CD38 genetic variation is associated with increased personal distress to an emotional stimulus.

Genetic variation in CD38-a putative oxytocin pathway gene-has been linked to higher oxytocin levels, empathy, and sensitive parenting, but also to more negative interpersonal outcomes (e.g., alienation from friends and family, poorer romantic relationship quality). To reconcile these seemingly contradictory findings, we drew upon the idea that CD38 variation may heighten social-emotional sensitivity and, consequently, make individuals prone to negative emotions in distressing interpersonal situations. To test this hypothesis, we performed a secondary analysis of a dataset including participants' (n = 171; 94 females) empathic concern ("sympathetic") and distress-related ("anxious") responses to an emotional video. Distress responses were higher for the CD38 rs3796863 AA/AC group vs. the CC group (p = 0.03, η2 = 0.027); however, there was no significant effect of genotype for empathic concern responses to the video or for indices of trait empathy. These findings provide preliminary evidence that, in the face of an interpersonal stressor, CD38 genetic variation may predict more self-focused, aversive emotional reactions. More broadly, this finding highlights the need to adopt a more nuanced perspective in which the influence of oxytocin system variation (assessed by oxytocin-related genetic variation) should be considered in light of the social context.

CD38 is associated with bonding-relevant cognitions and relationship satisfaction over the first 3 years of marriage.

Although there are numerous benefits to having a satisfying romantic relationship, maintaining high levels of relationship satisfaction is difficult. Many couples experience declines in relationship satisfaction in the early years of marriage, and such declines predict not only relationship dissolution but also poor mental and physical health. Several recent studies indicate that genetic variation on the CD38 gene (CD38), at the single nucleotide polymorphism (SNP) rs3796863, is associated with cognitions and behaviors related to pair bonding; we thus leveraged longitudinal data from a sample of newlywed couples (N = 139 genotyped individuals; 71 couples) to examine whether rs3796863 is associated with relationship maintenance processes and, in turn, relationship satisfaction in the early years of marriage. Replicating and extending prior research, we found that individuals with the CC genotype (vs. AC/AA) of rs3796863 reported higher levels of gratitude, trust, and forgiveness and that trust mediated the association between rs3796863 and marital satisfaction. Moreover, the benefits conferred to CC individuals lasted over the first 3 years of marriage. To our knowledge, this is the first study to examine the link between variation in CD38 rs3796863 and marital functioning over time.

CD38 is associated with communal behavior, partner perceptions, affect and relationship adjustment in romantic relationships.

Given the significance of close relationships for human survival, it is thought that biological mechanisms evolved to support their initiation and maintenance. The neuropeptide oxytocin is one such candidate identified in non-human animal research. We investigated whether variation in CD38, a gene involved in oxytocin secretion and attachment behavior in rodents, predicts romantic relationship dynamics in daily life. Community couples participated in an event-contingent recording (ECR) study in which they reported their social behavior, perception of their partner's behavior, and affect during their interactions with one another over a 20-day period; couples also completed various measures of relationship adjustment. Out of the 111 couples (N = 222 individuals) who provided either ECR and/or relationship adjustment information, we had information on CD38 for 118 individuals. As hypothesized, variation in rs3796863, a single nucleotide polymorphism (SNP) identified in prior work, predicted communal behaviors (e.g., the expression of affection), as well as overall relationship adjustment, such that individuals with the CC (vs. AC/AA) allele reported higher levels of communal behavior across their daily interactions with their romantic partner, as well as higher levels of relationship adjustment. Individuals with the CC (vs. AC/AA) allele of rs3796863 also reported less negative affect and felt insecurity in their interactions with their romantic partner. Notably, we found that variation in the romantic partner's rs3796863 SNP was related to the person's outcomes, independent of the person's rs3796863 genotype. These findings support the role of oxytocin in the interpersonal processes implicated in the maintenance of close relationships.

CD38 regulates oxytocin secretion and complex social behavior.

The peptide hormone oxytocin plays a critical role in regulating affiliative behaviors including mating, pair-bond formation, maternal/parenting behavior, social recognition, separation distress and other aspects of attachment. Jin and colleagues recently reported intriguing findings that CD38, a transmembrane receptor with ADP-ribosyl cyclase activity, plays a critical role in maternal nurturing behavior and social recognition by regulating oxytocin secretion. This research may have implications for understanding disorders marked by deficits in social cognition and social functioning, including autism, social anxiety disorder, borderline personality disorder and schizophrenia.