Background Huntington’s disease (HD) is consistently associated with deficits in facial expressions of emotion, and in eye gaze to human faces. These deficits have been linked to abnormal amygdala responsitivity to social cues in HD. A large body of research now supports an important role of oxytocin (OXT), a neuropeptide, in modulating responses to socio-emotional cues in humans. Evidence suggests that the actions of OXT, at least in part, are at the level of the amygdala. To date, the administration of intranasal OXT to HD patients has not been examined.

Aims This study examined whether OXT, when administered to patients with HD, has a beneficial effect on the amygdala and amygdala subregional responses to emotional cues using functional magnetic resonance imaging (fMRI).

Methods The study involved a randomised double-blind placebo-controlled design during which participants (HD=8 and controls=10) attended two visits, separated by at least one week. Two acute nasal spray treatment conditions were administered at each visit involving OXT (24 IU or 40.32μg Syntocinon-spray) and placebo (PBO).

Results We observed exaggerated amygdala response to negative emotions in patients with HD (vs. controls). Acute intranasal OXT (vs. PBO) strongly increased amygdala response during the perception of negative and positive emotions in the HD but not in controls. The hyperactivity and OXT effects were found across all amygdala subregions, however the magnitude of the amygdala response was greatest in the dorsal subregion which is linked to the aversion network.

Conclusions These findings are the first of its kind to examine OXT effects on abnormal brain related emotional processing in a neurodegenerative disease, thereby providing evidence for a broader physiological role of OXT in humans. The findings suggest that it may be worthwhile to explore a therapeutic approach related to this OXT effect in HD.