• ADHD
• callous unemotional
• CD
• emotional dysregulation
• methylphenidate
• ODD

Attention-deficit/hyperactivity disorder (ADHD) is a childhood onset neurodevelopmental condition, characterized by age-inappropriate and pervasive levels of inattention and /or hyperactivity-impulsiveness that cause significant impairment and often continue into adulthood.
Oppositional defiant disorder (ODD) and Conduct disorder (CD) coexist in 40-80% and in 20-56% of children and young people with ADHD, respectively. Callous unemotional (CU) traits and emotional dysregulation (ED) may be association with ODD and CD. CU traits are a pattern of callousness, uncaring behaviour, reduced guilt, and reduced empathy and are a defining feature of psychopathy and aggressive youth. CU traits influence the clinical evolution of ADHD and comorbid conduct problems. ED is an individual’s inability to modulate emotion regulation, to such a degree that the inability results in the individual functioning meaningfully below their baseline. The comorbidity of ADHD with ED represents a major source of impairment and predicts a poor clinical outcome. Whilst there is evidence that CU and ED predict poorer outcome in individuals with ADHD/ODD-CD, the extent to which they impact on response to ADHD pharmacological treatment is unclear.
The purpose of the present thesis was to assess if CU traits and ED are a predictor of response to methylphenidate in children with ADHD with and without ODD or CD.
Two samples, providing complementary information, were included: an Italian group of 36 children (aged 6-18) prospectively recruited at the IRCCS Stella Maris, Calambrone, Pisa and a UK group of 53 children (aged 5-18) from the South Hampshire ADHD Register (SHARE), Southampton University.
According to the Italian protocol, parents completed at baseline the ADHD-rating scale (ADHD-RS) to assess ADHD symptoms severity, the Child Behaviour Checklist Report Form school age version (CBCL 6-18) for the assessment of ODD, CD, and ED, the Inventory of Callous-Unemotional Traits (ICU) as well as the Antisocial Process Screening Device (APSD) to measure CU traits, and the Aggression Questionnaires (AQ) along with the Modified Overt Aggression Scale (MOAS) based on the parents’ interview to assess aggression. After one month of treatment with methylphenidate, parents completed again the ADHD-RS. The UK protocol included the Conners Comprehensive Behaviour Rating Scale (Conners CBRS), parent and teacher forms, for ADHD and ODD, the ICU, parent and teacher version, for CU traits and the Affective Reactivity Index (ARI) parent version for ED, all completed at baseline. Parents and teachers completed again the Conners CBRS after six months of therapy.
We first correlated the severity of baseline CU and ED to the changes in ADHD symptoms severity from baseline to follow-up (= “response to methylphenidate”). We then compared the response to methylphenidate in children with ADHD and CU traits and in those without CU traits.
We repeated the same comparison in the subgroups of children with ADHD and ODD/CD with and without CU traits and finally we compared the response to methylphenidate in children with ADHD and ED with the response in children without ED. We analysed data with the Statistical Package for Social Science (SPSS Inc.), version 24, using the Independent sample T Test and the Pearson correlation procedure. A probability level of P<0.05 was used to indicate statistical significance.
In the Italian group, we found a significant and positive correlation (Pearson coefficient of +0.442 and a P of 0.01) between the severity of baseline ED and the effectiveness of the treatment. Additionally, we found a significant and positive correlation between CU traits and response to methylphenidate (Pearson coefficient of +0.368 and a P of 0.05), even though this was not the case in the two subgroups of children with ODD and/or CD in comorbidity. On the contrary, scores of baseline aggressiveness did not correlate with the response to methylphenidate. Furthermore, the correlation between the ICU callousness and unemotional subscales scores and response to methylphenidate was not significant.
In the UK sample, we could analyse the response to the two ADHD domains (i.e., inattention and hyperactivity/impulsivity) separately. We did not find any significant correlation between the ARI-P scores and response to methylphenidate, even though T test showed higher decrease in ADHD scores in subjects with ARI=OPO scores ≥ 1.
As for CU traits, there was a significant and positive correlation between the scores on the ICU-P Callousness subscale and the response to methylphenidate, for the total ADHD scores as well as for the inattentive subscores. With regards to emotional traits, whilst there was no significant correlation between the scores on the ICU-P Unemotional subscale and response to treatment, we found significantly higher average post-pre score differences on the Conners CBRS-P ADHD scales.
In conclusion, this is the first study to assess ED and CU as predictors of response to methylphenidate. We found evidence showing that the severity of CU traits and ED have an impact on the response to methylphenidate in children with ADHD.
Our findings need to be replicated in further studies with a longer follow-up, larger samples and assessing several classes of ADHD medications. Overall, our findings highlight that ED and CU should be systematically assessed in the daily clinical practice with individuals with ADHD.