Faculty Bibliography

Whilst the association between Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity is supported by meta-analytic evidence, the mechanisms underpinning this link need to be further elucidated. Inflammatory processes may increase the risk of ADHD symptoms in individuals with obesity. This pilot study set out to start testing this hypothesis by assessing the correlation between serum levels of inflammatory cytokines and ADHD symptoms severity in a sample of children and adolescents with obesity. We measured ADHD symptoms severity in 52 children/adolescents with obesity (BMI > 95th centile) with the Conners questionnaire, revised, short version, parent (CPRS-R:S) and teacher (CTRS-R:S) versions. Additionally, a categorical diagnosis of ADHD was established using the Kiddie-SADS-PL. Serum levels of IL-6, Il-10, and TNF-alpha were also obtained. The prevalence of ADHD was 9.6%. We found a significant correlation between IL-6, as well as TNF-alpha, and hyperactivity/impulsivity subscores of the CPRS-R:S and CTRS-R:S, that held even after controlling for BMI and oppositional symptoms. This study provides a rationale for larger, longitudinal studies to gain insight into inflammatory processes underpinning the link between obesity and ADHD. This line of research has the potential to lead to novel, pathophysiologically-based management strategies for individuals with obesity and ADHD.

BACKGROUND:Prior follow-up studies of attention-deficit/hyperactivity disorder (ADHD) have mostly been from North America. They have provided a good deal of information about ADHD, but whether these results generalize to population samples and to other countries is not certain. Most prior studies have also not assessed predictors of possible new onsets of ADHD in non-ADHD youth or the validity of subthreshold forms of the disorder. METHODS:1,012 families were recruited at baseline, when a telephone interview assessed a child in the 6-12 years age range. The interview covered symptoms of ADHD, conduct disorder, and oppositional defiant disorder as well as family living situation, school performance, sleep disturbance, eating habits, use of supplemental iron, and history of ADHD treatment. Nine years later, the persistence of ADHD and its impairments and the emergence of new conditions were assessed. DSM-5 diagnostic criteria were used to diagnose ADHD. RESULTS:492 of the 1,012 participants seen at baseline were followed up 9 years later, at a mean age of 18 years. At follow-up, 16.7% of the children diagnosed with ADHD at baseline met full criteria for ADHD and 11.1% met criteria for subthreshold ADHD, yielding a persistence rate of 27.8%. Among children not diagnosed with ADHD at baseline, 1.1% met criteria for ADHD at follow-up. The persistence of ADHD and new onsets of ADHD were predicted by several baseline clinical features and by a family history of ADHD. CONCLUSIONS:We replicated predictors of the persistence of ADHD found in prior studies and provide new data about predictors of new ADHD onsets in the population. Our findings about subthreshold ADHD support a dimensional conceptualization of the disorder, highlighting the potential clinical utility of a subthreshold diagnostic category. This study also contributes to the ongoing debate regarding adult-onset ADHD.

OBJECTIVE:Sleep disturbances are a feature of attention-deficit/hyperactivity disorder (ADHD) and an adverse event (AE) of methylphenidate treatment. The authors sought to clarify methylphenidate-associated sleep problems and how studies are affected by confounding factors. DATA SOURCES/METHODS:Published studies in English collected via online databases and unpublished data from www.clinicaltrials.gov and US Food and Drug Administration websites. Sources were searched from inception to August 2017. STUDY SELECTION/METHODS:Included were blinded placebo-controlled studies of youth with ADHD conducted in naturalistic settings, leading to 35 studies yielding 75 observations of sleep-related AEs. These studies comprised 3,079 drug-exposed and 2,606 placebo-treated patients. DATA EXTRACTION/METHODS:Two PhD-level reviewers reviewed each study for inclusion. Four PhD/PharmD-level reviewers extracted data in duplicate. Discrepancies were resolved by discussion or, if needed, by the senior author. RESULTS:Increased pooled relative risks (RRs) were found for methylphenidate-associated sleep-related AEs for insomnia (general), initial insomnia, middle insomnia, combined insomnia, and sleep disorder. Several sample or study design features were significantly associated with the RR for sleep-related AEs and the methylphenidate formulation studied (P < .05). After correction for confounding variables, significant differences among drugs were found for initial insomnia, insomnia (general), and sleep disorder (P < .0001) as the other categories could not be tested due to insufficient studies. The findings also show that the RR and its interpretation are constrained by the placebo AE rate. CONCLUSIONS:Several types of insomnia and sleep problems are associated with methylphenidate treatment. Study design and sample features influence the RR statistic. By showing that the rate of placebo AEs impacts the RR, this study provides the field with a useful covariate for adjusting RR statistics.

The aim of this study was to conduct a systematic review of the literature and meta-analysis to estimate the association between psychophysiological activity and reactivity at baseline or after a psychological task with CP among children and adolescents. We systematically reviewed published studies reporting autonomic nervous system activity in youth with CP and meta-analyzed the relationship between CP and autonomic baseline as well as task-related reactivity in 66 studies (N = 10,227). Across 34 included case-control studies that were based on CP cut-off scores, we found a significant pooled effect for task related Skin-Conductance, Respiratory Sinus Arrhythmia, and cardiac Pre-Ejection Period, but no significant group differences for Heart Rate nor for any baseline measures. Findings suggested reduced parasympathetic and sympathetic reactivity to emotional tasks, pointing to co-inhibition of the two systems. However, across 32 studies with correlational design we only found a significant negative correlation of baseline and task-related heart rate with CP. The present meta-analysis derived several conclusions that have the potential to inform biological vulnerability models and biologically driven interventions.

The findings of neuroimaging studies in children/adolescents with ADHD, and even those of previous meta-analyses, are divergent. Here, Activation Likelihood Estimation meta-analysis, following the current best-practice guidelines, was conducted. We searched multiple databases and traced the references up to June 2018. Then, we extracted the reported coordinates reflecting group comparison between ADHD and healthy subjects from 96 eligible studies, containing 1914 unique participants. The analysis of pooled structural and functional, sub-analyses restricted to modality, and in-/decreased contrast did not yield any significant findings. However, further sub-analyses in the task-fMRI experiments (neutral stimuli only) led to aberrant activity in the left pallidum/putamen and decreased activity (male subjects only) in the left inferior frontal gyrus. The overall findings indicate a lack of regional convergence in children/adolescents with ADHD, which might be due to heterogeneous clinical populations, various experimental design, preprocessing, statistical procedures in individual publications. Our results highlight the need for further high-powered investigations, but may also indicate ADHD pathophysiology might rest in network interactions rather than just regional abnormality.

OBJECTIVE:Network meta-analyses (NMAs) are gaining traction as the preferred method for evidence synthesis of intervention studies. This review aimed to summarize the basics of NMAs and conduct a meta-review of available NMAs on the treatment of child and adolescent psychiatric disorders by appraising their quality. METHOD/METHODS:PubMed (Medline), PsycInfo, Embase, Ovid Medline, and Web of Knowledge were systematically searched (last update January 9, 2018). The quality of each included NMA was appraised using the AMSTAR-2 tool and the PRISMA-NMA checklist, which includes specific items for NMAs. RESULTS:Eighteen NMAs (6 on attention-deficit/hyperactivity disorder; 4 on psychotic disorders; 2 on depression; 2 on anxiety disorders; 1 on obsessive-compulsive disorder; 1 on disruptive behavior disorder, 1 on bipolar disorder, and 1 on antipsychotics across disorders) were retrieved. Results from the AMSTAR-2 assessment showed that only 27% of appraised NMAs were rated as moderate quality; most were rated as low (33%) or critically low (40%) quality. Only 3 of the appraised NMAs reported on all PRISMA-NMA items specific for NMAs; the network structure was graphically presented in most NMAs (80%), and inconsistency was described in only 47%. CONCLUSION/CONCLUSIONS:Given the paucity of head-to-head trials in child and adolescent psychiatry, NMAs have the potential to contribute to the field, because they provide evidence-based hierarchies for treatment decision making, even in the absence of trials directly comparing at least 2 treatments. However, because of important limitations in the included NMAs, additional methodologically sound NMAs are needed to inform future guidelines and clinical practice in child and adolescent psychiatry.

INTRODUCTION/BACKGROUND:The exact mechanisms underlying the established association between ADHD and obesity remain unclear. Food addiction and binge eating may contribute to this link. We examined for the first time the association between childhood/adult ADHD and food addiction/binge eating in patients with obesity, as well as the association between ADHD and sleep apnea syndrome. METHODS:We included 105 obese patients from the Nutrition Department of the University Hospital of Tours (France) between January and December 2014. We assessed categorical diagnoses of childhood/adulthood ADHD (semi-structured interview DIVA 2.0), food addiction (Yale Food Addiction Scale 2.0), binge eating (Binge Eating Scale), obstructive sleep apnea (clinical assessment), and BMI (clinical assessment). RESULTS:Patients with adult ADHD were at significantly higher risk of food addiction than patients without adult ADHD (28.6% vs. 9.1%; p = .016). Adult and childhood ADHD were significantly associated with self-reported food addiction, food addiction scores and binge eating scores, with a larger effect size for adult (ORs: 4.00 [1.29-12.40], 1.37 [1.14-1.65] and 1.08 [1.03-1.14], respectively) than childhood (ORs: 3.32 [1.08-10.23], 1.29 [1.08-1.55] and 1.06 [1.01-1.11], respectively) ADHD. ADHD diagnosis was not significantly correlated to obstructive sleep apnea. Mean age of onset of ADHD preceded mean age of onset of obesity. CONCLUSION/CONCLUSIONS:ADHD diagnosis is associated with food addiction and binge eating, with a larger effect size for adult than childhood ADHD. Our results provide a strong rationale for further longitudinal research on the link between ADHD, food addiction, binge eating and obesity, paving the way for evidence-based therapeutic interventions for these patients.

There is, in the content of the Journal, an embarrassment of riches, and picking a "best" seems to demand a certain qualification: is the "best" the most interesting, most surprising, most educational, most important, most provocative, most enjoyable? How to choose? We are hardly unbiased and can admit to a special affection for the ones that we and the authors worked hardest on, hammering version after version into shape. Acknowledging these biases, here are the 2018 articles that we think deserve your attention or at least a second read.