Oxytocin’s Promise for Autism Essay
This article presents our discovery that intranasal administration of oxytocin enhances activity in the brain for socially meaningful stimuli and attenuates its response to nonsocially meaningful stimuli in children with autism spectrum disorder (ASD) as measured via functional MRI. We also identified a relationship between changes in salivary oxytocin following administration and enhancements in brain function. These discoveries are particularly important given the urgent need for treatments that target the core social dysfunction in ASD. Oxytocin’s Promise for Autism Essay.The functional neural attunement we demonstrated might facilitate social learning, thus potentially bringing about long-term change in neural systems and subsequent behavioral improvements. Our results illustrate the power of a translational neuroscience approach to facilitate the development of pharmacological interventions for neurodevelopmental disorders like ASD.
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. Oxytocin’s Promise for Autism Essay. t hese findings further the development of a neurophysiological systems-level understanding of mechanisms by which OT may enhance social functioning in children with ASD.
Autism 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 empirical record shows that behavioral effects have been mixed at best (13⇓–15).Oxytocin’s Promise for Autism Essay. For example, two recent studies of the effects of repeated daily administration for a period of weeks have resulted in only modest improvements in social behavior (14, 15). The rapid movement from single administration studies in healthy adults and individuals with ASD to chronic administration to individuals with ASD has introduced a “translational hurdle” (13, 16), one that we aimed to tackle by exploring the neural basis of OT’s effects.
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In a randomized, double-blind, cross-over functional MRI (fMRI) study, we sought to identify the impact of single intranasal administration of OT on brain activity in 17 children and adolescents (aged 8–16.5 y) with ASD. We studied children and adolescents because previous reports had not included children younger than 12 y of age (11). We hypothesized that during a task involving social judgments, OT vs. Placebo would heighten brain activity in the neural circuits supporting reward [dorsal and ventral striatum and nucleus accumbens (NAcc)], as well as social attention and social cognition (e.g., posterior superior temporal cortex, cingulate, precuneus), that is, the “social brain” (17).
Participants were randomized to OT and Placebo nasal sprays on two consecutive visits. Forty-five minutes following administration, brain function was assessed using the “Reading the Mind in the Eyes Test” (RMET) (18, 19), a well-validated fMRI emotion judgment task. We selected this task because performance is reliably related to autistic traits (18, 20, 21) and behavioral performance is enhanced by intranasal OT in healthy adults, as well as individuals with ASD (11, 22). We modified the original (gender attribution) control condition of the RMET to dissociate social and nonsocial processing, and thus to examine the specificity of OT effects on social processing. We asked participants either to label a mental state from pictures of the Eyes (social entities) or to label the category of automobile presented in pictures of Vehicles (nonsocial objects). Each participant practiced the tasks before the functional scan began to ensure that he or she understood and could readily perform the tasks. Within the scanner, the tasks lasted a total of 5.1 min and alternated between the social and nonsocial judgment task conditions. There were five 25-s blocks of each condition (total of 10 blocks). In each block, five different images of either Eyes or Vehicles appeared for 5 s each. Blocks were separated by 12-s rest periods (blank screen and central fixation cross). The order of the presentation of social and nonsocial blocks was quasirandomized: on the first visit, all participants started by labeling a social block, and on the second visit, all participants started by labeling a nonsocial block. Fig. S1depicts the fMRI task design. Oxytocin’s Promise for Autism Essay.
To understand how the coordination of peripheral and central OT function may have an impact on neural systems-level function (23), we measured reactivity in OT concentration in saliva from baseline to 30 min postadministration. Given recent discoveries regarding associations between peripheral levels of OT and social behavior (24⇓–26), we explored how changes in peripheral OT are associated with changes in brain activity. Oxytocin’s Promise for Autism Essay.