Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice

Etude rétrospective de la prévalence et des caractéristiques cliniques des tentatives de suicide chez l enfant

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Postural Instability in Children with ADHD Is Improved by Methylphenidate

International audienceThe aim of this study was to examine postural control in children with ADHD and explore the effect of methylphenidate (MPH), using spatial and temporal analyses of the center of pressure (CoP). Thirty-eight children with ADHD (mean age 9.82 ± 0.37 years) and 38 sex- age- and IQ-matched children with typically development were examined. Postural stability was evaluated using the Multitest Equilibre machine (Framiral®) at inclusion and after 1 month of MPH in children with ADHD. Postural stability was assessed by recording under several conditions: with eyes open and fixed on a target, with eyes closed and with vision perturbed by optokinetic stimulation, on stable and unstable platforms. At inclusion, we observed poor spatial and temporal postural stability in children with ADHD. The spectral power index was higher in children with ADHD than in controls. Canceling time was shorter at low and medium frequencies of oscillation and longer at higher frequencies in children with ADHD. After 1 month of MPH, the surface area and mean velocity of the CoP decreased significantly under the most complex conditions (unstable platform in the absence of proprioceptive and visual inputs). The spectral power index decreased significantly after MPH while the canceling time did not change. Poor postural control in children with ADHD supports the hypothesis of cerebellar dysfunction in this disorder. Postural control could be improved by a more efficient processing of sensory inputs (a high-level process), as suggested by the decrease in spectral power index after MPH without changes in the canceling time (a low-level process)

Association between suicidal spectrum behaviors and Attention-Deficit/Hyperactivity Disorder: a systematic review and meta-analysis

The relationship between ADHD and suicidal spectrum behaviors (SSBs) remains uncertain. We conducted the first meta-analysis on the association between ADHD and SSBs taking possible confounders into account. Based on a pre-registered protocol (PROSPERO-CRD42018093003), we searched Pubmed, Ovid and Web of Knowledge databases through April 6th, 2018, with no language/publication type restrictions, and contacted study authors for unpublished data/information. From a pool of 2798 references, we retained 57 studies. Random-effects models were performed. Study quality was rated using the Newcastle-Ottawa Scale. After pooling crude ORs, we found a significant association between ADHD and suicidal attempts (2.37, 95% CI = 1.64–3.43; I2 = 98.21), suicidal ideations (3.53, 2.94–4.25; I2 = 73.73), suicidal plans (4.54, 2.46–8.37; I2 = 0), and completed suicide (6.69, 3.24–17.39; I2 = 87.53). Results did not substantially change when pooling adjusted ORs. Findings were also in general robust to sensitivity analyses to assess possible moderators. Awareness of the association between ADHD and SSBs should contribute to more effectively prevent SSBs

Oculomotor Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder Are Improved by Methylphenidate

International audienceBackground: There are relatively few studies of saccadic eye movements in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to examine inhibitory abilities of eye movements in children with ADHD and to explore the effect of methylphenidate (MPH) on eye movement performance.Methods: Thirty-one children with ADHD (mean age 9.9-0.4 years) and 31 sex-, age-, and IQ-matched children with normal development were examined. Saccades elicited not only by the gap, step, overlap, and antisaccade paradigms but also a simple fixation paradigm have been recorded using an eye tracker. The latency of each type of saccade, the error rate of antisaccades, and the number of saccades made during fixation have been measured.Results: Children with ADHD and naive to treatment with respect to controls showed significantly shorter mean latency of voluntary saccades (overlap paradigm), more frequent errors during the antisaccade paradigm, and higher number of saccades made during fixation. After 1 month of MPH treatment, all these parameters changed significantly and reached control values.Conclusion: Taken together, these results suggest that oculomotor abilities are poor in children with ADHD, which may correlate with deficits in inhibitory mechanisms. Treatment with MPH improves oculomotor performances through adaptive strategies, which may involve brain structures related to cognitive inhibition

Motor impairment in children with autistic spectrum disorder and in children with attention deficit hyperactivity disorder

International audienceWe summarize postural instabilities in children with autistic spectrum disorder (ASD) and in children with attention deficit hyperactivity disorder (ADHD), and we reported behavioral results suggesting poor cerebellar integration. We conclude that postural measures could be a promising method with which to indirectly observe cerebellar performance in children developmental disabilities such as ASD and/or ADHD

Discriminant validity of spatial and temporal postural index in children with neurodevelopmental disorders

International audienceAutism, learning disabilities and attention deficit/hyperactive disorder are often comorbid disorders. In order to try and find some markers that might be transnosographic, we hypothesized that abnormal postural sway profiles may discriminate children with neurodevelopmental disorders (NDDs) from typically developing children. The aim of our study was thus to compare spatial and temporal measures of the Center of Pressure in three distinct groups of children with NDDs (high functioning autism spectrum disorders, learning disabilities (dys-lexia) and attention deficit/hyperactive disorders) and in typically developing children. Postural performances were thus evaluated in 92 children (23 per group, sex-, age-and IQ-matched groups) by using the Multitest Equilibre platform (Framiral ®). Two viewing conditions (eyes open and eyes closed) were tested on a stable and unstable platform. Results reported similar poor postural instability for the three groups of children with NDDs with respect to the typically developing children, and this was observed for both spatial as well as temporal analysis of displacement of the center of pressure. Such postural instability observed in children with NDDs could be due to impairment in using sensorial inputs to eliminate body sway, probably due to poor cerebellar integration

Attentional Lapses in Attention-Deficit/Hyperactivity Disorder: Blank Rather Than Wandering Thoughts

International audiencePeople with attention-deficit/hyperactivity disorder (ADHD) have difficulties sustaining their attention on external tasks. Such attentional lapses have often been characterized as the simple opposite of external sustained attention, but the different types of attentional lapses, and the subjective experiences to which they correspond, remain unspecified. In this study, we showed that unmedicated children (ages 6–12) with ADHD, when probed during a standard go/no-go task, reported more mind blanking (a mental state characterized by the absence of reportable content) than did control participants. This increase in mind blanking happened at the expense of both focused and wandering thoughts. We also found that methylphenidate reverted the level of mind blanking to baseline (i.e., the level of mind blanking reported by control children without ADHD). However, this restoration led to mind wandering more than to focused attention. In a second experiment, we extended these findings to adults who had subclinical ADHD. These results suggest that executive functions impaired in ADHD are required not only to sustain external attention but also to maintain an internal train of thought

Abnormal bone mineral density and content in girls with early-onset anorexia nervosa

International audienceBackground: Early-onset anorexia nervosa (EO-AN) represents a significant clinical burden to paediatric and mental health services. The impact of EO-AN on bone mineral abnormalities has not been thoroughly investigated due to inadequate control for pubertal status. In this study, we investigated bone mineral abnormalities in girls with EO-AN regardless of pubertal development stage. Method: We conducted a cross-sectional study of 67 girls with EO-AN (median age = 12.4 [10.9-13.7 years]) after a median duration of disease of 1.3 [0.6-2.0] years, and 67 healthy age-, sex-, pubertal status-matched control subjects. We compared relevant bone mineral parameters between groups: the total body bone mineral density [TB-BMD], the lumbar spine BMD [LS-BMD], the total body bone mineral content [TB-BMC] and the ratio of the TB-BMC to lean body mass [TB-BMC/LBM]. Results: TB-BMD, TB-BMC, LS-BMD and TB-BMC/LBM were all significantly lower in patients with AN compared to controls. In the EO-AN group, older age, later pubertal stages and higher lean body mass were associated with higher TB-BMC, TB-BMD, and LS-BMD values. Discussion: Girls with EO-AN displayed deficits in bone mineral content and density after adjustment for pubertal maturation. Age, higher pubertal stage and lean body mass were identified as determinants of bone maturation in the clinical population of patients with EO-AN. Bone health should be promoted in patients, specifically in those with an onset of disorder before 14 years old and with a delayed puberty

Interactions between eye movements and posture in children with neurodevelopmental disorders

International audienceIn everyday life, our activities frequently involve the simultaneous performance of two or more tasks. Sharing attention between two concurrent tasks may result in a decrease in performance specifically among children with neurodevelopmental disorders. The objective of the study was to determine whether the influence of postural conditions (sitting condition, single task; standing condition, dual task) on eye movement performances on three visual tasks with high attentional load (visually-guided saccade task, memory-guided saccade task and fixation task) was different in children with neurodevelopmental disorders (attention deficit and hyperactive disorder, dyslexia, and high functioning autism spectrum disorder) when compared to typically developing children. One hundred and four children (26 per group, sex-age-and IQ-matched groups) were evaluated. We found that for the fixation task only, the three groups of children with neurodevelopmental disorders had poorer eye movements performances in the standing condition compared to the sitting condition while no such difference was found for typically developing children. We suggest that children with neurodevelopmental disorders have fewer attentional resources available for performing correctly oculomotor tasks with high atten-tional load leading to impairment of these tasks for maintaining a good level of postural stability