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In recent years, there has been a proliferation of instruments for assessing mental health (MH) among autistic people. This study aimed to review the psychometric properties of broadband instruments used to assess MH problems among autistic people. In accordance with the PRISMA guidelines (PROSPERO: CRD42022316571) we searched the APA PsycINFO via Ovid, Ovid MEDLINE, Ovid Embase and the Web of Science via Clarivate databases from 1980 to March 2022, with an updated search in January 2024, to identify very recent empirical studies. Independent reviewers evaluated the titles and abstracts of the retrieved records (n = 11,577) and full-text articles (n = 1000). Data were extracted from eligible studies, and the quality of the included papers was appraised. In all, 164empirical articles reporting on 35 instruments were included. The review showed variable evidence of reliability and validity of the various instruments. Among the instruments reported in more than one study, the Aberrant Behavior Checklist had consistently good or excellent psychometric evidence. The reliability and validity of other instruments, including: the Developmental Behavior Checklist, Emotion Dysregulation Inventory, Eyberg Child Behavior Inventory, Autism Spectrum Disorder-Comorbid for Children Scale, and Psychopathology in Autism Checklist, were less documented. There is a need for a greater evidence-base for MH assessment tools for autistic people.
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There is substantial comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), and there are well-documented executive functioning (EF) deficits in both populations. An important question concerns whether EF deficits in children with ASD are related to severity of ASD, ADHD, or both. We examined ADHD and ASD symptoms in relation to ratings of EF in the home and classroom. The sample comprised 64 children (55 males) diagnosed with ASD (mean age = 9.26 years; mean FSIQ = 92). Analyses indicated that parent and teacher ratings of EF (except Shift and Emotional Control) were consistently related to ADHD symptom severity, but not to ASD severity. Thus, functioning in the domains of Shift and Emotional control appear relatively spared, whereas performance in all other EF was impaired in relation to ADHD symptoms.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtorno Autístico , Masculino , Criança , Humanos , Transtorno do Espectro Autista/psicologia , Função Executiva , Transtorno Autístico/complicações , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , ComorbidadeRESUMO
BACKGROUND: In recent years, a number of studies have begun to explore the nature of Attention-Deficit/Hyperactivity Disorder (ADHD) in children with Autism Spectrum Disorder (ASD). In this study, we examined the relationship between both symptoms of ADHD and symptoms of ASD on cognitive task performance in a sample of higher-functioning children and adolescents with ASD. Participants completed cognitive tasks tapping aspects of attention, impulsivity/inhibition, and immediate memory. AIMS: We hypothesized that children with ASD who had higher levels of ADHD symptom severity would be at higher risk for poorer sustained attention and selective attention, greater impulsivity/disinhibition, and weaker memory. METHODS AND PROCEDURES: The sample included 92 children (73 males) diagnosed with ASD (Mean Age = 9.41 years; Mean Full Scale IQ = 84.2). OUTCOMES AND RESULTS: Using regression analyses, more severe ADHD symptomatology was found to be significantly related to weaker performance on tasks measuring attention, immediate memory, and response inhibition. In contrast, increasing severity of ASD symptomatology was not associated with higher risk of poorer performance on any of the cognitive tasks assessed. CONCLUSIONS AND IMPLICATIONS: These results suggest that children with ASD who have more severe ADHD symptoms are at higher risk for impairments in tasks assessing attention, immediate memory, and response inhibition-similar to ADHD-related impairments seen in the general pediatric population. As such, clinicians should assess various aspects of cognition in pediatric patients with ASD in order to facilitate optimal interventional and educational planning.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Cognição , Humanos , Masculino , Memória de Curto Prazo , Análise e Desempenho de TarefasRESUMO
Objective: The Aberrant Behavior Checklist (ABC) is a standardized rating scale used for assessing problematic behavior of individuals with developmental disabilities. It has five subscales: Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactivity, and Inappropriate Speech. A previous study in individuals with fragile X syndrome (FXS) reported six factors, with the Social Withdrawal factor bifurcating into Socially Unresponsive and Social Avoidance factors, suggesting a different factor structure in people with FXS. Methods: We assessed the ABC's factor structure (with both exploratory and confirmatory analyses) in 797 people with FXS and we compared these findings with exploratory factors derived from an independent sample of 357 individuals with FXS. In an ancillary analysis, we compared the overlap of the traditional ABC's Social Withdrawal scores with the Social Avoidance scores from the FXS-derived newer scale to determine whether overlap between these was very high and essentially redundant. Finally, we computed norms using both the traditional and the FXS-specific algorithms. Results: In confirmatory factor analyses, the FXS-specific algorithm produced the most consistent factor structure for the sample of 797 participants, but model fit was only marginally better than that derived by the original ABC scoring algorithm. Comparisons of factor structures from separate exploratory analyses revealed no consistent advantage of the FXS algorithm over the traditional algorithm. While a Social Avoidance subscale did emerge in some analyses, in other analyses, this was accompanied by loss of coherence on other domains of interest, such as the Socially Unresponsive/Social Withdrawal subscale. Conclusion: We question whether the newer FXS scoring algorithm contributes data that are consistently helpful in evaluating behavior of people with FXS. In general, we recommend continued use of the original ABC algorithm for scoring behavior of clients with FXS. However, we acknowledge that there may be circumscribed times when the new algorithm may be appropriate for scoring, namely when anxiety and/or social avoidance constructs are the central and unequivocal domains of interest.
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Lista de Checagem/normas , Análise Fatorial , Síndrome do Cromossomo X Frágil/complicações , Comportamento Problema , Algoritmos , Ansiedade , Criança , Feminino , Humanos , Humor Irritável , Masculino , Transtornos Mentais/complicações , Ajustamento SocialRESUMO
Objective: To examine the effectiveness of four doses of psychostimulant medication, combining extended-release methylphenidate (ER-MPH) in the morning with immediate-release MPH (IR-MPH) in the afternoon, on cognitive task performance. Method: The sample comprised 24 children (19 boys and 5 girls) who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text Revision (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-R and the Autism Diagnostic Observation Schedule, and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age = 8.8 years, SD = 1.7; mean intelligence quotient = 85; SD = 16.8). Effects of placebo and three dose levels of ER-MPH (containing 0.21, 0.35, and 0.48 mg/kg equivalent of IR-MPH) on cognitive task performance were compared using a within-subject, crossover, placebo-controlled design. Each of the four MPH dosing regimens (placebo, low-dose MPH, medium-dose MPH, and high-dose MPH) was administered for 1 week; the dosing order was counterbalanced across children. Results: MPH treatment was associated with significant performance gains on cognitive tasks tapping sustained attention, selective attention, and impulsivity/inhibition. Dose/response was generally linear in the dose range studied, with no evidence of deterioration in performance at higher MPH doses in the dose range studied. Conclusion: The results of this study suggest that MPH formulations are associated with significant improvements on cognitive task performance in children with ASD and ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Espectro Autista/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Cognição/efeitos dos fármacos , Preparações de Ação Retardada/uso terapêutico , Metilfenidato/uso terapêutico , Criança , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Resultado do TratamentoRESUMO
Objective: Study goals were to (1) provide a rationale for developing a composite primary outcome score that includes symptom severity for attention-deficit/hyperactivity disorder (ADHD) and emotional dysregulation, plus symptom-induced impairment; (2) demonstrate weighting methods to calculate the composite score using a sample of children diagnosed with ADHD and aggression; and (3) identify the optimal weighting method most sensitive to change, as measured by effect sizes. Methods: We conducted secondary data analyses from the previously conducted Treatment of Severe Childhood Aggression (TOSCA) study. Children aged 6-12 years were recruited through academic medical centers or community referrals. The composite primary outcome comprised the ADHD, oppositional defiant disorder, disruptive mood dysregulation disorder, and peer conflict subscales from the Child and Adolescent Symptom Inventory (CASI), a DSM (Diagnostic and Statistical Manual)-referenced rating scale of symptom severity and symptom-induced impairment. Five weighting methods were tested based on input from senior statisticians. Results: The composite score demonstrated a larger (Cohen's d) effect size than the individual CASI subscales, irrespective of the weighting method (10%-55% larger). Across all weighting methods, effect sizes were similar and substantial: approximately a two-standard deviation symptom reduction (range: -1.97 to -2.04), highest for equal item and equal subscale weighting, was demonstrated, from baseline to week 9, among all TOSCA participants. The composite score showed a medium positive correlation with the Clinical Global Impressions-Severity scores, 0.46-0.47 for all weighting methods. Conclusions: A composite score that included severity and impairment ratings of ADHD and emotional dysregulation demonstrated a more robust pre-post change than individual subscales. This composite may be a more useful indicator of clinically relevant improvement in heterogeneous samples with ADHD than single subscales, avoiding some of the statistical limitations associated with multiple comparisons. Among the five similar weighting methods, the two best appear to be the equal item and equal subscale weighting methods.
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Sintomas Afetivos/psicologia , Agressão/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Transtornos do Humor/psicologia , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
There is a need for measures to track symptom change in autism spectrum disorder (ASD). We conducted a validation study on a revised version of the Autism Behavior Inventory (ABI), and a short form (ABI-S). Caregivers of individuals (6-54 years) with confirmed diagnoses of ASD (N = 144) completed the ABI and other rating scales at 4 time points. Scale consistency for each domain, 3-5 day test-retest reliability, and construct validity, determined by comparison to pre-specified scales, were all good. Change in the ABI was congruent with changes in other instruments. Collectively, results suggest incipient suitability of the ABI as a measure of changes in core and associated symptoms of ASD.Trial Registration NCT02299700.
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Transtorno do Espectro Autista/diagnóstico , Cuidadores , Adulto , Criança , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos TestesRESUMO
Objective: To explore blinded observational outcomes in the Treatment of Severe Childhood Aggression (TOSCA) study. Methods: During a 9-week acute trial, children with severe physical aggression and attention-deficit/hyperactivity disorder received parent training + titrated psychostimulant for 3 weeks, and those who failed to show an optimal response during Week 4 through Week 6 received in addition either randomly assigned placebo (Basic treatment) or titrated risperidone (Augmented treatment). Child and parent behaviors were videotaped in a Standardized Observation Analogue Procedure (SOAP) designed to elicit problems and strengths in child and parent interactions. SOAPs were collected at baseline and Week 9 and 52 follow-up. Results: During the acute 9-week trial, augmented treatment was associated with better outcomes than basic treatment for 3 of 13 measures: increased Child Compliance (p = 0.004; significant after correction for multiple tests), greater use of positive Parent Reinforcement (p = 0.03), and more Shared Enjoyment (p = 0.04). At follow-up, when medication was no longer by randomized assignment, parents used more Alpha Commands and displayed fewer Parent Negative Behaviors, and the dyads showed more Shared Enjoyment regardless of original randomization. Thus, there were better parent-child interactions with Augmented treatment, and interactions improved overall at follow-up regardless of original treatment assignment. Conclusions: The SOAP demonstrated sensitivity to behavior changes between short-term treatments for a few (but not most) measures. The acute treatment differences for Child Compliance and Child Negative Behavior are generally consistent with the moderate superiority of Augmented over Basic treatment previously reported for the primary study outcome.
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Agressão/efeitos dos fármacos , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Risperidona/uso terapêutico , Agressão/psicologia , Antipsicóticos/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Criança , Terapia Combinada , Aconselhamento , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
Objectives: We recently found that metformin attenuated weight gain due to mixed dopamine and serotonin receptor antagonists, commonly termed atypical antipsychotics, in children and adolescents with autism spectrum disorder (ASD). Previous studies have found that genetic variation predicts response to metformin in diabetes. In this study, we aimed to assess whether response to metformin for weight gain in this population is associated with variants in five genes previously implicated in metformin response in diabetes. Methods: Youth with ASD who experienced significant weight gain while taking mixed receptor antagonist medications were randomly assigned to metformin or placebo for 16 weeks, followed by open-label metformin treatment for 16 weeks. In the 53 participants with available DNA samples, we used a linear, mixed model analysis to assess response in the first 16 weeks of metformin treatment, whether in the randomized or open-label period, based upon genotypes at polymorphisms in five genes previously associated with metformin response in diabetes: ATM, SLC2A2, MATE1, MATE2, and OCT1. Results: In the primary analysis, both ATM and OCT1 showed significant effects of genotype on change in body mass index z-scores, the primary outcome measure, during the first 16 weeks of treatment with metformin. No other polymorphism showed a significant difference. Conclusion: As has been shown for metformin treatment in diabetes, genetic variation may predict response to metformin for weight gain in youth with ASD treated with mixed receptor antagonists. Further work is needed to replicate these findings and evaluate whether they can be used prospectively to improve outcomes.
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Transtorno do Espectro Autista/tratamento farmacológico , Metformina/administração & dosagem , Farmacogenética , Aumento de Peso/efeitos dos fármacos , Adolescente , Proteínas Mutadas de Ataxia Telangiectasia/genética , Criança , Método Duplo-Cego , Feminino , Genótipo , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Fator 1 de Transcrição de Octâmero/genética , Polimorfismo Genético , Aumento de Peso/genéticaRESUMO
Three phase 2 trials were conducted to assess the efficacy and long-term safety of weight-based memantine extended release (ER) treatment in children with autism spectrum disorder. MEM-MD-91, a 50-week open-label trial, identified memantine extended-release treatment responders for enrollment into MEM-MD-68, a 12-week randomized, double-blind, placebo-controlled withdrawal trial. MEM-MD-69 was an open-label extension trial in which participants from MEM-MD-68, MEM-MD-91, and open-label trial MEM-MD-67 were treated ⩽48 weeks with memantine extended release. In MEM-MD-91, 517 (59.6%) participants were confirmed Social Responsiveness Scale responders at week 12; mean Social Responsiveness Scale total raw scores improved two to three times a minimal clinically important difference of 10 points. In MEM-MD-68, there was no difference between memantine and placebo on the primary efficacy parameter, the proportion of patients with a loss of therapeutic response (defined as ⩾10-point increase from baseline in Social Responsiveness Scale total raw score). MEM-MD-69 exploratory analyses revealed mean standard deviation improvement in Social Responsiveness Scale total raw score of 32.4 (26.4) from baseline of the first lead-in study. No new safety concerns were evident. While the a priori-defined efficacy results of the double-blind trial were not achieved, the considerable improvements in mean Social Responsiveness Scale scores from baseline in the open-label trials were presumed to be clinically important.
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Transtorno do Espectro Autista/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Memantina/uso terapêutico , Comportamento Social , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Criança , Preparações de Ação Retardada , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Feminino , Febre/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Humor Irritável , Masculino , Nasofaringite/induzido quimicamente , Resultado do TratamentoRESUMO
OBJECTIVE: Anxiety is common in youth with autism spectrum disorder (ASD). There is no accepted outcome measure for anxiety in this population. METHOD: Following a series of focus groups with parents of youth with ASD, we generated 72 items (scored 0-3). Parents of 990 youth with ASD (aged 5-17 years; 80.8% male) completed an online survey. Factor analysis and item response theory analyses reduced the content to a single factor with 25 items. Youth with at least mild anxiety (n = 116; aged 5-17 years; 79.3% male) participated in a comprehensive clinical assessment to evaluate the validity and reliability of the 25-item Parent-Rated Anxiety Scale for ASD (PRAS-ASD). RESULTS: In the online sample, the mean PRAS-ASD score was 29.04 ± 14.9 (range, 0-75). The coefficient α was 0.93. The item response theory results indicated excellent reliability across a wide range of scores with low standard errors. In the clinical sample (n = 116), the PRAS-ASD mean was 31.0 ± 15.6 (range, 1-65). Pearson correlations with parent ratings of ASD symptom severity, repetitive behavior, and disruptive behavior ranged 0.33 to 0.66, supporting divergent validity of the PRAS-ASD. Pearson correlation with a parent-rated measure of anxiety used in the general pediatric population of 0.83 supported convergent validity. A total of 40 participants (32 boys, 8 girls; mean age, 11.9 ± 3.4 years) returned at time 2 (mean, 12.2 days) and time 3 (mean, 24.2 days). Intraclass correlation showed test-retest reliabilities of 0.88 and 0.86 at time 2 and time 3, respectively. CONCLUSION: The 25-item PRAS-ASD is a reliable and valid scale for measuring anxiety in youth with ASD.
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Transtornos de Ansiedade/diagnóstico , Ansiedade/diagnóstico , Transtorno do Espectro Autista/diagnóstico , Escalas de Graduação Psiquiátrica , Adolescente , Ansiedade/complicações , Ansiedade/psicologia , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/psicologia , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/psicologia , Criança , Pré-Escolar , Análise Fatorial , Feminino , Humanos , Masculino , Pais , Psicometria/instrumentação , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
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 3-17â¯years; meanâ¯=â¯7.2â¯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.
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Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Adolescente , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Transtorno do Espectro Autista/epidemiologia , Criança , Pré-Escolar , Comorbidade , Transtorno da Conduta/diagnóstico , Transtorno da Conduta/epidemiologia , Transtorno da Conduta/psicologia , Feminino , Humanos , Masculino , Transtornos do Humor/diagnóstico , Transtornos do Humor/epidemiologia , Transtornos do Humor/psicologiaRESUMO
We thank Dr. Higdon et al. for their interest in our article on metformin and children with autism spectrum disorders (ASD) and for providing information about the MOBILITY study (a Patient-Centered Outcomes Research Institute (PCORI)-funded pragmatic clinical trial to examine the relative effectiveness of metformin plus healthy lifestyle instruction versus healthy lifestyle instruction alone).1 In our October 2017 article,2 we reported the results of a 16-week open-label extension study of a group of 61 children and adolescents with ASD prescribed second-generation antipsychotic medications (SGAs) who previously participated in a randomized controlled trial (RCT) of metformin for management of weight gain. Although Higdon et al. indicated that our study results were encouraging, they believed that the conclusion of the accompanying JAACAP editorial3 stating metformin be considered as an adjunct treatment for any child who is overweight and prescribed SGAs was premature. Instead, they recommended that the results of their current pragmatic trial for children with bipolar disorder (which includes some children with ASD and intellectual disability) would better provide information on relevant moderators and mediators of metformin's effects. Such information would be of use to clinicians in determining whether to prescribe metformin to their patients or to focus on lifestyle changes (or a combination of the 2).
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Antipsicóticos , Transtorno do Espectro Autista , Metformina , Adolescente , Criança , Humanos , Sobrepeso , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Frequent non-pathogenic genetic variants may act as moderators of phenotypic severity for complex disorders such as autism spectrum disorder (ASD). We previously identified polymorphisms affecting mRNA expression of candidate genes, including tryptophan hydroxylase 2 (TPH2), dopamine beta hydroxylase (DBH), and dopamine transporter (DAT, SLC6A3). METHOD: We compare genotypes and (1) clinical response to atomoxetine, (2) scores from the Autism Diagnostic Interview-Revised (ADI-R), and (3) severity of Attention Deficit Hyperactivity Disorder (ADHD) symptoms in a cohort of patients with ASD from multiple study sites. RESULTS: There was no association between CYP2D6 metabolizer status and atomoxetine response. TPH2 rs7305115 genotype was associated with ADI-R Restrictive/Repetitive Behavior score (p=0.03). DBH rs1611115 genotype was associated with ADI-R Social score (p=0.002) and Restrictive/Repetitive Behavior score (p=0.04). The DAT intron 8 5/6 repeat was associated with ADHD symptoms (ABC Hyperactivity p=0.01 and SNAP ADHD p=0.03), replicating a previous finding. CONCLUSIONS: We find associations between ASD phenotypes and regulatory variants in catecholamine biosynthesis genes. This work may help guide future genetics studies related to ASD.
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We would like to respond to the thought-provoking editorial by Dr. Jon McClellan1 regarding our article "Clinical Implications from the Treatment of Severe Childhood Aggression (TOSCA) Study: A Re-Analysis and Integration of Findings," published in the December 2017 issue of JAACAP.2 We address some issues on which we partially disagree, and comment on convergence of opinion.
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Transtorno Bipolar , Cloridrato de Lurasidona , Adolescente , Agressão , Criança , Depressão , Método Duplo-Cego , HumanosRESUMO
OBJECTIVE: To examine status of children with autism spectrum disorder (ASD) 10 months after a 34-week clinical trial of atomoxetine (ATX) and parent training (PT). METHODS: In a 2 × 2 design, 128 children with ASD and attention-deficit/hyperactivity disorder (ADHD) were randomly assigned ATX, PT+placebo, PT+ATX, or placebo alone. PT was weekly for 10 weeks, and then monthly. ATX/placebo was titrated over 6 weeks [≤1.8 mg/kg/d], and then maintained until week 10. Responders continued to week 34 or nonresponse. Placebo nonresponders had a 10-week ATX open trial; ATX nonresponders were treated clinically. All continued to week 34. With no further treatment from the study, all were invited to follow-up (FU) at 1.5 years postbaseline; 94 (73%) participated. Changes from Week 34 to FU and from baseline to FU were tested by one-way analysis of variance or chi-squared test. PT versus no PT was tested by chi-squared test, Fisher's exact test, Welch's t-test, Student's t-test, and Mann-Whitney's U test. RESULTS: For the whole sample, the primary outcomes (parent-rated ADHD on the Swanson, Nolan, and Pelham [SNAP] scale and noncompliance on the Home Situations Questionnaire [HSQ]) deteriorated mildly from week 34 to FU, but were still substantially better than baseline (SNAP: t = 12.177, df = 93, p < 0.001; HSQ: t = 8.999, df = 93, p < 0.001). On the SNAP, 61% improved ≥30% from baseline (67% did at week 34); on noncompliance, 56% improved ≥30% from baseline (77% did at week 34). Outcomes with PT were not significantly better than without PT (SNAP p = 0.30; HSQ p = 0.27). Originally assigned treatment groups did not differ significantly. Only 34% still took ATX; 27% were taking stimulants; and 25% took no medication. CONCLUSIONS: The majority retained their 34-week end-of-study improvement 10 months later, even though most participants stopped ATX. For some children, ATX continuation may not be necessary for continued benefit or other drugs may be necessary. Cautious individual clinical experimentation may be justified. Twelve sessions of PT made little long-term difference. ClinicalTrials.gov Identifier: Atomoxetine, Placebo and Parent Management Training in Autism (Strattera) (NCT00844753).
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Inibidores da Captação Adrenérgica/uso terapêutico , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Espectro Autista/tratamento farmacológico , Pais/educação , Comportamento Problema/psicologia , Adolescente , Criança , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVES: Studies in humans and rodents suggest that metformin, a medicine typically used to treat type 2 diabetes, may have beneficial effects on memory. We sought to determine whether metformin improved spatial or verbal memory in children with autism spectrum disorder (ASD) and overweight associated with atypical antipsychotic use. METHODS: We studied the effects of metformin (Riomet®) concentrate on spatial and verbal memory in 51 youth with ASD, ages 6 through 17 years, who were taking atypical antipsychotic medications, had gained significant weight, and were enrolled in a trial of metformin for weight management. Phase 1 was a 16-week, randomized, double-blind, placebo-controlled, parallel-group comparison of metformin (500-850 mg given twice a day) versus placebo. During Phase 2, all participants took open-label metformin from week 17 through week 32. We assessed spatial and verbal memory using the Neuropsychological Assessment 2nd Edition (NEPSY-II) and a modified children's verbal learning task. RESULTS: No measures differed between participants randomized to metformin versus placebo, at either 16 or 32 weeks, after adjustment for multiple comparisons. Sixteen-week change in memory for spatial location on the NEPSY-II was nominally better among participants randomized to placebo. However, patterns of treatment response across all measures revealed no systematic differences in performance, suggesting that metformin had no effect on spatial or verbal memory in these children. CONCLUSIONS: Although further study is needed to support these null effects, the overall impression is that metformin does not affect memory in overweight youth with ASD who were taking atypical antipsychotic medications.
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Antipsicóticos/uso terapêutico , Transtorno do Espectro Autista/tratamento farmacológico , Memória/efeitos dos fármacos , Metformina/uso terapêutico , Adolescente , Antipsicóticos/efeitos adversos , Criança , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Sobrepeso/induzido quimicamente , Sobrepeso/epidemiologia , Memória Espacial/efeitos dos fármacos , Resultado do TratamentoRESUMO
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.
Assuntos
Transtorno do Espectro Autista/complicações , Obesidade Infantil/complicações , Comportamento Problema , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Obesidade Infantil/psicologia , Comportamento Problema/psicologia , Fatores de RiscoRESUMO
OBJECTIVE: Sleep disturbance is often a problem for children with either autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD). Psychostimulant medications used to treat ADHD symptoms can exacerbate this problem. For children with ASD and ADHD, atomoxetine (ATX) is a viable alternative to psychostimulants. We investigated the effects of ATX and a manualized parent training (PT) program targeting noncompliance, on the sleep quality of children with ASD and ADHD. METHODS: Participants in a randomized clinical trial were treated with ATX + PT, ATX alone, PT alone, or placebo (PBO) alone, for 10 weeks. Fifty-four of 128 (42%) caregivers completed the Children's Sleep Habits Questionnaire (CSHQ) at baseline and endpoint. Analysis of covariance was used to investigate possible differences between treatment groups. RESULTS: There were no significant differences between treatment groups, including PBO on the CSHQ 33-Item total score, total hours of sleep per day, and total minutes awake after sleep onset at the study endpoint. CONCLUSION: ATX appears sleep neutral. Clinicians who treat ADHD symptoms in children and adolescents with ASD may prefer ATX over psychostimulants when sleep disturbance is an issue.