Serum Oxytocin Levels and an Oxytocin Receptor Gene Polymorphism (rs2254298) Indicate Social Deficits in Children and Adolescents with Autism Spectrum Disorders

Abstract

The neuropeptide oxytocin (OT) and its receptor (OXTR) have been predicted to be involved in the regulation of social functioning in autism spectrum disorders (ASD). Objective of the study was to investigate serum OT levels and the OXTR rs2254298 polymorphism in Chinese Han children and adolescents with ASD as well as to identify their social deficits relevant to the oxytocinergic system. We tested serum OT levels using ELISA in 55 ASD subjects and 110 typically developing (TD) controls as well as genotyped the OXTR rs2254298 polymorphism using PCR-RFLP in 100 ASD subjects and 232 TD controls. Autistic symptoms were assessed by the Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS). There were no significant associations between OXTR rs2254298 polymorphism and ASD, serum OT levels and age, as well as serum OT levels and intelligent quotient (IQ) in both ASD and TD groups. However, ASD subjects exhibited elevated serum OT levels compared to TD controls and positive correlations between serum OT levels and “adaptation to change score” in the CARS and CARS total scores. Moreover, in the ASD group, significant relationships were revealed between the single-nucleotide polymorphism (SNP) rs2254298 and serum OT levels, the category “stereotypes and object use” in the ABC and the category “adaptation to change” in the CARS. These findings indicated that individuals with ASD may exhibit a dysregulation in OT on the basis of changes in OXTR gene expression as well as environmentally induced alterations of the oxytocinergic system to determine their social deficits.

Oxytocin and vasotocin receptor variation sheds light into the evolution of human prosociality

“…Rs2254298(A) carriers performed better in self-reported empathy 37 and empathy for pain in particular 49 , parenting 50 and in attachment security tests (in a non-Caucasian children sample) 51 , while A-ADHD-carriers displayed fewer social deficits 26 . On the contrary, A-ASD-carriers presented more social deficits 26 and lower serum OXT-levels 52 . This allele has also been related to prosopagnosia 53 , high levels of physical aggression and hostility 54 and low emotion recognition and resilience skills 55 .…”

A randomized trial shows dose-frequency and genotype may determine the therapeutic efficacy of intranasal oxytocin

“…A further unresolved issue is that different OT receptor (OXTR) genotypes have been associated with social behaviors and may influence sensitivity of behavioral and neural responses to intranasal OT. In particular, OXTR polymorphisms rs53576 and rs2254298 have been associated with autism (Cataldo et al, 2018), deficits in social and emotional processing and anxiety (Jurek and Neumann, 2018; Parker et al, 2014; Yang et al, 2017) and individual variations in behavioral and neural responses to intranasal OT (Chen et al, 2015; Feng et al, 2015). Indeed, variants of rs2254298 may represent a trans-diagnostic biomarker for social dysfunctions (Brüne, 2012).…”

Genotype and dose-frequency determine acute and chronic effects of oxytocin on amygdala fear responses in humans: therapeutic implications

“…Different OT receptor (OXTR) genotypes have been associated with social behaviors and may also influence sensitivity of behavioral and neural responses to intranasal OT. In particular, OXTR polymorphisms rs53576 and rs2254298 have been associated with autism [17], deficits in social and emotional processing including empathy [18][19][20] and individual variations in behavioral and neural responses to intranasal OT [21,22]. Variants of rs2254298 may also be a more general biomarker for social dysfunction across a number of psychiatric disorders [23].…”