Methylphenidate is more effective to improve inhibitory control and working memory compared to tDCS in children and adolescents with attention deficit/hyperactivity disorder: a proof-of-concept study.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD. Methods: After completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH. Results: Our results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual-spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS. Discussion: In conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms.

Age-related clinical characteristics of children and adolescents with ADHD.

Introduction: Attention deficit hyperactivity disorder (ADHD) has been associated with difficulties in regulating aversion states, high functional impairment, and a high risk of psychopathology across the lifespan. ADHD is clinically heterogeneous, with a wide spectrum of severity and associated symptoms. Clinical characteristics need to be carefully defined in different periods of life as ADHD course, symptoms, and comorbidities may fluctuate and change over time. Adolescence usually represents the transition from primary to secondary education, with a qualitative and quantitative change in environmental and functional demands, thus driving symptoms' change. Methods: In order to characterize age-related clinical features of children (<11 years) and adolescents (≥11 years) with ADHD, we conducted a naturalistic study on 750 children and adolescents assessed for ADHD at our Neuropsychiatry Unit over the course of 3 years (2018-2020). Results: We found that ADHD symptoms were significantly higher in children than adolescents. More importantly, we found worse global functioning, lower adaptive skills, higher levels of anxiety and depressive symptoms, somatic complaints, emotional dysregulation, social problems, and aggression in adolescents, despite a lower severity of ADHD-specific symptoms. Conclusion: These results should be confirmed in longitudinal observational studies of adequate sample size in order to reliably describe a potential course characterized by worsening of functioning, reduction in ADHD-specific symptoms and increase in general psychopathology during the transition from childhood to adolescence.

Comparing the Effect of Methylphenidate and Anodal tDCS on Inhibitory Control and Working-Memory in Children and Adolescents with Attention Deficit/Hyperactivity Disorder: A Study Protocol for a Randomized, within-Subject Trial.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inappropriate levels of attention, hyperactivity, and impulsivity that interfere with individual functioning. The international guidelines recommend targeting ADHD-related neurochemical brain abnormalities by intervening via drug treatment, such as methylphenidate (MPH), as first choice. Drug treatments are usually associated with a huge amount of cost for families and the healthcare system, suspension for low compliance, poor long-term efficacy, and side effects. Transcranial direct current stimulation (tDCS) has been suggested as a possible noninvasive means to safely manipulate brain activity and, in turn, improve behavior and cognition in developmental ages. Several studies have shown that tDCS has the potential to improve ADHD-related cognitive deficits, but the effect of tDCS compared with MPH has never been evaluated. The aim of the present within-subject, sham-controlled, randomized proof-of-concept study is to demonstrate the positive effect of one-session anodal tDCS analogous to the MPH drug on inhibitory control and working memory in children and adolescents with ADHD. We strongly believe that this study protocol will serve to accelerate research into low-cost, drug-free, feasible interventions for ADHD.

Clinical characteristics of children and adolescents with ADHD with or without methylphenidate prescription at their first diagnostic assessment.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most prevalent neurodevelopmental disorder diagnosed in the scholar age. It is associated with significant impairment in global functioning, and in moderate/severe presentations the outcome is critically dependent on pharmacological optimization of the multi-modal treatment. Methylphenidate (MPH) is the first-choice pharmacological treatment in children and adolescents with ADHD, with substantial evidence of significant efficacy and effectiveness on global functioning and symptoms' severity. There is some evidence supporting a few clinical and socio-demographic variables as predictors of pharmacological treatment prescription in children with ADHD independently of ADHD symptoms severity. However, it is warranted to investigate clinical and general psychopathological characteristics potentially associated with negative outcomes and the need for pharmacological treatment to inform appropriate prescription strategies. In this context, we compared 268 children and adolescents who were prescribed MPH (ADHD/MPH) for the first time after their first diagnostic assessment at our center, and 444 children and adolescents with ADHD (ADHD/noMPH) who were recommended non-pharmacological evidence-based interventions alone. ADHD/MPH group had higher severity of non-ADHD psychopathological symptoms compared to the ADHD/noMPH group, as documented by higher scores on the Child Behavior Checklist (CBCL) subscales, higher severity of ADHD symptoms, lower average IQ and lower adaptive levels independently of IQ. More specifically, beside externalizing symptoms, also internalizing symptoms were significantly higher in the ADHD/MPH group. The presence of significant non-ADHD psychopathology should be considered as a clinical factor associated with the need for MPH prescription in children and adolescents with ADHD.

Moderators and Other Predictors of Methylphenidate Response in Children and Adolescents with ADHD.

Methylphenidate (MPH) is the treatment of first choice for developmental ADHD. To date, no reliable method to predict how patients will respond to MPH exists and conflicting results are reported on clinical characteristics of responders. The present study aims to give a more precise characterization of the patients who will respond best to MPH to help clinicians in defining the treatment plan. Age, neuropsychological functioning (i.e., attention and working memory), and behavioral/emotional symptoms of 48 drug-naïve children and adolescents with ADHD (42 boys and 6 girls, age-range 6-16 years, mean age 10.5 ± 2.5 years, mean IQ 101.3 ± 11.2) were studied to assess how these different characteristics affected a single-dose MPH response. Four hierarchical linear regression models were used to explore whether age, neuropsychological measures at baseline, and behavioral/emotional symptoms could predict attention and working memory measures after a single-dose MPH administration. We found that improvement in attention and working memory was predicted by age, neuropsychological measures at baseline, and severity of ADHD symptoms. No behavioral and emotional symptoms predicted single-dose MPH response with the exception of conduct symptoms.

Gender-Related Clinical Characteristics in Children and Adolescents with ADHD.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder in school-age children, and it is usually associated with a significant impairment in global functioning. Traditionally, boys with ADHD are more likely to be referred for clinical assessments due to a higher prevalence of externalizing symptoms. However, as regards gender-related differential clinical characteristics between boys and girls with ADHD, further investigation is warranted in light of conflicting results found in currently available literature. In fact, a more precise clinical characterization could help increase appropriate diagnoses and treatment planning. In this context, we carried out a retrospective observational study on 715 children and adolescents diagnosed with ADHD from 2018 to 2020 at our center, in order to describe their gender-related clinical characteristics. Boys displayed higher average IQs, but they were comparable to girls in functional impairments and adaptive skills. Girls displayed higher scores on the Attention Problems subscale of the CBCL 6-18 and on several CPRS-R:L subscales, suggesting higher general ADHD symptom severity. Boys showed higher scores on CBCL 6-18 subscales, such as withdrawn/depressed, internalizing, and obsessive-compulsive problems. In conclusion, girls showed more severe ADHD features and lower IQ in clinically referred settings, while boys showed more internalizing problems and obsessive-compulsive symptoms.

Gross, Fine and Visual-Motor Skills in Children with Language Disorder, Speech Sound Disorder and Their Combination.

Increasing evidence shows that children with Communication Disorders (CDs) may show gross, fine, and visual-motor difficulties compared to children with typical development. Accordingly, the present study aims to characterize gross, fine and visual-motor skills in children with CDs, distinguishing children with CDs into three subgroups, i.e., with Language Disorders (LD), Speech Sound Disorders (SSD), and LD + SSD. In Experiment 1, around 60% of children with CDs (4 to 7 years; 21 with LD, 36 with SSD, and 90 with LD + SSD) showed clinical/borderline scores in balance skills, regardless of the type of communication deficit. However, children with LD, SSD, and LD + SSD did not differ in gross and fine motor skills. In Experiment 2, a higher percentage of children with CDs (4 to 7 years; 34 with LD, 62 with SSD, 148 with LD + SSD) obtained clinical/borderline scores in Visual Perception skills. Moreover, children with LD + SSD performed significantly worsen in Visual Perception and Fine Motor Coordination skills compared to children with SSD only. Our results underlined that CDs are generally associated with gross motor difficulties and that visual-motor difficulties are related to the type of communication deficit. Paying earlier attention to the motor skills of children with CDs could help clinicians design effective interventions.

Risk Factors for Revolving Door in Children and Adolescents with Psychiatric Disorders.

Revolving Door (RD) is a frequent phenomenon afflicting children and adolescents with psychiatric diagnoses. Nevertheless, risk factors for RD are still a matter of debate. To better understand RD phenomenon, we conducted a retrospective study on 224 children and adolescents (165 females and 59 males, aged 6-16 years) with a psychiatric hospitalization, taking the multiple risk factors together. At this aim, 108 patients with multiple hospitalizations and 116 patients with only one hospitalization were compared on demographic characteristics, clinical conditions, psychiatric ward stay, and post-discharge management factors. More than half of psychiatric patients were readmitted within three months of discharge. RD patients presented greater severity of illness, needed longer stays, and were more frequently placed in residential facilities than non-RD patients. Non-suicidal self-injurious and adoption were the main predictors of RD. Clinical instruments that detected behavioural and emotional symptoms, suicidal ideation severity, and level of impairment of the person's functioning were useful to identify patients at high risk for RD. In conclusion, our findings pointed out that several risk factors have to be considered to better understand and, in the future, prevent RD phenomenon.