Faculty Bibliography

OBJECTIVE: To compare measures of sensation seeking in a clinical group of cocaine-dependent (CD) patients with and without a history of probable childhood ADHD and in non-cocaine-dependent (NCD) healthy volunteers. METHOD: Patients (n = 75; 42 with and 33 without probable childhood ADHD) and comparisons (n = 84) were assessed with the Diagnostic Interview for Genetic Studies, the Wender Utah Rating Scale for childhood ADHD, and the Zuckerman Seeking Sensation Scale. RESULTS: We found significantly higher prevalence rates of probable childhood ADHD in CD versus NCD (p < .001). The mean total scores of sensation seeking were significantly higher in CD versus NCD participants (p < .001) as well as in CD patients with versus those without a probable history of childhood ADHD (p < .001). CONCLUSION: Our study sets the basis for longitudinal investigation assessing whether the persistence of high level of sensation seeking in adults with childhood ADHD contributes to the transition to cocaine dependence.

BACKGROUND/PURPOSE: Melatonin, an indoleamine secreted by the pineal gland, plays a key role in regulating circadian rhythm. It has chronobiotic, antioxidant, anti-inflammatory and free radical scavenging properties. METHODS: A conference in Rome in 2014 aimed to establish consensus on the roles of melatonin in children and on treatment guidelines. RESULTS AND CONCLUSION: The best evidence for efficacy is in sleep onset insomnia and delayed sleep phase syndrome. It is most effective when administered 3-5 h before physiological dim light melatonin onset. There is no evidence that extended-release melatonin confers advantage over immediate release. Many children with developmental disorders, such as autism spectrum disorder, attention-deficit/hyperactivity disorder and intellectual disability have sleep disturbance and can benefit from melatonin treatment. Melatonin decreases sleep onset latency and increases total sleep time but does not decrease night awakenings. Decreased CYP 1A2 activity, genetically determined or from concomitant medication, can slow metabolism, with loss of variation in melatonin level and loss of effect. Decreasing the dose can remedy this. Animal work and limited human data suggest that melatonin does not exacerbate seizures and might decrease them. Melatonin has been used successfully in treating headache. Animal work has confirmed a neuroprotective effect of melatonin, suggesting a role in minimising neuronal damage from birth asphyxia; results from human studies are awaited. Melatonin can also be of value in the performance of sleep EEGs and as sedation for brainstem auditory evoked potential assessments. No serious adverse effects of melatonin in humans have been identified.

OBJECTIVE: The authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD. METHOD: The authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool. RESULTS: Sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09-0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14-0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01-0.40; inattention: SMD = 0.32, 95% CI = -0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24-0.80; visual: SMD = 0.47, 95% CI = 0.23-0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08-0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46-1.12). CONCLUSION: Despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to clinical symptoms.

Objective: The Child Behavior Checklist-Dysregulation Profile (CBCL-DP), characterized by elevated scores on the "Attention Problems," "Aggressive Behavior," and "Anxious/Depressed" scales in the CBCL, has been associated with later severe psychopathology. In a sample of children with ADHD, this study sought to further explore the clinical characteristics, the response to methylphenidate medication, and the cognitive features of ADHD children with CBCL-DP. Method: The sample consisted of 173 ADHD outpatients (age = 10.9 +/- 2.81) assessed using symptom severity scales, personality questionnaires (Emotionality Activity Sociability [EAS] and Junior Temperament and Character Inventory [JTCI]), and neuropsychological tests. A subsample of 136 participants was reassessed after optimal adjustment of methylphenidate dosage. Results and Conclusion: Variables that were independently associated with CBCL-DP were clinical severity (ADHD Rating Scale [ADHD-RS]), internalized disorders, high emotionality (EAS), and low self-directedness (JTCI). CBCL-DP was associated neither with poorer response to methylphenidate nor with more side effects. There were no differences in cognitive performances between participants with and without CBCL-DP. (J. of Att. Dis. 2012; XX(X) 1-XX).

Besides the crucial role of genetic susceptibility in the development of early-onset obesity, it has been shown that feeding behavior could contribute to increased body weight. A significant association between obesity/overweight and ADHD has been reported, suggesting that these two conditions, despite their heterogeneity, might share common molecular pathways. Although the co-occurrence of obesity and ADHD is increasingly supported by empirical evidence, the complex pathogenetic link between these two conditions is still unclear. Here, we focus on the relationship between MC4R gene mutations and ADHD in children with early-onset obesity. Mutations in the gene MC4R lead to the most common form of monogenic obesity. We hypothesize that dysregulated eating behavior in a subset of patients with MC4R mutation might be due to comorbid ADHD symptoms, underpinned by abnormal reward mechanisms. Therefore, we speculate that it is possible to prevent obesity in a subset of patients with MC4R mutation, even if these patients are genetically programmed to "be fat", via an appropriate treatment of ADHD symptoms. We hope that our paper will stimulate further studies testing if the early screening for ADHD symptoms and their appropriate treatment may be an effective way to prevent obesity in a subset of children with MC4R mutation.

Objectives. We aim to outline the neural correlates of atypical emotional face processing in individuals with ASD. Methods. A comprehensive literature search was conducted through electronic databases to identify functional magnetic resonance imaging (fMRI) studies of whole brain analysis with emotional-face processing tasks in individuals with ASD. The Signed Differential Mapping with random effects model was used to conduct meta-analyses. Identified fMRI studies were further divided into sub-groups based on contrast ("emotional-face vs. non-emotional-face" or "emotional-face vs. non-face") to confirm the results of a meta-analysis of the whole studies. Results. Thirteen studies with 226 individuals with ASD and 251 typically developing people were identified. We found ASD-related hyperactivation in subcortical structures, including bilateral thalamus, bilateral caudate, and right precuneus, and ASD-related hypoactivation in the hypothalamus during emotional-face processing. Sub-analyses with more homogeneous contrasts preserved the findings of the main analysis such as hyperactivation in sub-cortical structure. Jackknife analyses showed that hyperactivation of the left caudate was the most robust finding. Conclusions. Abnormalities in the subcortical structures, such as amygdala, hypothalamus and basal ganglia, are associated with atypical emotional-face processing in individuals with ASD.

BACKGROUND: Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. METHODS: Three hundred and forty six young adult students (M=23.87 years) completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as stress perception, coping with stress, emotion regulation, and mental toughness. RESULTS: Perfectionism was directly associated with poor sleep and poor psychological functioning. When stress, poor coping, and poor emotion regulation were entered in the equation, perfectionism traits no longer contributed substantively to the explanation of poor sleep. CONCLUSION: Though perfectionism traits seem associated with poor sleep, the direct role of such traits seemed small, when mediating factors such as stress perception and emotion regulation were taken into account.

OBJECTIVE: The aim of this study was to assess the type and frequency of adverse events (AEs) in children with attention-deficit/hyperactivity disorder (ADHD) treated with methylphenidate or atomoxetine over a 5-year period in a large naturalistic study. METHODS: We draw on data from the Italian ADHD Registry, a national database for postmarketing phase IV pharmacovigilance of ADHD medications across 90 centers. AEs were defined as severe or mild as per the classification of the Italian Medicines Agency. AE frequency in the two treatment groups was compared using incidence rates per 100 person-years (IR100PY) and incidence rate ratios (IRRs). Mantel-Haenszel adjusted IRRs were calculated to control for psychiatric comorbidity. RESULTS: A total of 1350 and 753 participants (aged 6-18 years, mean age 10.7 +/- 2.8) were treated with methylphenidate and atomoxetine, respectively, from 2007 to 2012. Ninety participants (7 %) were switched from methylphenidate to atomoxetine, and 138 (18 %) from atomoxetine to methylphenidate. Thirty-seven children treated with atomoxetine and 12 with methylphenidate had their medication withdrawn. Overall, 645 patients (26.8 %) experienced at least one mild AE (including decreased appetite and irritability, for both drugs) and 95 patients (3.9 %) experienced at least one severe AE (including severe gastrointestinal events). IR100PY were significantly higher in the atomoxetine-treated group compared with the methylphenidate-treated group for a number of mild and severe AEs and for any severe or mild AEs. After controlling for comorbidities, IRR was still significantly higher in the atomoxetine group compared with the methylphenidate group for a number of mild (decreased appetite, weight loss, abdominal pain, dyspepsia, stomach ache, irritability, mood disorder and dizziness) and severe (gastrointestinal, neuropsychiatric, and cardiovascular) AEs. CONCLUSIONS: In this naturalistic study, methylphenidate had a better safety profile than atomoxetine.