110 Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder
repetitive patterns of behavior. Defined by the Diagnostic and Statistical
Manual of Mental Disorders, 5th edition (DSM‐5), restricted, repetitive pat-
terns of behavior include stereotyped or repetitive motor movements, insist-
ence on sameness, inflexible adherence to routines, or ritualized patterns of
verbal or nonverbal behavior. Highly restricted, fixated interests that are
abnormal in intensity or focus, and hyper‐ or hyporeactivity to sensory input
or unusual interest in sensory aspects of the environment are also classified as
restricted and repetitive behaviors (RRBs).
Several studies, using intranasal and intravenous oxytocin, in patients with
ASD have been conducted (reviewed in Ref. [89]). It has been shown that
nonapeptides, like AVP, can be measured in cerebrospinal fluid after intranasal
administration [116]. Ease of giving intranasal drugs makes it a preferred route
for most ASD studies, although more research needs to be conducted on how
intranasal oxytocin reaches the brain and how it regulates receptors and neural
pathways with different or chronic dosing strategies. Several studies have
measured oxytocin responses to single dose challenges in ASD, while few have
examined longer term treatment effects. Studies have often focused on symp-
tom subdomains or defined social tasks including: RRB, emotion recognition,
affective speech comprehension, and facial recognition.Oxytocin Trials in ASD: Beyond the Hype and Hope
In the preceding sections, we summarized some of the research that shows that
potentially exogenous oxytocin may be helpful to ASD children. We have also
cautioned that oxytocin may not be that helpful if oxytocin receptors are
depleted during fetal development or due to SNPs that can render the recep-
tors useless or with less function. However, this has not tempered the enthusi-
asm of some physicians and investigators in trying to alleviate some of the ASD
symptoms via exogenous oxytocin. In a recent comprehensive study, Alvares
et al. [117] have reviewed the current status of oxytocin based therapy. After
much hyped early findings, subsequent clinical trials of longer term adminis-
tration of intranasal oxytocin have yielded mixed results. It is still unclear
whether many of the disappointing results reflect no real beneficial effects of
exogenous oxytocin or are diminished by methodological differences masking
true effects. The evidence to date suggests a number of methodical or design
differences that may be unified to improve research in this area. These include
considering the choice of ASD outcome measures, the amount of oxytocin
delivered by nasal spray devices, the types of delivery devices to be utilized, and
the selection of ASD patients and normotypic controls. Despite these limita-
tions in the field to date, there remains significant hope for delivery of exoge-
nous oxytocin to improve social impairments observed in ASD patients.
Alvares et al. [117] stated: “Given the considerable media hype around new