A randomized trial shows dose-frequency and genotype may determine the therapeutic efficacy of intranasal oxytocin

BackgroundThe neuropeptide oxytocin is proposed as a promising therapy for social dysfunction by modulating amygdala-mediated social-emotional behavior. Although clinical trials report some benefits of chronic treatment it is unclear whether efficacy may be influenced by dose frequency or genotype. MethodsIn a randomized, double blind, placebo-controlled pharmaco-fMRI trial (150 male subjects) we investigated acute and different chronic (every day or on alternate days for 5 days) intranasal oxytocin (24IU) effects and oxytocin receptor genotype-mediated treatment sensitivity on amygdala responses to face emotions. We also investigated similar effects on resting state functional connectivity between the amygdala and prefrontal cortex. ResultsA single dose of oxytocin reduced amygdala responses to all face emotions but for threatening (fear and anger) and happy faces this effect was abolished after daily doses for 5 days but maintained by doses given every other day. The latter dose regime also enhanced associated anxious-arousal attenuation for fear faces. Oxytocin effects on reducing amygdala responses to face emotions only occurred in AA homozygotes of rs53576 and A carriers of rs2254298. The effects of oxytocin on resting state functional connectivity were not influenced by either dose-frequency or receptor genotype. ConclusionsInfrequent chronic oxytocin administration may be therapeutically most efficient and its anxiolytic neural and behavioral actions are highly genotype-dependent in males.