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Transl Psychiatry. 2018 Dec 4;8(1):257. doi: 10.1038/s41398-018-0315-3.

Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain.

Author information

1
Department of Psychology, California National Primate Research Center, University of California-Davis, One Shields Avenue, Davis, CA, 95616, USA. smfreem@ucdavis.edu.
2
Department of Psychology, California National Primate Research Center, University of California-Davis, One Shields Avenue, Davis, CA, 95616, USA.
3
Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA, 30329, USA.
4
Department of Radiology and Imaging Sciences, Emory University, 1841 Clifton Road, Atlanta, GA, 30322, USA.

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.

PMID:
30514927
PMCID:
PMC6279786
DOI:
10.1038/s41398-018-0315-3
[Indexed for MEDLINE]
Free PMC Article

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