Intranasal oxytocin and OXTR genotype effects on resting state functional connectivity: A systematic review

•Effects of intranasal oxytocin seen during task fMRI may also be present at rest.•Intranasal oxytocin mediated intersection of the ventral attention and other networks.•Intranasal oxytocin has inconsistent effects on amygdala connectivity at rest.•Age, sex, and early life stress moderated both OXTR and intranasal oxytocin effects.•Effects may be most pronounced for individuals with psychosocial impairments. Evaluate effects of intranasal oxytocin (IN-OT) and OXTR genotype on resting state functional connectivity in the human brain. We searched research databases for peer-reviewed empirical studies. Of 71 unique citations, 18 articles (13 IN-OT, five OXTR) met full inclusion criteria. Two studies examined effects on large-scale networks; most examined acute effects on amygdala connectivity with other social and affective regions. OXTR studies identified three polymorphisms (rs2254298, rs2268498, rs53576) having allele- and sex-dependent effects on prefrontal functional connectivity, and additive effects of OXTR risk alleles on reward circuitry. Age, sex, early life stress, and psychopathology emerged as potential moderators of both IN-OT and OXTR effects. IN-OT appears to modulate resting state functional connectivity in a manner similar to its effects on task fMRI, consistent with hypothesized models of IN-OT. However, conclusions are limited by the narrow range of neuroanatomical seed regions, and methodological and experimental design heterogeneity. Future studies should take into account individual differences. Findings may provide insight into mechanisms through which IN-OT impacts human behavior.