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

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

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

Toward precision medicine in ADHD

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response

Default mode network maturation and environmental adversities during childhood

Default mode network (DMN) plays a central role in cognition and brain disorders. It has been shown that adverse environmental conditions impact neurodevelopment, but how these conditions impact in DMN maturation is still poorly understood. This article reviews representative neuroimaging functional studies addressing the interactions between DMN development and environmental factors, focusing on early life adversities, a critical period for brain changes. Studies focused on this period of life offer a special challenge: to disentangle the neurodevelopmental connectivity changes from those related to environmental conditions. We first summarized the literature on DMN maturation, providing an overview of both typical and atypical development patterns in childhood and early adolescence. Afterward, we focused on DMN changes associated with chronic exposure to environmental adversities during childhood. This summary suggests that changes in DMN development could be a potential allostatic neural feature associated with an embodiment of environmental circumstances. Finally, we discuss about some key methodological issues that should be considered in paradigms addressing environmental adversities and open questions for future investigations

Diagnostic operationalization and phenomenological heterogeneity in psychiatry : the case of attention deficit hyperactivity disorder

Introduction. We assessed the impact of polythetic conceptualizations of mental disorders on the validity and reliability of psychiatric diagnosis, with a specific focus on two levels of heterogeneity: phenomenological and pathophysiological. Objective. We investigated this issue using attention deficit hyperactivity disorder (ADHD) as an example. Method. We examined individuals from two samples enriched for psychopathology (n = 1 255 children in Porto Alegre and 1 257 children in São Paulo, Brazil). We conducted a series of data analyses to investigate phenomenological heterogeneity, including confirmatory factor analysis. We also investigated pathophysiological heterogeneity using symptom-level regressions between ADHD symptoms and four neurocognitive processes consistently linked to ADHD (working memory, inhibitory control, intra-subject variability in reaction times, and temporal processing). Lastly, we assessed the performance of polythetic systems for reliability testing inter-rater and test-rest reliability of two well-known symptomatic scales. Results. Among the 116 200 possible combinations of symptoms to achieve DSM symptomatic threshold for categorical ADHD diagnosis, we found 173 combinations in the two independent samples, and only four were replicated in both samples (2.3%). We also found that the number of ADHD symptoms is a poor indicator of variation in the general ADHD latent trait. Overall, symptoms did not have specific profiles of associations with any of the neurocognitive processes. Reliability analyses revealed that increasing the number of items augments overall reliability of measurements. Discussion and conclusion. Our findings illustrate both potential benefits and problems inherent to the polythetic system for ADHD. Implications for the search of mechanisms underlying psychiatric disorders are discussed.Antecedentes. Evaluamos el impacto de las conceptualizaciones politécnicas de los trastornos mentales en la validez y la fiabilidad del diagnóstico psiquiátrico, con un enfoque específico en dos niveles de heterogeneidad: fenomenológico y fisiopatológico. Objetivos. Investigamos este problema utilizando el trastorno por déficit de atención e hiperactividad (TDAH) como ejemplo. Método. Examinamos individuos de dos muestras enriquecidas por psicopatología (n = 1 255 niños en Porto Alegre y 1 257 niños en São Paulo, Brasil). Llevamos a cabo una serie de análisis de datos para investigar la heterogeneidad fenomenológica, incluido el análisis factorial confirmatorio. También investigamos la heterogeneidad fisiopatológica utilizando regresiones al nivel de síntomas entre los síntomas del TDAH y cuatro procesos neurocognitivos consistentemente vinculados al TDAH (memoria de trabajo, control inhibitorio, variabilidad intrasujeto en tiempos de reacción y procesamiento temporal). Por último, evaluamos el rendimiento de los sistemas politéticos para la prueba de confiabilidad interevaluador y la confiabilidad test-rest de dos escalas sintomáticas bien conocidas. Resultados. Entre las 116 200 posibles combinaciones de síntomas para alcanzar el umbral sintomático del DSM para el diagnóstico categórico de TDAH, encontramos 173 combinaciones en las dos muestras independientes y sólo cuatro se replicaron en ambas muestras (2.3%). También encontramos que la cantidad de síntomas de TDAH no es un buen indicador de la variación en el rasgo latente general del TDAH. En general, los síntomas no tenían perfiles específicos de asociaciones con ninguno de los procesos neurocognitivos. Los análisis de confiabilidad revelaron que aumentar el número de artículos aumenta la confiabilidad general de las mediciones. Discusión y conclusión. Nuestros hallazgos ilustran tanto los beneficios potenciales como los problemas inherentes al sistema politécnico para el TDAH. Se discuten las implicaciones para la búsqueda de mecanismos subyacentes a los trastornos psiquiátricos