Classifying ADHD subtypes/presentations considering the joint effect of three levels of investigation.

AIM: Discriminant validity of the Attention Deficits/Hyperactive Disorders (ADHD) subtypes/presentations is not yet clear. The purpose of this study was to investigate joint contribution of the strongest factors of the three dimensions, namely psychopathology, neuropsychology and electrophysiology for subtyping of presentations. METHOD: A sample of 104 boys aged 7-12 years was subdivided into three groups with ADHD combined (n = 22), inattentive (n = 25) and hyperactive/impulsive subtype (n = 14), and 43 typically developing controls (TDC). Children were investigated regarding the Child Behavior Checklist (CBCL), the Integrated Visual and Auditory Test (IVA), and EEG spectral power during eyes closed resting state. Subsequently, statistical analysis included discriminant functional analysis and principle component analysis. RESULTS: Neuropsychological parameters had the highest contribution in classifying of the groups. EEG parameters had no effect on differentiation of the groups, and among the psychopathological parameters, only the oppositional behavioral disorder score contributed to correctly classify 74.3% of the groups. Furthermore, we found four factors with eigenvalues higher than 1 in the ADHD and typical groups, with one factor characterized by four CBCL scales, another one by auditory and visual vigilance, speed and beta band power, the third by auditory and visual prudence, and forth by theta band power. CONCLUSIONS: Our results demonstrated that ADHD subtypes/presentations can be differentiated from each other at different levels of investigation despite some clinical symptoms overlap. The results suggested that not only psychopathology but also the impairment of sensory processing should be assessed in children with ADHD in order to use this additional information for a jointly multilevel clinical intervention, which may improve treatment success.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Emotion Regulation Over the Life Span.

PURPOSE OF REVIEW: Emotional symptoms are common and persistent in youth and adults with attention-deficit/hyperactivity disorder (ADHD) and cause clinically significant impairments. We review recent neuropsychological, neurophysiological, and peripheral psychophysiological evidence for emotion and emotion regulation deficits in ADHD across youth and adults. RECENT FINDINGS: Central and autonomous nervous system correlates argue in favor of more general self-regulation deficits and also specific emotional deficits in ADHD. These include general performance deficits in executive functions, and structural as well as functional impairments in neuronal networks associated with top-down self-regulation. Specific deficits with bottom-up emotional activation in the amygdala and emotion evaluation associated with the orbitofrontal cortex have also been described. Furthermore, vagally mediated, high-frequency heart rate variability is associated with emotional self-regulation deficits throughout the life span. The current evidence is based on multilevel studies that assess associations of emotion regulation. However, further studies that adequately consider the processual recursive character of emotion generation and regulation may give important new insights into emotional regulation of ADHD. Emotion regulation deficits in ADHD are associated with specific as well as general self-regulation deficits traceable on the level of neuropsychological, neurophysiological, and psychophysiological assessments. The temporal dynamics of the interplay of those different systems need further study in order to optimize and personalize treatment of emotion regulation difficulties, including emotional reactivity, in patients with ADHD.

Genetics of preparation and response control in ADHD: the role of DRD4 and DAT1.

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.

Ginkgo biloba extract EGb 761® in children with 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.

Neuropsychological correlates of emotional lability in children with ADHD.

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 6-18 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.

Independent oscillatory patterns determine performance fluctuations in children with attention deficit/hyperactivity disorder.

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 (<0.1 Hz) frequencies. In the present study, we analyse the time dynamics of performance accuracy to search for multisecond periodic fluctuations of error occurrence. Attentional lapses in attention deficit/hyperactivity disorder are proposed to originate from interferences from intrinsically oscillating networks. Identifying periodic error fluctuations with a frequency<0.1 Hz in patients with attention deficit/hyperactivity disorder would provide a behavioural evidence for such interferences. Performance was monitored during a visual flanker task in 92 children (7- to 16-year olds), 47 with attention deficit/hyperactivity disorder, combined type and 45 healthy controls. Using an original approach, the time distribution of error occurrence was analysed in the frequency and time-frequency domains in order to detect rhythmic periodicity. Major results demonstrate that in both patients and controls, error behaviour was characterized by multisecond rhythmic fluctuations with a period of ∼12 s, appearing with a delay after transition to task. Only in attention deficit/hyperactivity disorder, was there an additional 'pathological' oscillation of error generation, which determined periodic drops of performance accuracy each 20-30 s. Thus, in patients, periodic error fluctuations were modulated by two independent oscillatory patterns. The findings demonstrate that: (i) attentive behaviour of children is determined by multisecond regularities; and (ii) a unique additional periodicity guides performance fluctuations in patients. These observations may re-conceptualize the understanding of attentive behaviour beyond the executive top-down control and may reveal new origins of psychopathological behaviours in attention deficit/hyperactivity disorder.

ADHD subtypes: Do they hold beyond core symptoms? A multilevel testing of an additive model.

Attention Deficit Hyperactivity Disorder (ADHD) is characterized as a behavioral syndrome with core symptoms of inattention and/or hyperactivity/impulsivity that constitute, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), predominantly Inattentive and Hyperactive-Impulsive and a combined (additive) presentation that fulfills both criteria. The question remains if the pathophysiological background of both factors is also separate at levels of investigation beyond core symptoms. This would allow a clearer understanding and a more focused treatment approach even with tools derived from these levels. Hence, we assumed that an implicit additive diagnostic model also holds at the levels of associated psychopathology, neuropsychological performance and brain oscillations. We investigated this hypothesis using data of 61 boys (7-12 years old) with ADHD and 43 typically developing children. There were no significant differences in age and IQ between groups. Children were examined with Child Behavior Checklist (CBCL), the Integrated Visual and Auditory Test (IVA), and brain oscillations during eyes closed resting state. Inattention characteristics were associated with more pronounced internalizing problems, lower attention, and vigilance during IVA performance and at the Electroencephalography level with elevated Theta and diminished Beta power during eyes closed rest. In contrast, hyperactivity/impulsivity characteristics led to general psychopathology problems and showed at the neuropsychological level faster response speed and deficits in cognitive control and performance consistency, but were on the electroencephalography level without any deficits in EEG power. Considering differences in behavioral, neuropsychology, and electroencephalography levels in each subtype, separate clinical approaches should be recommended for them and an additive model for their combination.

Self-management training vs. neurofeedback interventions for attention deficit hyperactivity disorder: Results of a randomized controlled treatment study.

Objectives: Neurofeedback (NF) and self-management training (SMT) may be viable treatment options for patients with attention deficit hyperactivity disorder (ADHD) if they alleviate core symptoms, enhance the patients' self-concept and improve their quality of life (QoL). Aim of the current study is evaluating both interventions accordingly and to test whether specific improvements in core symptoms lead to more general improvements in self-concept and QoL. Methods: In a psychotherapeutic outpatient clinic in Germany, a total of N = 139 children with ADHD were screened for eligibility, of which 111 fulfilled inclusion criteria and participated in the study in accordance with the CONSORT 2010 statement. These were randomly assigned to NF vs. SMT interventions. Changes from pre- to post-intervention in core ADHD symptoms relying on parent and teacher reports (CONNERS 3) and objective tests (Qb-Test) as well as self-concept (interview with the children) and QoL assessments (using the KINDL-R self-report) were compared between patients receiving NF or SMT. Results: Significant improvements in ADHD symptoms were achieved similarly in both treatment groups, whilst QoL and self-concept improved after SMT only. Conclusion: This treatment study provides further evidence that SMT and NF may reduce core symptoms, but SMT may also improve patients' self-concept and QoL and may thus in its current form be the favorable treatment option in naturalistic settings. However, several limitations of the current study implicate that further research is required before definitive conclusions and recommendations for clinical practice can be given. Clinical trial registration: [www.clinicaltrials.gov], identifier [NCT01879644].

Symptom and performance validity in samples of adults at clinical evaluation of ADHD: a replication study using machine learning algorithms.

INTRODUCTION: Research has shown non-trivial base rates of noncredible symptom report and performance in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. The goal of this study is to estimate and replicate base rates of symptom and performance validity test failure in the clinical evaluation of adult ADHD and derive prediction models based on routine clinical measures. METHODS: This study reuses data of a previous publication of 196 adults seeking ADHD assessment and replicates the findings on an independent sample of 700 adults recruited in the same referral context. Measures of symptom and performance validity (one SVT, two PVTs) were applied to estimate base rates. Prediction models were developed using machine learning. RESULTS: Both samples showed substantial rates of noncredible symptom report (one SVT failure: 35.7% - 36.6%), noncredible test performance (one PVT failure: 32.1% - 49.3%; two PVT failures: 18.9% - 27.3%), or both (each one SVT and PVT failure: 13.3% - 22.4%; one SVT and two PVT failures: 9.7% - 13.7%). Machine learning algorithms resulted in generally moderate to weak prediction models, with advantages of the reused sample compared to the independent replication sample. Associations between measures of symptom and performance validity were negligible to small. CONCLUSIONS: This study highlights the necessity to include measures of symptom and performance validity in the clinical evaluation of adult ADHD. Further, this study demonstrates the difficulty to characterize the group failing symptom or performance validity assessment.

Can neurophysiological markers of anticipation and attention predict ADHD severity and neurofeedback outcomes?

Neurophysiological measures of preparation and attention are often atypical in ADHD. Still, replicated findings that these measures predict which patients improve after Neurofeedback (NF), reveal neurophysiological specificity, and reflect ADHD-severity are limited. METHODS: We analyzed children's preparatory (CNV) and attentional (Cue-P3) brain activity and behavioral performance during a cued Continuous Performance Task (CPT) before and after slow cortical potential (SCP)-NF or semi-active control treatment (electromyogram biofeedback). Mixed-effects models were performed with 103 participants at baseline and 77 were assessed for pre-post comparisons focusing on clinical outcome prediction, specific neurophysiological effects of NF, and associations with ADHD-severity. RESULTS: Attentional and preparatory brain activity and performance were non-specifically reduced after treatment. Preparatory activity in the SCP-NF group increased with clinical improvement. Several performance and brain activity measures predicted non-specific treatment outcome. CONCLUSION: Specific neurophysiological effects after SCP-NF were limited to increased neural preparation associated with improvement on ADHD-subscales, but several performance and neurophysiological measures of attention predicted treatment outcome and reflected symptom severity in ADHD. The results may help to optimize treatment.

Performance variability, impulsivity errors and the impact of incentives as gender-independent endophenotypes for ADHD.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is one of the most common and highly heritable child psychiatric disorders. There is strong evidence that children with ADHD show slower and more variable responses in tasks such as Go/Nogo tapping aspects of executive functions like sustained attention and response control which may be modulated by motivational factors and/or state-regulation processes. The aim of this study was (1) to determine if these executive functions may constitute an endophenotype for ADHD; (2) to investigate for the first time whether known modulators of these executive functions may also be familial; and (3) to explore whether gender has an impact on these measures. METHODS: Two hundred and five children with ADHD combined type, 173 nonaffected biological siblings and 53 controls with no known family history of ADHD were examined using a Go/Nogo task in the framework of a multi-centre study. Performance-measures and modulating effects of event-rate and incentives were examined. Shared familial effects on these measures were assessed, and the influence of gender was tested. RESULTS: Children with ADHD responded more slowly and variably than nonaffected siblings or controls. Nonaffected siblings showed intermediate scores for reaction-time variability, false alarms and omission errors under fast and slow event-rates. A slower event-rate did not lead to reduced performance specific to ADHD. In the incentive condition, mean reaction-times speeded up and became less variable only in children with ADHD and their nonaffected siblings, while accuracy was improved in all groups. Males responded faster, but also committed more false alarms. There were no interactions of group by gender. CONCLUSIONS: Reaction-time variability and accuracy parameters could be useful neuropsychological endophenotypes for ADHD. Performance-modulating effects of incentives suggested a familially driven motivational dysfunction which may play an important role on etiologic pathways and treatment approaches for ADHD. The effects of gender were independent of familial effects or ADHD-status, which in turn suggests that the proposed endophenotypes are independent of gender.

Neurofeedback training in children with ADHD: 6-month follow-up of a randomised controlled trial.

Neurofeedback (NF) could help to improve attentional and self-management capabilities in children with attention-deficit/hyperactivity disorder (ADHD). In a randomised controlled trial, NF training was found to be superior to a computerised attention skills training (AST) (Gevensleben et al. in J Child Psychol Psychiatry 50(7):780-789, 2009). In the present paper, treatment effects at 6-month follow-up were studied. 94 children with ADHD, aged 8-12 years, completed either 36 sessions of NF training (n = 59) or a computerised AST (n = 35). Pre-training, post-training and follow-up assessment encompassed several behaviour rating scales (e.g., the German ADHD rating scale, FBB-HKS) completed by parents. Follow-up information was analysed in 61 children (ca. 65%) on a per-protocol basis. 17 children (of 33 dropouts) had started a medication after the end of the training or early in the follow-up period. Improvements in the NF group (n = 38) at follow-up were superior to those of the control group (n = 23) and comparable to the effects at the end of the training. For the FBB-HKS total score (primary outcome measure), a medium effect size of 0.71 was obtained at follow-up. A reduction of at least 25% in the primary outcome measure (responder criterion) was observed in 50% of the children in the NF group. In conclusion, behavioural improvements induced by NF training in children with ADHD were maintained at a 6-month follow-up. Though treatment effects appear to be limited, the results confirm the notion that NF is a clinically efficacious module in the treatment of children with ADHD.

[The significance of functional psychophysiological methods in child and adolescent psychiatry]. / Bedeutung funktioneller psychophysiologischer Methoden in der Kinder- und Jugendpsychiatrie.

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.

BEST FOR CAN - bringing empirically supported treatments to children and adolescents after child abuse and neglect: study protocol.

Background: Despite a large body of evidence demonstrating the effectiveness of psychotherapy for posttraumatic stress for children and adolescents, the adoption of empirically supported treatments (ESTs) in routine care is low. Objective: This implementation study aims to evaluate the dissemination of Trauma-Focused Cognitive Behavioural Therapy (TF-CBT) for children and adolescents with posttraumatic stress symptoms (PTSS) after child abuse and neglect (CAN) with a focus on supervision. Method: In a cluster-randomized controlled trial, the study will evaluate the implementation of TF-CBT focussing on the training of therapists including the provision of supervision. The effectiveness of specialized trauma-focused supervision will be compared to supervision as usual with respect to the successful implementation of TF-CBT for youths with PTSS administered by psychotherapists with different levels of professional experience. The primary outcome is whether the patient receives a treatment with sufficient adherence to the TF-CBT manual. The unit of randomization will be the therapists. The main outcome will be analysed using multilevel logistic regressions. Secondary outcomes will concern further patient-related (reduction of PTSS and depressive symptoms) and therapist-related (professional quality of life) variables. Additional exploratory analyses are planned. Discussion: Since the trial is designed as an implementation study, it permits naturalistic referrals to the participating therapists by patients, caregivers, child and youth welfare agencies and paediatricians. The strict primary outcome will help evaluating the role of model-based supervision in the implementation process. The explorative outcomes will evaluate whether implementation success translates into better patient outcomes. We expect that the dissemination measures will lead to a successful implementation of TF-CBT and promote sustainable structures in routine care that will remain in place after study completion and offer access to ESTs for future children and youths with a history of CAN.

Antecedentes: A pesar de que existe un robusto cuerpo de evidencia que demuestra la efectividad de la psicoterapia para el trastorno de estrés postraumático en niños y adolescentes, la adherencia a tratamientos basados en evidencia (TBEs) es baja en la atención de rutina.Objetivo: El objetivo de este estudio de implementación es el de evaluar la difusión de la terapia cognitiva conductual enfocada en trauma (TCC-ET) para niños y adolescentes con síntomas de estrés postraumático (SEPT) secundarios al abuso y la negligencia infantiles con un enfoque en la supervisión.Método: Dentro de un estudio por racimos controlado y aleatorizado, el estudio evaluará la implementación de la TCC-ET enfocándose en el entrenamiento de terapeutas e incluyendo el brindar supervisión a este entrenamiento. La efectividad de la supervisión especializada enfocada en trauma se comparará con la supervisión habitual ya realizada en la implementación exitosa de la TCC-ET para jóvenes con SEPT brindada por psicoterapeutas con diferentes niveles de experiencia profesional. El objetivo primario es evaluar si el paciente recibe un tratamiento con adecuada adherencia al manual de la TCC-ET. La unidad de aleatorización serán los terapeutas. El objetivo principal será analizado empleando regresiones logísticas multinivel. Los objetivos secundarios serán variables relacionadas con preocupaciones asociadas a los pacientes (reducción de SEPT y de síntomas depresivos) y asociadas a los terapeutas (calidad de vida profesional). Se planea realizar análisis exploratorios adicionales.Discusión: Debido a que el ensayo clínico está diseñado como un estudio de implementación, este permite generar derivaciones naturalísticas a los terapeutas participantes por parte de los pacientes, cuidadores, organismos de bienestar de niños y adolescentes y por pediatras. El riguroso objetivo primario ayudará a evaluar el papel de la supervisión basada en modelos durante el proceso de implementación. Los resultados exploratorios evaluarán si el éxito de la implementación se traduce en mejores resultados para los pacientes. Se espera que las medidas adoptadas para la difusión de la TCC-ET conlleven a su implementación exitosa y promuevan estructuras sostenibles en el cuidado rutinario que continúen luego de terminado el estudio. Además, se espera que estas medidas permitan que en un futuro los niños y jóvenes con antecedentes de abuso y negligencia infantiles cuenten con acceso a TBEs.

Is neurofeedback an efficacious treatment for ADHD? A randomised controlled clinical trial.

BACKGROUND: For children with attention deficit/hyperactivity disorder (ADHD), a reduction of inattention, impulsivity and hyperactivity by neurofeedback (NF) has been reported in several studies. But so far, unspecific training effects have not been adequately controlled for and/or studies do not provide sufficient statistical power. To overcome these methodological shortcomings we evaluated the clinical efficacy of neurofeedback in children with ADHD in a multisite randomised controlled study using a computerised attention skills training as a control condition. METHODS: 102 children with ADHD, aged 8 to 12 years, participated in the study. Children performed either 36 sessions of NF training or a computerised attention skills training within two blocks of about four weeks each (randomised group assignment). The combined NF treatment consisted of one block of theta/beta training and one block of slow cortical potential (SCP) training. Pre-training, intermediate and post-training assessment encompassed several behaviour rating scales (e.g., the German ADHD rating scale, FBB-HKS) completed by parents and teachers. Evaluation ('placebo') scales were applied to control for parental expectations and satisfaction with the treatment. RESULTS: For parent and teacher ratings, improvements in the NF group were superior to those of the control group. For the parent-rated FBB-HKS total score (primary outcome measure), the effect size was .60. Comparable effects were obtained for the two NF protocols (theta/beta training, SCP training). Parental attitude towards the treatment did not differ between NF and control group. CONCLUSIONS: Superiority of the combined NF training indicates clinical efficacy of NF in children with ADHD. Future studies should further address the specificity of effects and how to optimise the benefit of NF as treatment module for ADHD.

Delay and reward choice in ADHD: an experimental test of the role of delay aversion.

Children with attention deficit/hyperactivity disorder (ADHD) choose smaller sooner (SS) over larger later (LL) rewards more than controls. Here we assess the contributions of impulsive drive for immediate rewards (IDIR) and delay aversion (DAv) to this pattern. We also explore the characteristics of, and the degree of familiality in, ADHD SS responders. We had 360 ADHD probands; 349 siblings and 112 controls (aged between 6 to 17 years) chose between SS (1 point after 2 s) and LL reward (2 points after 30 s) outcomes on the Maudsley Index of Delay Aversion (Kuntsi, Oosterlaan, & Stevenson, 2001): Under one condition SS choice led to less overall trial delay under another it did not. ADHD participants chose SS more than controls under both conditions. This effect was larger when SS choice reduced trial delay. ADHD SS responders were younger, had lower IQ, more conduct disorder and had siblings who were more likely to be SS responders themselves. The results support a dual component model in which both IDIR and DAv contribute to SS choice in ADHD. SS choice may be a marker of an ADHD motivational subtype.

Critical role of human T-lymphotropic virus type 1 accessory proteins in viral replication and pathogenesis.

Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated with a diverse range of lymphoproliferative and neurodegenerative diseases, yet pathogenic mechanisms induced by the virus remain obscure. This complex retrovirus contains typical structural and enzymatic genes but also unique regulatory and accessory genes in four open reading frames (ORFs) of the pX region of the viral genome (pX ORFs I to IV). The regulatory proteins encoded by pX ORFs III and IV, Tax and Rex, respectively, have been extensively characterized. In contrast the contribution of the four accessory proteins p12(I), p27(I), p13(II), and p30(II), encoded by pX ORFs I and II, to viral replication and pathogenesis remained unclear. Proviral clones that are mutated in either pX ORF I or II, while fully competent in cell culture, are severely limited in their replicative capacity in a rabbit model. Emerging evidence indicates that the HTLV-1 accessory proteins are critical for establishment of viral infectivity, enhance T-lymphocyte activation, and potentially alter gene transcription and mitochondrial function. HTLV-1 pX ORF I expression is critical to the viral infectivity in resting primary lymphocytes, suggesting a role for p12(I) in lymphocyte activation. The endoplasmic reticulum and cis-Golgi localizing p12(I), encoded from pX ORF I, activates NFAT, a key T-cell transcription factor, through calcium-mediated signaling pathways and may lower the threshold of lymphocyte activation via the JAK/STAT pathway. In contrast p30(II) localizes to the nucleus and represses viral promoter activity, but may regulate cellular gene expression through p300/CBP or related coactivators of transcription. p13(II) targets mitochondrial proteins, where it alters the organelle morphology and may influence energy metabolism. Collectively, studies of the molecular functions of the HTLV-1 accessory proteins provide insight into strategies used by retroviruses that are associated with lymphoproliferative diseases.

Normal response inhibition in boys with Tourette syndrome.

BACKGROUND: Inhibitory deficits are often a matter of debate in the pathophysiology of Tourette syndrome (TS). Previous neuropsychological studies on behavioral inhibition revealed equivocal results. METHODS: To overcome existing shortcomings (e.g. confounders like medication status, comorbid conditions) we compared medication naïve boys (10-14 years) suffering exclusively from TS with age, gender and IQ matched healthy controls using a highly demanding Go/Nogo task that controls for novelty effects. RESULTS: The performance did not differ between boys with TS and healthy boys. CONCLUSION: In TS normal response inhibition performance as measured by a Go/Nogo task can be assumed. However, there might be neurophysiological abnormalities in TS possibly related to compensatory mechanisms to control for tics. Hence, further studies combining neuropsychological and neurophysiological methods (e.g. electroencephalography, fMRI) using the same strictly controlled design along the whole range of development and tic severity are recommended.

Cognitive Control Over Visual Motion Processing - Are Children With ADHD Especially Compromised? A Pilot Study of Flanker Task Event-Related Potentials.

Performance deficits and diminished brain activity during cognitive control and error processing are frequently reported in attention deficit/hyperactivity disorder (ADHD), indicating a "top-down" deficit in executive attention. So far, these findings are almost exclusively based on the processing of static visual forms, neglecting the importance of visual motion processing in everyday life as well as important attentional and neuroanatomical differences between processing static forms and visual motion. For the current study, we contrasted performance and electrophysiological parameters associated with cognitive control from two Flanker-Tasks using static stimuli and moving random dot patterns. Behavioral data and event-related potentials were recorded from 16 boys with ADHD (combined type) and 26 controls (aged 8-15 years). The ADHD group showed less accuracy especially for moving stimuli, and prolonged response times for both stimulus types. Analyses of electrophysiological parameters of cognitive control revealed trends for diminished N2-enhancements and smaller error-negativities (indicating medium effect sizes), and we detected significantly lower error positivities (large effect sizes) compared to controls, similarly for both static and moving stimuli. Taken together, the study supports evidence that motion processing is not fully developed in childhood and that the cognitive control deficit in ADHD is of higher order and independent of stimulus type.