Faculty Bibliography

BACKGROUND:Emotional dysregulation (ED) and callous unemotional (CU) traits can be associated with ADHD in youth, influencing its natural history and outcome, but their effect on medication efficacy is unexplored. We examined whether two measures of baseline ED and CU traits, the Child Behavior Checklist-Dysregulation Profile (CBCL-DP) and the Antisocial Process Screening Device (APSD), respectively, were predictors of change of ADHD-Rating Scale (ADHD-RS) after a 4-week methylphenidate (MPH) monotherapy. METHODS:43 patients (37 males, 8-16 years, mean 9.9 ± 2.7 years) were included. Hierarchical linear regression models were used to explore whether CBCL-DP and APSD might predict ADHD-RS score, controlling for baseline severity. RESULTS:Baseline CBCL-DP predicted higher post-treatment ADHD-RS scores in total and hyperactivity-impulsivity, but not in inattention subscale. Baseline APSD was not significantly related to ADHD-RS scores at the follow-up. LIMITATIONS/CONCLUSIONS:Small sample size, lack of gender diversity, non-blind design and short period of observation. CONCLUSION/CONCLUSIONS:ED, assessed with that CBCL-DP, might be a negative predictor of change of hyperactive-impulsive symptoms after MPH treatment and should be systematically assessed at baseline.

Sleep problems are a common complaint in children/adolescents with autism spectrum disorder (ASD). Correctly diagnosing and treating sleep problems in individuals with ASD is key, as they can add to the psychosocial burden of the disorder and exacerbate associated symptoms, such as inattention or irritability. Here, we provide an overview of the epidemiology, diagnosis, and management of sleep problems/disorders in children and adolescents with ASD. This narrative review is mainly informed by a systematic search in PubMed and PsycInfo (last search: 10 October 2019) of available pertinent meta-analyses. We also searched for randomized controlled trials (RCTs) published after the search date of available meta-analyses. As for the epidemiology of sleep disorders in ASD, recent meta-analytic evidence shows a pooled prevalence of 13% (95% confidence interval [CI] 9-17) in the ASD population, compared with 3.7% in the general population. In terms of diagnosis of sleep disorders, it should be based on standardized criteria [e.g., the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or third edition of the International Classification of Sleep Disorders (ICSD)]; clinicians should bear in mind that the communication difficulties presented by individuals with ASD may make the diagnostic process more challenging. Regarding the treatment, a meta-analysis of behavioral interventions, including only three RCTs, found significant effects in terms of increase in total sleep time (24.41 min, 95% CI 5.71-43.11, P = 0.01), decrease in sleep-onset latency (- 18.31 min, 95% CI - 30.84 to - 5.77, P = 0.004), and a significant effect on sleep efficiency (5.59, 95% CI 0.87-10.31, P = 0.02), albeit the risk of bias of the included studies was rated "high" in relation to issues with the blinding. The bulk of the evidence for the pharmacological treatment is for melatonin, with a meta-analysis of five double-blind RCTs showing a large effect size, favoring melatonin, in sleep duration (44 min compared with placebo, Hedge's g 1.07 [95% CI 0.49-1.65]) and sleep-onset latency (39 min compared with placebo, Hedge's g - 2.46 [95% CI - 1.96 to - 2.98]). We conclude that additional RCTs are desperately needed to support the management of sleep disorders in ASD with an evidence-based, precision medicine approach.

OBJECTIVE:Previous research on adults with ADHD revealed high rates of overweight and obesity, as well as unhealthy diet habits. Other studies demonstrated that social-affective contexts can influence food choice. This study examines the sensitivity of adults with ADHD to cues of food attractiveness and convenience, for healthy and unhealthy foods. METHOD/METHODS:One hundred and seventy-two university students with (n = 59) and without (n = 113) ADHD, aged 19-40, participated in the study. Participants rated the level of appeal of 32 pictures of healthy and unhealthy foods, which varied in the degree of attractiveness and convenience. RESULTS:The findings reveal a higher level of appeal of attractive food items compared to non-attractive ones (p < .001), as well as of convenient compared to non-convenient food items (p = .005). Type of diagnostic group did not have an effect on the level of appeal. CONCLUSION/CONCLUSIONS:Increasing the attractiveness and convenience of food items increased the level of appeal for both students with and without ADHD. These findings emphasize the importance of environmental health intervention to potentially reduce abnormal eating pattern in the ADHD adult population, which may contribute in preventing the reported higher risk of obesity in this population.

The identification of biomarkers to support the diagnosis and prediction of treatment response for attention-deficit/hyperactivity disorder (ADHD) is still a challenge. Our previous works highlighted the DRD4 (dopamine receptor D4) as the best potential genetic marker for childhood diagnosis and methylphenidate (MPH) response. Here, we aimed to provide additional evidence on biomarkers for ADHD diagnosis and treatment response, by using more specific approaches such as meta-analytic and bioinformatics tools. Via meta-analytic approaches including over 3000 cases and 16,000 controls, we demonstrated that, among the different variants studied in DRD4 gene, the 48-base pair, Variable Tandem Repeat Polymorphism, VNTR in exon 3 showed an age/population-specificity and an allelic heterogeneity. In particular, the 7R/"long" allele was identified as an ADHD risk factor in European-Caucasian populations (d = 1.31, 95%CI: 1.17-1.47, Z = 4.70/d = 1.36, 95%CI: 1.20-1.55, Z = 4.78, respectively), also, from the results of last meta-analysis, linked to the poor MPH efficacy. The 4R/"short" allele was a protective factor in European-Caucasian and South American populations (d = 0.83, 95%CI: 0.75-0.92, Z = 3.58), and was also associated to positive MPH response. These results refer to children with ADHD. No evidence of such associations was detected for adults with persistent ADHD (data from the last meta-analysis). Moreover, we found evidence that the 4R allele leads to higher receptor expression and increased sensitivity to dopamine, as compared with the 7R allele (d = 1.20, 95%CI: 0.71-1.69, Z = 4.81), and this is consistent with the ADHD protection/susceptibility effects of the respective alleles. Using bioinformatics tools, based on the latest genome-wide association (GWAS) meta-analysis of the Psychiatry Genomic Consortium (PGC), we demonstrated that the 48 bp VNTR is not in Linkage Disequilibrium with the DRD4 SNPs (Single Nucleotide Polymorphisms), which were not found to be associated with ADHD. Moreover, a DRD4 expression downregulation was found in ADHD specific brain regions (Putamen, Z score = -3.02, P = 0.00252). Overall, our results suggest that DRD4 48 bp VNTR variants should be considered as biomarkers to support the diagnosis of ADHD and to predict MPH response, although the accuracy of such a biomarker remains to be further elucidated.

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 2019 articles that we think deserve your attention or at least a second read.

Antidepressants are prescribed for the treatment of a number of psychiatric disorders in children and adolescents, however there is still controversy about whether they should be used in this population. This meta-review aimed to assess the effects of antidepressants for the acute treatment of attention-deficit/hyperactivity disorder (ADHD), anxiety disorders (ADs), autistic spectrum disorder (ASD), enuresis, major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) in children and adolescents. Efficacy was measured as response to treatment (either as mean overall change in symptoms or as a dichotomous outcome) and tolerability was measured as the proportion of patients discontinuing treatment due to adverse events. Suicidality was measured as suicidal ideation, behavior (including suicide attempts) and completed suicide. PubMed, EMBASE, and Web of Science were systematically searched (until 31 October 2019) for existing systematic reviews and/or meta-analyses of double-blind randomized controlled trials. The quality of the included reviews was appraised using AMSTAR-2. Our meta-review included nine systematic reviews/meta-analyses (2 on ADHD; 1 on AD; 2 on ASD; 1 on enuresis; 1 on MDD, 1 on OCD and 1 on PTSD). In terms of efficacy this review found that, compared to placebo: fluoxetine was more efficacious in the treatment of MDD, fluvoxamine and paroxetine were better in the treatment of AD; fluoxetine and sertraline were more efficacious in the treatment of OCD; bupropion and desipramine improved clinician and teacher-rated ADHD symptoms; clomipramine and tianeptine were superior on some of the core symptoms of ASD; and no antidepressant was more efficacious for PTSD and enuresis. With regard to tolerability: imipramine, venlafaxine, and duloxetine were less well tolerated in MDD; no differences were found for any of the antidepressants in the treatment of anxiety disorders (ADs), ADHD, and PTSD; tianeptine and citalopram, but not clomipramine, were less well tolerated in children and adolescents with ASD. For suicidal behavior/ideation, venlafaxine (in MDD) and paroxetine (in AD) were associated with a significantly increased risk; by contrast, sertraline (in AD) was associated with a reduced risk. The majority of included systematic reviews/meta-analyses were rated as being of high or moderate in quality by the AMSTAR-2 critical appraisal tool (one and five, respectively). One included study was of low quality and two were of critically low quality. Compared to placebo, selected antidepressants can be efficacious in the acute treatment of some common psychiatric disorders, although statistically significant differences do not always translate into clinically significant results. Little information was available about tolerability of antidepressants in RCTs of OCD and in the treatment of ADHD, ASD, MDD, and PTSD. There is a paucity of data on suicidal ideation/behavior, but paroxetine may increase the risk of suicidality in the treatment of AD and venlafaxine for MDD. Findings from this review must be considered in light of potential limitations, such as the lack of comparative information about many antidepressants, the short-term outcomes and the quality of the available evidence.

Objective: Previous research in adults with ADHD showed high rates of obesity and unhealthy food choices. There is evidence that contextual cues, for example, advertisements, influence food choices. This study assessed the sensitivity of university students with ADHD to advertised food. Method: University students (N = 457) with and without ADHD participated in a cafeteria field experiment. Food choices were examined in periods of advertising either healthy or unhealthy sandwiches. Results: Students with ADHD (a) chose less healthy food items, (b) were more influenced by advertising, (c) showed the same overall healthy food choices as controls when exposed to healthy advertising. Conclusion: Students with ADHD chose unhealthier foods at the cafeteria but were also more influenced by advertising. Healthy food advertisements raised their healthy food choices. As this population has strong association with unhealthy dietary patterns, it is important to investigate the influence of food cues on their eating habits.

For this Debate article, we asked two experts in the field, Prof. James Swanson (University of California at Irvine) and Prof. David Coghill (University of Melbourne), to argue for "against" and "for," respectively, in relation to the motion "Are stimulant medications for ADHD effective in the long-term"?

This narrative review is aimed at presenting the most recent evidence on the association between attention-deficit/hyperactivity disorder (ADHD) and obesity. The review is informed by previous relevant systematic reviews and a search in Pubmed and PsycINFO up to 1 August 2019. Although the association between ADHD and obesity would seem, at first, paradoxical, in the past two decades there has been an increasing number of studies on this topic. The present review shows that there is meta-analytic evidence supporting a significant association between these two conditions, at least in adults. Growing evidence is also being published on the genetic and environmental factors underlying the association. However, the cause-effects paths, as well as the exact mechanisms explaining the association, remain unclear. Additionally, empirical evidence guiding the management/treatment of patients with the two conditions is still limited. Therefore, after almost 20 years from the first report of a link between ADHD and obesity, this association continues to be puzzling.