A Pilot Twin Study of Psychological Measures of Attention Deficit Hyperactivity Disorder Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder Dissecting the attention deficit hyperactivity disorder (ADHD) phenotype: Sustained attention, response variability and spatial attentional asymmetries in relation to dopamine transporter (DAT1) genotype [The prevalence of attention-deficit/hyperactivity disorder (ADHD) among children and adolescents in Germany. Initial results from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. Absence of the 7‐repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls The effect of polyphenolic extract from pine bark, Pycnogenol® on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD) A longitudinal examination of neuropsychological and clinical functioning in boys with attention deficit hyperactivity disorder (ADHD): improvements in executive functioning do not explain clinical improvement. Executive functioning in children with attention-deficit/hyperactivity disorder: combined type with and without a stimulant medication history. The effectiveness of methylphenidate in the management of Attention Deficit Hyperactivity Disorder (ADHD) in people with intellectual disabilities: A systematic review. Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status. Does EEG-neurofeedback improve neurocognitive functioning in children with attention-deficit/hyperactivity disorder? A systematic review and a double-blind placebo-controlled study. Impulsiveness as a timing disturbance: neurocognitive abnormalities in attention-deficit hyperactivity disorder during temporal processes and normalization with methylphenidate Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children. Depression, anxiety and obsessive-compulsive symptoms and quality of life in children with attention-deficit hyperactivity disorder (ADHD) during three-month methylphenidate treatment Developmental course of attention deficit hyperactivity disorder and its predictors.
There has been much interest in the genetics of attention deficit hyperactivity disorder and molecular genetic studies are now underway . The success of genetic studies will depend on how well the phenotype is defined . Twin studies using parent and teacher rated question naires or interviews all appear to yield highly heritable measures . Nevertheless , there is evidence to suggest that parent measures are subject to rater bias . Consequently there has been much interest in obtaining more objective measures of related traits such as attention span and impulsiveness using , computerised neuropsychological tasks . However there have been few twin studies examining the genetic contribution to these neuropsychological measures . The present study aims to investigate whether performance on the  Matching Familiar Figures Test ( MFFT ) and Continuous Performance Task ( CPT )  is genetically influenced in childhood . 20 monozygotic ( MZ ) and 20 dizygotic ( DZ ) twin pairs were r and omly selected from the Greater Manchester Twin Register . Preliminary data suggest that MZ twins perform more similarly than DZ twins on the MFFT , but not the CPT . Future work needs to examine whether other neuropsychological measures commonly used in research on ADHD are genetically influenced using larger twin sample Attention-deficit/hyperactivity disorder ( ADHD ) is the most common behavioral disorder in childhood with substantial heritability . Pharmacological and molecular genetic studies as well as characterization of animal models have implicated serotonergic dysfunction in the pathophysiology of ADHD . Here , we investigated the effect of polymorphic variants in the gene of the tryptophan hydroxylase-2 ( TPH2 ) , the rate-limiting enzyme of serotonin ( 5-HT ) synthesis in the brain , in children and adolescents with ADHD . We analyzed three single nucleotide polymorphisms ( SNPs ) in and downstream of the transcriptional control region of the TPH2 gene in 103 families with 225 affected children .  Allelic association in families with more than one affected child was assessed using the pedigree disequilibrium test . Preferential transmissions were detected for the two SNPs in TPH2 's regulatory region ( rs4570625 , P=0.049 ; rs11178997 , P=0.034 ) , but not for the third SNP in intron 2 ( rs4565946 , P=0.3517 ) . Haplotype analysis revealed a strong trend of association between the regulatory region SNPs ( rs4570625 , rs11178997 ) and ADHD ( P=0.064 ) . Our results link potentially functional TPH2 variations to the pathophysiology of ADHD , and further support the relevance of 5-HT in disorders related to altered motor activity and cognitive processes ADHD is a childhood-onset behavioural disorder with a heterogeneous profile of neuropsychological impairment . Neuropsychological heterogeneity may , in part , reflect underlying genetic differences . Here we examined sustained attention , response variability and spatial attentional asymmetries in a sample of children and adolescents with ADHD ( n=22 ) in relation to dopamine transporter genotype ( DAT1 ) and also controls ( n=20 ) . Participants performed the sustained attention to response task ( SART ) ( testing sustained attention and response variability ) and the greyscales task ( a perceptual measure of attentional bias ) . The latter has previously been shown to yield a robust leftward attentional asymmetry in healthy subjects . The 10-repeat allele of the DAT1 gene has been associated with ADHD in a number of studies and appears to have biological significance . The ADHD group was sub-divided into those individuals with two copies of the " high-risk " 10-repeat allele ( high-risk DAT1 ) versus those with one or no copies of this allele ( low-risk DAT1 ) . The high-risk DAT1 ADHD group displayed greater response variability on the SART than either the low-risk DAT1 group or healthy controls , whereas the latter two groups did not differ . Further , the high-risk DAT1 group showed an attenuated spatial asymmetry , relative to the low-risk DAT1 ADHD group , who showed the typical leftward attentional asymmetry . Our results suggest that the 10-repeat DAT1 allele may mediate neuropsychological impairment in ADHD . The application of molecular genetics may help to define neuropsychological impaired subgroups of ADHD The cardinal symptoms of attention-deficit/hyperactivity disorder ( ADHD ) are inattention , hyperactivity and impulsivity . Etiologically , ADHD is mainly put down to genetic causes ; it entails a considerable range of psychosocial problems for those affected and their social environment . The parents of a total of 7,569 boys ( B ) and 7,267 girls ( G ) aged 3 - 17 who took part in the German Health Interview and Examination Survey for Children and Adolescents ( KiGGS ) answered a self-administered question naire including an ADHD diagnosis question and the  Strengths and Difficulties Question naire ( SDQ )  . In addition behavioural observations of 7,919 children ( aged 3 - 11 ) were carried out during the medical and physical tests . Participants whose parents reported that they had ever been given an ADHD diagnosis by a doctor or psychologist were classified as ADHD cases . Participants were classified as suspected cases of ADHD if they had a value of > or = 7 on the SDQ inattention/hyperactivity scale . ADHD had ever been diagnosed in 4.8 % of the children and adolescents altogether ( B : 7.7 % , G : 1.8 % ) . Another 4.9 % of the participants can be considered as suspected cases . Already 1.8 % of the preschoolers had been given an ADHD diagnosis . At primary school age ( 7 - 10 years old ) the frequency of diagnosis rises sharply . At age 11 - 17 , ADHD had ever been diagnosed in 1 in 10 boys and 1 in 43 girls . ADHD had been diagnosed significantly more frequently among participants of low socio-economic status ( SES ) than among participants of high SES . A diagnosis of ADHD is reported less often for migrants , they rank more frequently among the suspected cases . The discrepancy between confirmed and suspected cases of ADHD among migrants may point to lower diagnosis rates or lower utilization of medical services . The short- and long-term medical , social and health-economic effects of ADHD illustrate the major public health relevance of the disorder . As for prevention , the high share of genetic factors in ADHD etiology primarily suggests secondary prevention ( early support and early diagnosis ) and tertiary prevention measures . Further analysis of the KiGGS data could prospect ively identify risk groups more precisely and refine preventional approaches Many genetic studies have demonstrated an association between the 7‐repeat ( 7r ) allele of a 48‐base pair variable number of t and em repeats ( VNTR ) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder ( ADHD ) . Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD . We investigated the performance of 128 children with and without ADHD on the Fixed and R and om versions of the Sustained Attention to Response Task ( SART ) . We employed time‐series analyses of reaction‐time data to allow a fine‐grained analysis of reaction time variability , a c and i date endophenotype for ADHD . Children were grouped into either the 7r‐present group ( possessing at least one copy of the 7r allele ) or the 7r‐absent group . The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment‐to‐moment variability than the control group , but no effect of genotype was found on these measures . Children with ADHD without the 7r allele made significantly more omission errors , were significantly more variable in the slow frequency domain and showed less sensitivity to the signal ( d ' ) than those children with ADHD the 7r and control children with or without the 7r . These results highlight the utility of time‐series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR . Absence of the 7‐repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance . © 2008 Wiley‐Liss , Abstract Attention deficit hyperactivity disorder ( ADHD ) belongs to the neurodevelopmental disorders characterized by impulsivity , distractibility and hyperactivity . In the pathogenesis of ADHD genetic and non-genetic factors play an important role . It is assumed that one of non-genetic factors should be oxidative stress . Pycnogenol ® , an extract from the pine bark , consists of bioflavonoids , catechins , procyanidins and phenolic acids . Pycnogenol ® acts as powerful antioxidant , chelating agent ; it stimulates the activities of some enzymes , like SOD , eNOS , and exhibits other biological activities . Aim : The aim of this r and omized , double-blind , placebo-controlled trial was to investigate the influence of administered Pycnogenol ® or placebo on the level of reduced ( GSH ) and oxidized ( GSSG ) glutathione in children suffering from ADHD and on total antioxidant status ( TAS ) . This is the first investigation of the redox glutathione state in relation to ADHD . Results : One month of Pycnogenol ® administration ( 1 mg/kg body weight/day ) caused a significant decrease in GSSG and a highly significant increase in GSH levels as well as improvement of GSH/GSSG ratio in comparison to a group of patients taking a  placebo . TAS in children with ADHD was decreased in comparison with reference values . Pycnogenol ® administration normalizes TAS of ADHD children BACKGROUND Attention deficit hyperactivity disorder ( ADHD ) often , but not always , persists into adulthood . Investigations of the associations between clinical and biological markers of persistence can shed light on causal pathways . It has been proposed that compensatory improvements in executive neuropsychological functioning are associated with clinical improvements . This is the first study to test this hypothesis prospect ively . METHOD The clinical and neuropsychological functioning of 17 boys with ADHD ( mean age 10.45 years at time 1 ; 14.65 years at time 2 ) and 17 typically developing ( TYP ) boys ( mean age 10.39 years at time 1 ; 14.47 years at time 2 ) was tested on two occasions , 4 years apart . This was done using a battery of st and ardized neuropsychological tests that included tasks with high and low executive dem and s. RESULTS Clinical improvements were observed over time . Neuropsychological performance improvements were also evident , with ADHD boys developing with a similar pattern to TYP boys , but with a developmental lag . Whilst there was an association between reduced symptoms and superior performance at retest for one task with a high executive dem and ( spatial working memory ) , this was not seen with two further high executive dem and tasks [ Stockings of Cambridge and intra-dimensional extra-dimensional ( ID/ED ) set shifting ] . Also , there was no association between change in executive functioning and change in symptoms . Baseline performance on the ID/ED set-shifting task predicted better clinical outcome . Only change in performance on the low executive dem and delayed matching-to- sample task predicted better clinical outcome . CONCLUSIONS These data highlight the importance of longitudinal measurements of cognition , symptoms and treatment response over time in children and adolescents with ADHD Behavioral and neuropsychological functioning in unmedicated children with attention-deficit/hyperactivity disorder ( ADHD ) who have a history of medication treatment ( Rx ) versus those who are treatment naïve ( TN ) has , to our knowledge , not been previously studied . Ninety-four children in four groups ( ADHD/Rx , ADHD/TN , learning disabilities [ LD ] , and controls ) were evaluated , while unmedicated , on measures of achievement , neuropsychological functioning , and behavior . The ADHD/Rx group performed significantly better than the TN group on writing , Stroop interference , and measures of attention , and performed as well as the control group on executive functioning , verbal working memory , and academics . Behaviorally , the ADHD groups showed more difficulty with mood and externalizing behaviors compared with the LD and control groups , with the ADHD/TN performing the most poorly . Findings suggest that the ADHD/Rx group shows better executive and academic functioning even when unmedicated BACKGROUND The effectiveness of psychostimulants , primarily methylpheni date ( MPH ) , in the treatment of Attention Deficit Hyperactivity Disorder ( ADHD ) in the general population of typically growing children and adolescents is well established through many R and omised Controlled Trials ( RCTs ) . AIMS AND METHODS We carried out a systematic review of all the RCTs in people with intellectual disabilities ( ID ) that assessed effectiveness of MPH on the core ADHD symptoms . OUTCOMES AND RESULTS We included 15 papers from 13 studies that were all on children and adolescents with ID ( 315 participants were on MPH and placebo respectively ) , 12 of which used a cross over design , and one used a parallel design . On average around 40 - 50 % responded to MPH in the ID group whereas around 70 - 80 % response rate is reported among the non-ID children . Because of the heterogeneity of the outcome data it was not possible to carry out a meta- analysis . Significant adverse events included sleep difficulties and poor appetite along with weight loss and also irritability , social withdrawal and increased motor activities including tic . CONCLUSIONS AND IMPLEMENTATION On the basis of the poor quality evidence that is available , it seems that MPH may be effective in some but not all children and adolescents with ID and ADHD OBJECTIVE The paucity of data concerning the long-term natural history of attention-deficit hyperactivity disorder ( ADHD ) , a common childhood psychiatric disorder , prompted a longitudinal study to investigate the adult sequelae of the childhood disorder . DESIGN Prospect i ve study , follow-up intervals ranging from 13 to 19 years ( mean , 16 years ) , with blind systematic clinical assessment s. SUBJECTS Ninety-one white males ( mean age , 26 years ) , representing 88 % of a cohort systematic ally diagnosed as hyperactive in childhood , and 95 ( 95 % ) of comparison cases of similar race , gender , age , whose teachers had voiced no complaints about their school behavior in childhood . RESULTS Prob and s had significantly higher rates than comparisons of ADHD symptoms ( 11 % vs 1 % ) , antisocial personality disorders ( 18 % vs 2 % ) , and drug abuse disorders ( 16 % vs 4 % ) . Significant comorbidity occurred between antisocial and drug disorders . Educational and occupational achievements were significantly compromised in the prob and s. These disadvantages were independent of psychiatric status . We did not find increased rates of affective or anxiety disorders in the prob and s. CONCLUSIONS Childhood ADHD predicts specific adult psychiatric disorders , namely antisocial and drug abuse disorders . In the adolescent outcome of this cohort , we found that these disturbances were dependent on the continuation of ADHD symptoms . In contrast , in adulthood , antisocial and drug disorders appeared , in part , independent of sustained ADHD . In addition , regardless of psychiatric status , ADHD placed children at relative risk for educational and vocational disadvantage . The results do not support a relationship between childhood ADHD and adult mood or anxiety disorders BACKGROUND The number of placebo-controlled r and omized studies relating to EEG-neurofeedback and its effect on neurocognition in attention-deficient/hyperactivity disorder ( ADHD ) is limited . For this reason , a double blind , r and omized , placebo-controlled study was design ed to assess the effects of  EEG-neurofeedback  on neurocognitive functioning in children with ADHD , and a systematic review on this topic was performed . METHODS Forty-one children ( 8 - 15 years ) with a DSM-IV-TR diagnosis of ADHD were r and omly allocated to EEG-neurofeedback or placebo-neurofeedback treatment for 30 sessions , twice a week . Children were stratified by age , electrophysiological state of arousal , and medication use . Neurocognitive tests of attention , executive functioning , working memory , and time processing were administered before and after treatment . Research ers , teachers , children and their parents , with the exception of the neurofeedback-therapist , were all blind to treatment assignment . Outcome measures were the changes in neurocognitive performance before and after treatment . CLINICAL TRIAL REGISTRATION www . clinical trials.gov : NCT00723684 . RESULTS No significant treatment effect on any of the neurocognitive variables was found . A systematic review of the current literature also did not find any systematic beneficial effect of EEG-neurofeedback on neurocognitive functioning . CONCLUSION Overall , the existing literature and this study fail to support any benefit of neurofeedback on neurocognitive functioning in ADHD , possibly due to small sample sizes and other study limitations We argue that impulsiveness is characterized by compromised timing functions such as premature motor timing , decreased tolerance to delays , poor temporal foresight and steeper temporal discounting . A model illustration for the association between impulsiveness and timing deficits is the impulsiveness disorder of attention-deficit hyperactivity disorder ( ADHD ) . Children with ADHD have deficits in timing processes of several temporal domains and the neural substrates of these compromised timing functions are strikingly similar to the neuropathology of ADHD . We review our published and present novel functional magnetic resonance imaging data to demonstrate that ADHD children show dysfunctions in key timing regions of prefrontal , cingulate , striatal and cerebellar location during temporal processes of several time domains including time discrimination of milliseconds , motor timing to seconds and temporal discounting of longer time intervals . Given that impulsiveness , timing abnormalities and more specifically ADHD have been related to dopamine dysregulation , we tested for and demonstrated a normalization effect of all brain dysfunctions in ADHD children during time discrimination with the dopamine agonist and treatment of choice , methylpheni date . This review together with the new empirical findings demonstrates that neurocognitive dysfunctions in temporal processes are crucial to the impulsiveness disorder of ADHD and provides first evidence for normalization with a dopamine reuptake inhibitor BACKGROUND Executive function deficits have been reported repeatedly in children with Attention Deficit Hyperactivity Disorder ( ADHD ) .  Stimulant medication has been shown to be effective in improving cognitive performance on most executive function tasks , but neuropsychological tests of executive function in this population have yielded inconsistent results . Method ological limitations may explain these inconsistencies . This study aim ed to measure executive function in medicated and non-medicated children with ADHD by using a computerized battery , the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) , which is sensitive to executive function deficits in older patients with frontostriatal neurological impairments . METHODS Executive function was assessed in 30 children with ADHD : 15 were stimulant medication naive and 15 were treated with stimulant medication .  These two groups were compared to 15 age , sex and IQ matched controls . RESULTS The unmedicated children with ADHD displayed specific cognitive impairments on executive function tasks of spatial short-term memory , spatial working memory , set-shifting ability and planning ability . Impairments were also seen on spatial recognition memory and delayed matching to sample , while pattern recognition memory remained intact . The medicated children with ADHD were not impaired on any of the above executive function tasks except for deficits in spatial recognition memory . CONCLUSIONS ADHD is associated with deficits in executive function .  Stimulant medication is associated with better executive function performance . Prospect i ve follow-up studies are required to examine these effects The current study was design ed to investigate the changes that occur in depression , anxiety , obsessive — compulsive symptoms and health-related quality of life during methylpheni date ( MPH ) treatment in children with attention-deficit hyperactivity disorder ( ADHD ) . Forty-five treatment naive children with ADHD , aged 8—14 , were assessed based on self , parent and teacher reports at the baseline and at the end of the first and third month of MPH treatment regarding changes in inattention , hyperactivity , impulsivity , depression , anxiety and obsessive — compulsive symptoms . Changes in the quality of life were also noted . Repeated measures of analysis of variance ( ANOVA ) tests with Bonferroni corrections were conducted in order to evaluate the data . Symptoms of inattention , hyperactivity and impulsivity were significantly reduced ( p < 0.017 ) following a three-month MPH treatment . There were significant decreases in depression ( p = 0.004 ) , trait anxiety ( p = 0.000 ) and checking compulsion symptom scores ( p = 0.001 ) . Moreover , parents reported significant improvements in psychosocial ( p = 0.001 ) and total scores ( p = 0.009 ) of quality of life , despite no change in physical health scores ( p > 0.05 ) . Children ’s ratings of quality of life measures showed no significant changes in physical health and psychosocial scores ( p > 0.05 ) , while total scores significantly improved ( p = 0.001 ) after the treatment . Over a three-month MPH treatment , depression , trait anxiety and checking compulsion symptoms decreased and quality of life seemed to improve along with those of inattention , hyperactivity and impulsivity OBJECTIVE To outline the key features of the developmental progression of ADHD and to consider the most prominent influences on its developmental course and outcomes . METHODS This is a selective review focusing primarily on prospect i ve follow-up studies . Relevant publications were selected by search ing the MEDLINE and PubMed data bases using keywords : ADHD , development , preschool , adolescent , adult , follow up , outcome , long-term , predictors , and treatment . Reference lists of the result ing articles were then review ed for additional publications . RESULTS Presentation of ADHD and associated impairments evolve across development , as do outcome predictors . In early development , in addition to genetics , some forms of prenatal adversity increase the risk for ADHD . In preschool years , symptom severity , cognitive function , and family factors become significant predictors of school age outcomes . These continue to predict long-term outcomes in school aged children , and comorbidity emerges as another significant long-term outcome predictor at this stage . CONCLUSIONS Presentation of ADHD and risk factors for later adversity evolve across development , which calls for developmentally-informed clinical practice
Association of high reaction time variability with the 7-repeat allele absence appears to be the most consistent result and seems to be specific to ADHD .
Speed of processing , set-shifting and cognitive impulsiveness were less frequently investigated but seem to be altered in the 7-repeat allele carriers .
High reaction time variability seems to be the most replicated cognitive marker associated with the 10-repeat homozygosity .
BACKGROUND We review ed systematic ally the results of genetic studies investigating associations between putative susceptibility genes for attention-deficit hyperactivity disorder ( ADHD ) and neuropsychological traits relevant for this disorder .