98 Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder
Although much remains to be learned about the oxytocin–oxytocin receptor
system and its role in social behavior, low levels of oxytocin have also been
associated with other neurodegenerative disorders. In Alzheimer patients,
decreased oxytocin binding site density in the nucleus basalis of Meynert in the
brain has been observed [8,10]. Similarly, individuals with Parkinson’s disease
have fewer neurons with oxytocin receptors in the hypothalamus [8,10].
The exact causes of oxytocin receptor down regulation are not entirely clear;
however, we have discovered that some fragrances have been linked to lower
levels of the receptor [22,25]). Sex differences have also been observed, with
females often exhibiting higher levels of oxytocin than males, which may help
explain ASD male bias [22,29–44]. Environmental factors have been linked to
oxytocin receptor expression changes during fetal development. Increased
oxytocin receptor binding in the nucleus accumbens and CA3 region of the
hippocampus has been observed with exposure to nicotine and ethanol
[22,23,25,27,29,45–54]. Oxytocin receptors are also upregulated in mu‐opioid
knockout mice, indicating a connection between oxytocin receptor expression
and the opioid reward system [10].
Another factor that could suppress arginine vasopressin (AVP) and oxytocin
receptor binding is underdevelopment of olfactory bulb neurons, which has
been observed in children with ASD [52–54]. Fragrances are known to bind to
olfactory neurons in the brain and could contribute to this underdevelopment
[22,25,29]. Excessive exposure during critical periods of fetal development could
overwhelm the natural system of regeneration, thereby inhibiting the normal
development of the olfactory neurons [22,25,27,29,45–51]. Chemical fragrance
exposure may also contribute to axon thinning/elongation and increased syn-
apses [25,29]. Children with ASD are unable to eliminate excess neurons and
synapses, resulting in excessive communication between different parts of the
brain. The end result is inhibition of oxytocin and AVP binding, which can result
in neurodevelopmental delays and social impairment, as is observed in ASD.
Treatment with synthetic oxytocin hormone improves symptoms in children
with autism. In a pilot study, treatment with 0.4 IU/kg/dose oxytocin for
12 weeks had positive impacts on social and behavioral parameters that per-
sisted for 3 months following administration [55–57]. In a subsequent section
we have provided a detail account of oxytocin treatment for ASD. Another
study examining intranasal oxytocin at 12 IU for 5 weeks showed improvement
in social interaction deficits with minimal side effects. These studies illustrate
the important role of oxytocin in the regulation of social, emotional, and
behavioral parameters and the potential amelioration of autistic symptoms by
targeting this mechanism. In primates, oxytocin receptors are concentrated
around the cholinergic regions that regulate visual and auditory processing,
including response to visual cues [58–60]. Studies in nonhuman primates have
shown that oxytocin delivered intranasally can increase oxytocin in cerebro-
spinal fluid and plasma and may, thereby, affect brain oxytocin signaling