Oxytocin's Signature in Social Deficits of Patients with Autism Spectrum Disorders

Background: Our daily life is a constant stream of complex social situations, and adaptation is a key element of Human fitness. Patients suffering from autism lack social adaptation partially due to difficulties in feeling appropriate emotional states. Recently, oxytocin is attracting considerable attention for its role in Autism. Oxytocin is a fundamental mediator for a large range of behavior such as maternal attachment, pair bonding, social learning and prosocial behaviors. Since oxytocin plays a key role in social affiliation, and given that the major suffering of patients with autism is the social deficit, a key question is whether oxytocin plays a role in social deficits of patients with Autism.

Objectives:

-       Studying whether patients with autism have deficits in their plasma oxytocin concentration and whether this measure can be used as a biomarker of decrease levels of affiliation.

-       Investigating the structural correlates of plasma oxytocin variability among individuals in order to infer the mechanisms of action of this molecule.

-       Determining whether intranasal administration of oxytocin can modulate prosocial feelings in healthy volunteers and in patients with Autism.

Methods:

Plasma oxytocin was measured using specific enzyme-immunoassay method of analysis in 30 healthy volunteers and 13 patients with Autism. Healthy individuals performed the Revised NEO Personality Inventory. Voxel-based Morphometry analysis was used to study the structural images of participants. Intranasal oxytocin spray was administrated to healthy subjects and patients with Autism in a double blind oxytocin-placebo controlled study. Oxytocin’s effects were measured on self-perception of prosocial feelings toward others. Patients performed a social game where they interacted with three fictitious partners endowed with different levels of trust and reported their feelings of trust. Healthy subjects self-reported their general feelings of trust toward others during personality test.

Results:

Baseline plasma oxytocin concentration in patients was intensely below the values observed in healthy subjects. Interestingly, plasma oxytocin was found positively correlated with social personality scores in healthy volunteers. In other terms, individuals with introverted personality presented lower levels of plasma oxytocin compared to extraverted individuals.

We also found that individual variability in endogenous oxytocin and in social affiliation is echoed in differences in grey matter volume of specific brain regions, the amygdala and hippocampus, regions controlling fear and anxiety. Moreover, oxytocin intake enhanced patients’ capacities to process social cues and to report appropriate feelings of trust toward the trustworthy partner. These results are supported by the effects of oxytocin on enhancing healthy subjects’ self-report of general trust toward.

Conclusions:

Endogenous plasma oxytocin might be a biomarker of the degree of engagement of individuals in their social life and eventually of social deficits encountered in psychiatric disorders such as Autism. Moreover, our findings suggest potential therapeutical implications of oxytocin in modulating adaptive prosocial feelings in these patients, a core deficit of autism. Potentially, the neuropeptide oxytocin is endowing key emotional brain regions such as the amygdala and hippocampus with the capacity to develop affiliation, by overcoming fear and stress of being deceived.