Development Of Attention Deficit Hyperactivity Disorder Research Articles

Exposure to intimate partner violence and parental depression increases risk of ADHD in preschool children

A substantial body of research has documented that exposure to childhood adversity, including witnessing intimate partner violence (IPV) and parental depression, influences millions of children annually, and is associated with...

Methylphenidate and the Response to Growth Hormone Treatment in Short Children Born Small for Gestational Age

BackgroundGrowth hormone (GH) treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA). Children born SGA have a higher risk of developing attention deficit hyperactivity disorder (ADHD). Treatment of ADHD with methylphenidate (MP) has greatly increased in recent years, therefore more children are being treated with GH and MP simultaneously. Some studies have found an association between MP treatment and growth deceleration, but data are contradictory.ObjectiveTo explore the effects of MP treatment on growth in GH-treated short SGA childrenMethodsAnthropometric measurements were performed in 78 GH-treated short SGA children (mean age 10.6 yr), 39 of whom were also treated with MP (SGA-GH/MP). The SGA-GH/MP group was compared to 39 SGA-GH treated subjects. They were matched for sex, age and height at start of GH, height SDS at start of MP treatment and target height SDS. Serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels were yearly determined. Growth, serum IGF-I and IGFBP-3 levels during the first three years of treatment were analyzed using repeated measures regression analysis.ResultsThe SGA-GH/MP group had a lower height gain during the first 3 years than the SGA-GH subjects, only significant between 6 and 12 months of MP treatment. After 3 years of MP treatment, the height gain was 0.2 SDS (±0.1 SD) lower in the SGA-GH/MP group (P = 0.17). Adult height was not significantly different between the SGA-GH/MP and SGA-GH group (−1.9 SDS and −1.9 SDS respectively, P = 0.46). Moreover, during the first 3 years of MP treatment IGF-I and IGFBP-3 measurements were similar in both groups.ConclusionMP has some negative effect on growth during the first years in short SGA children treated with GH, but adult height is not affected.

Complementary, Holistic, and Integrative Medicine: Therapies for Neurodevelopment in Preterm Infants

Complementary, Holistic, and Integrative Medicine: Therapies for Neurodevelopment in Preterm Infants

Complementary, Holistic, and Integrative Medicine: Therapies for Neurodevelopment in Preterm Infants

1. Elaine Galicia-Connolly, MD* 2. Larissa Shamseer, MSc* 3. Sunita Vohra, MD, MSc* 1. *Department of Paediatrics, CARE Program for Integrative Health and Healing, University of Alberta, Edmonton General Hospital, Edmonton, Alberta, Canada. * Abbreviations: CCT: : controlled clinical trial CI: : confidence interval DHA: : docosahexanoic acid fVEP: : flash visual evoked potential IQR: : interquartile range LBW: : low birthweight LCPUFA: : long-chain polyunsaturated fatty acid MDI: : Mental Developmental Index RCT: : randomized controlled trial WMD: : weighted mean difference Preterm birth is defined as birth occurring at age <37 weeks, with extremely preterm birth occurring at <26 weeks. (1) Children born prematurely have been shown to have significantly lower cognitive scores compared with children born at term by age 5 years, with scores being significantly positively correlated to both birthweight and gestational age. (2) In addition, preterm children are significantly more likely to develop attention deficit hyperactivity disorder and other behavioral problems at school age than children born at term. Complementary and alternative medicine therapies are used to help alleviate long-term consequences of preterm birth. In this article, we review commonly used complementary and alternative medicine therapies (long-chain polyunsaturated fatty acid [LCPUFA] supplementation, massage therapy, and music therapy) and their effects on the neurodevelopment of preterm infants. The following electronic bibliographic databases were searched: MEDLINE, EMBASE, Cochrane’s Database of Systematic Reviews and Register of Controlled Trials (CENTRAL), and PsycInfo. The search was limited to systematic reviews and clinical trials. Search terminology included neurodevelopment, premature infant, nutritional supplementation, massage therapy, music therapy, and their respective synonyms according to database. No language limits were imposed. Included studies were restricted to clinical studies. ### Long-chain Polyunsaturated Fatty Acids The n-3 LCPUFA, docosahexanoic acid (DHA), is a major brain lipid believed to play a role in brain development. It is thought that preterm infants may receive less DHA than full-term infants due to a shortened third trimester. (3)(4) A systematic review included 32 randomized controlled trials (RCTs) of which 10 studies were meta-analyzed. The RCTs examined the effect of enteral feeds of LCPUFA-supplemented formulas on neurodevelopment …

On the track of function of KLHL12-mediated dopamine D4 receptor ubiquitination

Event Abstract Back to Event On the track of function of KLHL12-mediated dopamine D4 receptor ubiquitination Kamila Skieterska1*, Pieter Rondou1, Dasiel O. Borroto-Escuela2, Dorien Clarisse1, Béatrice Lintermans1, Guy Haegeman1, Kjell Fuxe2 and Kathleen Van Craenenbroeck1 1 Ghent University, Physiology, Belgium 2 Karolinska Institutet, Neuroscience, Sweden The dopamine D4 receptor belongs to the superfamily of G protein-coupled receptors (GPCRs), the most common drug targets. The dopamine D4 gene displays a remarkable polymorphisms that differ in a variable number of tandem repeats in the region encoding the third intracellular loop. The most frequent variants in the human population are respectively: the 4-repeat allele (D4.4R), 7-repeat allele (D4.7R) and 2-repeat allele (D4.2R), of which the D4.7R polymorphic variant is associated with a predisposition to develop Attention Deficit Hyperactivity Disorder (ADHD). The functional role of the receptor polymorphic region is still poorly understood. We have identified a BTB-Kelch protein, KLHL12, which specifically interacts with the polymorphic repeats and enhances ubiquitination of the D4R. Interestingly, however, we have found that KLHL12 only marginally affects ubiquitination of the D4.7R variant, in contrast to strong induction of ubiquitination of the D4.2R and D4.4R variants. This suggests that differential ubiquitination of the D4R has functional implications. Most studies have focused on the role of GPCR ubiquitination in receptor degradation; nevertheless, our experimental results gave clear evidence that KLHL12-mediated D4R ubiquitination does not lead to receptor degradation. Moreover, our preliminary data suggest that KLHL12 might mediate a non-lysine ubiquitination of the receptor which is currently studied more profoundly. Furthermore, we are investigating the influence of ubiquitination on receptor signaling and found a role in modulation of cAMP level upon D4R activation. Acknowledgements This work was financially supported by FWO (Fonds voor Wetenschappelijk Onderzoek) Vlaanderen: project No. G.0109.09N. K. Skieterska is a recipient of a pre-doctoral FWO fellowship. K. Van Craenenbroeck has a post-doctoral FWO fellowship. Keywords: dopamine D4 receptor, Ubiquitination, KLHL12, ADHD, GPCR Conference: Belgian Brain Council, Liège, Belgium, 27 Oct - 27 Oct, 2012. Presentation Type: Poster Presentation Topic: Other basic/clinical neurosciences topic Citation: Skieterska K, Rondou P, Borroto-Escuela DO, Clarisse D, Lintermans B, Haegeman G, Fuxe K and Van Craenenbroeck K (2012). On the track of function of KLHL12-mediated dopamine D4 receptor ubiquitination. Conference Abstract: Belgian Brain Council. doi: 10.3389/conf.fnhum.2012.210.00053 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 Sep 2012; Published Online: 12 Sep 2012. * Correspondence: Ms. Kamila Skieterska, Ghent University, Physiology, Ghent, 9000, Belgium, kamila.skieterska@ugent.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kamila Skieterska Pieter Rondou Dasiel O Borroto-Escuela Dorien Clarisse Béatrice Lintermans Guy Haegeman Kjell Fuxe Kathleen Van Craenenbroeck Google Kamila Skieterska Pieter Rondou Dasiel O Borroto-Escuela Dorien Clarisse Béatrice Lintermans Guy Haegeman Kjell Fuxe Kathleen Van Craenenbroeck Google Scholar Kamila Skieterska Pieter Rondou Dasiel O Borroto-Escuela Dorien Clarisse Béatrice Lintermans Guy Haegeman Kjell Fuxe Kathleen Van Craenenbroeck PubMed Kamila Skieterska Pieter Rondou Dasiel O Borroto-Escuela Dorien Clarisse Béatrice Lintermans Guy Haegeman Kjell Fuxe Kathleen Van Craenenbroeck Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Altered Serotonergic Function may Partially Account for Behavioral Endophenotypes in Steroid Sulfatase-deficient Mice

The X-linked gene STS encodes the steroid hormone-modulating enzyme steroid sulfatase. Loss-of-function of STS, and variation within the gene, have been associated with vulnerability to developing attention deficit hyperactivity disorder (ADHD), a neurodevelopmental condition characterized by inattention, severe impulsivity, hyperactivity, and motivational deficits. ADHD is commonly comorbid with a variety of disorders, including obsessive-compulsive disorder. The neurobiological role of steroid sulfatase, and therefore its potential role in ADHD and associated comorbidities, is currently poorly understood. The 39,X(Y)*O mouse, which lacks the Sts gene, exhibits several behavioral abnormalities relevant to ADHD including inattention and hyperactivity. Here, we show that, unexpectedly, 39,X(Y)*O mice achieve higher ratios than wild-type mice on a progressive ratio (PR) task thought to index motivation, but that there is no difference between the two groups on a behavioral task thought to index compulsivity (marble burying). High performance liquid chromatography analysis of monoamine levels in wild type and 39,X(Y)*O brain tissue regions (the frontal cortex, striatum, thalamus, hippocampus, and cerebellum) revealed significantly higher levels of 5-hydroxytryptamine (5-HT) in the striatum and hippocampus of 39,X(Y)*O mice. Significant correlations between hippocampal 5-HT levels and PR performance, and between striatal 5-HT levels and locomotor activity strongly implicate regionally-specific perturbations of the 5-HT system as a neurobiological candidate for behavioral differences between 40,XY and 39,X(Y)*O mice. These data suggest that inactivating mutations and functional variants within STS might exert their influence on ADHD vulnerability, and disorder endophenotypes through modulation of the serotonergic system.

Cortical Thickness in Fetal Alcohol Syndrome and Attention Deficit Disorder

Fetal alcohol syndrome represents the classic and most severe manifestation of epigenetic changes induced by exposure to alcohol during pregnancy. Often these patients develop attention deficit hyperactivity disorder. We analyzed cortical thickness in 20 children and adolescents with fetal alcohol syndrome and attention deficit hyperactivity disorder (group 1), in 20 patients without fetal alcohol syndrome (group 2), and in 20 control cases. The first group revealed total cortical thickness significantly superior to those of the other two groups. In per-lobe analyses of cortical thickness, group 1 demonstrated greater cortical thickness in the frontal, occipital, and right temporal and left frontal lobes compared with the second group, and in both temporal lobes and the right frontal lobe compared with the control group. This study demonstrated greater cortical thickness in patients with attention deficit hyperactivity disorder and heavy prenatal exposure to alcohol, probably as an expression of immature or abnormal brain development.

Interrelations Between Executive Function and Symptoms of Hyperactivity/Impulsivity and Inattention in Preschoolers: A Two Year Longitudinal Study

The present study, including children at risk for developing Attention Deficit Hyperactivity Disorder (ADHD), examined the idea that complex executive functions (EFs) build upon more simple ones. This notion was applied in the study of longitudinal interrelations between core EF components - simple and complex inhibition, selective attention, and working memory (WM) - at age 5 and 6 as well as their predictive relations to ADHD symptoms at age 7. The results showed that simple inhibition and selective attention at age 5 independently predicted complex inhibition and WM at age 6. In addition, EFs primarily predicted symptoms of inattention rather than hyperactivity/impulsivity even at this young age. Finally, age 6 complex inhibition was shown to act as a mediator in the relations between simple inhibition and selective attention at age 5 and symptoms of inattention at age 7. These findings provide novel longitudinal support for the theory that fundamental EF components show a progression with age toward more complex executive control (see Garon et al. Psychological Bulletin 134(1):31-60 2008). Further, complex inhibition, implicating both inhibition and WM, seems to be a particularly strong correlate of ADHD symptoms in young children and should as such be the focus of future studies examining the relation between cognitive function and ADHD symptoms from a developmental perspective.

Early head injury and attention deficit hyperactivity disorder: retrospective cohort study

. Keenan H. T., Hall G. C. &amp; Marshall S.W. ( 2008 ) , 337 , a1984 . DOI:10.1136/bmj.a1984 . Objective To explore the hypothesis that medically attended head injury in young children may be causal in the later development of attention deficit hyperactivity disorder.Design Retrospective cohort study.Setting Health improvement network database (1988–2003), a longitudinal UK general practice dataset.Participants All children registered in the database from birth until their 10th birthday.Main outcome measures Risk of a child with a head injury before age 2 developing attention deficit hyperactivity disorder before age 10 compared with children with a burn injury before age 2 and children with neither a burn nor a head injury.Results Of the 62 088 children who comprised the cohort, 2782 (4.5%) had a head injury and 1116 (1.8%) had a burn injury. The risk of diagnosis of attention deficit hyperactivity disorder before 10 years of age after adjustment for sex, prematurity, socio‐economic status and practice identification number was similar in the head injury (relative risk 1.9, 95% confidence interval 1.5 to 2.5) and burn injury groups (1.7, 1.2 to 2.5) compared with all other children.Discussion Medically attended head injury before 2 years of age does not seem to be causal in the development of attention deficit hyperactivity disorder. Medically attended injury before 2 years of age may be a marker for subsequent diagnosis of attention deficit hyperactivity disorder.

Early head injury and attention deficit hyperactivity disorder: retrospective cohort study

Objective To explore the hypothesis that medically attended head injury in young children may be causal in the later development of attention deficit hyperactivity disorder.Design Retrospective cohort study.Setting Health improvement...

A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder

The norepinephrine transporter critically regulates both neurotransmission and homeostasis of norepinephrine in the nervous system. In this study, we report a previously uncharacterized and common A/T polymorphism at -3081 upstream of the transcription initiation site of the human norepinephrine transporter gene [solute carrier family 6, member 2 (SLC6A2)]. Using both homologous and heterologous promoter-reporter constructs, we found that the -3081(T) allele significantly decreases promoter function compared with the A allele. Interestingly, this T allele creates a new palindromic E2-box motif that interacts with Slug and Scratch, neural-expressed transcriptional repressors binding to the E2-box motif. We also found that both Slug and Scratch repress the SLC6A2 promoter activity only when it contains the T allele. Finally, we observed a significant association between the -3081(A/T) polymorphism and attention-deficit hyperactivity disorder (ADHD), suggesting that anomalous transcription factor-based repression of SLC6A2 may increase risk for the development of attention-deficit hyperactivity disorder and other neuropsychiatric diseases.

The marriage‐related risk factors during maternal pregnancy in children with attention‐deficit hyperactivity disorder

The purpose of this research was to investigate the relationship between marriage-related risk factors during maternal pregnancy and subsequent development of attention-deficit hyperactivity disorder (ADHD). The research design was a retrospective case-control study. The case group included 60 patients that fulfilled the ADHD criteria of Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The controls were normal children randomly selected and matched for their sex and age. Their biological mothers completed a questionnaire about marital adaptation, marital satisfaction and the incidence of stressful life events during pregnancy. The results showed that the incidence of positive life events, marital adaptation and marital satisfaction during maternal pregnancy was significantly lower in the case group, and conditional logistic regression analysis showed that marital adaptation during pregnancy and pregnancy before marriage were important risk factors for ADHD. Negative emotion during maternal pregnancy may be an important risk factor for ADHD.

Gene for the serotonin transporter and ADHD: No association with two functional polymorphisms

Evidence from both human and animal studies implicates the serotonergic system in the development of attention-deficit hyperactivity disorder (ADHD) including positive association studies for several key serotonergic genes. The serotonin transporter (HTT) regulates the availability of serotonin by reuptake of the neurotransmitter from the synaptic cleft. Several studies have reported an association of this gene to ADHD, specifically the long variant of a common insertion/deletion polymorphism located in the promoter of this gene that results in increased transcription and higher HTT expression. An additional study found no evidence for an association with this polymorphism. Recently, an A/G single nucleotide polymorphism (SNP) was found within the promoter polymorphism with functional studies indicating that the long variant containing the G allele at this site behaves like the short variant. This previously unidentified functional change may have confounded earlier association studies. We investigated the relationship of several variants to ADHD: the promoter polymorphisms, SNP in the 3' untranslated region (3'UTR) with a reported association to ADHD and a rare, non-synonymous coding SNP. These polymorphisms were genotyped in 209 ADHD families identified through an affected proband. We did not find evidence for an association of these polymorphisms, or haplotypes of these polymorphisms, to ADHD in this sample.

Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD

Genetic and pharmacological studies have emphasised the role of serotonin 5-hydroxytryptamine (5-HT) as a possible etiologic factor in the development of attention-deficit hyperactivity disorder (ADHD). Tryptophan hydroxylase (TPH) is a rate-limiting enzyme in the biosynthesis of serotonin from tryptophan. Originally, the TPH gene was thought to be widely expressed, but a second form of TPH, TPH2, was recently identified and the TPH2 gene was found to be solely expressed in the brain. We examined eight single nucleotide polymorphisms (SNP) in the TPH2 gene for association with ADHD in 179 Irish nuclear families. Transmission disequilibrium test analysis revealed significant association between the T allele of marker rs1843809 with the disorder (chi2=12.2, P=0.0006, OR=2.36). Stratifying data by the sex of the transmitting parent showed that this association was enhanced when paternal transmission was considered (OR=3.7). In addition, several haplotypes (all including the associated marker) were associated with ADHD. These preliminary findings suggest that TPH2 is a susceptibility locus for ADHD. Further confirmation, preferably from different ethnic groups, is required to firmly implicate TPH2 in the pathophysiology of ADHD.

ASSOCIATION ANALYSIS OF SEROTONIN TRANSPORTER PROMOTER GENE POLYMORPHISM WITH ADHD AND RELATED SYMPTOMATOLOGY

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders. Genetic factors contribute to the underlying liability to develop attention deficit hyperactivity disorder. Several investigations have reported associations between ADHD and serotonin transporter promoter polymorphisms, but the results have been inconsistent. The present study did not find significant association between ADHD and serotonin transporter promoter polymorphisms, but did find an effect of serotonin transporter promoter polymorphisms on some ADHD symptomatology. Patients homozygous for the short allele showed more Withdrawn or Somatic complaint scores than subjects with the long allele.

Application of a data-mining method based on Bayesian networks to lesion-deficit analysis

Although lesion-deficit analysis (LDA) has provided extensive information about structure-function associations in the human brain, LDA has suffered from the difficulties inherent to the analysis of spatial data, i.e., there are many more variables than subjects, and data may be difficult to model using standard distributions, such as the normal distribution. We herein describe a Bayesian method for LDA; this method is based on data-mining techniques that employ Bayesian networks to represent structure-function associations. These methods are computationally tractable, and can represent complex, nonlinear structure-function associations. When applied to the evaluation of data obtained from a study of the psychiatric sequelae of traumatic brain injury in children, this method generates a Bayesian network that demonstrates complex, nonlinear associations among lesions in the left caudate, right globus pallidus, right side of the corpus callosum, right caudate, and left thalamus, and subsequent development of attention-deficit hyperactivity disorder, confirming and extending our previous statistical analysis of these data. Furthermore, analysis of simulated data indicates that methods based on Bayesian networks may be more sensitive and specific for detecting associations among categorical variables than methods based on chi-square and Fisher exact statistics.

Lack of association between the tryptophan hydroxylase gene A218C polymorphism and attention-deficit hyperactivity disorder in Chinese Han population.

Previous studies have suggested that the serotonergic (5-HT) system might be involved in the development of Attention-deficit hyperactivity disorder (ADHD). ADHD is frequently characterized by aggressive and impulsive behavior, a major symptom associated with reduction in serotonergic function. The tryptophan hydroxylase (TPH) gene is a reasonable candidate for ADHD because it encodes the rate-limiting enzyme in the process of 5-HT biosynthesis. In this study, we examined the relationship between the A218C polymorphism in TPH gene and ADHD. Sixty-nine ADHD patients and their biological parents were investigated. The A218C polymorphism in intron 7 of TPH gene was detected by PCR-RFLP method. No allele or genotype concerned with this A218C polymorphism was found to be associated with ADHD when analyzed with the haplotype relative risk method. Therefore, our data indicate that the TPH gene A218C polymorphism may not be a susceptibility factor of ADHD in the Chinese Han population.

Classification of brain image data using measures of distributional distance

Methods: We developed a method for classifying spatial distributions of regions of interest (ROIs) in brain images. The proposed method is based on computing the Mahalanobis distance between a new sample and datasets related to each considered class (condition). We predict that the new sample belongs to the class corresponding to the dataset that has the smaller Mahalanobis distance from the given subject. We also compared this method to an alternative classification method based on computing the Kullback-Leibler probabilistic distance between distributions estimated through a non-parametric procedure. After the normalization of image data to a common coordinate system, the proposed method can be applied to both structural and functional brain imaging. Here, we applied it to lesion-deficit analysis and MR datasets, performing classification of realistic brain lesion distributions generated using a lesion-deficit simulator [l]. The spatial statistical model of lesion distributions conformed to the Frontal Lobe Injury in Childhood (FLIC) study [2]. The subjects were classified into two classes according to the subsequent development of attention-deficit hyperactivity disorder (ADHD) after closed head injury. Given a new subject with a set of lesioned voxels, the goal was to determine the more plausible class. In experiments, we varied both the size of datasets for the classes and the number of lesioned voxels belonging to a new subject. For each combination of these parameters, we performed the experiments and monitored the classification performance, measuring accuracy rate as the ratio of the number of hits and the total number of rounds. Results: Experiments showed that the proposed method based on Mahalonobis distance could provide a reliable and accurate classification between the subjects who did and did not develop ADHD confirming earlier observation of disparity between these two distributions [3]. Prediction accuracy of 90% or better can be achieved with sufficiently high number of lesioned voxels for examined subject. The method based on Kullback-Leibler distance was inferior to the “Mahalanobis” approach, due to difficulties in estimation of a new subject lesion distribution. Conclusions: The proposed method has been shown capable of providing accurate classification of the subjects regarding the development of ADHD. In addition to lesion-deficit analysis, the proposed approach can be potentially applied to task-activation analysis and classification of 3D-probabilistic activation maps.

Discriminación de factores genéticos en el déficit de atención

In order to elucidate the genetic and environmental components involved in the susceptibility to develop attention deficit hyperactivity disorder (ADHD), a complex segregation analysis on nuclear families (n = 53) ascertained from affected probands belonging to Medellín, in the Antioquian State, Colombia, was performed. Models of cohort effect (non-inheritance), multifactorial, recessive major gene, non-major gene component and non-transmission of major gene were rejected. Contrarily, dominant and codominant major gene models and non-multifactorial component could not be rejected. Thus, the better model fitting the data was that of the major gene (dominant/codominant). This major gene explains more than 99.99% of the ADHD phenotypic variance (value of heritability in the mixed model equal to 0.007%), which permit to assume a low aport of the environmental component to the phenotype ADHD. Gene frequency of the major gene was 3% in the general population of Antioquia and its penetrance was closed to 30%. Some cautions and aspects related to the bias of the interview and diagnosis of the parents are discussed.