Effects of a Common Variant in the CD38 Gene on Social Processing in an Oxytocin Challenge Study: Possible Links to Autism

Abstract

The intranasal application of oxytocin (OT) has been shown to influence behavioral and neural correlates of social processing. These effects are probably mediated by genetic variations within the OT system. One potential candidate could be the CD38 gene, which codes for a transmembrane protein engaged in OT secretion processes. A common variation in this gene (rs3796863) was recently found to be associated with autism spectrum disorders (ASD). Using an imaging genetics approach, we studied differential effects of an intranasal OT application on neural processing of social stimuli in 55 healthy young men depending on their CD38 gene variant in a double-blind placebo-controlled crossover design. Genotype had a significant influence on both behavioral and neuronal measures of social processing. Homozygotic risk allele carriers showed slower reaction times (RT) and higher activation of left fusiform gyrus during visual processing of social stimuli. Under OT activation differences between genotypes were more evident (though not statistically significantly increased) and RT were accelerated in homozygotic risk allele carriers. According to our data, rs3796863 mainly influences fusiform gyrus activation, an area which has been widely discussed in ASD research. OT seems to modulate this effect by enhancing activation differences between allele groups, which suggests an interaction between genetic makeup and OT availability on fusiform gyrus activation. These results support recent approaches to apply OT as a pharmacological treatment of ASD symptoms.

Associations between oxytocin-related genes and autistic-like traits

“…If, indeed, the transcription levels are increased by the G allele, these two findings taken together would be in line with our results, where homozygotic carriers of the G allele scored lower for ALTs related to language impairment. We were not able to find any statistical association between ALTs and rs3796863, a CD38 SNP previously investigated by Munesue et al, finding an association with ASD in a clinical subset (Munesue et al, 2010), and Sauer et al, finding an association with fusiform gyrus activation (implicated in ASD research) (Sauer et al, 2012).…”

“…In humans, there have been indications that SNPs in the CD38 gene are associated with reduced oxytocin plasma levels and ASD symptoms, as well as effects on visual processing of, and fusiform gyrus activation by, social stimuli (Munesue et al, 2010;Sauer et al, 2012).…”

Genetic Variation in the Maternal Oxytocin System Affects Cortisol Responsiveness to Breastfeeding in Infants and Mothers

“…Frequencies are similar to those observed in other studies (Sauer et al 2013;Sauer et al 2012), and no Mendelian inheritance inconsistencies were detected regarding transference of alleles from mothers to offspring. Hardy-Weinberg equilibrium was tested in mothers and infants separately; no deviations were detected (all p-values >0.05).…”

“…In humans, the common SNP CD38 rs3796863 has been associated with differences in social functioning. Specifically, the CC genotype has been associated with lower levels of oxytocin, reduced sensitive parenting, impaired social memory, and reduced responsiveness to gratitude (Algoe and Way 2014;Feldman et al 2012;Sauer et al 2013;Sauer et al 2012). Furthermore, the C allele is more common in autism spectrum disorder (ASD) than controls and is considered a risk allele for atypical social development (Lerer et al 2010;Munesue et al 2010).…”

Perception of Facial Aging and Its Relationship to Two Single Nucleotide Polymorphisms (OXTR rs53576, CD38 rs3796863)

“…Prior to beginning this study and based on similar studies (Marsh et al, 2012;Sauer et al, 2012), we anticipated the need to recruit between 40 and 45 participants. Our sample consisted of nine male (two Asian-, two Hispanic-, five Caucasian Americans; M = 20.7 years, SD = 1.82) and 34 female (one Asian-, two African-, seven Hispanic-, 24 Caucasian Americans; M = 20.8 years, SD = 1.41) young adults.…”