Personalized at-home neurofeedback compared to long-acting methylphenidate in children with ADHD: NEWROFEED, a European randomized noninferiority trial.

BACKGROUND: Neurofeedback is considered a promising intervention for the treatment of attention-deficit hyperactivity disorder (ADHD). NEWROFEED is a prospective, multicentre, randomized (3:2), reference drug-controlled trial in children with ADHD aged between 7 and 13 years. The main objective of NEWROFEED was to demonstrate the noninferiority of personalized at-home neurofeedback (NF) training versus methylphenidate in the treatment of children with ADHD. METHODS: The NF group (n = 111) underwent eight visits and two treatment phases of 16 to 20 at-home sessions with down-training of the theta/beta ratio (TBR) for children with high TBR and enhancing the sensorimotor rhythm (SMR) for the others. The control group (n = 67) received optimally titrated long-acting methylphenidate. The primary endpoint was the change between baseline and endpoint in the Clinician ADHD-RS-IV total score in the per-protocol population (90 NF/59 controls). TRIAL REGISTRATION: US National Institute of Health, ClinicalTrials.gov #NCT02778360. RESULTS: Our study failed to demonstrate noninferiority of NF versus methylphenidate (mean between-group difference 8.09 90% CI [8.09; 10.56]). However, both treatment groups showed significant pre-post improvements in core ADHD symptoms and in a broader range of problems. Reduction in the Clinician ADHD-RS-IV total score between baseline and final visit (D90) was 26.7% (SMD = 0.89) in the NF and 46.9% (SMD = 2.03) in the control group. NF effects increased whereas those of methylphenidate were stable between intermediate and final visit. CONCLUSIONS: Based on clinicians' reports, the effects of at-home NF were inferior to those of methylphenidate as a stand-alone treatment.

A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms.

OBJECTIVE: Clinical trials and inconclusive meta-analyses have investigated the effects of omega-3 supplements in children with Attention-Deficit Hyperactivity Disorder (ADHD). We performed a randomised placebo-controlled trial to evaluate the efficacy of omega-3 fatty acids. METHODS: Children aged 6-15 years with established diagnosis of ADHD were randomised 1:1 to receive either supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or a placebo for 3 months. Psychotropic or omega-3-containing treatments were not authorised during the study. The primary outcome was the change in the Attention-Deficit Hyperactivity Disorder Rating Scale version 4 (ADHD-RS-IV). Other outcomes included safety, lexical level (Alouette test), attention (Test of Attentional Performance for Children-KiTAP), anxiety (48-item Conners Parent Rating Scale-Revised-CPRS-R), and depression (Children's Depression Inventory-CDI). RESULTS: Between 2009 and 2011, 162 children were included in five French child psychiatry centres. The mean age was 9.90 (SD 2.62) years and 78.4% were boys. The inclusion ADHD-RS-IV at was 37.31 (SD 8.40). The total ADHD-RS-IV score reduction was greater in the placebo group than in the DHA-EPA group: -19 (-26, -12)  % and -9.7 (-16.6, -2.9) %, respectively, p = 0.039. The other components of the Conners score had a similar variation but the differences between groups were not significant. Two patients in the DHA-EPA group and none in the placebo group experienced a severe adverse event (hospitalisation for worsening ADHD symptoms). CONCLUSION: This study did not show any beneficial effect of omega-3 supplement in children with mild ADHD symptoms.

Validation of the French Version of Conners' Parent Rating Scale Revised, Short Version: Factorial Structure and Reliability.

OBJECTIVE: Attention-deficit hyperactivity disorder is one of the most frequent neurodevelopmental disorders. Its diagnosis requires reference questionnaires such as the Conners' Parent Rating Scale (CPRS). Presently, in French-speaking countries, a few translations of the revised short CPRS have been put to use without previous formal validation. We sought here for the validation of a French version (Lausanne, Switzerland) of the revised short CPRS regarding construct validity, internal consistency, and item reliability in a sample of French schoolchildren. METHOD: The study involved 795 children and adolescents aged 9 to 19 years from a single school. The factorial structure and item reliability were assessed with a confirmatory factor analysis for ordered categorical variables. The dimension internal consistency was assessed with Guttman's lambda 6 coefficient. RESULTS: The results confirmed the original and strong 3-dimensional factorial structure (Oppositional, Cognitive Problems/Inattention, and Hyperactivity), showed satisfactory item reliability, and indicated a good dimension internal consistency (Guttman's lambda 6 coefficient: 0.87, 0.90, and 0.82, respectively, to the 3 dimensions). CONCLUSIONS: Thus, the Lausanne French version of the revised short CPRS may be considered validated regarding construct validity and item and dimension reliability; it can be now more confidently used in clinical practice.

Atopic Dermatitis and Self-Image Design: A Real-Life Study in Children Using Drawings.

Background: Atopic dermatitis (AD) induces alterations of external appearance and self-esteem, with impact on the personal development of the children. However, tools for estimating such suffering are lacking. We aimed to assess how children with AD represent themselves through their drawings. Methods: In this retrospective study, we included children (<18 years) suffering from AD who followed the instruction "draw yourself with and without eczema" at the end of a routine follow-up consultation. Drawings were interpreted with the child and then classified in different analysis groups by 5 independent evaluators. Results: A total of 64 children (41 [64.1%] girls and 23 [35.9%] boys, median [range] age 8 [3-7] years) made 64 drawings. Five groups of drawing were identified: "amputee" (n = 8, 12.5%), "identical" (n = 18, 28.1%), "sad" (n = 19, 29.7%), "complex" (n = 11, 17.2%), and "other" (n = 8, 12.5%). Univariate analysis found that age was differently distributed among the different drawing groups (P = 0.0047), as was the predominance of light colors (P = 0.038). The distribution of the other variables (gender, investigator global assessment score, active AD, and duration of activity) was not different among drawing groups. Conclusions: The drawing allows a majority of the AD children to express their self-image with and without eczema, as well as their feelings and their interactions with the environment and with their entourage. The visual tool proposed herein could be used during consultations, to (a) become aware of the need to treat AD, (b) better evaluate the impact of AD burden in childhood, and (c) adjust appropriately AD treatment.

Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD.

Introduction: Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers. Methods: Children and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response. Results: For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only. Discussion: Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

Explanatory hypotheses of the ecology of new clinical presentations of Dissociative Identity Disorders in youth.

Dissociative Identity Disorders (DIDs) are controversial psychiatric conditions encountered in clinical practice and nosology. DID as described in the international classifications has little similarity with the clinical picture of "DID" met in current youth psychiatry. From this Perspective, we hypothesize that this current clinical presentation does not satisfy the categorical criteria of the international classifications. Based on the two terminological challenges related to the definition of DID (i.e., the notion of dissociative disorders and the different meanings of the term identity), we propose to differentiate two distinct entities from each other. The first is medical and listed in diagnostic criteria of international classifications; the second comes from popular culture and refers to the vast majority of clinical presentations received in daily clinical practice-presented under the term Dissociative Identity Conditions (DIC). Since the status of DIC is a hot topic in current clinical psychiatry, we aim to identify eight possible explanations that can be provided to support its occurrence: (1) impact of iatrogenicity; (2) factors of suggestibility and desire for social acceptability; (3) psychoanalytic explanations; (4) neuropsychological explanations; (5) socio-cognitive explanations; (6) emotional labeling; (7) narrative explanations; (8) and transient illnesses explanations. In conclusion, we sustain that DIC results from a narrative interpretation of medical discourse by popular culture, developing in patients presenting undeniable distress. Such a transient disease fits in an ecological niche, which echoes the values of society, persisting under the action of a need for narrative continuity of the self.

Sleep and Psychosocial Characteristics of Children with Narcolepsy According to Their Intellectual Profile: A Case-Control Study.

Adequate intellectual abilities are a protective factor for psychosocial adjustments in chronic disorders. The main objective of this study was to assess the cognitive abilities, sleep, and psychosocial characteristics of children with narcolepsy compared to controls, according to their intellectual profile. Children underwent a polysomnography, completed an intellectual ability assessment, and filled out standardized questionnaires. The group with an intelligence quotient (IQ) in the area of high intellectual potential (high IQ, HIQ) consisted of 25 children with narcolepsy (HIQ-N, 40% boys, median age 11.5 years, 48% with obesity, 60% under treatment) and 25 controls (HIQ-C, 68% boys, median age 11.7 years). Compared to HIQ-C, HIQ-N had a lower perceptual reasoning index and fewer conduct disorders. The group with an IQ in the normal range (NIQ) consisted of 22 children with narcolepsy (NIQ-N, 55% boys, median age 12.1 years, 59% with obesity, 64% under treatment) and 21 controls (NIQ-C, 68% boys, median age 10 years). NIQ-N presented the same intellectual profile as NIQ-C but reported more school difficulties. In children with HIQ, those with narcolepsy appear to have a different cognitive profile than controls. NIQ seems to predict a greater impact of narcolepsy on daily-life functioning.

[Preteen visit]. / Consultation de la préadolescence.

Preadolescence, which is considered as an uneventful period since a long time, deserves to be rediscovered. It offers the clinician the opportunity to locate the emergence of diseases hitherto ignored (masked childhood disorders, early beginnings of adolescent pathologies), and to start the care before the pubertal transformations... The challenge is important at a time when the therapeutic alliance is simpler to establish, promotes the accompaniment of anxiety disorders in all their forms (separation anxiety, OCD), mood disorders or ADHD for example. We will touch the specificities of consultations proposed to a population more and more "sucked" by adolescence, and whose profile evolves singularly.

Validation of the French Version of Conners' Parent Rating Scale-Revised, Short Form in ADHD-Diagnosed Children and Comparison With Control Children.

Objective: The objective of this study was to examine measurement invariance and discriminant validity of the French Lausanne version (FLV) of the Conners' Parent Rating Scale-Revised, Short Form (CPRS-R:S) and assess its convergent validity against the ADHD Symptoms Rating Scale (ADHD-SRS) and the Child Behavior Checklist (CBCL). Method: A confirmatory factor analysis and Tobit models were used in 108 ADHD children (aged 6-17) vs. 794 controls (aged 9-15) and score correlations were examined between FLV and ADHD-SRS then CBCL. Results: The factorial structure and reliability of the FLV is confirmed in ADHD children. The FLV showed configural invariance, metric invariance, and scalar invariance. FLV scores were significantly higher in ADHD than in control children in all three dimensions (p < .001). There were strong correlations between FLV Hyperactivity and Cognitive problems/Inattention scores and ADHD-SRS scores of Impulsivity/Hyperactivity (r = .90) and Inattention (r = .68) and also strong correlations between FLV Opposition score and the CBCL scores of Aggressive behavior (r = .84) and Rule-breaking behavior (r = .66). Conclusion: The study brings support for validation of the FLV regarding invariance in ADHD children, discriminant validity, and convergent validity.

Sleep of Children with High Potentialities: A Polysomnographic Study.

The involvement of sleep in cognitive functioning is well known, but only a few studies have examined objective sleep parameters in children with high intellectual potential (HP). The main objective of this study was to compare sleep characteristics of 33 children with high intellectual potentialities (HP) (median 10 years old, 64% of boys) compared to 25 controls (median 11 years old, 64% of boys) and assess the difference between children with a homogeneous vs. a heterogeneous intelligence quotient (IQ) (i.e., a difference ≥15 points between verbal and non-verbal IQ). All children underwent a one-night polysomnography, an evaluation of intellectual quotient (IQ) and filled standardized questionnaires. Using non-parametric tests to compare groups' characteristics, we found that children with HP had more heterogeneous IQ, more rapid eyes movement (REM) sleep and tended to have less stage 1 sleep than controls. They also had more insomnia and sleep complaints. The high amount of REM sleep in children with HP could be advantageous for learning and could partially explain their gift. This study highlights the necessity of investigating sleep disorders in children with HP during clinical routine and reinforces the hypothesis of the involvement of nocturnal sleep, and especially REM sleep, in daytime cognition and behavior.

White matter microarchitecture and structural network integrity correlate with children intelligence quotient.

The neural substrate of high intelligence performances remains not well understood. Based on diffusion tensor imaging (DTI) which provides microstructural information of white matter fibers, we proposed in this work to investigate the relationship between structural brain connectivity and intelligence quotient (IQ) scores. Fifty-seven children (8-12 y.o.) underwent a MRI examination, including conventional T1-weighted and DTI sequences, and neuropsychological testing using the fourth edition of Wechsler Intelligence Scale for Children (WISC-IV), providing an estimation of the Full-Scale Intelligence Quotient (FSIQ) based on four subscales: verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI). Correlations between the IQ scores and both graphs and diffusivity metrics were explored. First, we found significant correlations between the increased integrity of WM fiber-bundles and high intelligence scores. Second, the graph theory analysis showed that integration and segregation graph metrics were positively and negatively correlated with WISC-IV scores, respectively. These results were mainly driven by significant correlations between FSIQ, VCI, and PRI and graph metrics in the temporal and parietal lobes. In conclusion, these findings demonstrated that intelligence performances are related to the integrity of WM fiber-bundles as well as the density and homogeneity of WM brain networks.

Validation of the French Version of Conners' Parent Rating Scale-Revised, Short Version (CPRS-R:S): Scale Measurement Invariance by Sex and Age.

Objective: ADHD is one of the most frequent neurodevelopmental disorders. In addition to clinical assessment, its diagnosis requires the use of validated and reliable behavior questionnaires such as the Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S). Though various French versions of the CPRS-R:S have been already put to use in clinical practice and research, only a few have undergone a stringent validation process. After a previous validation of the factorial structure of Lausanne French version, we sought here for the analysis of its invariance across sex and age. Method: This validation step was carried out in a rather homogeneous French population of 365 boys and 374 girls from a single school. Two-age classes were considered: children (boys and girls) aged 9 to 11 years (n = 258) and adolescents aged 12 to 15 years (n = 481). Results: Regarding age, dimension Oppositional showed a strong invariance whereas dimensions Hyperactivity and Cognitive problems/Inattention showed a partially strong invariance. Regarding sex, dimensions Oppositional and Hyperactivity showed a partially strong invariance whereas dimension Cognitive problems/Inattention showed a partially weak invariance. The distribution of the CPRS-R:S scores is given by sex and age class. Conclusion: The Lausanne French version of the CPRS-R:S, already validated regarding its factorial structure, internal consistency, and reliability, is here validated regarding its invariance across sex and age. Caution should be taken in using dimension Cognitive problems/Inattention in comparisons between boys and girls.

Normal intellectual skills in patients with Rhombencephalosynapsis.

OBJECTIVES: Rhombencephalosynapsis (RES) is a very rare cerebellar malformation. Neurodevelopmental outcome of apparently isolated RES remains poorly documented and standardized cognitive assessment, reported in only nine published cases so far, is lacking. Prenatal counselling is challenging considering the uncertain prognosis of isolated RES. The aim of this study was to focus on cognitive and motor outcome of isolated RES with a clinical description of six new cases and a detailed review of the literature. METHODS: A single-centre retrospective study of all RES patients over a 15-year period. Ataxia and fine motor skills were scored using a five-grade scale, according to the degree of disturbance of daily living. Intelligence Quotient (IQ) was established according to age-related Weschler Intelligence Scales. A systematic literature review included published cases with relevant outcome data. RESULTS: Six new cases of apparently isolated RES were reported, including three diagnosed in prenatal settings. The onset age for walking was delayed in four patients. Three patients had head shaking and three had a strabismus. One patient had a mild motor disability, one had subtle ataxia that did not impair daily life and four patients had a normal neurological examination at the last visit. Intellectual abilities were normal in all patients (full IQ score from 90 to 142), although three had ADHD. All received standard schooling. Based on these six new cases, as well as cases from 12 publications in the literature, a total of 28 patients with non-syndromic RES were analysed. Concerning motor outcome, 72% had no complaint or minimal impairment, 16% moderate and 12% severe impairment. Concerning cognitive outcome, 68% had normal cognitive skills, 18% borderline intellectual functioning and 14% moderate to severe disability.

Topological Modification of Brain Networks Organization in Children With High Intelligence Quotient: A Resting-State fMRI Study.

The idea that intelligence is embedded not only in a single brain network, but instead in a complex, well-optimized system of complementary networks, has led to the development of whole brain network analysis. Using graph theory to analyze resting-state functional MRI data, we investigated the brain graph networks (or brain networks) of high intelligence quotient (HIQ) children. To this end, we computed the "hub disruption index κ," an index sensitive to graph network modifications. We found significant topological differences in the integration and segregation properties of brain networks in HIQ compared to standard IQ children, not only for the whole brain graph, but also for each hemispheric graph, and for the homotopic connectivity. Moreover, two profiles of HIQ children, homogenous and heterogeneous, based on the differences between the two main IQ subscales [verbal comprehension index (VCI) and perceptual reasoning index (PRI)], were compared. Brain network changes were more pronounced in the heterogeneous than in the homogeneous HIQ subgroups. Finally, we found significant correlations between the graph networks' changes and the full-scale IQ (FSIQ), as well as the subscales VCI and PRI. Specifically, the higher the FSIQ the greater was the brain organization modification in the whole brain, the left hemisphere, and the homotopic connectivity. These results shed new light on the relation between functional connectivity topology and high intelligence, as well as on different intelligence profiles.

Corrigendum: Topological Modification of Brain Networks Organization in Children With High Intelligence Quotient: A Resting-State fMRI Study.

[This corrects the article DOI: 10.3389/fnhum.2019.00241.].

Hemispheric Differences in White Matter Microstructure between Two Profiles of Children with High Intelligence Quotient vs. Controls: A Tract-Based Spatial Statistics Study.

Objectives: The main goal of this study was to investigate and compare the neural substrate of two children's profiles of high intelligence quotient (HIQ). Methods: Two groups of HIQ children were included with either a homogeneous (Hom-HIQ: n = 20) or a heterogeneous IQ profile (Het-HIQ: n = 24) as defined by a significant difference between verbal comprehension index and perceptual reasoning index. Diffusion tensor imaging was used to assess white matter (WM) microstructure while tract-based spatial statistics (TBSS) analysis was performed to detect and localize WM regional differences in fractional anisotropy (FA), mean diffusivity, axial (AD), and radial diffusivities. Quantitative measurements were performed on 48 regions and 21 fiber-bundles of WM. Results: Hom-HIQ children presented higher FA than Het-HIQ children in widespread WM regions including central structures, and associative intra-hemispheric WM fasciculi. AD was also greater in numerous WM regions of Total-HIQ, Hom-HIQ, and Het-HIQ groups when compared to the Control group. Hom-HIQ and Het-HIQ groups also differed by their hemispheric lateralization in AD differences compared to Controls. Het-HIQ and Hom-HIQ groups showed a lateralization ratio (left/right) of 1.38 and 0.78, respectively. Conclusions: These findings suggest that both inter- and intra-hemispheric WM integrity are enhanced in HIQ children and that neural substrate differs between Hom-HIQ and Het-HIQ. The left hemispheric lateralization of Het-HIQ children is concordant with their higher verbal index while the relative right hemispheric lateralization of Hom-HIQ children is concordant with their global brain processing and adaptation capacities as evidenced by their homogeneous IQ.

Asperger syndrome and early-onset schizophrenia associated with a novel MECP2 deleterious missense variant.

Methyl-CpG-binding protein 2 (MECP2) deleterious variants, which are responsible for Rett syndrome in girls, are involved in a wide spectrum of developmental disabilities in males. A neuropsychiatric phenotype without intellectual disability is uncommon in patients with MECP2 deleterious variants. We report on two dizygotic twins with an MECP2-related psychiatric disorder without intellectual disability. Neuropsychological and psychiatric phenotype assessments were performed, and a genetic analysis was carried out. Both patients fulfilled the Pervasive Developmental Disorder criteria on Autism Diagnostic Observation Schedule and Asperger syndrome criteria on Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). One patient developed early-onset schizophrenia (DSM-IV criteria) with two acute psychotic episodes, the latest one following corticosteroids and sodium valproate intake, with major hyperammonemia. A novel MECP2 gene transversion c.491 G>T [p.(Ser164Ile)] was found in both twins. Pathogenicity of this variant was considered on the basis of strong clinical and molecular data. The underlying molecular basis of neuropsychiatric disorders may have important consequences on genetic counseling and therapeutic strategies.

Wechsler profiles in referred children with intellectual giftedness: Associations with trait-anxiety, emotional dysregulation, and heterogeneity of Piaget-like reasoning processes.

BACKGROUND/PURPOSE: It is common that intellectually gifted children (IQ ≥ 130) are referred to paediatric or child neuropsychiatry clinics for socio-emotional problems and/or school underachievement or maladjustment. Among them, those displaying developmental asynchrony - a heterogeneous developmental pattern reflected in a significant verbal-performance discrepancy (SVPD) on Wechsler's intelligence profile - are thought to be more emotionally and behaviourally impaired than others. Our purpose was to investigate this clinical dichotomy using a cognitive psychopathological approach. METHODS: Trait-anxiety and emotional dysregulation were investigated in two groups of referred gifted children (n = 107 and 136, respectively), a pilot-study of reasoning processes on extensive Piaget-like tasks was also performed in an additional small group (n = 12). RESULTS: Compared to those with a homogenous Wechsler profile, children with a SVPD exhibited: 1) a decreased prevalence of social preoccupation-anxiety (11.1% versus 27.4%; p < 0.05); 2) an increased prevalence of emotional dysregulation (58.7% versus 41.3%; p < 0.05); and 3) an increased prevalence of pathological cognitive disharmony on Piaget-like tasks (87.5% versus 0.0%; p < 0.05). CONCLUSION: The results support a clinical dichotomy of behaviourally-impaired children with intellectual giftedness, with developmentally asynchronous ones exhibiting more severe psychopathological features. This suggests that developmental asynchrony matters when examining emotional and behavioural problems in gifted children and call for further investigation of this profile.