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BACKGROUND: Methylphenidate is the most frequently prescribed medication for the treatment of ADHD in children and adolescents in many countries. Although many randomised controlled trials support short-term efficacy, tolerability, and safety, data on long-term safety and tolerability are scarce. The aim of this study was to investigate the safety of methylphenidate over a 2-year period in relation to growth and development, psychiatric health, neurological health, and cardiovascular function in children and adolescents. METHODS: We conducted a naturalistic, longitudinal, controlled study as part of the ADDUCE research programme in 27 European child and adolescent mental health centres in the UK, Germany, Switzerland, Italy, and Hungary. Participants aged 6-17 years were recruited into three cohorts: medication-naive ADHD patients who intended to start methylphenidate treatment (methylphenidate group), medication-naive ADHD patients who did not intend to start any ADHD medication (no-methylphenidate group), and a control group without ADHD. Children with ADHD diagnosed by a qualified clinician according to the DSM-IV criteria and, in the control group, children who scored less than 1·5 on average on the Swanson, Nolan, and Pelham IV rating scale for ADHD items, and whose hyperactivity score on the parent-rated Strengths and Difficulties Questionnaire was within the normal range (

The trait impulsivity theory suggests that a single, highly heritable externalizing liability factor, expressed as temperamental trait impulsivity, represents the core vulnerability for externalizing disorders. The present study sought to test the application of latent factor models derived from this theory to a clinical sample of children. Participants were 474 German children (age 6-12 years, 81% male) with symptoms of attention-deficit/hyperactivity disorder and externalizing behavior problems participating in an ongoing multicenter intervention study. Using confirmatory factor analyses (CFA) and exploratory structural equation modeling (ESEM), we evaluated several factor models of externalizing spectrum disorders (unidimensional; first-order correlated factors; higher-order factor; fully symmetrical bifactor; bifactor S-1 model). Furthermore, we assessed our prevailing factor models for measurement invariance across raters (clinicians, parents, teachers) and assessment modes (interview, questionnaires). While both CFA and ESEM approaches provided valuable insights into the multidimensionality, ESEM solutions were generally superior since they showed a substantially better model fit and less biased factor loadings. Among the models tested, the bifactor S-1 CFA/ESEM models, with a general hyperactivity-impulsivity reference factor, displayed a statistically sound factor structure and allowed for straightforward interpretability. Furthermore, these models showed the same organization of factors and loading patterns, but not equivalent item thresholds across raters and assessment modes, highlighting cross-situational variability in child behavior. Our findings are consistent with the assumption of the trait impulsivity theory that a common trait, presented as hyperactivity-impulsivity symptoms, underlies all externalizing disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Zusammenfassung. Hintergrund und Zielsetzung: Die Elektrokonvulsionstherapie (EKT) ist ein hoch wirksames und in der Erwachsenenpsychiatrie gut untersuchtes Therapieverfahren, das gerade bei schwerwiegenden depressiven und psychotischen Erkrankungen erfolgreich eingesetzt wird. Obwohl schwere Krankheitsverläufe auch im kinder- und jugendpsychiatrischen Bereich vorkommen, erfolgt ein Einsatz der EKT hier deutlich seltener. Dies liegt womöglich auch daran, dass kaum systematisch erhobene Daten zur Anwendung, Wirksamkeit und Verträglichkeit der EKT bei kinder- und jugendpsychiatrischen Patient_innen existieren. Ziel dieser Arbeit ist die Untersuchung und Darstellung von Krankheitsverläufen unter EKT-Behandlung im kinder- und jugendpsychiatrischen Bereich und damit eine Vergrößerung der bestehenden Datenbasis zu diesem Thema. Methoden: Es erfolgte eine retrospektive Erhebung zur EKT bei unter 18-jährigen Patient_innen an drei deutschen universitären Zentren. Hier wurden alle dokumentierten Fälle erfasst und auf Wirksamkeit und Verträglichkeit hin untersucht. Darüber hinaus erfolgte eine umfassende PubMed-basierte Datenbankrecherche. Ergebnisse und Schlussfolgerungen: International existieren keine Meta-Analysen oder kontrollierte randomisierte Studien und aus Deutschland kaum veröffentlichte Fälle zum Thema Elektrokonvulsionstherapie in der Kinder- und Jugendpsychiatrie. Unsere Daten zur EKT bei 29 12- bis 17-jährigen Patient_innen zeigen eine gute Wirksamkeit. Nebenwirkungen traten selten auf. Es ergaben sich keine Hinweise auf Unterschiede bezüglich Indikation (Depression, Katatonie, Schizophrenie), Wirksamkeit, negative Prädiktoren und Verträglichkeit einer EKT zwischen erwachsenen und minderjährigen Patient_innen. Die Ergebnisse deuten zudem darauf hin, dass der Einsatz der EKT bei Adoleszenten früher im therapeutischen Prozess in Erwägung gezogen werden sollte.

Electroconvulsive therapy (ECT) is a well-established, safe, and efficacious treatment for severe psychiatric disorders. In children and adolescents, it is used much less frequently than in adults, likely because of a lack of knowledge.We retrospectively analyzed all patients aged 12 to 17 years who completed a course of ECT at 3 psychiatric university hospitals in Germany between 2010 and 2020. Clinical Global Impression Severity (CGI-S) scores were assessed based on electronic medical records. Changes in CGI-S scores were assessed using a paired samples t test. Predictors for response and remission were assessed using binomial logistic regression.We included 32 patients. The CGI-S scores improved significantly from before to after ECT treatment (6.9 vs 3.9, t = 10.0, P0.01). A total of 40.6% of patients responded (CGI ≤ 3) and 21.9% remitted (CGI ≤ 2). The number of ineffective medication trials in the 6 months before ECT treatment was significantly associated with response (odds ratio, 0.54; P = 0.028) and remission (odds ratio, 0.31; P = 0.048). Five patients reported subjective cognitive adverse effects, 2 patients exhibited a prolonged seizure, 1 patient reported headaches, and 1 patient experienced a mild allergic reaction after anesthesia with etomidate. A total of 65.6% of patients experienced no adverse effects at all.This retrospective analysis found ECT to be effective and safe in children and adolescents irrespective of their main diagnosis. The reported data point to the importance of an early use of ECT for severe psychiatric diseases in child and adolescent psychiatry.

Background: Randomized controlled trials have shown that dexamphetamine sulfate (DEX) is efficacious in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents; however, data on the effectiveness and safety of DEX in routine practice are scarce. Objective: This study investigated the long-term effectiveness and safety of Attentin® (immediate-release DEX) in children and adolescents with ADHD in routine practice. Methods: ATTENTION was a multicenter, prospective, observational, non-interventional study that enrolled pediatric patients with ADHD (aged 6-17 years) with a clinically inadequate response to previous methylphenidate (MPH) treatment. Patients were assessed at baseline and two follow-up visits after approx. 6 and 12 months of DEX treatment. The primary endpoint was the investigator-rated ADHD rating scale IV (ADHD-RS-IV) total score change from baseline to the first follow-up visit. Results: The study enrolled 140 patients (mean age: 11.2 years). Significant reductions in ADHD-RS-IV total scores were observed in the titration phase and were maintained up to the second follow-up visit. The mean ADHD-RS-IV total score change from baseline to the first follow-up visit was -11.9 (27.1 vs. 13.4, p < .001). Beneficial effects of DEX were observed on both ADHD-RS-IV subscales (‘hyperactivity/impulsivity’ and ‘inattention’) and in both children and adolescents. Clinical response, defined as a reduction in the ADHD-RS-IV total score of at least 30% at the first follow-up visit, was observed in 78.1% of patients. Patients reported an average onset of action of 36.2 minutes and an average duration of action of 6.5 hours after intake of the first dose of DEX in the morning. DEX was well tolerated. Small significant increases in mean systolic and diastolic blood pressure compared to baseline were observed. Conclusions: Attentin® is an effective and well-tolerated long-term treatment for pediatric ADHD patients with a clinically inadequate response to previous MPH treatment.

The historic development of the attention deficit hyperactivity disorder (ADHD) construct is, in many cases, paralleled by research questions addressed with the continuous performance test (CPT). This task, the use of which dates back to the 1950s for the diagnosis of brain damage, requires responding to rare targets in a sequence of stimuli during prolonged assessment. In our review, we illustrate how the CPT was and still is used for the assessment of sustained attention and impulsivity as core features of ADHD. In addition to impaired performance at the neuropsychological level, the CPT also taps underlying brain activity that can be registered by neuroimaging techniques such as fMRI and EEG. The latter allows more detailed operationalization of ADHD theories, and reveals impairments at different stages of information processing. The CPT has also been applied for treatment evaluation. Recently, distinct genetic effects on preparation and response control or impulsivity were detected using the CPT. As such, the task remains a valuable tool for further investigations of genetic and environmental factors of ADHD.

Background. Detecting genetic factors involved in attention deficit hyperactivity disorder (ADHD) is complicated because of their small effect sizes and complex interactions. The endophenotype approach eases this by coming closer to the relevant genes. Different aspects of temporal information processing are known to be affected in ADHD. Thus, some of these aspects could represent candidate endophenotypes for ADHD. Method. Fifty-four sib-pairs with at least one child with ADHD and 40 control children aged 6-18 years were recruited and asked to perform two duration discrimination tasks, one with a base duration of 50 ms on automatic timing and one with a base duration of 1000 ms on cognitively controlled timing. Results. Whereas children with ADHD, but not their unaffected siblings, were impaired in discrimination of longer intervals, both groups were impaired in discriminating brief intervals. Furthermore, a significant within-family correlation was found for discrimination of brief intervals. Task performances of subjects of the control group correlated with individual levels of hyperactivity/impulsivity for discrimination of brief intervals, but not of longer intervals. Conclusions. Cognitively controlled and also automatic processes of temporal information processing are impaired in children with ADHD. Discrimination of longer intervals appears as a typical' disease marker' whereas discrimination of brief intervals shows up as a 'vulnerability marker'. Discrimination of brief intervals was found to be familial and linked to levels of hyperactivity/impulsivity. Taken together, discrimination of brief intervals represents a candidate endophenotype of ADHD.

Objectives: The side effects, nonresponse, and prejudices against conventional pharmacological treatments call for complementary or alternative medical treatments (CAM) for ADHD. One possible treatment, at least for cognitive problems, might be the administration of Ginkgo biloba, though evidence is currently rare. This study tests the clinical efficacy of a Ginkgo biloba special extract (EGb 761®) and its correlation with brain electrical activity in children with ADHD combined type according to DSM-IV. Method: In this open clinical pilot study, EGb 761® was administered to 20 children with ADHD over 3 to 5 weeks. Dosage was increased to a maximum of 240 mg daily if attention problems persisted. Possible drug side effects were assessed using the Side Effect Rating Scale. Efficacy was assessed in a multilevel approach including clinical assessment, quality of life (QoL), as well as performance and preparatory brain-electrical activity evoked during a Continuous Performance Test (Cue-CNV in the CPT). Results: A very low rate of mild adverse effects occurred during the observation period. Following EGb 761® administration, possible improvements in QoL, ADHD core symptoms as well as CPT performance were detected. Improved core symptoms were positively related to elevated CNV amplitude. Conclusion: This preliminary evidence suggests that EGb 761® at a maximal dosage of 240 mg daily might be a clinically useful alternative treatment for children with ADHD, but further evidence is required before firm conclusions can be made.

Background: Emotional lability (EL) is commonly seen in patients with attention-deficit/hyperactivity disorder (ADHD). The reasons for this association remain currently unknown. To address this question, we examined the relationship between ADHD and EL symptoms, and performance on a range of neuropsychological tasks to clarify whether EL symptoms are predicted by particular cognitive and/or motivational dysfunctions and whether these associations are mediated by the presence of ADHD symptoms. Methods: A large multi-site sample of 424 carefully diagnosed ADHD cases and 564 unaffected siblings and controls aged 618 years performed a broad neuropsychological test battery, including a Go/No-Go Task, a warned four-choice Reaction Time task, the Maudsley Index of Childhood Delay Aversion and Digit span backwards. Neuropsychological variables were aggregated as indices of processing speed, response variability, executive functions, choice impulsivity and the influence of energetic and/or motivational factors. EL and ADHD symptoms were regressed on each neuropsychological variable in separate analyses controlling for age, gender and IQ, and, in subsequent regression analyses, for ADHD and EL symptoms respectively. Results: Neuropsychological variables significantly predicted ADHD and EL symptoms with moderate-to-low regression coefficients. However, the association between neuropsychological parameters on EL disappeared entirely when the effect of ADHD symptoms was taken into account, revealing that the association between the neuropsychological performance measures and EL is completely mediated statistically by variations in ADHD symptoms. Conversely, neuropsychological effects on ADHD symptoms remained after EL symptom severity was taken into account. Conclusions: The neuropsychological parameters examined, herein, predict ADHD more strongly than EL. They cannot explain EL symptoms beyond what is already accounted for by ADHD symptom severity. The association between EL and ADHD cannot be explained by these cognitive or motivational deficits. Alternative mechanisms, including overlapping genetic influences (pleiotropic effects) and/or alternative neuropsychological processes need to be considered.

The maintenance of stable goal-directed behaviour is a hallmark of conscious executive control in humans. Notably, both correct and error human actions may have a subconscious activation-based determination. One possible source of subconscious interference may be the default mode network that, in contrast to attentional network, manifests intrinsic oscillations at very low (

Item does not contain fulltext BACKGROUND: Impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in attention-deficit/hyperactivity disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion would be associated with serotonin-regulating genes. METHODS: Impulsive drive for immediate reward and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) with a laboratory choice task. The sample was genotyped for the 5HTT (SLC6A4) promoter serotonin-transporter-linked polymorphic region polymorphism and a DAT1 (SLC6A3) 40-base pair variable number tandem repeat located in the 3'-untranslated region of the gene. RESULTS: There was no effect of dopamine transporter (DAT)1 on IDIR. As predicted, serotonin-transporter-linked polymorphic region s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G single nucleotide polymorphism and were independent of age, IQ, and oppositional defiant disorder symptoms. CONCLUSIONS: The results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presented.

BackgroundTwin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ.MethodMultivariate familial models were run on data from 1265 individuals aged 6–18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice–delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI).ResultsSignificant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41–0.71) and IQ (rF=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80–87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ.ConclusionsThe aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.

Die psychophysiologische Erforschung der kindlichen Entwicklung sowie der psychischen Störungen im Kindes- und Jugendalter hat erhebliche Fortschritte zu verzeichnen. So gelang es mit Methoden der kognitiven Neurowissenschaften, insbesondere der Elektroenzephalographie und Magnetresonanztomographie, aber auch durch Betrachtung peripherer physiologischer Parameter, die physiologische Basis verschiedener kognitiver Prozesse wie Aufmerksamkeit, Gedächtnis, Lernen und Sprache im Hinblick auf Störungen der kindlichen Entwicklung einschließlich psychiatrischer Erkrankungen besser zu verstehen. Die gewonnenen Erkenntnisse ermöglichen es, Therapien zu evaluieren und weiter zu verbessern, sowie neue Therapieformen zu entwickeln. In der folgenden selektiven Übersichtsarbeit sollen psychophysiologische, insbesondere elektrophysiologische Methoden in ihrer Bedeutung für kinder und jugendpsychiatrische Fragestellungen vorgestellt und diskutiert werden.

Response processing may comprise multiple systems working in parallel at different functional levels of performance monitoring. In time-frequency decompositions of response-locked event-related potentials from adults, a subprocess operating in the delta frequency band was interpreted as an index of cognitive error monitoring, distinguishable from a process with theta frequency probably related to motor control. However, it remains unclear whether such subprocesses can also be distinguished in children. In the current study, error processing was assessed in 22 normal boys aged 8 to 15 years using an Erikson Flanker task. Performance data revealed the expected indices of conflicting task demands, such as increased reaction times and error rates. A clear error-negativity was found in the response-locked event-related potentials after incompatible stimuli, and correct responses show a slow negative deflection immediately preceding the button-press, which is absent in errors. Time-frequency decompositions disclosed that a subprocess in the lower delta band preceding correct responses may reflect a more general action monitoring process sensitive to conflicting task demands that, moreover, may prevent one from making an error if it is active early enough. Processes in the delta and theta bands are modulated specifically by errors and may index motor-related monitoring in children. Moreover, these processes occurred considerably earlier for correct responses compared to errors, suggesting that their timing reflects some performance capacity. These considerations may help to clarify response processing in tasks with conflicting demands.

Preliminary findings suggest that color perception, particularly of blue-yellow stimuli, is impaired in attention-deficit/hyperactivity disorder (ADHD) as well as in chronic tic disorders (CTD). However, these findings have been not replicated and it is unclear what these deficits mean for the comorbidity of ADHD + CTD. Four groups (ADHD, CTD, ADHD + CTD, controls) of children with similar age, IQ and gender distribution were investigated with the Farnsworth-Munsell 100 Hue Test (FMT) and the Stroop-Color-Word Task using a factorial design. Color perception deficits, as indexed by the FMT, were found for both main factors (ADHD and CTD), but there were no interaction effects. A preponderance of deficits on the blue-yellow compared to the red-green axis was detected for ADHD. In the Stroop task only the 'pure' ADHD group showed impairments in interference control and other parameters of Stroop performance. No significant correlations between any FMT parameter and color naming in the Stroop task were found. Basic color perception deficits in both ADHD and CTD could be found. Beyond that, it could be shown that these deficits are additive in the case of comorbidity (ADHD + CTD). Performance deficits on the Stroop task were present only in the 'pure' ADHD group. Hence, the latter may be compensated in the comorbid group by good prefrontal capabilities of CTD. The influence of color perception deficits on Stroop task performance might be negligible. © 2007 Springer-Verlag.

Electrophysiologically, Tourette syndrome (Tp. is characterized by shortened cortical silent period (CSP), reflecting decreased motor inhibition. However, voluntary versus involuntary aspects of inhibitory functions in TS are not well understood. Hence, investigating voluntary motor drive (VMD) could help to elucidate this issue. A group of 14 healthy adolescents was compared with subjects of same age suffering from TS with (N = 6) and without (N = 6) presence of distal tics. Basic resting and active motor thresholds (RMT and AMT, respectively) as well as suprathreshold transcranial magnetic stimulation-conditioned RMT and AMT were determined during the CSP. The difference between AMT and RMT was considered as VMD quantum. No group-differences were found in RMT or AMT. Subjects with distal tics showed reduced VMD compared to healthy controls while patients without distal tics did not differ from controls. In the second half of CSP, patients with distal tics showed also diminished VMD compared to tic-patients without distal tics. The findings support the notion, that TS shows possible reduction of VMD and is associated with central motor threshold alterations confined to the very motor networks related to the tics observed. peerReviewed

Deficits in interference control are ascribed to patients suffering from ADHD by a number of cognitive theories. However, previous research using the Stroop Colour Word Interference Task has demonstrated mixed results that may be explained by methodological issues (e.g., possible impact of colour perception abilities on interference liability, different approaches to calculate interference scores, conflation of speed and accuracy factors). Hence, this study included two computerized versions of the Stroop (Colour-Stroop, Counting Stroop) which allowed to calculate separate measures of speed and accuracy, provided a more rigorous approach to calculate interference, and permitted to investigate the effects of stimulus properties on interference. Participants were 14 children with a DSM-IV diagnosis of ADHD combined type and 15 matched controls. Children completed a traditional Stroop as well as both a computerized Colour- and Counting-Stroop. Results indicated that the ADHD group showed higher interference scores than controls in the Colour-Stroop, but not in the Counting-Stroop. Thus, interference control may be not generally impaired in ADHD, and examinations with the Colour Stroop should be interpreted with care. © 2007 Springer-Verlag.

Contains fulltext : 69215.pdf (Publisher’s version ) (Closed access) Common disorders of childhood and adolescence are attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD). For one to two cases in three diagnosed with ADHD the disorders may be comorbid. However, whether comorbid conduct problems (CP) represents a separate disorder or a severe form of ADHD remains controversial. We investigated familial recurrence patterns of the pure or comorbid condition in families with at least two children and one definite case of DSM-IV ADHDct (combined-type) as part of the International Multicentre ADHD Genetics Study (IMAGE). Using case diagnoses (PACS, parental account) and symptom ratings (Parent/Teacher Strengths and Difficulties [SDQ], and Conners Questionnaires [CPTRS]) we studied 1009 cases (241 with ADHDonly and 768 with ADHD + CP), and their 1591 siblings. CP was defined as > or =4 on the SDQ conduct-subscale, and T > or = 65, on Conners' oppositional-score. Multinomial logistic regression was used to ascertain recurrence risks of the pure and comorbid conditions in the siblings as predicted by the status of the cases. There was a higher relative risk to develop ADHD + CP for siblings of cases with ADHD + CP (RRR = 4.9; 95%CI: 2.59-9.41); p < 0.001) than with ADHDonly. Rates of ADHDonly in siblings of cases with ADHD + CP were lower but significant (RRR = 2.9; 95%CI: 1.6-5.3, p < 0.001). Children with ADHD + CP scored higher on the Conners ADHDct symptom-scales than those with ADHDonly. Our finding that ADHD + CP can represent a familial distinct subtype possibly with a distinct genetic etiology is consistent with a high risk for cosegregation. Further, ADHD + CP can be a more severe disorder than ADHDonly with symptoms stable from childhood through adolescence. The findings provide partial support for the ICD-10 distinction between hyperkinetic disorder (F90.0) and hyperkinetic conduct disorder (F90.1).

Zusammenfassung: Fragestellung: Charakterisierung des Schlafmusters einer größeren Gruppe Kinder mit Tic-Störung sowie Untersuchung ob und wie Veränderungen des Schlafs mit der Schwere der Tic-Störung assoziiert sind. Methodik: Das Schlafverhalten von 25, zum Untersuchungszeitpunkt unmedizierten Kinder mit chronischer Tic-Störung wurde polysomnographisch untersucht und mit den Befunden von 22 gesunden Kontrollen verglichen. Zwischen beiden Gruppen bestanden keine Unterschiede hinsichtlich Alter, Geschlechtsverhältnis und Intelligenz. Ergebnisse: Kinder mit einer Tic-Störung zeigten eine reduzierte Schlafqualität sowie vermehrtes, bewegungsbezogenes Arousal im Vergleich zu gesunden Kontrollen. Hinsichtlich des Schlafs ging bei Kindern mit Tic-Störung eine schwerere Ausprägung der Tics mit häufigeren bewegungsbezogenen Arousals einher. Die Anzahl der kurzen, mit motorischen Phänomenen assoziierten Arousals korrelierte mit geringerer Schlafeffizienz, verzögertem Schlafbeginn und verlängerter Tiefschlaflatenz. Des weiteren bestimmten geringere Schlafeffizienz und verlängerte Tiefschlaflatenz bei Kindern mit Tic-Störung die Schwere der Tics am Tag. Schlussfolgerungen: Bei Kindern mit Tic-Störung scheint ein Zusammenhang zwischen den bewegungsbezogenen Arousals im Schlaf und der Ausprägung der Tics am Tag zu bestehen. Beeinträchtigungen des Schlafs bei Tic-Störungen könnten die Tic-Symptomatik am Tag verschlechtern.

Attention-deficit/hyperactivity disorder (ADHD) is associated with unexplained impairments on speeded naming of coloured stimuli. These deficits may reflect hypofunctioning retinal dopaminergic mechanisms impairing particularly blue-yellow colour discrimination. Colour perception and rapid colour naming ability were investigated in 14 children with ADHD and 13 healthy peers matched for age, gender, and IQ, using the Farnsworth-Munsell 100 Hue Test (FMT) and the Stroop-Colour-Word test. Children with ADHD committed more errors on the FMT, particularly on discrimination of colours along the blue-yellow axis, and were slower on Stroop subtests involving colour naming. However, the latter deficit was accounted for similarly by blue-yellow and red-green discrimination abilities. Blue-yellow colour perception problems in ADHD contribute to but do not fully explain the observed slowed colour naming.

ZusammenfassungLangzeitwirksame Methylphenidatpräparate mit einer zweistufigen Freisetzungsdynamik (Stufe 1: rasch; Stufe 2: verzögert) erlauben eine morgendliche Einmalgabe und werden so der Unterstützung von Schulkindern mit ADHS besser gerecht. Das diesbezüglich erste deutsche Arzneimittel (Medikinet® Retard 20 mg) sollte daher auf seine Wirksamkeit und Verträglichkeit geprüft werden.In einer plazebokontrollierten, randomisiert-parallelen, doppelblinden, multizentrischen Studie wurden 85 normal intelligente Kinder (Alter 6–16 Jahre, Diagnose ADHS) untersucht. Die Dauer der Behandlung mit Medikinet Retard (n = 43) bzw. Plazebo (n = 42) betrug 4 Wochen mit wöchentlichen Visiten und einer wöchentlichen Titrierung. Hauptzielkriterium war die Symptomatik im Fremdbeurteilungsbogen für hyperkinetische Störungen (FBB-HKS durch die Lehrer) im Vergleich der Woche 0 (Anfangswert) gegenüber der Woche 4 (Endwert). Unerwünschte Ereignisse und unerwünschte Arzneimittelwirkungen (UAW) sowie laborchemische und kardiovaskuläre Parameter wurden erfasst und EEG, internistische und neurologische Untersuchung durchgeführt.Es zeigte sich eine deutlich positive Medikamentenwirkung (U-Test: p Damit liegen im deutschsprachigen Raum erstmals Daten für eine erfolgreiche Symptomreduktion und gute Verträglichkeit eines langzeitwirksamen Methylphenidatpräparates (Medikinet Retard) vor. Die zweistufige Freisetzungsdynamik erlaubt eine praxistaugliche morgendliche Einmalgabe.

Zusammenfassung Fragestellung: Die Anwendung von Methylphenidat (MPH) in der Alltagspraxis niedergelassener Ärzte wird immer wieder hinterfragt. Ziel der Studie war es daher, die Handhabung, Wirksamkeit, Verträglichkeit und Akzeptanz der Behandlung unter breiter Anwendung im niedergelassenen ärztlichen Bereich zu untersuchen. Methode: Im Rahmen einer nicht-interventionellen PostMarketing-Surveillance-Studie wurde die Behandlung von 659 Kindern und Jugendlichen (Alter: 3 bis 20 Jahre) mit hyperkinetischen Störungen, die Methylphenidat (Medikinet®) erhielten, anhand von Fragebogen deskriptiv dokumentiert. Der Beobachtungszeitraum lag bei durchschnittlich 11,4 Wochen. Ergebnisse: Die Behandlung der ADHS bei Kindern und Jugendlichen mit MPH erwies sich als sehr effektiv, gut verträglich und für die Patienten annehmbar. Die Wirksamkeit wurde nicht durch Alter, Geschlecht, Art der Subdiagnose, Schweregrad oder den Zeitpunkt des Beginns erster Auffälligkeiten modifiziert. Relativer Risikofaktor für das Auftreten von unerwünschten Arzneimittelwirkungen war ein junges Alter sowie die körpergewichtsbezogene hohe Dosis (insbesondere bei jüngeren Kindern). Sowohl die absolute als auch die körpergewichtsbezogene durchschnitt liche Tagesdosis lag aber in der Regel im empfohlenen Bereich. Schlussfolgerung: Die Daten belegen erneut die gute Wirksamkeit und Verträglichkeit von MPH und zeigen eine generell adäquate Dosierung der Substanz durch Kinderund Jugendpsychiater sowie Pädiater. Dies widerspricht den Auffassungen, wonach MPH häufig zu hoch dosiert oder unkritisch verschrieben werde.

Attention deficit hyperactivity disorder (ADHD) is characterized by severe and age-inappropriate levels of hyperactivity, impulsivity and inattention. ADHD is a heterogeneous disorder, and the majority of patients show comorbid or associated problems from other psychiatric disorders. Also, ADHD is associated with cognitive and motivational problems as well as resting-state abnormalities, associated with impaired brain activity in distinct neuronal networks. This needs to be considered in a multimodal treatment, of which neurofeedback (NF) may be a promising component. During NF, specific brain activity is fed-back using visual or auditory signals, allowing the participants to gain control over these otherwise unaware neuronal processes. NF may be used to directly improve underlying neuronal deficits, and/or to establish more general self-regulatory skills that may be used to compensate behavioral difficulties. The current manuscript describes pathophysiological characteristics of ADHD, heterogeneity of ADHD subtypes and gender differences, as well as frequently associated behavioral problems such as oppositional defiant/conduct or tic disorder. It is discussed how NF may be helpful as a treatment approach within these contexts.

The side effects, nonresponse, and prejudices against conventional pharmacological treatments call for complementary or alternative medical treatments (CAM) for ADHD. One possible treatment, at least for cognitive problems, might be the administration of Ginkgo biloba, though evidence is currently rare. This study tests the clinical efficacy of a Ginkgo biloba special extract (EGb 761®) and its correlation with brain electrical activity in children with ADHD combined type according to DSM-IV.In this open clinical pilot study, EGb 761® was administered to 20 children with ADHD over 3 to 5 weeks. Dosage was increased to a maximum of 240 mg daily if attention problems persisted. Possible drug side effects were assessed using the Side Effect Rating Scale. Efficacy was assessed in a multilevel approach including clinical assessment, quality of life (QoL), as well as performance and preparatory brain-electrical activity evoked during a Continuous Performance Test (Cue-CNV in the CPT).A very low rate of mild adverse effects occurred during the observation period. Following EGb 761® administration, possible improvements in QoL, ADHD core symptoms as well as CPT performance were detected. Improved core symptoms were positively related to elevated CNV amplitude.This preliminary evidence suggests that EGb 761® at a maximal dosage of 240 mg daily might be a clinically useful alternative treatment for children with ADHD, but further evidence is required before firm conclusions can be made.Fragestellung: Unerwünschte Arzneimittelwirkungen, fehlende Wirksamkeit und Vorurteile gegenüber herkömmlichen medikamentösen Behandlungsformen verlangen nach alternativen medizinischen Behandlungsmöglichkeiten der ADHS. Eine erfolgversprechende, bislang kaum untersuchte Möglichkeit zur Behandlung kognitiver Aspekte ist die Gabe von Ginkgo biloba. Ziel der vorliegenden Studie war die Prüfung klinischer Wirksamkeit und deren Zusammenhang mit hirnelektrischer Aktivität unter der Gabe von Ginkgobiloba-Extrakt EGb 761® bei Kindern mit ADHS vom kombinierten Subtyp nach DSM-IV. Methodik: EGb 761® wurde in einer offenen, klinischen Studie 20 Kindern mit ADHS über 3 bis 5 Wochen verabreicht. Die Dosis wurde bis maximal 240 mg täglich erhöht, solange klinisch relevante Aufmerksamkeitsprobleme bestanden. Klinische Wirksamkeit wurde auf mehreren Ebenen untersucht und beinhaltete klinische Untersuchung, Lebensqualität und Verhaltens- und hirnelektrische Aktivitätsparameter während eines Continuous Performance Tests (Cue-CNV im CPT). Ergebnisse: Im Beobachtungszeitraum traten nur wenige leicht ausgeprägte unerwünschte Wirkungen auf. Nach Gabe von EGb 761® kam es zu möglichen Verbesserung von Lebensqualität, ADHS-Kernsymptomatik und Leistung im CPT. Verbesserungen der Kernsymptomatik waren gleichzeitig mit erhöhter CNV-Amplitude korreliert. Schlussfolgerung: Die Ergebnisse lassen vermuten, dass EGb 761® mit einer Dosis von bis zu 240 mg täglich eine verträgliche und klinisch wirksame alternative Behandlungsmöglichkeit für Kinder mit ADHS darstellt, wenngleich weitere Studien erforderlich sind, um diese vorläufigen Befunde zu stützen.

BACKGROUND: Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children.METHODS: Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype.RESULTS: Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions.CONCLUSIONS: This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.

Psychological Medicine, 43 (9), ISSN:0033-2917, ISSN:1469-8978

Sleep problems are a prominent feature in children with attention-deficit/hyperactivity disorder (ADHD) but their relationships to sleep structure are not consistent across studies. We aimed at further examining the sleep architecture in children with ADHD, while considering the role of the first-night effect (FNE) as a possible confounder. Twenty unmedicated children with ADHD combined type (8–15 years old; mean 11.24, SD 2.31) and 19 healthy controls, matched for age and gender, underwent polysomnography during an adaptation and a consecutive second night. ADHD and controls displayed a typical FNE without group differences. Independently of testing night, children with ADHD spent more time in sleep and had shortened rapid eye movement (REM) sleep latency and a greater amount of REM sleep relative to controls. However, the increased REM sleep amount in ADHD children was more expressed in the second night when it was also significantly related to scores of inattention and hyperactivity. Our results (1) document similar sleep adaptation processes in children with ADHD and typically developing children, (2) reveal that REM sleep changes in association with ADHD-specific psychopathology may characterize sleep in ADHD children, which is evident only when the FNE is accounted for, (3) indicate that ADHD psychopathology and adaptation night may exert opposite effects on REM sleep in children. These results may prompt the awareness of clinicians about the importance of actual sleep alterations and their precise evaluation in children with ADHD, which could significantly contribute to better diagnostic, treatment and early prevention strategies.

Contains fulltext : 69677.pdf (Publisher’s version ) (Closed access) A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify individual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] findings in a clinical sample and to extend the analysis to a large range of alternative SNP markers of putative ADHD risk alleles identified in a recent study [Brookes et al. (2006); Mol Genet 11:934-953]. Participants were 1081 children and adolescents with a research-confirmed combined type ADHD diagnosis and 1300 unaffected siblings who took part in the International Multi-centre ADHD Genetics (IMAGE) project. They were recruited from multiple settings from across Europe: Belgium, Britain, Germany, Ireland, Israel, Netherlands, Spain and Switzerland. The results were that ADHD was associated with reduced IQ. However, there was no association between the two dopamine-related risk polymorphisms and IQ in either the probands or their siblings. Furthermore, other selected genetic markers previously demonstrated to be associated with ADHD in this sample were not associated with IQ. This large scale study with a clinically ascertained and regorously diagnosed sample failed to replicate the association between genetic polymorphisms in the dopamine system and IQ in ADHD. We also observed no association of other SNPs with IQ in ADHD.

Psychophysiological research focusing on child development and on child and adolescent psychiatric disorders has provided many important insights. The use of cognitive neuroscience methods along with the assessment of peripheral psychophysiological measures - particularly functional magnetic resonance imaging and electroencephalography reflecting brain activity - have advanced our understanding of the physiological basis of many cognitive processes such as attention, memory, learning, and language in the context of child development and psychiatric disorders. These insights are proving increasingly helpful when evaluating and advancing treatment. The following review introduces the reader to psychophysiological and particularly electrophysiological methods widely used in child and adolescent psychiatry research.

Background Although the performance of children with attention-deficit/hyperactivity disorder (ADHD) is impaired in a variety of cognitive tasks, the specific capacity of strategic readaptation after errors as a source of behavioral deficits is not sufficiently understood. This study used an extended and refined behavioral parameterization to assess performance monitoring and posterror adaptation in children with ADHD. Methods Twenty-eight healthy control subjects and 47 ADHD patients (7–16 years of age, all males, matched for age and IQ) performed a visual flanker task in which targets were congruent or incongruent with preceding flankers. Posterror adaptation was measured for response speed (posterror slowing), accuracy, and variability by using normalized individual rates of change. Markers of error detection and general performance were also analyzed. Results Postcorrect response speed and accuracy did not differ between the groups, in contrast to posterror behaviors. Whereas posterror slowing was not evident in any of the groups, the error rate and performance instability (reaction time variance) substantially increased after errors only in ADHD patients, not in control subjects. No reliable between-group differences were found for error detection and global performance. Conclusions In healthy children, posterror adaptation preserves performance at its ongoing level. No such adaptation was evident in ADHD, leading to consecutive errors and increased behavioral instability. Performance deficits in ADHD were only present after error but not after correct behaviors, which shapes the general profile of performance impairment in ADHD. The findings have practical implications for strategic designs of behavioral therapy in ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a frequent and highly heritable disorder overrepresented in boys. In a recent study investigating boys only, we found that action monitoring deficits as reflected by certain behavioral and electrophysiological parameters were familially driven. As gender may also have an important impact, this was examined in the current study with nonaffected children aged 8-15 years having relatives suffering from ADHD (N=37, 21 female symbol) and with age-matched controls without family history of ADHD (N=33, 11 female symbol). Extending our previous findings that action monitoring is a potential endophenotype for boys with ADHD, familially driven deficits were confirmed independently of gender. Thus, despite sharing the phenotype with controls, nonaffected siblings showed ADHD-like impairments albeit of smaller magnitude. However, girls performed generally more accurately, which in turn may have produced the differences between nonaffected siblings and controls in affective error processing that were not present in our boys-only assessment.

Contains fulltext : 80353.pdf (Publisher’s version ) (Closed access) It is hypothesised that autism symptoms are present in Attention-Deficit/Hyperactivity Disorder (ADHD), are familial and index subtypes of ADHD. Autism symptoms were compared in 821 ADHD probands, 1050 siblings and 149 controls. Shared familiality of autism symptoms and ADHD was calculated using DeFries-Fulker analysis. Autism symptoms were higher in probands than siblings or controls, and higher in male siblings than male controls. Autism symptoms were familial, partly shared with familiality of ADHD in males. Latent class analysis using SCQ-score yielded five classes; Class 1(31%) had few autism symptoms and low comorbidity; Classes 2-4 were intermediate; Class 5(7%) had high autism symptoms and comorbidity. Thus autism symptoms in ADHD represent a familial trait associated with increased neurodevelopmental and oppositional/conduct disorders.

As part of the International Multi-centre ADHD Gene (IMAGE) project we have completed an affected sibling pair study of 142 narrowly defined DSM-IV combined type ADHD proband-sibling pairs. We found suggestive linkage on chromosomes 9 and 16 with non-parametric multipoint peak LOD scores of 2.13 and 3.1 respectively. There have been several previous ADHD linkage scans. The UCLA study (Fisher et al. 2002; Ogdie et al. 2004; Ogdie et al. 2003), the Dutch study (Bakker et al. 2003), the German study (Hebebrand et al. 2006) and the MGH Study (Faraone et al., submitted) applied the affected sib pair (ASP) strategy; the Columbian study used extended pedigrees ascertained from a population isolate (Arcos-Burgos et al. 2004). No linkage was observed on the most established ADHD linked genomic regions from these studies on 5p and 17p. The highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (LOD=3.1) overlapped with data published from UCLA (LOD>1, ~95cM) and Holland (LOD>1, ~100cM). The second highest peak in this study was on chromosome 9q22 at 90cM (LOD=2.13). Both the UCLA study and the German study also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93cM; German LOD=0.68 at 100cM). The overlap of the two main peaks from this study with those from previous studies suggests that true loci linked to ADHD may lie within these regions

To characterize precisely the sleep pattern in children with co-existence of TD + ADHD.By means of polysomnography, sleep pattern was investigated in 19 children with TD + ADHD unmedicated before and during study and 19 healthy controls, matched for age, gender, and intelligence.Compared with healthy controls, children with TD + ADHD displayed shorter REM sleep latency and increased REM sleep duration. There was a negative correlational relationship between these REM-sleep alterations and they were determined by hyperactivity symptoms.Sleep in children with coexistence of TD + ADHD may be characterized by an elevated REM sleep drive. Common mechanisms are suggested to underpin hypermotor symptoms and REM sleep regulation.

Contains fulltext : 69485.pdf (Publisher’s version ) (Closed access) BACKGROUND: Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan specifically designed to map ADHD quantitative trait loci (QTL). METHODS: A set of 1094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative single nucleotide polymorphism (SNP) panel. Two quantitative traits measuring the children's symptoms in home and school settings were collected and standardized according to a population sample of 8000 children to reflect the developmental nature and gender prevalence difference of ADHD. Univariate linkage test was performed on both traits and their mean score. RESULTS: A significant common linkage locus was found at chromosome 1p36 with a locus-specific heritability of 5.1% and a genomewide empirical p < .04. Setting-specific suggestive linkage signals were also found: logarithm of odds (LOD) = 2.2 at 9p23 for home trait and LOD = 2.6 at 11q21 for school trait. CONCLUSIONS: These results indicate that given large samples with proper phenotypic measures, searching for ADHD genes with a QTL strategy is an important alternative to using the clinical diagnosis. The fact that our linkage region 1p36 overlaps with the dyslexia QTL DYX8 further suggests it is potentially a pleiotropic locus for ADHD and dyslexia.

Study objectives included the characterization of the sleep pattern in a large sample of children with chronic tic disorder (TD), as well if whether or not sleep changes and movement-related arousals are associated with tic severity.The sleep pattern of 25 children with a chronic tic disorder and who were unmedicated at the time of and during the study was investigated by means of polysomnography and compared to that of 22 healthy children matched for age, gender and intelligence.Children with a chronic tic disorder displayed a reduced quality of sleep, as well as an increased number of movement-related arousals during sleep compared to healthy controls. Children with TD exhibited more frequent movement-related arousals the more severe the tics were during the day. The number of short arousals associated with motor phenomena correlated with lower sleep efficiency, and longer sleep onset and slow-wave sleep (SWS) latency. Moreover, lower sleep efficiency and longer SWS latency in children with TD may determine the severity of the tics during the day.In children with TD, motor activity during sleep seems to be related to the severity of the tics during the day. Impaired sleep in cases of TD might worsen the tic symptoms during the day.

BackgroundReaction time (RT) variability is one of the strongest findings to emerge in cognitive-experimental research of attention deficit hyperactivity disorder (ADHD). We set out to confirm the association between ADHD and slow and variable RTs and investigate the degree to which RT performance improves under fast event rate and incentives. Using a group familial correlation approach, we tested the hypothesis that there are shared familial effects on RT performance and ADHD.MethodA total of 144 ADHD combined-type probands, 125 siblings of the ADHD probands and 60 control participants, ages 6–18, performed a four-choice RT task with baseline and fast-incentive conditions.ResultsADHD was associated with slow and variable RTs, and with greater improvement in speed and RT variability from baseline to fast-incentive condition. RT performance showed shared familial influences with ADHD. Under the assumption that the familial effects represent genetic influences, the proportion of the phenotypic correlation due to shared familial influences was estimated as 60–70%.ConclusionsThe data are inconsistent with models that consider RT variability as reflecting a stable cognitive deficit in ADHD, but instead emphasize the extent to which energetic or motivational factors can have a greater effect on RT performance in ADHD. The findings support the role of RT variability as an endophenotype mediating the link between genes and ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a very common and highly heritable child psychiatric disorder associated with dysfunctions in fronto-striatal networks that control attention and response organization. The aim of this study was to investigate whether features of action monitoring related to dopaminergic functions represent endophenotypes that are brain functions on the pathway from genes and environmental risk factors to behavior. METHODS: Action monitoring and error processing as indicated by behavioral and electrophysiological parameters during a flanker task were examined in boys with ADHD combined type according to DSM-IV (n = 68), their nonaffected siblings (n = 18), and healthy control subjects with no known family history of ADHD (n = 22). RESULTS: Boys with ADHD displayed slower and more variable reaction-times. Error negativity (Ne) was smaller in boys with ADHD compared with healthy control subjects, whereas nonaffected siblings displayed intermediate amplitudes following a linear model predicted by genetic concordance. The three groups did not differ on error positivity (Pe). The N2 amplitude enhancement due to conflict (incongruent flankers) was reduced in the ADHD group. Nonaffected siblings also displayed intermediate N2 enhancement. CONCLUSIONS: Converging evidence from behavioral and event-related potential findings suggests that action monitoring and initial error processing, both related to dopaminergically modulated functions of anterior cingulate cortex, might be an endophenotype related to ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is associated with unexplained impairments on speeded naming of coloured stimuli. These deficits may reflect hypofunctioning retinal dopaminergic mechanisms impairing particularly blue-yellow colour discrimination. Colour perception and rapid colour naming ability were investigated in 14 children with ADHD and 13 healthy peers matched for age, gender, and IQ, using the Farnsworth-Munsell 100 Hue Test (FMT) and the Stroop-Colour-Word test. Children with ADHD committed more errors on the FMT, particularly on discrimination of colours along the blue-yellow axis, and were slower on Stroop subtests involving colour naming. However, the latter deficit was accounted for similarly by blue-yellow and red-green discrimination abilities. Blue-yellow colour perception problems in ADHD contribute to but do not fully explain the observed slowed colour naming.

BackgroundThe objective of this study was to analyze the extracellularly acting semicarbazide-sensitive amine oxidase (SSAO) serum levels in children with ADHD for the first time. SSAO is known to show deviations from normal in various somatic disorders and to interplay with the intracellularly active MAO. In humans two forms of SSAO a circulating form in plasma and a membrane-bound form are involved in monoaminergic metabolism.MethodsWe analyzed serum levels of SSAO in 27 children meeting ICD-10 criteria of Hyperkinetic Disorder (F90) or DSM-IV criteria of ADHD combined type by HPLC method and fluorimetric detection. A group of 42 healthy volunteers within the same age range (7.0 – 14.0 years) served as controls.ResultsNo significant differences between children with ADHD (SSAO activity M = 773, SD = 217 mU/l) and healthy controls (SSAO activity M = 775, SD = 256 mU/l) in SSAO serum levels were found (F = 2.18; p > 0.14). Further, stimulant medication status had no influence on the result (F = 2.52; p > 0.11).ConclusionThere is no evidence for a deviation of SSAO serum activity in ADHD. Hence, extracellularly acting SSAO does not seem to be a promising factor for further research in ADHD. But progress in knowledge of its physiologic role and of the relationship between the membrane-bound and the circulating serum form may open new avenues for research on SSAO in ADHD.

Recent research on structural and functional anatomy related to ADHD has concentrated on fronto-striatocerebellar circuits. These findings and resultant neurobiological models of ADHD may explain some of the disturbances. On the other hand, there is some evidence that the restricted look at anteriorposterior anomalies might neglect the important additional information of lateralization problems related to hemispheric connectivity. Hence, the role of lateralization in the pathophysiology of ADHD should be reconsidered. After a short review of imaging studies in ADHD the special role of the corpus callosum (including the influence of its anomalies on general brain development, lateralization and functioning) is outlined and the first case of total agenesis of corpus callosum in a child with ADHD is presented and discussed within this context. In view of the remaining inconsistencies concerning structural and functional brain anomalies in ADHD, attention should be paid not only to anterior- posterior but also to leftright aspects of functional and structural brain anomalies. This should include disturbances probably related to anomalies of the corpus callosum, especially in regard to co-existing problems like dyslexia and developmental coordination disorder.

Given the dosing limitations of methylphenidate short–acting preparations in treating ADHD, galenics with longer release of the substance were developed mainly to avoid drug intake during school hours. This investigation was conducted to assess the efficacy and the duration of action of a new extended-release formulation of methylphenidate (Medikinet® retard) as a once–daily treatment for children with attention–deficit hyperactivity disorder (ADHD). This was a randomized, double–blind, crossover multicentre study with three treatment conditions: once–daily extended–release methylphenidate, twice–daily immediate–release methylphenidate and placebo given to 79 children (8–14 years old) with ADHD. Daily assessments in an analogue classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained 5 times over an 8–hour period. Secondary measures included an ADHD rating scale, based on DSMIV/ ICD–10 separately rated for the morning and the afternoon. Both active treatment conditions displayed significant time course effects and were superior to placebo in improving all efficacy measures. Once a day extended–release methylphenidate was not different from the same dose of twice daily immediate–release methylphenidate. These data provide support for the benefit of this novel, once-daily methylphenidate preparation in the treatment of ADHD. The longer duration of action of Medikinet Retard has the potential to simplify psychostimulant treatment, thus reducing dose diversion and eliminating the need for in–school administration.