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. Adult outcome of attention-deficit/hyperactivity disorder: a controlled 16-year follow-up study. Sex Differences in Effectiveness of Extended-Release Stimulant Medication among Adolescents with Attention-Deficit/Hyperactivity Disorder PREVALENCE ESTIMATIONS OF ATTENTION-DEFICIT/HYPERACTIVITY DISORDER: DIFFERENTIAL DIAGNOSES AND COMORBIDITIES IN A COLOMBIAN SAMPLE Erratum to: Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review Association and linkage of alpha-2A adrenergic receptor gene polymorphisms with childhood ADHD. Acetyl-L-carnitine (ALC) in attention-deficit/hyperactivity disorder: a multi-site, placebo-controlled pilot trial. The homozygosity for 10-repeat allele at dopamine transporter gene and dopamine transporter density in Korean children with attention deficit hyperactivity disorder: relating to treatment response to methylphenidate
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 OBJECTIVE To estimate the risks for psychopathology and functional impairments in adulthood among a longitudinal sample of youth with and without attention-deficit/hyperactivity disorder ( ADHD ) diagnosed in childhood . METHOD This was a case-controlled , 16-year ( 15 - 19 years ) prospect i ve follow-up study of ADHD . 140 boys with and 120 without DSM-III-R ADHD were recruited from pediatric and psychiatric setting s. The main outcome measures were  structured diagnostic interviews and measures of psychosocial , educational , and neuropsychological functioning . Data were collected from 1988 to 2006 . RESULTS At the 16-year follow-up , subjects with ADHD continued to significantly differ from controls in lifetime rates of antisocial , mood , anxiety , and addictive disorders , but with the exception of a higher interval prevalence of anxiety disorders ( 20 % vs 8 % ; z = 2.32 , P = .02 ) and smoking dependence ( 27 % vs 11 % ; z = 2.30 , P = .02 ) , the incidence of individual disorders in the 6-year interval between the current and prior follow-up did not differ significantly from controls . At follow-up , the ADHD subjects compared with controls were significantly ( P < .05 ) more impaired in psychosocial , educational , and neuropsychological functioning , differences that could not be accounted for by other active psychopathology . CONCLUSIONS These long-term prospect i ve findings provide further evidence for the high morbidity associated with ADHD across the life cycle , stressing the importance of early recognition of this disorder for prevention and early intervention strategies . These findings also indicate that , in adulthood , ADHD confers significant risks for impairment that can not be accounted for by other psychopathology This study examined whether adolescent females with attention-deficit/hyperactivity disorder ( ADHD ) are differentially responsive than their male counterparts to extended-release stimulant medications . This investigation may bear special importance for an adolescent ( as opposed to child ) population , because hormonal and metabolism differences between sexes are most likely to emerge at this time . Male ( n = 19 ) and female ( n = 16 ) adolescents , ages 16–19 with ADHD , participated in a r and omized , double-blind crossover study evaluating the effectiveness of osmotic-release methylpheni date , extended release amphetamine salts , placebo , and routine limited medication regimen . Medication efficacy was evaluated using ADHD symptom ratings from adolescent self-report and parent report , along with objective measures of inattention and hyperactivity/impulsivity during driving performance and neuropsychological tasks . Males and females were largely equivalent in impairment , and medication was similarly effective in reducing symptoms . No interactions were found between sex and medication on any measure of effectiveness or side effects . This finding suggests that the efficacy and tolerability of extended-release stimulant medications is equivalent for male and female adolescents with ADHD The aim of this article was to analyze the prevalence of Attention Deficit/ Hyperactivity Disorder ( ADHD ) in Colombian Paisa children and adolescents . A r and omized sample of 4- to 17-year-old children and adolescents--176 males and 154 females -- was selected from schools in Manizales , Colombia . The diagnosis of ADHD was obtained using a semistructured psychiatric and neurological interview , medical histories revision , and neurological or psychiatric evaluations .  Several rating scales and a neuropsychological assessment  were administered in order to confirm the diagnosis . Children with Full Scale Intelligence Quotient ( FSIQ ) between 71 and 84 were recorded as having Borderline Intellectual Functioning ( BIF ) , and those with a history of mild motor retardation , and /or Performance Intelligence Quotient ( PIQ ) lower than 71 , were recorded as having a Developmental Coordination disorder ( DCD ) , after confirmation by neurological and neuropsychological examinations . BIF and DCD children were excluded from the ADHD group . Total prevalence of ADHD adjusted by sex was 16.4 % ( males 19.8 % and females 12.3 % ) . Prevalence of clean ADHD cases was 11.5 % , distrib uted as follows : combined type , 6.4 % ; inattentive , 4.8 % ; and hyperactive-impulsive , 0.3 % . Distribution by sex was as follows : males , 14.8 % ; and females , 7.7 % ; with an odds ratio of 2.1 ( 95 % CI : 1 - 4.5 , h 2 = 4.0 , p < . 05 ) . Clean prevalence of ADHD adjusted by equal sex distribution was 11.3 % . Prevalence of BIF was 5.8 % , DCD 3.0 % , and mild mental retardation 3.9 % . Prevalence of ADHD did not show differences by socioeconomic status ( SES ) , in contrast to mild mental retardation in which BIF and DCD were significantly more frequent in the lower SES Background : The stimulant methylpheni date ( MPH ) has been a mainstay of treatment for attention-deficit/hyperactivity disorder ( ADHD ) for many years . Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations , a new generation of long-acting MPH formulations has emerged . Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy ; however , to date , relatively few head-to-head studies have been performed . The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection . Methods : A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms : attention deficit disorder with hyperactivity/drug therapy ; methylpheni date /therapeutic use and All Fields : Concerta ; Ritalin LA ; OROS and ADHD ; Medikinet ; Equasym XL and ADHD ; long-acting methylpheni date ; Diffucaps and ADHD ; SODAS and methylpheni date . No filters were applied and no language , publication date or publication status limitations were imposed . Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age ; non- systematic review articles and unpublished data were not included . Results : Of 15,295 references returned in the literature search and screened by title , 34 articles were identified for inclusion : nine articles from pharmacokinetic studies ( nine studies ) ; nine articles from laboratory school studies ( six studies ) ; two articles from r and omized controlled trials ( two studies ) ; three articles from switching studies ( two studies ) and three articles from one observational study . Conclusions : Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available . At a group level , efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation . No formulation is clearly superior to another ; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment . For patients achieving suboptimal symptom control , switching long-acting MPH formulations may be beneficial . When switching formulations , it is usually appropriate to titrate the immediate-release component of the formulation ; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components . Further studies are necessary to provide guidance in clinical practice , particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response We conducted a review of systematic review s ( SRs ) and r and omized-controlled trials ( RCTs ) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders . Five data bases were systematic ally search ed ( 2006—August 2018 ) ; 4 SRs ( of 11 RCTs ) and 14 RCTs ( 1629 participants ) were included . Diagnoses were : dementia , cannabis and opioid dependence , psychoses/schizophrenia , general social anxiety , posttraumatic stress disorder , anorexia nervosa , attention-deficit hyperactivity disorder , and Tourette`s disorder . Outcome variables were too heterogeneous to conduct a meta- analysis . A narrative synthesis method was applied . The study quality was assessed using the risk-of-bias tool and SIGN-checklists . THC- and CBD-based medicines , given as adjunct to pharmaco- and psychotherapy , were associated with improvements of several symptoms of mental disorders , but not with remission . Side effects occurred , but severe adverse effects were mentioned in single cases only . In order to provide reliable treatment recommendations , more and larger RCTs with follow-up assessment s , consistent outcome measures and active comparisons are needed Attention-deficit hyperactivity disorder ( ADHD ) is a heritable disorder , prevalent from childhood through adulthood . Although the noradrenergic ( NA ) system is thought to mediate a portion of the pathophysiology of ADHD , genes in this pathway have not been investigated as frequently as those in the dopaminergic system . Previous association studies of one c and i date gene in the NA system , ADRA2A , showed inconsistent results with regard to an MspI polymorphism . In the current study , two nearby single-nucleotide polymorphisms , which define HhaI and DraI restriction fragment length polymorphisms , were also genotyped and were in significant linkage disequilibrium with the MspI RFLP . Transmission disequilibrium tests ( TDTs ) in a sample of 177 nuclear families showed significant association and linkage of the DraI polymorphism with the ADHD combined subtype ( P=0.03 ) , and the quantitative TDT showed association of this polymorphism with the inattentive ( P=0.003 ) and hyperactive-impulsive ( P=0.015 ) symptom dimensions . The haplotype that contained the less common allele of the DraI polymorphism likewise showed a strong relationship with the inattentive ( P=0.001 ) and hyperactive-impulsive ( P=0.004 ) symptom dimensions . This study supports the hypothesis that an allele of the ADRA2A gene is associated and linked with the ADHD combined subtype and suggests that the DraI polymorphism of ADRA2A is linked to a causative polymorphism OBJECTIVE To determine whether acetyl-L-carnitine ( ALC ) , a metabolite necessary for energy metabolism and essential fatty acid anabolism , might help attention-deficit/hyperactivity disorder ( ADHD ) . Trials in Down 's syndrome , migraine , and Alzheimer 's disease showed benefit for attention . A preliminary trial in ADHD using L-carnitine reported significant benefit . METHOD A multi-site 16-week pilot study r and omized 112 children ( 83 boys , 29 girls ) age 5 - 12 with systematic ally diagnosed ADHD to placebo or ALC in weight-based doses from 500 to 1500 mg b.i.d . The 2001 revisions of the Conners ' parent and teacher scales ( including DSM-IV ADHD symptoms ) were administered at baseline , 8 , 12 , and 16 weeks . Analyses were ANOVA of change from baseline to 16 weeks with treatment , center , and treatment-by-center interaction as independent variables . RESULTS The primary intent-to-treat analysis , of 9 DSM-IV teacher-rated inattentive symptoms , was not significant . However , secondary analyses were interesting . There was significant ( p = 0.02 ) moderation by subtype : superiority of ALC over placebo in the inattentive type , with an opposite tendency in combined type . There was also a geographic effect ( p = 0.047 ) . Side effects were negligible ; electrocardiograms , lab work , and physical exam unremarkable . CONCLUSION ALC appears safe , but with no effect on the overall ADHD population ( especially combined type ) . It deserves further exploration for possible benefit specifically in the inattentive type The symptoms of attention deficit hyperactivity disorder ( ADHD ) can be treated with methylpheni date ( MPH ) , a potent blocker of dopamine transporter ( DAT ) . The homozygosity of the 10-repeat allele at the DAT gene ( DAT1 ) seems to be associated with a poor response to MPH in children with ADHD . In the present study , we investigated the association between DAT density using I-123-N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane [123I]IPT single photon emission computed tomography ( SPECT ) ] and the homozygosity for 10-repeat allele at DAT1 and response to MPH in Korean children with ADHD . Eleven drug-naive children with ADHD were included in the study and treated with MPH for about 8 weeks . After the genotyping and SPECT were performed , we compared DAT density between ADHD children with and without the homozygosity for 10-repeat allele at DAT1 and investigated the correlation between the homozygosity for 10-repeat allele and response to MPH .  ADHD children with 10/10 genotype ( n=7 ) had a significantly greater increase of the DAT density in basal ganglia than the children without 10/10 genotype ( n=4 ) . We found that while only 28.6 % ( 2/7 ) of the subject with 10/10 genotype showed good response to  MPH  treatment , 100 % ( 4/4 ) of the subjects without 10/10 genotype showed good response to  MPH treatment . Our findings support an association between homozygosity for 10-repeat allele at DAT1 and the DAT density assessed in vivo and correlation between the homozygosity for 10-repeat allele and poor response to MPH
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 .