute to the propensity to engage in prosocial behavior. The oxytocin receptor gene (OXTR) has also been associated with prosocial tendencies and behaviors. There has been little research, however, investigating whether the relationship between OXTR and prosocial behaviors is mediated by prosocial tendencies. This relationship may also vary among different types of prosocial behavior. The current study examines the relationship between OXTR, gender, prosocial tendencies, and both altruistic and public prosocial behavior endorsement. Students at a midwestern university (N = 398; 89.2% Caucasian; Mage = 20.76; 26.6% male) provided self-report measures of prosocial tendencies and behaviors and buccal cells for genotyping OXTR polymorphisms. Results indicated that OXTR single nucleotide polymorphism (SNP) rs2268498 genotype significantly predicted empathic concern, whereas gender moderated the association between several other OXTR SNPs and prosocial tendencies. Increased prosocial tendencies predicted increased altruistic prosocial behavior endorsement and decreased public prosocial behavior endorsement. Our findings suggest an association between genetic variation in OXTR and endorsement of prosocial behavior indirectly through prosocial tendencies, and that the pathway is dependent on the type of prosocial behavior and gender.

[Aggression and empathy as genetic differentiation factors of urban population].

Permanent residents of Kharkiv (637 men and 856 women at the age of 45­65 years) are tested on the level of aggression and empathy. The average aggression level (41.7 points) is higher in migrants (born outside Kharkiv) than in indigenous people (36.3 points); the average empathy level is lower in migrants (3.2 points) than in indigenous people (5.5 points). The average values of the aggression and empathy indices are not associated with ethnicity and degree of miscegenation. The correlation between spouses (r) by these personal features is within 0.20­0.31; the marriage conjugation index (K) is 0.13­0.18. Genotyping of the married couples for the rs2235186 SNP of X-linked monoaminooxidase (MAO-A) gene detected a positive marriage assortativeness: the C × CC and T × TT pairs are developed more frequently than during panmixia; the C × TT and T × CC pairs, less frequently. The T allele is coupled with increased aggression level and decreased empathy level. The phenotypes of heterozygous women indicate the intermediate inheritance of these traits.

Oxytocin receptor and vasopressin receptor 1a genes are respectively associated with emotional and cognitive empathy.

Empathy is the ability to recognize and share in the emotions of others. It can be considered a multifaceted concept with cognitive and emotional aspects. Little is known regarding the underlying neurochemistry of empathy and in the current study we used a neurogenetic approach to explore possible brain neurotransmitter pathways contributing to cognitive and emotional empathy. Both the oxytocin receptor (OXTR) and the arginine vasopressin receptor 1a (AVPR1a) genes contribute to social cognition in both animals and humans and hence are prominent candidates for contributing to empathy. The following research examined the associations between polymorphisms in these two genes and individual differences in emotional and cognitive empathy in a sample of 367 young adults. Intriguingly, we found that emotional empathy was associated solely with OXTR, whereas cognitive empathy was associated solely with AVPR1a. Moreover, no interaction was observed between the two genes and measures of empathy. The current findings contribute to our understanding of the distinct neurogenetic pathways involved in cognitive and emotional empathy and underscore the pervasive role of both oxytocin and vasopressin in modulating human emotions.

The genetic and environmental foundations of political, psychological, social, and economic behaviors: a panel study of twins and families.

Here we introduce the Genetic and Environmental Foundations of Political and Economic Behaviors: A Panel Study of Twins and Families (PIs Alford, Hatemi, Hibbing, Martin, and Smith). This study was designed to explore the genetic and environmental influences on social, economic, and political behaviors and attitudes. It involves identifying the psychological mechanisms that operate on these traits, the heritability of complex economic and political traits under varying conditions, and specific genetic correlates of attitudes and behaviors. In addition to describing the study, we conduct novel analyses on the data, estimating the heritability of two traits so far unexplored in the extant literature: Machiavellianism and Baron-Cohen's Empathizing Quotient.

Thin-slicing study of the oxytocin receptor (OXTR) gene and the evaluation and expression of the prosocial disposition.

Individuals who are homozygous for the G allele of the rs53576 SNP of the oxytocin receptor (OXTR) gene tend to be more prosocial than carriers of the A allele. However, little is known about how these differences manifest behaviorally and whether they are readily detectable by outside observers, both critical questions in theoretical accounts of prosociality. In the present study, we used thin-slicing methodology to test the hypotheses that (i) individual differences in rs53576 genotype predict how prosocial observers judge target individuals to be on the basis of brief observations of behavior, and (ii) that variation in targets' nonverbal displays of affiliative cues would account for these judgment differences. In line with predictions, we found that individuals homozygous for the G allele were judged to be more prosocial than carriers of the A allele. These differences were completely accounted for by variations in the expression of affiliative cues. Thus, individual differences in rs53576 are associated with behavioral manifestations of prosociality, which ultimately guide the judgments others make about the individual.

Catechol-O-methyltransferase (COMT) genotype biases neural correlates of empathy and perceived personal distress in schizophrenia.

BACKGROUND: The catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism (rs4680) influences enzyme activity with valine (Val) allele associated with higher enzymatic activity. Several studies suggest that factors influencing dopaminergic transmission could control response to stressful situations. Empathy is an essential element of human behavior, requires the ability to adopt another person's perspective, and has been found to be dysfunctional in schizophrenia. METHODS: Twenty-eight schizophrenic patients underwent functional magnetic resonance imaging performing an empathy task. Perceived empathy has been evaluated with the Interpersonal Reactivity Index. RESULTS: An effect of COMT on perceived distress subscale has been shown, with methionine (Met)/Met subjects reporting lower rates of stress compared with Val/Val. Moreover, imaging results showed an effect of genotype on empathy processing in the anterior cingulate with Val/Val subjects showing the lowest activation. DISCUSSION: This is the first study of the effect of rs4680 on interpersonal distress and neural correlates of empathy in schizophrenia. We found a decrease in neural responses in areas that ensure a cognitive control of emotion that is paralleled by perceived distress in interpersonal situation; this functional pattern seems to be influenced by rs4680 COMT polymorphism.

Reduced C-afferent fibre density affects perceived pleasantness and empathy for touch.

We examined patients with a heritable disorder associated with a mutation affecting the nerve growth factor beta gene. Their condition has been classified as hereditary sensory and autonomic neuropathy type V. Carriers of the mutation show a reduction in density of thin and unmyelinated nerve fibres, including C afferents. A distinct type of unmyelinated, low-threshold mechanoreceptive C fibre, the C-tactile afferent, is present in hairy but not glabrous skin of humans and other mammals. They have been implicated in the coding of pleasant, hedonic touch of the kind that occurs in affiliative social interactions. We addressed the relationship between C fibre function and pleasant touch perception in 10 individuals from a unique population of mutation carriers in Sweden. We also investigated the effect of reduced C-fibre density on patients' evaluation of observed interpersonal touch (empathy). Results showed that patients perceived gentle, slow arm stroking, optimal for eliciting C-tactile afferent responses (1-10 cm/s), as less pleasant than did matched controls and also differed in their rating patterns across stimulation velocities. Further, patients' blood-oxygen-level-dependent responses in posterior insular cortex--a target for C afferents--were not modulated by stimulation optimal for activating C-tactile afferents. Hence, perception of the hedonic aspect of dynamic touch likely depends on C-tactile afferent density. Closely similar patterns between individuals' ratings of felt and seen touch suggest that appraisal of others' touch is anchored in one's own perceptual experience, whether typical or atypical.

Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans.

Oxytocin, a peptide that functions as both a hormone and neurotransmitter, has broad influences on social and emotional processing throughout the body and the brain. In this study, we tested how a polymorphism (rs53576) of the oxytocin receptor relates to two key social processes related to oxytocin: empathy and stress reactivity. Compared with individuals homozygous for the G allele of rs53576 (GG), individuals with one or two copies of the A allele (AG/AA) exhibited lower behavioral and dispositional empathy, as measured by the "Reading the Mind in the Eyes" Test and an other-oriented empathy scale. Furthermore, AA/AG individuals displayed higher physiological and dispositional stress reactivity than GG individuals, as determined by heart rate response during a startle anticipation task and an affective reactivity scale. Our results provide evidence of how a naturally occurring genetic variation of the oxytocin receptor relates to both empathy and stress profiles.

Communicative genes in the evolution of empathy and altruism.

This paper discusses spontaneous communication and its implications for understanding empathy and altruism. The question of the possibility of "true" altruism-giving up one's genetic potential in favor of the genetic potential of another-is a fundamental issue common to the biological, behavioral, and social sciences. Darwin regarded "social instincts and sympathies" to be critical to the social order, but the possibility of biologically-based prosocial motives and emotions was questioned when selection was interpreted as operating at the level of the gene. In the selfish gene hypothesis, Dawkins argued that the unit of evolutionary selection must be an active, germ-line replicator: a unit whose activities determine whether copies of it are made across evolutionary timescales. He argued that the only active replicator existing across evolutionary timescales is the gene, so that the "selfish gene" is a replicator motivated only to make copies of itself. The communicative gene hypothesis notes that genes function by communicating, and the phenotype communication involves not only the individual sending and receiving abilities of the individual genes involved, but also the relationship between them relative to other genes. Therefore the selection of communication as phenotype involves the selection of individual genes and also their relationship. Relationships become replicators, and are selected across evolutionary timescales including social relationships (e.g., sex, nurturance, dominance-submission). An interesting implication of this view: apparent altruism has been interpreted by selfish gene theorists as due to kin selection and reciprocity, in which the survival of kin and comrade indirectly favor the genetic potential of the altruist. From the viewpoint of the communicative gene hypothesis, rather than underlying altruism, kin selection and reciprocity are ways of restricting altruism to kin and comrade: they are mechanisms not of altruism but of xenophobia.

Influence of Two Single-Nucleotide Polymorphisms of the Oxytocin Receptor Gene (OXTR) on Empathy: the Mediation Role of a Primary Emotion, CARE.

To feel other's pain would elicit empathy. Some theorists hypothesized that observing other's pain may activate the primary emotion of maternal care instinct, which may function as a precursor of empathy. The maternal care instinct and empathy share the same genetic background and neuroendocrine underpinnings. An extensive body of research has shown that maternal behaviors relate to the oxytocinergic system, which has a strong influence on empathy. These studies suggest that the maternal care instinct may mediate the effect of oxytocin receptor gene (OXTR) on empathy. To provide evidence for this mediation, we used the subscale of CARE in Affective Neuroscience Personality Scales (ANPS) to measure the maternal care instinct and tested two OXTR single-nucleotide polymorphisms (SNPs), rs53576 and rs13316193, in 880 high school participants (588 females, 292 males; Mage = 16.51 years old, SD = 0.65). Results showed that the genotype of rs13316193 was indirectly associated with empathy via CARE, suggesting a mediating role of CARE in the pathway from OXTR to empathy. These findings may contribute to an understanding of how empathy emerges when one witnesses another person in pain.