Faculty Bibliography

Methylphenidate (MPH) is a commonly used medication for the treatment of children with Attention-Deficit/Hyperactivity Disorders (ADHD). However, its prescription to adult with ADHD and narcoleptic patients raises the question of how the brain would be impacted by MPH exposure during pregnancy. The goal of this study was to elucidate the long-term neurobiological consequences of a prenatal exposure to MPH using a rat model. We focused on the effects of such treatment on the adult dopamine (DA) system and on the reactivity of animals to natural rewards. This study shows that adult male rats prenatally exposed to MPH displayelevated expression of presynaptic DA markers in the DA cell bodies and the striatum. Our results also suggest that MPH-treated animals could exhibited an increased tonic DA activity in the mesolimbic pathway, an altered signal-to-noise ratio after a pharmacological stimulation, and a decreased reactivity to the locomotor effects of cocaine.Finally, we demonstrated that MPH rats displaya decreased preference and motivation for sucrose.This is the first preclinical study reporting long-lasting neurobiological alterations of DA networks as well as alterations in motivational behaviors for natural rewards after a prenatal exposure to MPH. These results raise concerns about the possible neurobiological consequences of MPH treatment during pregnancy.

Considerable scientific effort has been directed at developing effective treatments for attention-deficit/hyperactivity disorder (ADHD). Among alternative treatment approaches, neurofeedback has gained some promising empirical support in recent years from controlled studies as a treatment of core ADHD symptoms. However, a recent stringent meta-analysis of 8 randomized controlled trials published in 2013 found that the effects were stronger for unblinded measures and 3 recent subsequently published well-controlled trials found no effects for the most blinded ADHD outcome. Firmer conclusions must await upcoming evidence from larger controlled studies and future meta-analyses contrasting different forms of neurofeedback and different outcome measures.

There has been an increasing interest in and the use of computer-based cognitive training as a treatment of attention-deficit/hyperactivity disorder (ADHD). The authors' review of current evidence, based partly on a stringent meta-analysis of 6 randomized controlled trials (RCTs) published in 2013, and an overview of 8 recently published RCTs highlights the inconsistency of findings between trials and across blinded and nonblinded ADHD measures within trials. Based on this, they conclude that more evidence from well-blinded studies is required before cognitive training can be supported as a frontline treatment of core ADHD symptoms.

OBJECTIVE: Behavioral interventions are recommended as attention-deficit/hyperactivity disorder (ADHD) treatments. However, a recent meta-analysis found no effects on core ADHD symptoms when raters were probably blind to treatment allocation. The present analysis is extended to a broader range of child and parent outcomes. METHOD: A systematic search in PubMed, Ovid, Web of Knowledge, ERIC, and CINAHAL databases (up to February 5, 2013) identified published randomized controlled trials measuring a range of patient and parent outcomes for children and adolescents diagnosed with ADHD (or who met validated cutoffs on rating scales). RESULTS: Thirty-two of 2,057 nonduplicate screened records were analyzed. For assessments made by individuals closest to the treatment setting (usually unblinded), there were significant improvements in parenting quality (standardized mean difference [SMD] for positive parenting 0.68; SMD for negative parenting 0.57), parenting self-concept (SMD 0.37), and child ADHD (SMD 0.35), conduct problems (SMD 0.26), social skills (SMD 0.47), and academic performance (SMD 0.28). With probably blinded assessments, significant effects persisted for parenting (SMD for positive parenting 0.63; SMD for negative parenting 0.43) and conduct problems (SMD 0.31). CONCLUSION: In contrast to the lack of blinded evidence of ADHD symptom decrease, behavioral interventions have positive effects on a range of other outcomes when used with patients with ADHD. There is blinded evidence that they improve parenting and decrease childhood conduct problems. These effects also may feed through into a more positive parenting self-concept but not improved parent mental well-being.

The exact etiopathophysiology of attention-deficit/hyperactivity disorder (ADHD) remains elusive, likely because of its phenotypic heterogeneity. Given the involvement of iron in neurocognitive and behavioral functions, iron deficiency (ID) has been suggested as a possible etiopathophysiological factor in a subsample of individuals with ADHD. Most studies assessing ID in ADHD have focused on serum ferritin, a marker of peripheral iron status. Results from these studies are mixed, and the largest studies failed to find a significant association between ADHD and low serum ferritin levels. However, serum ferritin may be influenced by several conditions, including inflammatory status. Increasing evidence, especially from epidemiological studies, points to a significant association between ADHD and obesity. Interestingly, obesity is associated with a chronic inflammatory status, characterized by ID with normal-to-high serum ferritin levels. This article reviews the literature on iron status in ADHD and on the relationship between ADHD and obesity; discusses a possible link among ADHD, ID, and obesity; and proposes that comorbid obesity contributes to ID, via chronic inflammation, in a subsample of individuals with ADHD. Thus, the comorbidity between ADHD and obesity suggests moving beyond serum ferritin levels and assessing the molecular pathways of chronic inflammation that lead to ID in individuals with ADHD and obesity. In turns, this may pave the way for novel treatment strategies for cognitive and behavioral dysfunctions related to ID in ADHD.

Data on the relationship between sleep disturbances and refractory epileptic encephalopathies (EEs) are scarce. Our aim was to assess, by means of nocturnal polysomnography, if children with EEs present with objective alterations in sleep organization. Twenty-three children with EEs (12 males; mean age: 8.7+/-1.4years) and 40 healthy controls (22 males; mean age: 8.8+/-1.1years) underwent an overnight full polysomnography (PSG). Relative to controls, children with EEs showed a significant reduction in all PSG parameters related to sleep duration time in bed (TIB-min p<0.001), total sleep time (TST-min p<0.001), and sleep percentage (SPT-min p<0.001), as well as significantly higher REM latency (FRL-min p<0.001), rate in stage shifting (p=0.005), and number of awakenings/hour (p=0.002). Relative to controls, children with EEs also showed significant differences in respiratory parameters (AHI/h p<0.001, ODI/h p<0.001, SpO2% p<0.001, SpO2 nadir% p<0.001) and a higher rate of periodic limb movements (PLMs% p<0.001). Our findings suggest that sleep evaluation could be considered mandatory in children with refractory epileptic encephalopathy in order to improve the clinical management and the therapeutic strategies.

BACKGROUND: The efficacy of three dietary treatments for ADHD has been repeatedly tested in randomized controlled trials (RCTs). These interventions are restricted elimination diets (RED), artificial food colour elimination (AFCE) and supplementation with free fatty acids (SFFA). There have been three systematic reviews and associated meta-analyses of the RCTs for each of these treatments. SCOPE: The aim of this review is to critically appraise the studies on the dietary treatments of ADHD, to compare the various meta-analyses of their efficacy that have been published and to identify where the design of such RCTs could be improved and where further investigations are needed. FINDINGS: The meta-analyses differ in the inclusion and exclusion criteria applied to potentially eligible studies. The range of average effect sizes in standard deviation units is RED (0.29-1.2), AFCE (0.18-0.42) and SFFA (0.17-0.31). The methodology of many of the trials on which the meta-analyses are based is weak. CONCLUSIONS: Nevertheless, there is evidence from well-conducted studies for a small effect of SFFA. Restricted elimination diets may be beneficial, but large-scale studies are needed on unselected children, using blind assessment and including assessment of long-term outcome. Artificial food colour elimination is a potentially valuable treatment but its effect size remains uncertain, as does the type of child for whom it is likely to be efficacious. There are additional dietary supplements that have been used with children with ADHD. A systematic search identified 11 RCTs that investigated the effects of these food supplements. Despite positive results for some individual trials, more studies are required before conclusions can be reached on the value in reducing ADHD symptoms of any of these additional supplements.

Increasing attention is being paid to the relationship between attention deficit/hyperactivity disorder (ADHD) and obesity. While most available research focused on determining the extent of the association between ADHD and obesity, a few studies have examined the clinical implications of diagnosing/treating ADHD in individuals with obesity. Here, we provide a narrative review of studies addressing the impact of ADHD, or its treatment, in individuals with obesity. Reviewed studies suggest that ADHD impedes the successful treatment of obesity in individuals with comorbid ADHD and obesity. Preliminary evidence also suggests that ADHD treatment might significantly increase the effectiveness of weight management strategies. We discuss the limitations of the reviewed studies and provide suggestions for future research in the field.

BACKGROUND: The DSM-IV age at onset criterion for attention-deficit/hyperactivity disorder (ADHD) has been a subject of debate. In DSM-5, the required age at onset (ie, the age by which impairing symptoms must have been present) has increased from 7 years to 12 years. The present study examined measurement properties of ADHD symptoms according to age at onset. METHOD: Data were derived from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions, which included 34,653 US participants. Among participants with a lifetime DSM-IV diagnosis of ADHD (assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV), we compared the psychometric properties of the 18 ADHD symptoms according to 3 categories of age at onset ( 7 and 12 and 7 and 12 and