Placebo Effect in Children With Attention Deficit Disorder and/or Hyperactivity Disorder

Attention Deficit with or without Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects 2 to 7% worldwide youth population and 6.2% of children aged 6 to 11 years in Quebec [1-3]. The main symptoms of this disorder are difficulties in regulating behaviour and/or concentration [4]. These difficulties have significant negative consequences in someone's life, particularly in terms of their academic success [5] and has significant negative consequences in the medical context, increasing accidents and mortality risk [6].

Children's academic performance can be modulated by the Pygmalion (or Rosenthal) effect, which refers to an improvement or decrease in an individual's performance depending on the degree of belief in his or her abilities on the part of an authority or the environment [7]. Thus, these beliefs have an influence on a person's expectations of his or her ability to do a task, and thus on final performance [8]. The expectations of an individual and his or her entourage is therefore a major factor to consider, especially in school-age children [9]. Expectations also play an important role in the placebo effect. Whereas a placebo is a treatment without any real influence on a particular condition (drug or therapeutic technique), the placebo effect is the perceived beneficial effect following this treatment. Furthermore, a placebo effect is almost always added to the beneficial effect of a treatment in different ways (for example, an analgesic effect could occur faster or in a shorter delay) and to different degrees [10]. The placebo effect is regularly studied and increasingly understood in the context of pain [11]. Although the perception of pain is influenced by placebo treatment, this effect is itself modulated by the expectations of the person in pain [12]. The dorsolateral prefrontal cortex (DLPFC) is an essential region for the placebo's mechanism of action [10]. In children with ADHD, there is a delay in the maturation of the cortical thickness of DLPFC between the ages of 7 and 10 years [13]. These differences in neuronal activity in the prefrontal region are associated with difficulties in attention control and inhibition in these children: inhibitory functions measured using transcranial magnetic stimulation (TMS) show a lower inhibition capacity in individuals with ADHD than without ADHD [14].

Considering the important consequences generated by the symptoms of this disorder, it is essential to better understand the role of the placebo/nocebo effect and expectations in children with ADHD in a medical (pain) and academic (attentional skills) context. Our goal is to better understand how this placebo/nocebo effects and expectations are associated with changes in the DLPFC and the inhibitory functions. This study also aims to better characterize the role of neurophysiological and neuroanatomical factors in these contexts, with the distant goal of contributing to the development of stronger tools for differential diagnostics.

Objectives (1) To compare the placebo/nocebo effect on pain and (2) on attention abilities in children with and without ADHD. (3) To determine if there is a relationship between the placebo/nocebo effect and neurophysiological (inhibitory mechanisms) and neuroanatomical (DLPFC) measures.

Assumptions