The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder

Abstract

BackgroundIntranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD.MethodsIn this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes.ResultsCentral analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards.ConclusionsThe effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD.Electronic supplementary materialThe online version of this article (10.1186/s11689-018-9228-y) contains supplementary material, which is available to authorized users.

Association of oxytocin receptor gene polymorphisms with autism spectrum disorder in Bengali of Bangladesh population

“…A group of conditions defined by qualitative abnormalities in reciprocal social interaction, distinctive patterns of communication and by a restricted, stereotyped, repetitive repertoire of interests and actions (WHO, 1992) was classified by ICD-10 as Autism Spectrum Disorder (ASD) under the Pervasive developmental disorders. Interest in the role of Oxytocin (OXT) hormone in the development of ASD has increased with the demonstration that this hormone plays an essential role in social attraction, affiliative behavior and bonding, as well as any disruption or change in this cascade, may lead to the development of social deficit (Greene et al, 2018;Busnelli and Chini, 2017;Hernandez, 2017;Olff et al, 2013). Failure of social adaptation on repeated exposure was seen in OXT knockout mice supports the function of oxytocin in integrating social olfactory information and facilitating the consolidation of social memory (Young et al, 2002).…”

Mechanisms of impairments in visual social attention in autism spectrum disorders

“…催产素在奖赏系统中起重要作用 [61] , 给ASD患者 注射催产素可以提高其社会认知能力 [62] . 研究表明, 给ASD患者注射催产素可以提高其加工社会情感信息 的脑区的活动, 而且还可以加强奖赏系统和社会情感 系统的联结 [62] , 能够增加他们对面孔的注意 [63] , 提高 其联合注意能力 [64] .…”

“…研究表明, 给ASD患者注射催产素可以提高其加工社会情感信息 的脑区的活动, 而且还可以加强奖赏系统和社会情感 系统的联结 [62] , 能够增加他们对面孔的注意 [63] , 提高 其联合注意能力 [64] . 但是也有研究表明, 催产素可能 只对非社会奖赏起作用 [61] . 未来应进一步探究催产素 对于与社会奖赏加工有关的神经系统的作用.…”

Imaging-genetics of sex differences in ASD: distinct effects of OXTR variants on brain connectivity

“…As social deficits are a core feature of ASD, the oxytocin system has attracted considerable attention as a potential target for pharmacological manipulation in individuals with autism [7][8][9] . Indeed, in males with ASD, treatment with intranasal oxytocin has been shown to improve social responsivity, seemingly through effects on reward-related subcortical brain areas and frontal brain regions important for social cognition [10][11][12][13][14][15][16] .…”