Oxytocin and Social Cognition in Children With Attention Deficit Hyperactivity Disorder: Impact of Methylphenidate

Attention deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder affecting approximately 7% of children and adolescents, is associated with considerable impairments in social functioning. Children with ADHD, in comparison to healthy children, suffer from more social rejection and problems in reciprocal relationships. Deficits in interpersonal functioning in children with ADHD have been attributed in previous studies to, among other things, impairments in theory of mind (ToM) - the ability to attribute mental states, beliefs, and intentions to self and to others. For example, some studies have shown deficits in the ability to recognize facial expressions among children with ADHD. Other studies have found impairments in first- and second-order ToM tests. There is also evidence showing that empathic functions in children with ADHD are impaired. However, small sample sizes, as well as high percentages of comorbid disruptive disorders, served as limitations in these studies.

One's ToM ability depends on, among other things, the integrity of dopaminergic and serotonergic systems, as well as on their interaction with other neurotransmitters and neurohormones (e.g., acetylcholine, oxytocin).

Oxytocin (OT) is a neuropeptide found to accelerate the formation of social relationships, the expression of behaviors of closeness, and the recognition of affect in the facial expressions of others. Oxytocin has been hypothesized to raise the salience of social cues by modulating attention-orienting responses to external contextual social cues. Its secretion increases in response to interpersonal interactions. Studies found connections between blood and saliva OT levels, OT receptor gene polymorphism, and the strength of social relationships and behaviors in healthy individuals, as well as in patients suffering from mental disorders. Oxytocin reciprocally interacts with dopaminergic neurons in the mesolimbic tract. Anatomical and immonucytochemical studies have found that neuronal fibers and receptor binding-sites of OT and dopamine are located in the same areas in the central nervous system (CNS), sometimes in very close proximity to one another. Oxytocin-secreting cells in the hypothalamus carry dopamine receptors. Indeed, patients with mental disorders related to dysregulation of dopamine (e.g., autistic spectrum disorders, schizophrenia, depression) show changes in their CNS and peripheral OT levels. Given the fact that injury of dopaminergic transporters and receptors is a central component in the etiology of ADHD, it is also possible that OT plays a role as a mediator of social deficits, and mainly in ToM impairment in children with ADHD.

To date, only a few studies have shown decreased OT levels in children with ADHD when compared to healthy controls. These studies found a negative correlation between serum OT levels and ADHD rating scale total scores, and aggression scores, and a positive correlation between the serum OT level and empathy scores in patients with ADHD. However, in both studies, only baseline OT levels were assessed; therefore, changes in OT levels following an interpersonal interaction were not measured. This is an important point, as social abilities are dynamic and interaction-related; the reactivity of the OT system to interpersonal interaction is thus probably highly relevant to the understanding of social difficulties in ADHD patients.

Stimulants reduce negative social interactions and improve social and behavioral functioning in children with ADHD, and also improve empathy scores. In a previous study, the investigators showed that a single dose of methylphenidate (MPH) improved the performance of children with ADHD on ToM tests. To date, no study examined a possible effect of stimulants on OT levels in children with ADHD. This is a pivotal issue in the understanding of the neurobiological underpinnings of improvement in social cognition measures among children with ADHD who are treated with stimulants, given that OT might have a role in mediating this improvement.