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Objective A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children’s Yale−Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes. Method A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively. Results The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7−84.1; specificity = 81.7, 95% CI = 81.5−81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8−82.2; specificity = 84.6, 95% CI = 84.4−84.8). Conclusion Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD.

This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler's vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early childhood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child.

Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by several motor and phonic tics.In this study, we aimed to compare activated regulatory T cell (Treg) values between patients with TS/chronic tic disorder (CTD) and age- and sex-matched healthy controls (HCs).Patients with TS/CTD and age- and sex-matched HCs were included in the study. The severity of the disease was evaluated using the Yale Global Tic Severity Scale. CD4The study included 48 patients diagnosed with TS/CTD (36 males and 12 females, mean age: 11.58 ± 2.61) and 24 HCs (18 males and 6 females, mean age: 11.63 ± 2.60). The TS/CTD group had significantly higher activated regulatory T percentile with respect to the T helper value compared to the HCs (Our results suggest that Tregs may have a role in the pathogenesis of TS/CTD.

BACKGROUND: Improvements in executive functioning (EF) may lead to improved quality of life and lessened functional impairment for children with mood disorders. The aim was to assess the impact of omega-3 supplementation (Ω3) and psychoeducational psychotherapy (PEP), each alone and in combination, on EF in youth with mood disorders. We completed secondary analyses of two randomized controlled trials (RCTs) of Ω3 and PEP for children with depression and bipolar disorder. METHODS: Ninety-five youth with depression or bipolar disorder-not otherwise specified/cyclothymic disorder were randomized in 12-week RCTs. Two capsules (Ω3 or placebo) were given twice daily (1.87g Ω3 total daily, mostly eicosapentaenoic acid). Families randomized to PEP participated in twice-weekly 50-minute sessions. Analyses assess impact of interventions on the Behavior Rating Inventory of Executive Functioning (BRIEF) parent-report Global Executive Composite (GEC) and two subscales, Behavior Regulation (BRI) and Metacognition (MI) Indices. Intent-to-treat repeated measures ANOVAs, using multiple imputation for missing data, included all 95 randomized participants. Trials were registered with www.clinicaltrials.gov, NCT01341925 & NCT01507753. RESULTS: Participants receiving Ω3 (aggregating combined and monotherapy) improved significantly more than aggregated placebo on GEC (p=0.001, d=0.70), BRI (p=0.004, d=0.49), and MI (p=0.04, d=0.41). Ω3 alone (d=0.49) and combined with PEP (d=0.67) each surpassed placebo on GEC. Moderation by ADHD comorbidity was non-significant although those with ADHD showed nominally greater gains. PEP monotherapy had negligible effect. CONCLUSIONS: Decreased impairment in EF was associated with Ω3 supplementation in youth with mood disorders. Research examining causal associations of Ω3, EF, and mood symptoms is warranted.

Objective To examine the efficacy of pharmacological treatments for restricted and repetitive behaviors (RRB) in autism spectrum disorders (ASD). Method We searched PubMed, Embase, and CENTRAL to identify all double-blind, randomized, placebo-controlled trials that examined the efficacy of pharmacological agents in the treatment of ASD and measured RRB as an outcome. Our primary outcome was the standardized mean difference in rating scales of RRB. Results We identified 64 randomized, placebo-controlled trials involving 3,499 participants with ASD. Antipsychotics significantly improved RRB outcomes compared to placebo (standardized mean difference [SMD] = 0.28, 95% CIs = 0.08−0.49), z = 2.77, p = .01) demonstrating a small effect size. Larger significant positive effects on RRB in ASD were seen in individual studies with fluvoxamine, buspirone, bumetanide, divalproex, guanfacine, and folinic acid that have not been replicated. Other frequently studied pharmacological treatments in ASD including oxytocin, omega-3 fatty acids, selective serotonin reuptake inhibitors (SSRI), and methylphenidate did not demonstrate significant benefit in reducing RRB compared to placebo (oxytocin: SMD = 0.23, 95% CI = −0.01 to 0.47, z = 1.85, p = .06; omega-3 fatty acids: SMD = 0.19, 95% CI = −0.05 to 0.43, z = 1.54, p = .12; SSRI: SMD = 0.09, 95% CI = −0.21 to 0.39, z = 0.60, p = .56; methylphenidate: SMD = 0.18, 95% CI = −0.11 to 0.46, z = 1.23, p = .22). Conclusion The results of the present meta-analysis suggest that currently available pharmacological agents have at best only a modest benefit for the treatment of RRB in ASD, with the most evidence supporting antipsychotic medications. Additional randomized controlled trials with standardized study designs and consistent and specific assessment tools for RRB are needed to further understand how we can best help ameliorate these behaviors in individuals with ASD.

Novel pharmacological treatments are needed for Tourette syndrome. Our goal was to examine the current evidence base and biological rationale for the use of cannabis-derived medications or medications that act on the cannabinoid system in Tourette syndrome. We conducted a comprehensive literature search of PubMed for randomized controlled trials or clinical trials of cannabis-derived medications in Tourette syndrome. Data regarding the population, intervention, safety profile, and outcomes for each trial were extracted and reported and the evidence supporting use of individual cannabis-derived medications was critiqued. There is a strong biological rationale regarding how cannabis-derived medications could affect tic severity. Anecdotal case reports and series have noted that many patients report that their tics improve after using cannabis. However, only two small randomized, placebo-controlled trials of Δ9-tetrahydrocannabinol have been published; these suggested possible benefits of cannabis-derived agents for the treatment of tics. Trials examining other agents active on the cannabinoid system for tic disorders are currently ongoing. Cannabinoid-based treatments are a promising avenue of new research for medications that may help the Tourette syndrome population. However, given the limited research available, the overall efficacy and safety of cannabinoid-based treatments is largely unknown. Further trials are needed to examine dosing, active ingredients, and optimal mode of administration of cannabis-derived compounds, assuming initial trials suggest efficacy. Clinical use for refractory patients should at the very least be restricted to adult populations, given the uncertain efficacy and risk of developmental adverse effects that cannabinoids may have in children. Even in adult populations, cannabis-derived medications are associated with significant issues such as the effects they have on driving safety and the fact that they cause positive urine drug screens that can affect employment.

OBJECTIVE To examine the efficacy of pharmacologic treatments for tardive dyskinesia (TD). DATA SOURCES PubMed was searched on December 12, 2017, for randomized, placebo-controlled trials examining the treatment of TD using the search terms (drug-induced dyskinesia OR tardive dyskinesia) AND (psychotic disorders OR schizophrenia). STUDY SELECTION Studies were included if they examined tardive dyskinesia treatment as the primary outcome and were randomized and placebo-controlled trials. DATA EXTRACTION The effect size (standard mean difference) of improvement (compared to placebo) stratified by medication class is reported for each of the trials included in this systematic review. A meta-analysis was conducted utilizing a fixed-effects model. RESULTS Vitamin E was associated with significantly greater reduction in TD symptoms compared to placebo (standardized mean difference [SMD] = 0.31 ± 0.08; 95% CI, 0.16 to 0.46; z = 4.1; P < .001). There was significant evidence of publication bias in vitamin E studies (Egger test: P = .02). Shorter duration of treatment and lower dose of vitamin E were significantly associated with greater measured treatment benefit. Vitamin B₆ was associated with significantly greater reduction in TD symptoms compared to placebo (SMD = 1.41 ± 0.22; 95% CI, 0.98 to 1.85; z = 6.4; P < .001) in 2 trials conducted by the same research group. Vesicular monoamine transporter 2 (VMAT2) inhibitors demonstrated significant benefit on tardive dyskinesia symptoms compared to placebo (SMD = 0.63 ± 0.11; 95% CI, 0.41 to 0.85; z = 5.58; P < .005). Amantadine was associated with significantly greater score reduction compared to placebo (SMD = 0.46 ± 0.21; 95% CI, 0.05 to 0.87; z = 2.20; P < .05). Calcium channel blockers were not associated with significantly greater score reduction compared to placebo (SMD = 0.31 ± 0.33; 95% CI, -0.34 to 0.96; z = 0.93; P = .35). CONCLUSIONS Data from multiple trials suggests that VMAT2 inhibitors, vitamin E, vitamin B₆, and amantadine may be effective for the treatment of TD. Evidence of publication bias and a significant negative association of dose and duration of treatment with measured efficacy suggest that the benefits of vitamin E in TD may be overstated. Head-to-head trials are needed to compare the efficacy and cost-effectiveness of pharmacologic agents for TD.

The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) compared the efficacy of risperidone, olanzapine, and molindone over 8 weeks in 119 youths age 8-19 years with early-onset schizophrenia or schizoaffective disorder. From this large dataset, we examined predictors of treatment response and drop out using stepwise regression and receiver operating characteristics curve (ROC) analysis. Treatment response was defined as having both a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) score and a Clinical Global Impression-Improvement (CGI-I) score < 3. More severe baseline symptoms, having a history of being in an early education program, and previous prescription of a mood stabilizer increased the likelihood of responding to treatment. Anhedonia and poor community functioning predicted a reduction in symptom severity on the PANSS. Random assignment to different antipsychotic treatment was not predictive of outcome. Parental report of aggressive behaviors at baseline and being African American were associated with a greater likelihood of drop out. Our results suggest youth with more severe psychotic symptoms are most likely to benefit from treatment with antipsychotics and that aggressive youth may require additional support to improve treatment adherence. Further investigation is needed to understand potentially modifiable predictors of response like early education programs.