Pre-Existing Comorbid Emotional Symptoms Moderate Short-Term Methylphenidate Adverse Effects in a Randomized Trial of Children with Attention-Deficit/Hyperactivity Disorder.
- 作者列表："Froehlich TE","Brinkman WB","Peugh JL","Piedra AN","Vitucci DJ","Epstein JN
Objective: We sought to ascertain whether baseline anxiety/depression and oppositional defiant disorder (ODD) symptoms impacted the experience of short-term methylphenidate (MPH) adverse effects (AEs) in 7- to 11-year-old children with attention-deficit/hyperactivity disorder (ADHD) (n = 171) undergoing a double-blind MPH crossover trial. Method: The Vanderbilt ADHD Diagnostic Parent Rating Scale measured baseline child anxiety/depression and ODD symptomology. The parent-completed Pittsburgh Side Effect Rating Scale assessed the AEs of anxiety, sadness, and irritability at baseline, on placebo, and on three MPH dosages. For each AE, we evaluated comorbidity main effects, dose main effects, and comorbidity × dose interactions. Results: Baseline anxiety/depression × dose and ODD × dose interactions were significant for the AEs of anxiety, sadness, and irritability. Compared with premedication baseline, these AEs attenuated on MPH for children with initially higher comorbidity symptoms, whereas those with initially lower comorbidity symptoms tended toward no change or increasing AE levels. Conclusion: Premedication anxiety/depressive and ODD symptoms may be important predictors of short-term MPH emotional AEs.
目标: 我们试图确定基线焦虑/抑郁和对立违抗性障碍 (ODD) 症状是否影响短期哌甲酯 (MPH) 不良反应 (AEs) 的体验在 7-11 岁注意缺陷/多动障碍 (ADHD) 儿童 (n = 171) 中进行双盲 MPH 交叉试验。 方法: Vanderbilt ADHD 诊断家长评定量表测量基线儿童焦虑/抑郁和奇怪症状。父母完成的匹兹堡副作用评定量表在基线、安慰剂和 3 个 MPH 剂量下评估了焦虑、悲伤和易怒的 ae。对于每种 AE，我们评估了合并症主效应、剂量主效应和合并症 × 剂量相互作用。 结果: 基线焦虑/抑郁 × 剂量和 odd × 剂量相互作用对焦虑、悲伤和易激惹的 ae 有显著意义。与用药前基线相比，对于最初有较高合并症症状的儿童，这些 AE 在 MPH 上减弱，而最初有较低合并症症状的儿童倾向于无变化或 AE 水平升高。 结论: 用药前焦虑/抑郁和奇怪症状可能是短期 MPH 情绪 ae 的重要预测因子。
METHODS:Abstract Background Attention-deficit/hyperactivity disorder (ADHD) is a psychosocially impairing and cost-intensive mental disorder, with first symptoms occurring in early childhood. It can usually be diagnosed reliably at preschool age. Early detection of children with ADHD symptoms and an early, age-appropriate treatment are needed in order to reduce symptoms, prevent secondary problems and enable a better school start. Despite existing ADHD treatment research and guideline recommendations for the treatment of ADHD in preschool children, there is still a need to optimise individualised treatment strategies in order to improve outcomes. Therefore, the ESCApreschool study (Evidence-Based, Stepped Care of ADHD in Preschool Children aged 3 years and 0 months to 6 years and 11 months of age (3;0 to 6;11 years) addresses the treatment of 3–6-year-old preschool children with elevated ADHD symptoms within a large multicentre trial. The study aims to investigate the efficacy of an individualised stepwise-intensifying treatment programme. Methods The target sample size of ESCApreschool is 200 children (boys and girls) aged 3;0 to 6;11 years with an ADHD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) or a diagnosis of oppositional defiant disorder (ODD) plus additional substantial ADHD symptoms. The first step of the adaptive, stepped care design used in ESCApreschool consists of a telephone-assisted self-help (TASH) intervention for parents. Participants are randomised to either the TASH group or a waiting control group. The treatment in step 2 depends on the outcome of step 1: TASH responders without significant residual ADHD/ODD symptoms receive booster sessions of TASH. Partial or non-responders of step 1 are randomised again to either parent management and preschool teacher training or treatment as usual. Discussion The ESCApreschool trial aims to improve knowledge about individualised treatment strategies for preschool children with ADHD following an adaptive stepped care approach, and to provide a scientific basis for individualised medicine for preschool children with ADHD in routine clinical care. Trial registration The trial was registered at the German Clinical Trials Register (DRKS) as a Current Controlled Trial under DRKS00008971 on 1 October 2015. This manuscript is based on protocol version 3 (14 October 2016).
METHODS:Prefrontal volume reductions commonly are demonstrated in ADHD, but the literature examining prefrontal volume in reading disorders (RD) is scant despite their also having executive functioning (EF) deficits. Furthermore, only a few anatomical studies have examined the frontal lobes in comorbid RD/ADHD, though they have EF deficits similar to RD and ADHD. Hence, we examined frontal gyri volume in children with RD, ADHD, RD/ADHD and controls, as well as their relationship to EF for gyri found to differ between groups. We found right inferior frontal (RIF) volume was smaller in ADHD, and smaller volume was related to worse behavioral regulation. Left superior frontal (LSF) volume was larger in RD than ADHD, and its size was negatively related to basic reading ability. Left middle frontal (LMF) volume was largest in RD/ADHD overall. Further, its volume was not related to basic reading nor behavioral regulation but was related to worse attentional control, suggesting some specificity in its EF relationship. When examining hypotheses on the etiology of RD/ADHD, RD/ADHD was commensurate with ADHD in RIF volume and both RD and ADHD in LSF volume (being midway between the groups), consistent with the common etiology hypothesis. Nevertheless, they also had an additional gyrus affected: LMF, consistent with the cognitive subtype hypothesis in its specificity to RD/ADHD. The few other frontal aMRI studies on RD/ADHD supported both hypotheses as well. Given this, future research should continue to focus on frontal morphology in its endeavors to find neurobiological contributors to the comorbidity between RD and ADHD.
METHODS:BACKGROUND:Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children. METHODS:Children 7-15 years old were recruited for a case-control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577). RESULTS:ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = -0.147 (-0.27 to -0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score. CONCLUSION:Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.