Abstract
The prosocial hormone oxytocin (OXT) has become a new target for research on the etiology and treatment of autism spectrum disorder (ASD), a condition characterized by deficits in social function. However, it remains unknown whether there are alterations in OXT receptor (OXTR) levels in the ASD brain. This study quantified the density of OXTR and of the structurally related vasopressin 1a receptor (AVPR1a) in postmortem brain tissue from individuals with ASD and typically developing individuals. We analyzed two regions known to contain OXTR across all primates studied to date: the nucleus basalis of Meynert (NBM), which mediates visual attention, and the superior colliculus, which controls gaze direction. In the NBM specimens, we also analyzed the neighboring ventral pallidum (VP) and the external segment of the globus pallidus. In the superior colliculus specimens, we also analyzed the adjacent periaqueductal gray. We detected dense OXTR binding in the human NBM and VP and moderate to low OXTR binding in the human globus pallidus, superior colliculus, and periaqueductal gray. AVPR1a binding was negligible across all five regions in all specimens. Compared to controls, ASD specimens exhibited significantly higher OXTR binding in the NBM and significantly lower OXTR binding in the VP, an area in the mesolimbic reward pathway. There was no effect of ASD on OXTR binding in the globus pallidus, superior colliculus, or periaqueductal gray. We also found a significant negative correlation between age and OXTR binding in the VP across all specimens. Further analysis revealed a peak in OXTR binding in the VP in early childhood of typically developing individuals, which was absent in ASD. This pattern suggests a possible early life critical period, which is lacking in ASD, where this important reward area becomes maximally sensitive to OXT binding. These results provide unique neurobiological insight into human social development and the social symptoms of ASD.
Highlights
Extensive research has established the potent ability of the hypothalamic neuropeptide oxytocin (OXT) to modulate social behavior across species, including humans[1]
Post hoc comparisons between the OXT receptor (OXTR) radioligandalone and AVPR1a radioligand-alone conditions revealed significantly higher OXTR radioligand binding in all five regions (GP: t = 7.349, p < 0.0001; ventral pallidum (VP): t = 14.39, p < 0.0001; nucleus basalis of Meynert (NBM): t = 7.028, p < 0.0001; periaqueductal gray (PAG): t = 6.450, p < 0.0001; superior colliculus (SC): t = 5.816, p < 0.0001)
In the NBM, autism spectrum disorder (ASD) specimens had significantly higher OXTR binding compared to typically developing (TD) specimens
Summary
Extensive research has established the potent ability of the hypothalamic neuropeptide oxytocin (OXT) to modulate social behavior across species, including humans[1]. Convincing results from animal research led to examinations of the effects of OXT administration to humans, as well as a variety of investigations into the possible involvement of the OXT system in the etiology and treatment of psychiatric disorders, especially autism spectrum disorder (ASD)[2]. The increased research effort into the Freeman et al Translational Psychiatry (2018)8:257 potential involvement of OXT and its receptor (OXTR) in ASD includes genetic studies, analyses of OXT levels in biological fluids, and assessments of OXT treatment, which will be described further below. Neurobiological studies on the OXT system in ASD, such as the current study, are more rare than these system-wide investigations, they contribute essential information to the larger body of work by providing direct assessments of the ASD brain
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
