Transcutaneous electrical acupoint stimulation for children with attention-deficit/hyperactivity disorder : a randomized clinical trial

Little is known about the effects of transcutaneous electrical acupoint stimulation (TEAS) for children with attention-deficit/ hyperactivity disorder (ADHD). Here, we carried out a 4 week randomized clinical trial in which patients aged 6–12 years old with an ADHD diagnosis received TEAS or sham TEAS. The primary outcome measure was the investigator-rated Clinical Global Impression-Improvement (CGI-I) score at week 4. Secondary outcomes included changes from baseline to week 4 in the investigator-rated Clinical Global Impression-Severity of Illness (CGI-S) score, the Conners’ Parent/Teacher Rating Scales-Revised: Short Form (CPRS-R: S/CTRS-R: S) score, go/no-go task performance, and functional near-infrared spectroscopy (fNIRS)-based oxygenated hemoglobin level within the prefrontal cortex. At week 4, the CGI-I score indicated improvement in 33.3% of the TEAS group compared with 7.7% of the sham group (P = 0.005). The TEAS group had a greater decrease in the mean CGI-S score (−0.87) than the sham TEAS group (−0.28) (P = 0.003). A greater enhancement in the mean cerebral oxygenated hemoglobin within the prefrontal cortex was found in the TEAS group (0.099 mM mm) compared with the sham TEAS group (0.005 mM mm) (P < 0.001). CPRS-R: S score, CTRS-R: S score, and go/no-go performance exhibited no significant improvement after TEAS treatment. The manipulation-associated adverse events were uncommon in both groups, and events were very mild. Our results show that noninvasive TEAS significantly improved general symptoms and increased prefrontal cortex blood flow within 4 weeks for children with ADHD. Further clinical trials are required to understand the long-term efficacy in a larger clinical sample. This trial was registered on ClinicalTrials.gov (NCT 03917953)

208 evidence-based conclusions about the disorder

Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma

O tratamento farmacológico do transtorno bipolar na infância e adolescência

Juvenile Bipolar Disorder (JBD) has been recognized more frequently in the last years. The disorder might have an atypical presentation in this age range. Thus, irritability with "affective storms" are more frequent than euphoria, the evolution of the disorder is more chronic than episodic and mixed symptoms are more frequent. High prevalence of comorbid conditions, specially Attention-Deficit/Hyperactivity Disorder, seems to be the rule. Despite the devastating effect of JBD in the child development, few pharmacological investigations were conducted in these patients. This review aims to present a critical discussion of the findings from this emerging new area of research, the psychopharmacology of the JBD. To accomplish this task, a systematic computerized search of the literature was conducted through the PUBMED. Findings are presented in three sections: 1) the strength of the scientific evidence in the field; 2) critical description of the main investigations; 3) proposition of an algorithm to guide treatment options. Only one randomized, double-blind, controlled trial was found in the literature. Almost all studies are open prospective trials, case series, or retrospective analyses of medical records. The most investigated drugs are lithium and valproate sodium. This review suggest that a scarce availability of high quality evidence to guide clinicians in the decision on which pharmacological treatment should be used to address bipolar disorder in children and adolescents.O reconhecimento do transtorno do humor bipolar (THB) em crianças e adolescentes tem aumentado significativamente nos últimos anos. O THB, nessa faixa etária, parece freqüentemente se apresentar de forma atípica, assim, humor irritável com "tempestades afetivas" são mais freqüentes do que euforia, o curso da doença é mais crônico do que episódico e sintomas mistos com depressão e mania concomitantes são comuns. Alta prevalência de comorbidades, em especial com transtorno do déficit de atenção/hiperatividade, parece ser a regra. Apesar do efeito devastador do THB no desenvolvimento infantil, poucos estudos têm investigado intervenções farmacológicas nesses pacientes. Essa revisão tem como objetivo apresentar uma discussão crítica dos achados provenientes de estudos recentes nessa nova área de pesquisa, a psicofarmacologia do THB em crianças e adolescentes. Para realizar essa tarefa, uma revisão computadorizada e sistemática da literatura foi realizada por meio do PUBMED. Os dados sobre tratamento psicofarmacológico do THB em crianças e adolescentes são apresentados em três seções: 1) a força da evidência científica na área; 2) descrição crítica dos estudos principais; 3) proposição de um algoritmo de decisão. Apenas um estudo randomizado duplo-cego e controlado por placebo foi encontrado. A quase totalidade dos estudos é composta de ensaios prospectivos abertos, séries de casos e análises retrospectivas de prontuários. Os fármacos mais estudados são o lítio e o valproato de sódio. Essa revisão indica uma escassa disponibilidade de evidência científica de qualidade para guiar o clínico na decisão do tratamento farmacológico a ser indicado para o THB em crianças e adolescentes

Teaching facts of addition to Brazilian children with attention-deficit/hyperactivity disorder

Storage and/or automatic retrieval of the basic facts of addition from the long-term memory seems to be impaired in children with ADHD presenting arithmetical difficulties. The present study was carried out to evaluate the effectiveness of an educational intervention model designed to teach basic facts of addition as a means of advancing from counting procedures to memory-based processes in 7 children with ADHD, divided into two groups (control and intervention). The main hypothesis was that the explicit teaching of decomposition strategies would lead to an advanced use of a memory-based procedure. It is an experimental study involving the use of a blind, parallel, randomized, controlled clinical trial. The intervention group participated in 10 one-hour sessions over a 10-week period, while the control group received the same quantity and distribution of teaching time. They carried out the kind of activities generally carried out in the classroom. Although there was no apparent statistical difference between the groups, our findings suggest that the tested educational intervention model is effective at promoting the retrieval of memory-based facts, since the intervention group came to predominantly adopt a memory-based strategy. A carefully designed educational program enhances memory-based processes in students with ADHD. These findings have important implications for further research considering interventions for both students with ADHD and those who perform poorly in arithmetic

Decline in attention-deficit hyperactivity disorder traits over the life course in the general population : trajectories across five population birth cohorts spanning ages 3 to 45 years

Background Trajectories of attention-deficit hyperactivity disorder (ADHD) traits spanning early childhood to mid-life have not been described in general populations across different geographical contexts. Population trajectories are crucial to better understanding typical developmental patterns. Methods We combined repeated assessments of ADHD traits from five population-based cohorts, spanning ages 3 to 45 years. We used two measures: (i) the Strengths and Difficulties Questionnaire (SDQ) hyperactive-inattentive subscale (175 831 observations, 29 519 individuals); and (ii) scores from DSM-referenced scales (118 144 observations, 28 685 individuals). Multilevel linear spline models allowed for non-linear change over time and differences between cohorts and raters (parent/teacher/self). Results Patterns of age-related change differed by measure, cohort and country: overall, SDQ scores decreased with age, most rapidly declining before age 8 years (-0.157, 95% CI: -0.170, -0.144 per year). The pattern was generally consistent using DSM scores, although with greater between-cohort variation. DSM scores decreased most rapidly between ages 14 and 17 years (-1.32%, 95% CI: -1.471, -1.170 per year). Average scores were consistently lower for females than males (SDQ: -0.818, 95% CI: -0.856, -0.780; DSM: -4.934%, 95% CI: -5.378, -4.489). This sex difference decreased over age for both measures, due to an overall steeper decrease for males. Conclusions ADHD trait scores declined from childhood to mid-life, with marked variation between cohorts. Our results highlight the importance of taking a developmental perspective when considering typical population traits. When interpreting changes in clinical cohorts, it is important to consider the pattern of expected change within the general population, which is influenced by cultural context and measurement

The challenge of new RBP editors

Universidade Federal de São Paulo (UNIFESP)Universidade de São PauloUniversidade Federal do Rio Grande do Sul Departament of PsychiatryUNIFESPSciEL

Abnormal brain connectivity patterns in adults with ADHD : a coherence study

Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach – unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD agematched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits

Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents

Extracellular vesicles (EVs) are present in numerous peripheral bodily fluids and function in critical biological processes, including cellto-cell communication. Most relevant to the present study, EVs contain microRNAs (miRNAs), and initial evidence from the field indicates that miRNAs detected in circulating EVs have been previously associated with mental health disorders. Here, we conducted an exploratory longitudinal and cross-sectional analysis of miRNA expression in serum EVs from adolescent participants. We analyzed data from a larger ongoing cohort study, evaluating 116 adolescent participants at two time points (wave 1 and wave 2) separated by three years. Two separate data analyses were employed: A cross-sectional analysis compared individuals diagnosed with Major Depressive Disorder (MDD), Anxiety disorders (ANX) and Attention deficit/Hyperactivity disorder (ADHD) with individuals without psychiatric diagnosis at each time point. A longitudinal analysis assessed changes in miRNA expression over time between four groups showing different diagnostic trajectories (persistent diagnosis, first incidence, remitted and typically developing/control). Total EVs were isolated, characterized by size distribution and membrane proteins, and miRNAs were isolated and sequenced. We then selected differentially expressed miRNAs for target prediction and pathway enrichment analysis. In the longitudinal analysis, we did not observe any statistically significant results. In the cross-sectional analysis: in the ADHD group, we observed an upregulation of miR-328-3p at wave 1 only; in the MDD group, we observed a downregulation of miR-4433b-5p, miR-584-5p, miR-625-3p, miR-432-5p and miR-409-3p at wave 2 only; and in the ANX group, we observed a downregulation of miR-432-5p, miR-151a-5p and miR-584-5p in ANX cases at wave 2 only. Our results identified previously observed and novel differentially expressed miRNAs and their relationship with three mental health disorders. These data are consistent with the notion that these miRNAs might regulate the expression of genes associated with these traits in genome-wide association studies. The findings support the promise of continued identification of miRNAs contained within peripheral EVs as biomarkers for mental health disorders

Combined intervention of working memory and arithmetic reasoning in students with ADHD

This study compared the effects of a combined intervention of working memory (WM) and arithmetic reasoning (AR) vs WM intervention alone on the arithmetic reasoning performance of students with ADHD. Third- and fourth-grade elementary school students (n = 46) completed measures for AR, mathematical calculations, and WM. Participants were randomised using a minimisation approach taking age and IQ as variables of interest and assigned to one of the two groups: Combined Intervention (CI, n = 24) and Working Memory Intervention (WMI, n = 22). The results using GEE analysis indicated a significant group × time interaction (Waldχ2 = 6.414; gl = 2; p = 0.04) in AR performance in the immediate post-test. CI students showed significantly better performance on AR than WMI students immediately after intervention (pB = 0.042). There was an effect of time on mathematical calculations in the post-test (Waldχ2 = 48.305; gl = 2; p < 0.001). Despite the fact that the results for AR were not maintained in the deferred post-test, a combined intervention of WM and AR seems to be more efficient in improving arithmetic reasoning in ADHD students than a WM intervention alone. Nevertheless, this is not the case with other mathematical issues, such as calculation, where there was no significant difference between groups, but the effects had been maintained in the deferred post-test for both