Problems most concerning to parents of children with ADHD and emotional dysregulation in a randomized controlled trial of multinutrients: MADDY secondary analysis.

OBJECTIVE: With dual focus on structured, objective quantification of parent observations of child's behavior and identifying behaviors most amenable to change, this report examines Parent Target Problems (PTP) as a secondary outcome in a randomized clinical trial (RCT) of children with attention-deficit/ hyperactivity disorder (ADHD) in which one primary outcome, Clinical Global Impression-Improvement, showed a significant advantage of multinutrients over placebo and the other, Likert-type parent ratings, showed significant improvement in both groups, without significant difference between them. METHOD: In a multisite 8-week RCT of broad-spectrum micronutrients ("multinutrients"), parents of children ages 6-12 (N = 126, 73% male, 88% white) with ADHD and emotional dysregulation nominated their child's most concerning problem(s) at baseline and quantified them by frequency, duration, impairment, and consequences. At subsequent visits, parents re-quantified the problem(s). Blinded child psychiatrists independently reviewed the PTPs and rated change at two timepoints compared to baseline. PTPs were grouped into 9 categories. Mean ratings were compared between active and placebo groups and explored by category. RESULTS: By week 8, a significant separation favored multinutrients: 38% of the multinutrient group were "definitely improved" or better, compared to 25% of the placebo group, and ratings of "no change" or "worse" occurred in 35% with placebo versus 23% with multinutrients (p = 0.04). Inattention (72.2%) and emotional dysregulation (69.1%) were the most frequently reported PTP categories. Inattention and internalizing symptoms improved more with multinutrients than placebo (p = 0.01, d = 0.55; p = 0.03, d = 0.80, respectively). The multinutrient advantage was not significant for 7 other symptoms, including hyperactivity/impulsivity, aggression, autistic symptoms, or emotional dysregulation/irritable oppositionality. CONCLUSIONS: This secondary analysis found that the multinutrients, compared to placebo, were associated with improvements in parental concerns overall, and in two domains specifically: inattention and internalizing symptoms (anxiety/depression), but not in seven domains: hyperactivity/impulsivity, aggression, autistic symptoms or physiological symptoms, peer relationships or emotional dysregulation/irritable oppositionality.

Effectiveness of vergence/accommodative therapy for accommodative dysfunction in children with convergence insufficiency.

PURPOSE: To determine the effectiveness of office-based vergence/accommodative therapy for improving accommodative amplitude and accommodative facility in children with symptomatic convergence insufficiency and accommodative dysfunction. METHODS: We report changes in accommodative function following therapy among participants in the Convergence Insufficiency Treatment Trial - Attention and Reading Trial with decreased accommodative amplitude (115 participants in vergence/accommodative therapy; 65 in placebo therapy) or decreased accommodative facility (71 participants in vergence/accommodative therapy; 37 in placebo therapy) at baseline. The primary analysis compared mean change in amplitude and facility between the vergence/accommodative and placebo therapy groups using analyses of variance models after 4, 8, 12 and 16 weeks of treatment. The proportions of participants with normal amplitude and facility at each time point were calculated. The average rate of change in amplitude and facility from baseline to week 4, and from weeks 4 to 16, were determined in the vergence/accommodative therapy group. RESULTS: From baseline to 16 weeks, the mean improvement in amplitude was 8.6 dioptres (D) and 5.2 D in the vergence/accommodative and placebo therapy groups, respectively (mean difference = 3.5 D, 95% confidence interval (CI): 1.5 to 5.5 D; p = 0.01). The mean improvement in facility was 13.5 cycles per minute (cpm) and 7.6 cpm in the vergence/accommodative and placebo therapy groups, respectively (mean difference = 5.8 cpm, 95% CI: 3.8 to 7.9 cpm; p < 0.0001). Significantly greater proportions of participants treated with vergence/accommodative therapy achieved a normal amplitude (69% vs. 32%, difference = 37%, 95% CI: 22 to 51%; p < 0.0001) and facility (85% vs. 49%, difference = 36%, 95% CI: 18 to 55%; p < 0.0001) than those who received placebo therapy. In the vergence/accommodative therapy group, amplitude increased at an average rate of 1.5 D per week during the first 4 weeks (p < 0.0001), then slowed to 0.2 D per week (p = 0.002) from weeks 4 to 16. Similarly, facility increased at an average rate of 1.5 cpm per week during the first 4 weeks (p < 0.0001), then slowed to 0.6 cpm per week from weeks 4 to 16 (p < 0.0001). CONCLUSION: Office-based vergence/accommodative therapy is effective for improving accommodative function in children with symptomatic convergence insufficiency and coexisting accommodative dysfunction.

An exploration of concomitant psychiatric disorders in children with autism spectrum disorder.

OBJECTIVE: We explored patterns of concomitant psychiatric disorders in a large sample of treatment-seeking children and adolescents with autism spectrum disorder (ASD). METHODS: Participants were 658 children with ASD (age 3-17 years; mean = 7.2 years) in one of six federally-funded multisite randomized clinical trials (RCT) between 1999 and 2014. All children were referred for hyperactivity or irritability. Study designs varied, but all used the Child and Adolescent Symptom Inventory or Early Childhood Inventory to assess Attention Deficit Hyperactivity Disorder (ADHD), Oppositional-Defiant Disorder (ODD), Conduct Disorder (CD), Anxiety Disorders, and Mood Disorders. In addition, several measures in common were used to assess demographic and clinical characteristics. RESULTS: Of the 658 children, 73% were Caucasian and 59% had an IQ >70. The rates of concomitant disorders across studies were: ADHD 81%, ODD 46%, CD 12%, any anxiety disorder 42%, and any mood disorder 8%. Two or more psychiatric disorders were identified in 66% of the sample. Of those who met criteria for ADHD, 50% also met criteria for ODD and 46% for any anxiety disorder. Associations between types of concomitant disorders and a number of demographic and clinical characteristics are presented. CONCLUSION: In this well-characterized sample of treatment-seeking children with ASD, rates of concomitant psychiatric disorders were high and the presence of two or more co-occurring disorders was common. Findings highlight the importance of improving diagnostic practice in ASD and understanding possible mechanisms of comorbidity.

Correlates, stability and predictors of borderline personality disorder among previously suicidal youth.

This article examines a large cohort of previously suicidal adolescents, identifying those that surpassed threshold criteria for borderline personality disorder (BPD), according to the Abbreviated Diagnostic Interview of Borderlines (Ab-DIB), and determining the stability, correlates and predictors of BPD from early-to-late adolescence. Two hundred and eighty-six youth (mean baseline age 14.6 years; SD 1.5), presenting consecutively to a metropolitan pediatric hospital emergency department for evaluation of suicidality, were assessed at initial consultation for Axis I and II disorders and demographic and clinical variables. Two hundred and twenty-nine (80%) were re-assessed for those variables 4 years later and 204 (70.3%) had complete data sets at recruitment and follow-up. Previously suicidal youths who met BPD threshold on the Ab-DIB at recruitment were distinguishable at baseline from those who did not in conduct disorder symptoms (p < 0.003), lower levels of functioning (p < 0.001), drug use (p < 0.001), stressful life events (p < 0.003) and family relations (p < 0.001). The BPD diagnosis was consistent, according to this measure, at baseline and follow-up for 76% of participants. Four groups with respect to borderline pathology (persisting, remitting, emerging and never) were identified (ICC = 0.603, 95% CI = 0.40-0.78). Persistent BPD status was predictable by older age at presentation (p < 0.01) and level of functioning (p < 0.05). Eight percent were also suicidal at the 4-year follow-up. Using a self-report measure of BPD, we suggest that suicidal youth can indeed be diagnosed with the disorder at 14 years old, supporting the shift from DSM-IV to DSM-5, given what appears to be its temporal stability, differentiation of those suffering with considerable symptomatology or not, and predictors of its status in late adolescence. The low suicidality rate at follow-up indicates a good short-term prognosis.

Developing the Diagnostic Interview for Adolescents and Adults with Mild/Moderate Intellectual Disabilities: An interview schedule of mental disorders (DIAAID).

Introduction: Young people with intellectual disabilities (ID) are at an increased risk for experiencing mental health issues compared to their peers without disabilities. Further, there are limited resources available to help accurately assess mental health disorders and that are accessible for adolescents with ID. Method: This paper describes the iterative development and pilot testing of the Diagnostic Interview for Adolescents and Adults with Intellectual Disabilities (DIAAID). The authors utilized Evidence Center Design and Universal Design principals to develop the DIAAID; a multi-informant diagnostic interview. Results: The DIAAID development resulted in the creation of 15 adolescents disorder interviews and 24 caregiver disorder interviews. Preliminary results suggest that the DIAAID is a feasible and accessible diagnostic interview for adolescents with ID and their caregivers. Discussion: Lessons learned from DIAAID implementation and future areas research are discussed.

Commentary: Filling out the evidence base for treatment of attention-deficit hyperactivity disorder symptoms in children with intellectual and developmental disability: conclusions for clinicians--a response to Simonoff et al. (2013).

This randomized clinical trial of methylphenidate in children with intellectual disability (ID) by Simonoff et al. (2013) advances the field in several ways useful to clinicians. The three-figure widely representative sample more definitively confirms findings previously reported from smaller studies and studies with a differently selected sample. The medium placebo-controlled effect size found is in line with previous more tentative suggestions for ID, such as those summarized by Aman et al. This sample, selected for ID but coincidentally including some children with autism (a third of the sample), nicely complements the RUPP Autism Network (2005) study of 72 children with autism, most of whom also had ID (mean IQ 62.6, range 16-135). Similar effect was found in both studies, suggesting that one might expect a medium effect widely in the intellectual & developmental disability (IDD) population, with a 40-50% response rate.

Cognitive markers for efficacy of neurofeedback for attention-deficit hyperactivity disorder - personalized medicine using computational psychiatry in a randomized clinical trial.

BACKGROUND: Exploring whether cognitive components (identified by baseline cognitive testing and computational modeling) moderate clinical outcome of neurofeedback (NF) for attention-deficit hyperactivity disorder (ADHD). METHOD: 142 children (aged 7-10) with ADHD were randomly assigned to either NF (n = 84) or control treatment (n = 58) in a double-blind clinical trial (NCT02251743). The NF group received live, self-controlled downtraining of electroencephalographic theta/beta ratio power. The control group received identical-appearing reinforcement from prerecorded electroencephalograms from other children. 133 (78 NF, 55 control) children had cognitive processing measured at baseline with the Integrated Visual and Auditory Continuous Performance Test (IVA2-CPT) and were included in this analysis. A diffusion decision model applied to the IVA2-CPT data quantified two latent cognitive components deficient in ADHD: drift rate and drift bias, indexing efficiency and context sensitivity of cognitive processes involving information integration. We explored whether these cognitive components moderated the improvement in parent- and teacher-rated inattention symptoms from baseline to treatment end (primary clinical outcome). RESULTS: Baseline cognitive components reflecting information integration (drift rate, drift bias) moderated the improvement in inattention due to NF vs. control treatment (p = 0.006). Specifically, those with either the most or least severe deficits in these components showed more improvement in parent- and teacher-rated inattention when assigned to NF (Cohen's d = 0.59) than when assigned to control (Cohen's d = -0.21). CONCLUSIONS: Pre-treatment cognitive testing with computational modeling identified children who benefitted more from neurofeedback than control treatment for ADHD.

Vitamin D levels in children with attention deficit hyperactivity disorder: Association with seasonal and geographical variation, supplementation, inattention severity, and theta:beta ratio.

We examined seasonal and geographic effects on vitamin D [25(OH)D] levels, association with attention-deficit/hyperactivity disorder (ADHD) symptom severity, and effects of supplementation in 222 children age 7-10 with rigorously diagnosed ADHD. 25(OH)D insufficiency rates were 47.2 % in Ohio and 28.5 % 400 miles south in North Carolina. Nadir of 25(OH)D levels was reached by November in Ohio, not until January in NC. Thirty-eight children with insufficiency/deficiency took vitamin D (1000-2000 IU/day for a month); levels rose 52 %. Although inattention did not correlate with 25(OH)D at screen nor improve significantly with supplementation, inattention improvement after supplementation correlated with 25(OH)D increase (rho = 0.41, p = 0.012). A clinically significant proportion of children with ADHD have insufficient 25(OH)D even at summer's end, more so in the winter and north of the 37th parallel. The significant correlation of inattention improvement with 25(OH)D increase suggests further research on 25(OH)D as ADHD treatment.

Overweight and obese status in children with autism spectrum disorder and disruptive behavior.

Overweight and obesity are common in pediatric populations. Children with autism spectrum disorder and disruptive behavior may be at higher risk. This study examined whether children with autism spectrum disorder and disruptive behavior are more likely to be overweight or obese than matched controls. Baseline data from medication-free children with autism spectrum disorder who participated in trials conducted by the Research Units on Pediatric Psychopharmacology Autism Network (N = 276) were compared to 544 control children from the National Health and Nutrition Examination Survey database matched on age, sex, race, parent education, and era of data collection. The mean age of the children with autism spectrum disorder was 7.9 ± 2.6 years; 84.4% were males. In the autism spectrum disorder group, the prevalence was 42.4% for overweight and 21.4% for obesity compared to 26.1% for overweight and 12.0% for obesity among controls (p < 0.001 for each contrast). Within the autism spectrum disorder sample, obesity was associated with minority status and lower daily living skills. These findings suggest that children with autism spectrum disorder and disruptive behavior are at increased risk for obesity and underscore the need for weight management interventions in this population.

Decreased functional connectivity in the fronto-parietal network in children with mood disorders compared to children with dyslexia during rest: An fMRI study.

Background: The DSM-5 separates the diagnostic criteria for mood and behavioral disorders. Both types of disorders share neurocognitive deficits of executive function and reading difficulties in childhood. Children with dyslexia also have executive function deficits, revealing a role of executive function circuitry in reading. The aim of the current study is to determine whether there is a significant relationship of functional connectivity within the fronto-parietal and cingulo-opercular cognitive control networks to reading measures for children with mood disorders, behavioral disorders, dyslexia, and healthy controls (HC). Method: Behavioral reading measures of phonological awareness, decoding, and orthography were collected. Resting state fMRI data were collected, preprocessed, and then analyzed for functional connectivity. Differences in the reading measures were tested for significance among the groups. Global efficiency (GE) measures were also tested for correlation with reading measures in 40 children with various disorders and 17 HCs. Results: Significant differences were found between the four groups on all reading measures. Relative to HCs and children with mood disorders or behavior disorders, children with dyslexia as a primary diagnosis scored significantly lower on all three reading measures. Children with mood disorders scored significantly lower than controls on a test of phonological awareness. Phonological awareness deficits correlated with reduced resting state functional connectivity MRI (rsfcMRI) in the cingulo-opercular network for children with dyslexia. A significant difference was also found in fronto-parietal global efficiency in children with mood disorders relative to the other three groups. We also found a significant difference in cingulo-opercular global efficiency in children with mood disorders relative to the Dyslexia and Control groups. However, none of these differences correlate significantly with reading measures. Conclusions/significance: Reading difficulties involve abnormalities in different cognitive control networks in children with dyslexia compared to children with mood disorders. Findings of the current study suggest increased functional connectivity of one cognitive control network may compensate for reduced functional connectivity in the other network in children with mood disorders. These findings provide guidance to clinical professionals for design of interventions tailored for children suffering from reading difficulties originating from different pathologies.

Reaction time distribution analysis of neuropsychological performance in an ADHD sample.

Differences in reaction time (RT) variability have been documented between children with and without Attention Deficit Hyperactivity Disorder (ADHD). Most previous research has utilized estimates of normal distributions to examine variability. Using a nontraditional approach, the present study evaluated RT distributions on the Conners' Continuous Performance Test in children and adolescents from the Multimodal Treatment Study of ADHD sample compared to a matched sample of normal controls (n = 65 pairs). The ex-Gaussian curve was used to model RT and RT variability. Children with ADHD demonstrated faster RT associated with the normal portion of the curve and a greater proportion of abnormally slow responses associated with the exponential portion of the curve. These results contradict previous interpretation that children with ADHD have slower than normal responding and demonstrate why slower RT is found when estimates of variability assume normal Gaussian distributions. Further, results of this study suggest that the greater number of abnormally long RTs of children with ADHD reflect attentional lapses on some but not all trials.

Brief Report: social disability in autism spectrum disorder: results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network trials.

There is growing interest in measuring social disability as a core element of autism spectrum disorders in medication trials. We conducted a secondary analysis on the Aberrant Behavior Checklist Social Withdrawal subscale using data from two federally-funded, multi-site, randomized trials with risperidone. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. Study 2 included 49 subjects assigned to risperidone only and 75 subjects assigned to risperidone plus parent training. After 8 weeks of treatment, all active treatments were superior to placebo (effect sizes ranging from 0.42 to 0.65). The findings suggest that the Social Withdrawal subscale may be a useful measure of social disability in acute treatment trials.

Adolescent substance use in the multimodal treatment study of attention-deficit/hyperactivity disorder (ADHD) (MTA) as a function of childhood ADHD, random assignment to childhood treatments, and subsequent medication.

OBJECTIVE: To determine long-term effects on substance use and substance use disorder (SUD), up to 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA; n = 436); to test whether medication at follow-up, cumulative psychostimulant treatment over time, or both relate to substance use/SUD; and to compare substance use/SUD in the ADHD sample to the non-ADHD childhood classmate comparison group (n = 261). METHOD: Mixed-effects regression models with planned contrasts were used for all tests except the important cumulative stimulant treatment question, for which propensity score matching analysis was used. RESULTS: The originally randomized treatment groups did not differ significantly on substance use/SUD by the 8-year follow-up or earlier (mean age = 17 years). Neither medication at follow-up (mostly stimulants) nor cumulative stimulant treatment was associated with adolescent substance use/SUD. Substance use at all time points, including use of two or more substances and SUD, were each greater in the ADHD than in the non-ADHD samples, regardless of sex. CONCLUSIONS: Medication for ADHD did not protect from, or contribute to, visible risk of substance use or SUD by adolescence, whether analyzed as randomized treatment assignment in childhood, as medication at follow-up, or as cumulative stimulant treatment over an 8-year follow-up from childhood. These results suggest the need to identify alternative or adjunctive adolescent-focused approaches to substance abuse prevention and treatment for boys and girls with ADHD, especially given their increased risk for use and abuse of multiple substances that is not improved with stimulant medication. Clinical trial registration information-Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); http://clinical trials.gov/; NCT00000388.

Predictors and moderators of parent training efficacy in a sample of children with autism spectrum disorders and serious behavioral problems.

The Research Units on Pediatric Psychopharmacology--Autism Network reported additional benefit when adding parent training (PT) to antipsychotic medication in children with autism spectrum disorders and serious behavior problems. The intent-to-treat analyses were rerun with putative predictors and moderators. The Home Situations Questionnaire (HSQ) and the Hyperactivity/Noncompliance subscale of the Aberrant Behavior Checklist were used as outcome measures. Candidate predictors and moderators included 21 demographics and baseline measures of behavior. Higher baseline HSQ scores predicted greater improvement on the HSQ regardless of treatment assignment, but no other predictors of outcome were observed. None of the variables measured in this study moderated response to PT. Antipsychotic medication plus PT appears to be equally effective for children with a wide range of demographic and behavioral characteristics.

Dietary status and impact of risperidone on nutritional balance in children with autism: a pilot study.

BACKGROUND: Risperidone may be effective in improving tantrums, aggression, or self-injurious behaviour in children with autism, but often leads to weight gain. METHOD: Using a quantitative Food Frequency Questionnaire (FFQ), we prospectively examined the nutritional intake of 20 children with autism participating in a randomised placebo-controlled trial of risperidone for disruptive behaviours. RESULTS: At baseline, the mean intakes for macronutrients, vitamins and minerals exceeded Dietary Reference Intakes (DRIs). However there was substantial inter-participant variability, with individual deficiencies (<80% of DRI) in the intake of calcium (9 of 20 participants), pantothenic acid (6 of 20), vitamin D (5 of 20) and vitamin K (8 of 20). For the participants for whom FFQs were available, there was an increase in weight and an increase in vitamin K intake after 2 months of risperidone treatment (n = 9) compared to placebo (n = 8). An additional 4 months of risperidone treatment (n = 8) did not result in significant changes in reported nutritional balance. CONCLUSION: These pilot data suggest that treatment with risperidone did not significantly affect the nutritional balance of this small group of children.