Oxytocin receptor gene (OXTR) is related to psychological resources Shimon Saphire-Bernsteina, Baldwin M. Wayb, Heejung S. Kimc, David K. Shermanc, and Shelley E. Taylora,1 aDepartment of Psychology, University of California, Los Angeles, CA 90095; bDepartment of Psychology, Ohio State University, Columbus, OH 43210; and cDepartment of Psychology, University of California, Santa Barbara, CA 93106 Contributed by Shelley E. Taylor, August 10, 2011 (sent for review May 19, 2011) Psychological resources—optimism, mastery, and self-esteem—buffer throughout the body and the brain (30; for review, see ref. 31). the deleterious effects of stress and are predictors of neurophysiolog- Several studies report associations of the SNP rs53576, located in ical and psychological health-related outcomes. These resources have intron 3 of OXTR, with stress-related and psychological traits, with been shown to be highly heritable, yet the genetic basis for this her- the majority suggesting that carriers of the A allele (i.e., A/G and itability remains unknown. Here, we report a link between the A/A genotypes) have an increased sensitivity to stress, reduced oxytocin receptor (OXTR) SNP rs53576 and psychological resources, social skills, and more negative mental health outcomes relative to such that carriers of the “A” allele have lower levels of optimism, individuals with two copies of the G allele (32–38; but see ref. 39). mastery, and self-esteem, relative to G/G homozygotes. OXTR was For example, Lucht et al. (35) found that adult A/A homozygotes also associated with depressive symptomatology. Mediation analysis had lower self-reported positive affect and higher negative affect indicates that the effects of OXTR on depressive symptoms may be and loneliness. Another study found that G/G homozygotes out- largely mediated by the influence of OXTR on psychological resources. performed carriers of the A allele of rs53576 on the ability to detect emotion from pictures of human faces showing only the sychological resources refer to individual differences that are eyes (37). Other research has found that among mothers of re- OXTR Pdirectly predictive of physical and psychological health (1–3). cently born infants, rs53576 A-allele carriers demonstrated The most well-studied of these resources are optimism, mastery, lower maternal sensitivity relative to G-allele carriers (32). A and self-esteem (4–6). Optimism refers to the extent to which subsequent study of reproductive-age women without children people hold favorable expectations about the future (4, 7); as a revealed greater heart-rate response to baby cries in GG women dispositional variable, it reflects positive expectations across a relative to A-allele carriers (36), which was interpreted as in- ’ broad array of outcomes. Mastery involves the belief that one dicating greater sensitivity to the baby s needs and emotional state fi OXTR can determine one’s own behavior, influence one’s environment, among GGs. Taken together, these ndings suggest that and bring about desired outcomes; it also has a strong disposi- rs53576 may play a role in human social behaviors and psycho- logical resources (see also refs. 26–29). tional component (8). Self-esteem is a dispositional concept that fi refers to a person’s overall evaluation of self-worth (9). Previous Although these are intriguing and consistent ndings, it is difficult to assess their meaning without a functional account of research has established that these three resources are closely fl interrelated (4, 6, 10) and, both independently and as a cluster, how variation at the rs53576 locus in uences behavior via the they are known to buffer the effects of stressful life events and circuits and networks of the brain. Although not complete, a experimentally manipulated stressors on physiological stress picture has begun to emerge regarding the consequences of responses (for reviews, see refs. 2 and 5). Moreover, considerable variation at this SNP for the structure and function of brain areas involved in a wide range of cognitive and social-cognitive pro- research demonstrates that susceptibility to depression and other cesses. For example, Tost et al. (38) found that A-allele carriers forms of psychological distress is lower among individuals high in had reduced volume of the hypothalamus and increased struc- optimism (4, 11, 12), mastery (13, 14), and self-esteem (15–17). tural (correlated structure sizes) and functional (coactivation in The model guiding the present research attributes the origins response to faces picturing emotions) connectivity of the hypo- of psychological resources to developmental and genetic factors thalamus to both the amygdala and the dorsal anterior cingulate (2, 5). Aspects of the early environment that affect the devel- cortex (dACC). These brain regions have been tied previously to opment of these resources include family socioeconomic status stress responses (10, 40, 41), which have also been associated (15, 18, 19), childhood adversities (20), and parental practices with rs53576 (37) and vulnerability to social distress (dACC) (18, 20). Psychological resources may continue to be influenced (40–42). As such, these findings provide suggestive evidence for by life experiences in adolescence, young adulthood, and beyond a biological stress-related phenotype associated with OXTR (18), but less research is available on this question. Although we rs53576. The link between OXTR and the dACC is especially acknowledge the importance of these environmental factors in interesting in light of findings that self-esteem attenuates dACC the developmental origins of psychological resources, the present activation in response to social rejection (42). The connection to research is primarily concerned with the second primary source: the amygdala is consistent with previous research showing that human genetics. intranasal administration of oxytocin modulates activation of the Twin studies have shown that a large proportion of the variance – – amygdala to emotional and neutral faces (42 46). Petrovic et al. in psychological resources is heritable (21 25). The extant research (46) also found an effect of intranasal oxytocin on dACC acti- suggests a narrow range for the heritability of optimism, with in- vation. Thus, a growing literature supports a role for OXTR in dependent reports ranging from 20% (21) to 36% (24). Estimates the structure and function of the amygdala, hypothalamus, and for the heritability of self-esteem range more widely, from a low of 29% (23) to a high of 73% (22). Research on the behavioral ge- netics of mastery has not, to our knowledge, been conducted. Author contributions: S.S.-B., B.M.W., H.S.K., D.K.S., and S.E.T. designed research; B.M.W. Despite evidence for the heritability of psychological resources, the and S.E.T. performed research; S.S.-B. and B.M.W. analyzed data; and S.S.-B. and S.E.T. genetic bases of this heritability have yet to be elucidated. wrote the paper. The oxytocin system appears to play a role in socioemotional The authors declare no conflict of interest. functioning and positive emotion (26–29). Located on chromo- 1To whom correspondence should be addressed. E-mail: [email protected]. OXTR some 3p25.3, codes for the oxytocin receptor, the receptor This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. by which the neurohormone oxytocin exerts a range of effects 1073/pnas.1113137108/-/DCSupplemental. 15118e15122 | PNAS | September 13, 2011 | vol. 108 | no. 37 www.pnas.org/cgi/doi/10.1073/pnas.1113137108 Downloaded by guest on September 28, 2021 dACC, structures of known relevance to psychological resources, The allelic distribution differed between the Asian and non- and their influence on stress processes (10, 40–42). Asian participants [χ2(2) = 51.6, P < 0.0001], with lower prev- On the basis of this literature, we hypothesized that variation in alence of G-allele homozygotes among Asians and conversely OXTR at rs53576 may be associated with psychological resources, lower prevalence of A-allele homozygotes among non-Asians such that self-esteem, optimism, and mastery would be higher (Table S2). This difference is consistent with past reports in the among G/G homozygotes relative to carriers of the A allele. Ad- literature (33, 34, 48). In addition, levels of psychological ditionally, because the A allele may confer risk for lower psy- resources were lower and levels of depressive symptomatology chological resources, which are protective against stress and were higher in the Asian participants (Table S3). The overall negative self-views, we predicted that OXTR A allele carriers pattern of relations between OXTR genotypes and psychological would have higher levels of depressive symptomatology, which resources, however, was the same for Asians and non-Asians (SI may potentially be mediated by (lack of) psychological resources. Text and Table S4). Additional analyses for ethnicity and anal- yses for sex appear in the SI Text and Table S5. Results OXTR The distribution of genotypes for OXTR was 108 G/Gs (33.1%), Mediation Analysis. The effect of on depressive symptom- 153 A/Gs (46.9%), and 65 A/As (19.9%). This distribution does atology may be indirectly mediated by psychological resources, – not deviate from the Hardy-Weinberg equilibrium, χ2(1) = 0.65, which are known to be protective against depression (4, 6, 11 P = 0.419. 17). We tested this possibility using mediation analysis (49). The To test the relation between OXTR and psychological re- hypothesized