Oxytocin modulation of self-referential processing is partly replicable and sensitive to oxytocin receptor genotype

Intranasal oxytocin (OXT) has been associated with effects on diverse social-emotional domains in humans, however progress towards a therapeutic application of OXT in disorders with social-emotion impairments is currently hampered by poor replicability. Limited statistical power and individual differences in biological factors, such as oxytocin receptor (OXTR) genetics, may have contributed to these variable findings. To this end, employing a validated oxytocin-sensitive trait judgment paradigm, we present a pharmaco-genetic study aiming at (1) replicating previous findings suggesting that intranasal oxytocin (24 IU) reduces the self-referential bias in a large sample of n = 170 male subjects, (2) determining whether variations in common receptor polymorphisms (rs237887, rs2268491, rs2254298, rs53576, rs2268498) influence sensitivity to oxytocin's behavioral effects. We confirmed that in the whole sample oxytocin influenced self-other distinction in terms of reduced decision time. However, oxytocin only influenced decision time in rs53576 G carriers, whereas effects on subsequent memory performance were only found in rs2268498 TT homozygotes. In summary, the current study partially replicates our previous findings showing that oxytocin reduces the self-referential bias and suggests that sensitivity to its effects in this domain are receptor genotype dependent.