102 Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder
Hormones, Neuropeptide Arginine Vasopressin
and Oxytocin in ASD
The neuropeptides oxytocin and vasopressin increasingly have been identified as
modulators of human social behaviors and have been associated with neuropsy-
chiatric disorders characterized by social dysfunction, including autism [1–3,65–
68]. It has been shown that the measured volume of the olfactory bulb correlates
with the functional capacity in normal individuals (e.g., larger olfactory bulbs
exhibit finer olfactory discrimination). The ability to discriminate between dis-
tinct smells, which is dependent on intact functioning of the olfactory bulb, has
been shown to be impaired in autism. It can be assumed, therefore, that a substan-
tial reduction in size (or total absence) of the olfactory bulb, as observed in autism,
may explain some of the symptoms. This abnormality may have impacts beyond
olfactory discrimination due to utilization of the olfactory bulb in social and emo-
tional processing. Of note, the neuropeptide AVP has been hypothesized to play a
role in the etiology of autism based on demonstrated involvement in social bond-
ing and in the regulation of a variety of socially relevant behaviors in animal mod-
els. AVP regulates male social behavior not just through higher expression in
males but also through steroid‐sensitive brain sexual dimorphisms in AVP neu-
rons. AVP may therefore influence sexually dimorphic social behaviors in a range
of species. The role of sex hormones on AVP is of interest in the context of autism
considering that the ratio of affected males with autism compared with females is
markedly skewed (4:1). This may be due to the fact that a large number of fra-
grances have hormone‐like effects, perhaps partially explaining the underdevel-
opment of olfactory bulbs and male preference. Olfactory bulbs contain a high
density of oxytocin and vasopressin receptors and the actions of these neuro-
transmitters are dependent on the proper functioning of this region of the brain.
Any impairment of the olfactory bulbs during development would compromise a
key mechanism of action mediating these social behaviors. As shown below, fra-
grances are designed to bind the smell receptors of olfactory neurons. Therefore,
the binding of any substance that may hinder or modulate normal development of
fetal brains may theoretically contribute to the development of autism.
Although there is no reliable neurophysiologic marker associated with ASD,
low levels of plasma oxytocin and AVP have been reported [8,20,45]. The twin
nonapeptides oxytocin and AVP are mainly produced in the brain of mammals
[18], and dysregulation of these neuropeptides has been associated with
changes in behavior, especially social interactions. Both peptides are produced
by nonoverlapping populations of neurons in the same hypothalamic nuclei,
the supraoptic nucleus and the paraventricular nucleus. The supraoptic
nucleus and paraventricular nucleus contain large magnocellular peptidergic
neurons that send their axons to the posterior pituitary where they release AVP
and oxytocin into the blood [1–3,64–66] (Figure 4.3). The AVP and oxytocin
signals evoke their physiological effects via their respective receptors [8,10].