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KUL-EC-LAuRes

Abstract:

Background. Autism spectrum disorders (ASD) are characterized by impairments in social communication and interaction. To date, no pharmacological treatments exists targeting the core symptoms of ASD. The past years, the pharmacological use of a neuropeptide, called oxytocin (OT), has gained increasing interest from the research community to explore its potential for elevating the core social deficits in ASD. In the brain, OT acts as a neurotransmitter where it is considered to form a mediator of prosocial behavior by increasing social salience, social motivation, and social awareness. Objectives. With this study, we aim to evaluate both immediate (single-dose) and long-term (multiple dose) effects of OT administration in adult male patients with ASD in a double-blind randomized placebo-controlled trial. Both neural and behavioral measures are assessed. Methods. A multi-modal neuroimaging approach is adopted to assess neural effects (i) at baseline; (ii) after a single-dose (24 IU) of nasal spray administration (OT or placebo); (iii) after 4 weeks of daily nasal spray administration; and (iv) one month post-trial to assess potential retention effects. Behavioral changes are assessed using emotion processing tasks and questionnaires assessing social responsiveness, attachment, mood state, and quality of life. Sixteen male patients with ASD (8 OT/ 8 placebo) are currently enrolled in the study and recruitment is still ongoing. All patients are characterized using IQ and ADOS-scales and thoroughly screened for adverse indications for participation in fMRI research. To date, we only have preliminary data available assessing changes in functional connectivity based on resting-state fMRI scans. Resting-state fMRI is a technique for measuring spontaneous fluctuations in low-frequency brain activity while participants are at rest in the scanner (not performing an explicit task). Changes in whole-brain functional connectivity were assessed after a single-dose (immediate effect) or after 4-weeks of daily nasal spray administration (long-term effect). Retention data (one month post-trial) are not yet available. To explore changes in functional connectivity, an exploratory analysis was performed using the Conn-toolbox based on a whole-brain ROI-to-ROI network comprising of 106 ROIs based on the FSL Harvard-Oxford Atlas (maximum likelihood cortical (91 ROIs)/ subcortical atlas (15 ROIs)). Regions that showed significant changes in the OT group (not in the placebo group) from baseline to post are listed in the figure (two-sided statistics, p < 0.05 FDR-seed level correction). Results. Preliminary analyses indicated changes in whole-brain ROI-to-ROI network connectivity for several regions of the social brain (e.g. fusiform gyrus, orbito-frontal cortex, frontal operculum, insula) (see figure). Interestingly, changes in network connectivity of these regions were evident both immediately after a single dose of OT (figure panel A), as well as after 4-weeks of daily OT administration (figure panel B). After long-term OT administration (not after a single-dose) connectivity changes were additionally identified for the thalamus and middle/superior temporal gyri (figure panel B). These preliminary results are in agreement with results of a recent voxel-based meta-analysis of 11 task-based fMRI studies exploring single-dose effects of OT in neurotypical individuals (Wigton et al., 2015). This study similarly identified the insula, temporal lobes, thalamus and (pre/orbito) frontal cortex as the most implicated regions. Conclusion. Our highly preliminary results provide first indications that OT can induce changes in network connectivity of the social brain in patients with ASD. Further research is however necessary to explore whether these neural changes can be replicated in larger samples; whether and how they are paralleled by behavioral changes and whether the effects will outlast the time of intervention.