Oxytocin enhances brain function in children with autism

Abstract

Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, left posterior superior temporal sulcus, and left premotor cortex, OT increased activity during social judgments and decreased activity during nonsocial judgments. Changes in salivary OT concentrations from baseline to 30 min postadministration were positively associated with increased activity in the right amygdala and orbitofrontal cortex during social vs. nonsocial judgments. OT may thus selectively have an impact on salience and hedonic evaluations of socially meaningful stimuli in children with ASD, and thereby facilitate social attunement. These findings further the development of a neurophysiological systems-level understanding of mechanisms by which OT may enhance social functioning in children with ASD.A utism spectrum disorder (ASD) is a common, early-onset neurodevelopmental disorder characterized by devastating difficulties in social interaction, communication, and repetitive or restricted interests and behaviors. ASD displays great phenotypic heterogeneity and etiological diversity, but its original characterization, social dysfunction, has been its hallmark and unifying feature (1). There is no established pharmacological treatment for social impairment in ASD.When given acutely, intranasal oxytocin (OT) leads to enhanced processing of social stimuli in typically developing adults, as evidenced by increased eye contact, in-group trust, and emotion recognition from facial expressions (2-4). At the level of neural systems, intranasal OT heightens activity in a set of neuroanatomical structures involved in processing socially meaningful stimuli in typically developing adults (5, 6). Recently, the first brain imaging study in adults with ASD examined the effects of OT administration and identified increased activation in the right amygdala during social information processing (7).Behavioral studies demonstrate that in children and adults with ASD, a single administration of intranasal OT leads to increased willingness to interact socially (8), better comprehension of affective speech (9), reduced repetitive behaviors (10), increased understanding of others' mental states (11), and improved social cognition (12). Despite cautionary calls regarding the use of OT in children to treat ASD before understanding the neural mechanisms underlying OT's complex impact on behavior (13), there have been no studies on the effects of OT administration on brain activity in children. Furthermore, although there are several large-scale clinical trials currently underway (www. clinicaltrials.gov) to examine the effects of chronically administered OT in ASD, the e...

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