A Systematic Review of Literatures onFactors Associated with Educational ndAcademic Performance in Attention DeficitHyperactivity Disorder

__Abstract__ Attention Deficit Hyperactivity Disorder (ADHD) has been shown to impair major life activities including educational functioning. However, there is no consensus on the specific cause for the impact on this worse educational outcome. This systematic review aims to identify factors that have been associated with educational and academic underperformance of children and adolescents with ADHD. A literature search was conducted using PubMed and the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The study focused on articles presenting results of data-based analyses related to ADHD and keywords related to education. The search resulted in 376 records that were screened by title. Of these, 185 articles were screened by abstract and 35 met the eligibility criteria for inclusion in the review. These 35 articles were related to seven domains: educational training, educational environment, pharmacological treatment, ADHD symptoms, associations of ADHD with academic outcomes, self-concept, and specific skills. The main source of educational challenges seems to be related to the inattentive symptoms (or subtype) of ADHD. This outcome is different than expected, since hyperactive symptoms are pronounced more prominently and often refer children to clinical practice. Inattentive symptoms amongst others refer to difficulties in organization skills and can lead to decreased self-efficacy and development of depressive symptoms. This decreased self-efficacy and the depressive symptoms were also found to be related to influence the relation between ADHD and academic performance. Educational outcomes were shown to be improved using small group work, learning via a computer-based service and as a result of coaching and pharmacological treatment. To help children and adults achieve educational goals that now are out of reach, more attention should be spent to the inattentive symptoms of ADHD and possibilities to overcome experienced problems

Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study

Background: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare. A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence implicating enhanced serotonergic neurotransmission in CFS. Genetic studies and imaging studies support the hypothesis of upregulated serotonin system in CFS. In line with the hypothesis of an increased serotonergic state in CFS, we performed a randomised clinical trial investigated the effect of 5-HT3 receptor antagonism in CFS. No benefit was found of the 5-HT3 receptor antagonist ondansetron compared to placebo. To further investigate the involvement of serotonin in CFS we performed a placebo controlled cross over pilot study investigating the effect of Acute Tryptophan Depletion. Findings: Five female CFS-patients who met the US Center for Disease Control and Prevention criteria for CFS were recruited. There were two test days, one week apart. Each participant received placebo and ATD. To evaluate the efficacy of the ATD procedure tryptophan and the large neutral amino acids were measured. The outcome measures were fatigue severity, concentration and mood states. ATD resulted in a significant plasma tryptophan to large neutral amino acid ratio reduction of 96%. There were no significant differences in fatigue-, depression and concentration between the placebo- and ATD condition. Conclusions: These first five CFS-patients did not respond to the ATD procedure. However, a much larger sample size is needed to draw final conclusions on the hypothesis of an increased serotonergic state in the pathophysiology of CFS. Trial registration: ISRCTN0751814

Probabilistic markov model estimating cost effectiveness of methylphenidate osmotic-release oral system versus immediate-release methylphenidate in children and adolescents: Which information is needed?

Background: Incidence of attention deficit hyperactivity disorder (ADHD) in children and adolescents has been increasing. The disorder results in high societal costs. Policymakers increasingly use health economic evaluations to inform decisions on competing treatments of ADHD. Yet, health economic evaluations of first-choice medication of ADHD in children and adolescents are scarce and generally do not include broader societal effects. Objectives: This study presents a probabilistic model and analysis of methylphenidate osmotic-release oral system (OROS) versus methylphenidate immediate-release (IR). We investigate and include relevant societal aspects in the analysis so as to provide cost-effectiveness estimates based on a broad societal perspective. Methods: We enhanced an existing Markov model and determined the cost effectiveness of OROS versus IR for children and adolescents responding suboptimally to treatment with IR. Enhancements included screening of a broad literature base, updated utilit

Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

Background: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and com

Pleiotropic contribution of MECOM and AVPR1A to aggression and subcortical brain volumes

Reactive and proactive subtypes of aggression have been recognized to help parse etiological heterogeneity of this complex phenotype. With a heritability of about 50%, genetic factors play a role in the development of aggressive behavior. Imaging studies implicate brain structures related to social behavior in aggression etiology, most notably the amygdala and striatum. This study aimed to gain more insight into the pathways from genetic risk factors for aggression to aggression phenotypes. To this end, we conducted genome-wide gene-based cross-trait meta-analyses of aggression with the volumes of amygdala, nucleus accumbens and caudate nucleus to identify genes influencing both aggression and aggression-related brain volumes. We used data of large-scale genome-wide association studies (GWAS) of: (a) aggressive behavior in children and adolescents (EAGLE, N = 18,988); and (b) Magnetic Resonance Imaging (MRI)-based volume measures of aggression-relevant subcortical brain regions (ENIGMA2, N = 13,171). Second, the identified genes were further investigated in a sample of healthy adults (mean age (SD) = 25.28 (4.62) years; 43% male) who had genome-wide genotyping data and questionnaire data on aggression subtypes available (Brain Imaging Genetics, BIG, N = 501) to study their effect on reactive and proactive subtypes of aggression. Our meta-analysis identified two genes, MECOM and AVPR1A, significantly associated with both aggression risk and nucleus accumbens (MECOM) and amygdala (AVPR1A) brain volume. Subsequent in-depth analysis of these genes in healthy adults (BIG), including sex as an interaction term in the model, revealed no significant subtype-specific gene-wide associations. Using cross-trait meta-analysis of brain measures and psychiatric phenotypes, this study generated new hypotheses about specific links between genes, the brain and behavior. Results indicate that MECOM and AVPR1A may exert an effect on aggression through mechanisms involving nucleus accumbens and amygdala volumes, respectively

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

A graph theory study of resting-state functional connectivity in children with Tourette syndrome

Contains fulltext : 218561.pdf (Publisher’s version ) (Open Access

Study into the Impact of Nutrition on Children with Attention-Deficit Hyperactivity Disorder - ADHD (INCA STUDY)

Dutch randomised controlled trial into the effects of food on the behaviour of a random group of school-going children meeting the DSM-IV criteria for ADHD, including immunological testing