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Psychophysiological activity and reactivity in children and adolescents with conduct problems: A systematic review and meta-analysis

Fanti, Kostas A; Eisenbarth, Hedwig; Goble, Poppy; Demetriou, Chara; Kyranides, Melina Nicole; Goodwin, Daniel; Zhang, Junhua; Bobak, Billy; Cortese, Samuele
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.
PMID: 30797946
ISSN: 1873-7528
CID: 3698842

Brain alterations in children/adolescents with ADHD revisited: a neuroimaging meta-analysis of 96 structural and functional studies

Samea, Fateme; Soluki, Solmaz; Nejati, Vahid; Zarei, Mojtaba; Cortese, Samuele; Eickhoff, Simon B; Tahmasian, Masoud; Eickhoff, Claudia R
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.
PMID: 30790635
ISSN: 1873-7528
CID: 3686622

Meta-Review: Network Meta-Analyses in Child and Adolescent Psychiatry

Cortese, Samuele; Tomlinson, Anneka; Cipriani, Andrea
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.
PMID: 30738544
ISSN: 1527-5418
CID: 3663792

Reply to Leon et al [Letter]

Cortese, Samuele; Coghill, David
PMID: 30692143
ISSN: 1468-960x
CID: 3627142

Adulthood and childhood ADHD in patients consulting for obesity is associated with food addiction and binge eating, but not sleep apnea syndrome

Brunault, Paul; Frammery, Julie; Montaudon, Pauline; De Luca, Arnaud; Hankard, Régis; Ducluzeau, Pierre Henri; Cortese, Samuele; Ballon, Nicolas
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.
PMID: 30641157
ISSN: 1095-8304
CID: 3627092

Editors' Best of 2018 [Editorial]

Novins, Douglas K; Althoff, Robert R; Cortese, Samuele; Drury, Stacy S; Frazier, Jean A; Henderson, Schuyler W; McCauley, Elizabeth A; White, Tonya J H
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.
PMID: 30577925
ISSN: 1527-5418
CID: 3680122

Effects of melatonin in children with attention-deficit/hyperactivity disorder with sleep disorders after methylphenidate treatment

Masi, Gabriele; Fantozzi, Pamela; Villafranca, Arianna; Tacchi, Annalisa; Ricci, Federica; Ruglioni, Laura; Inguaggiato, Emanuela; Pfanner, Chiara; Cortese, Samuele
Purpose/UNASSIGNED:Methylphenidate (MPH), the first-line medication in children with attention-deficit/hyperactivity disorder (ADHD), is associated with increased risk of sleep disorders. Melatonin has both hypnotic and chronobiotic properties that influence circadian rhythm sleep disorders. This study explores the effectiveness of melatonin in children with ADHD who developed sleep problems after starting MPH. Patients and methods/UNASSIGNED:This study, based on a clinical database, included 74 children (69 males, mean age 11.6±2.2 years) naturalistically treated with MPH (mean dosage 33.5±13.5 mg/d). The severity of sleep disorder (sleep onset delay) was recorded at baseline and after a follow-up of at least 4 weeks using a seven-point Likert scale according to the Clinical Global Impression Severity score. Effectiveness of melatonin on sleep (mean dosage 1.85±0.84 mg/d) after 4 weeks was assessed using a seven-point Likert scale according to the Clinical Global Impression Improvement (CGI-I) score, and patients who scored 1 (very much improved) or 2 (much improved) were considered responders. Results/UNASSIGNED:<0.001). According to the CGI-I score, 45 patients (60.8%) responded to the treatment with melatonin. Gender and age (children younger and older than 12 years) did not affect the response to melatonin on sleep. Patients with or without comorbidities did not differ according to sleep response. Specific comorbidities with disruptive behavior disorders (oppositional defiant disorder or conduct disorder), affective (mood and anxiety) disorders and learning disabilities did not affect the efficacy of melatonin on sleep. Treatment was well tolerated, and no side effects related to melatonin were reported. Conclusion/UNASSIGNED:In children with ADHD with sleep problems after receiving MPH treatment, melatonin may be an effective and safe treatment, irrespective of gender, age and comorbidities.
PMCID:6410756
PMID: 30880992
ISSN: 1176-6328
CID: 3748492

Need for further analysis to explore the association between ADHD and asthma - Authors' reply [Letter]

Cortese, Samuele; Sun, Shihua; Zhang, Junhua; Sharma, Esha; Chang, Zheng; Kuja-Halkola, Ralf; Almqvist, Catarina; Larsson, Henrik; Faraone, Stephen V
PMID: 30477652
ISSN: 2215-0374
CID: 3500252

Metformin for Weight Gain Associated with Second-Generation Antipsychotics in Children and Adolescents: A Systematic Review and Meta-Analysis

Ellul, Pierre; Delorme, Richard; Cortese, Samuele
BACKGROUND:Weight gain is a potentially concerning side effect of second-generation antipsychotics (SGAs). Metformin, a biguanide with antihyperglycemic effects, is used to manage weight gain in adults treated with SGAs. OBJECTIVE:The objective of this study was to perform the first systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of metformin on weight gain in children and adolescents treated with SGAs. METHODS:Based on a pre-registered protocol (PROSPERO-CRD42017074839), we searched the PubMed, EMBASE, PsychoINFO, BIOSIS, Science Direct, Cochrane Central, and ClinicalTrials.gov electronic databases through March 2018 (with no restrictions on language, date, or type of publication) for RCTs that assessed the effect of metformin or placebo on body weight in children or adolescents (< 18 years of age) treated with selected SGAs (risperidone, aripiprazole, olanzapine, and clozapine) for any psychiatric disorder. We also contacted relevant drug manufacturers for possible additional pertinent studies/data. A random effects model was used and the quality of the included RCTs was assessed using the Cochrane Risk of Bias tool. RESULTS:Five RCTs (205 participants in total) were included in the meta-analysis. We found a significant weight decrease in the metformin group compared with placebo after 4, 12, and 16 weeks of treatment {mean difference - 0.98 kg (95% confidence interval [CI] - 1.26, - 0.69); - 1.83 kg (95% CI - 2.47, - 1.18); and - 3.23 kg (95% CI - 5.59, - 0.86), respectively}. A weight decrease at weeks 2 and 8 did not reach statistical significance. The decrease in body mass index (BMI) paralleled that of weight, with a significant effect at weeks 4, 12, and 16. Overall, four studies were rated as unclear, and one study was rated as high, risk of bias. CONCLUSION/CONCLUSIONS:Meta-analytical evidence shows that metformin might decrease weight in children/adolescents treated with SGAs but additional high-quality evidence is needed. Clinicians need to be aware that this use of metformin is currently off-label.
PMID: 30238318
ISSN: 1179-1934
CID: 3300882

Study Registration: Encouraging the Practice of Hypothetical-Deductive Research in the Journal [Editorial]

Novins, Douglas K; Althoff, Robert R; Billingsley, Mary K; Cortese, Samuele; Drury, Stacy S; Frazier, Jean A; Henderson, Schuyler W; McCauley, Elizabeth A; White, Tonya J H
Earlier this year, we shared with you our commitment to supporting the dissemination of research that is well designed, carefully conducted, and properly interpreted, and our belief that authors, reviewers, editors, publishers, and readers should jointly strive to ensure the integrity of the science that we publish.1 Toward this end, we are pleased to announce a new submission type beginning in 2019: Registered Reports.
PMID: 30522731
ISSN: 1527-5418
CID: 3678592