108 Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder
Exogenous Oxytocin Treatments in Humans
This and other research has set the stage for a series of recent studies on the
effects of exogenous oxytocin treatments in humans (reviewed in Ref. [89]). For
example, intranasal oxytocin administration in healthy human males has been
shown to increase prosocial behaviors and trust, especially as measured by
experimental economic games. Exogenous oxytocin may also increase gaze
towards the eye region of the face, and has been associated with improved facial
memory, enhanced salience of social cues, and improved performance in the
“Reading the Mind in the Eyes” (or RMET) test. Multiple studies have demon-
strated the positive effect of oxytocin on social interactions, fear reduction, and
social cue interpretation and the negative effects that occur when oxytocin is
downregulated, resulting in neuropsychiatric disorders. More recently,
researchers have discovered defective oxytocin receptor genes in ASD patients
[90] these are generally single nucleotide polymorphisms (SNPs; single nucleo-
tide deletions or changes). Significant associations have been reported in ASD
and oxytocin receptor SNPs. Of note, there are multiple different kinds of SNPs
at different loci in the oxytocin receptor DNA, suggesting environmental insults
have induced point mutations rather than a genetic basis of ASD [91–101].
There are many diseases that are caused by environmental insults [102–108].
A single oxytocin receptor and two subtypes of vasopressin receptor (i.e.,
V1α and V1β) are centrally expressed and distributed widely throughout the
brain. Centrally, particularly high expressions of these receptors are found in
regions underlying the control of many social behaviors, such as the nucleus
accumbens, ventral tegmental area, amygdala, and hippocampus (Figure 4.2).
Although oxytocin and vasopressin exert a range of neuropeptide specific
physiological functions, there is a possibility that they also cross‐react at the
receptor levels (given similarities in structure), which suggests that increased
activity of one peptide may also can modulate the expressivity of the other.
In summary, a large body of research suggests that lower concentrations of
oxytocin in peripheral circulation may be causally associated with social impair-
ments, particularly in ASD children but also in schizophrenia. Evidence in favor
of this idea has often been used to support trials of oxytocin administration to
increase oxytocin levels in individuals with an “oxytocin deficit”. However, incon-
sistent evidence in individuals with ASD does not favor such a treatment. Several
studies have reported lower oxytocin levels in ASD [109–111], while others have
not exhibited any differences [112–114] and one has reported increased oxy-
tocin levels in ASD [115]. Here, again, we remind our reader that ASD is a spec-
trum, and it all depends when a fetus suffered the insult that disturbed the
oxytocin and oxytocin receptor developmental pathways (Figure 4.2). We believe,
the spectrum in ASD is due to exogenous insults (mainly the environmental
chemicals). It is when, how much, and at what stage of brain development that a
fetus encountered an insult that perturbs the balance of differentiation.