Oxytocin Trials in ASD: Beyond the Hype and Hope 111treatments for ASD, as well as the needs of eager families, there is an urgent
need for researchers to prioritise considering such factors when conducting
well‐designed and controlled studies to further advance this field.”
Availability of intranasal oxytocin (most commonly Syntocinon) for the
study of psychological and behavioral phenomena has attracted many physi-
cians and other investigators to evaluate its effects on ASD patients. Kosfeld
et al. (118) were the first to publish an influential paper reporting that acute
intranasal oxytocin increased trusting behavior in socially deficit patients.
This study led to the flood of subsequent studies and clinical trials utilizing a
single‐dose administration suggesting that oxytocin was the panacea for
improving individuals with deficits in social cognition, who were emotionally
disturbed, and those with high stress and anxiety. Many studies were backed
up by fMRI evidence that suggested oxytocin increases activity in brain
regions associated with social cognition and modulates function connectivity
between these regions, indicating a role in modulating not just social behav-
iors but the neural and network underlying social interaction. Subsequent
studies to utilize oxytocin to alleviate ASD symptoms and identify effective
therapeutics for ASD to reduce core social communication deficits were rap-
idly carried out.
In the last decade or so, there have been numerous studies to investigate the
use of either a single dose oxytocin or multi‐dose or long‐lasting oxytocin in
ASD patients and the results have been mixed. The first, very promising study
was by Guastella et al. [(119] who used intranasal oxytocin in adolescent ASD
males, and found that oxytocin administration improved the accuracy of clas-
sifying emotions, particularly with less challenging items; they were the first
report to indicate feasibility and efficacy for intranasal oxytocin for improving
social cognition in younger individuals with ASD. Subsequent studies demon-
strated effects of intranasal oxytocin on a range of experimental outcomes.
Andari et al. [110] first demonstrated oxytocin significantly increased eye gaze
to social regions of faces in adults with ASD compared with placebo and nor-
mally developing control groups. Auyeung et al. [120] also reported that oxy-
tocin modulated changes in eye gaze during a real‐time social interaction. Of
note, in healthy individuals, a well‐replicated finding has been in the modula-
tion of eye gaze to static facial image after oxytocin administration. Within the
ASD group, this beneficial effect of oxytocin was particularly prominent for
those individuals who spent less time looking at the eye region under placebo.
These cumulative experimental findings from single‐dose studies suggest that
the short term and immediate effects of oxytocin, mostly in males with ASD,
with average‐to‐high cognitive functioning, imparted beneficial effects. Several
studies that used fMRI reported significant changes in activation brain areas
involved in social information processing, including the amygdala, medial pre-
frontal cortex, and anterior insula, as well as in broader areas involved in
reward processing in a child study [117]. In all of these studies, the participants