Hugo Peyre

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

SHANK 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.

Gender differences in autism spectrum disorders: Divergence among specific core symptoms

Community‐based studies have consistently shown a sex ratio heavily skewed towards males in autism spectrum disorders (ASD). The factors underlying this predominance of males are largely unknown, but the way girls score on standardized categorical diagnostic tools might account for the underrecognition of ASD in girls. Despite the existence of different norms for boys and girls with ASD on several major screening tests, the algorithm of the Autism Diagnosis Interview‐Revised (ADI‐R) has not been reformulated. The aim of our study was to investigate which ADI‐R items discriminate between males and females, and to evaluate their weighting in the final diagnosis of autism. We then conducted discriminant analysis (DA) on a sample of 594 probands including 129 females with ASD, recruited by the Paris Autism Research International Sibpair (PARIS) Study. A replication analysis was run on an independent sample of 1716 probands including 338 females with ASD, recruited through the Autism Genetics Resource Exchange (AGRE) program. Entering the raw scores for all ADI‐R items as independent variables, the DA correctly classified 78.9% of males and 72.9% of females (P < 0.001) in the PARIS cohort, and 72.2% of males and 68.3% of females (P < 0.0001) in the AGRE cohort. Among the items extracted by the stepwise DA, four belonged to the ADI‐R algorithm used for the final diagnosis of ASD. In conclusion, several items of the ADI‐R that are taken into account in the diagnosis of autism significantly differentiates between males and females. The potential gender bias thus induced may participate in the underestimation of the prevalence of ASD in females. Autism Res 2016,.

Examining sex differences in DSM-IV borderline personality disorder symptom expression using Item Response Theory (IRT).

Limited literature suggests that there may be differences in how women and men experience borderline personality disorder (BPD) symptoms. The aim of the current study was to use methods based on item response theory (IRT) to examine whether, when equating for levels of BPD symptom severity, there are sex differences in the likelihood of reporting DSM-IV BPD symptoms. We conducted these analyses using a large, nationally representative sample from the USA (n = 34,653), the second wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Data from women and men were compared. There were statistically and clinically significant sex differences for 3 out of the 9 DSM-IV BPD symptoms. We found that women were more likely to experience suicidal/self-mutilation behavior, affective instability and chronic feelings of emptiness and tended to be less likely to endorse impulsivity at lower levels of borderline personality disorder severity than men, while affective instability and chronic feelings of emptiness appeared to be significantly less discriminant in terms of severity in men than in women. There were no significant differences between women and men on the remaining DSM-IV symptoms. Overall, our findings indicate substantial sex differences in borderline personality disorder symptom expression. Although our results may reflect sex-bias in diagnostic criteria, they are in keeping with recent arguments suggesting that BPD could be understood as a clinical phenomenon that may partially differ in men and women.

Persistent maternal depressive symptoms trajectories influence children's IQ: The EDEN mother–child cohort

This study assessed the association between timing and course of maternal depression from pregnancy onwards and childrens cognitive development at ages 5 to 6. Potential interaction effects with child sex and family socioeconomic status were explored.

Effects of Antenatal Maternal Depression and Anxiety on Children's Early Cognitive Development: A Prospective Cohort Study

Introduction Studies have shown that depression or anxiety occur in 10–20% of pregnant women. These disorders are often undertreated and may affect mothers and children’s health. This study investigates the relation between antenatal maternal depression, anxiety and children’s early cognitive development among 1380 two-year-old children and 1227 three-year-old children. Methods In the French EDEN Mother-Child Cohort Study, language ability was assessed with the Communicative Development Inventory at 2 years of age and overall development with the Ages and Stages Questionnaire at 3 years of age. Multiple regressions and structural equation modeling were used to examine links between depression, anxiety during pregnancy and child cognitive development. Results We found strong significant associations between maternal antenatal anxiety and poorer children’s cognitive development at 2 and 3 years. Antenatal maternal depression was not associated with child development, except when antenatal maternal anxiety was also present. Both postnatal maternal depression and parental stimulation appeared to play mediating roles in the relation between antenatal maternal anxiety and children’s cognitive development. At 3 years, parental stimulation mediated 13.2% of the effect of antenatal maternal anxiety while postnatal maternal depression mediated 26.5%. Discussion The partial nature of these effects suggests that other mediators may play a role. Implications for theory and research on child development are discussed.

Attention-deficit/hyperactivity disorder symptom expression: a comparison of individual age at onset using item response theory.

BACKGROUND The DSM-IV age at onset criterion for attention-deficit/hyperactivity disorder (ADHD) has been a subject of debate. In DSM-5, the required age at onset (ie, the age by which impairing symptoms must have been present) has increased from 7 years to 12 years. The present study examined measurement properties of ADHD symptoms according to age at onset. METHOD Data were derived from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions, which included 34,653 US participants. Among participants with a lifetime DSM-IV diagnosis of ADHD (assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV), we compared the psychometric properties of the 18 ADHD symptoms according to 3 categories of age at onset (≤ 7 years, > 7 and ≤ 12 years, and > 12 and ≤ 18 years). A 2-parameter item response model was used to estimate differential item functioning (DIF) between these groups. RESULTS 364 participants with a lifetime DSM-IV diagnosis of ADHD had an age at onset ≤ 7 years, 252 had an age at onset > 7 and ≤ 12 years, and 148 had an age at onset > 12 and ≤ 18 years. In both dimensions of ADHD (ie, inattention and hyperactivity-impulsivity), there was no significant DIF between age at onset groups. CONCLUSIONS Expression of DSM-IVADHD symptoms was not affected by age at onset in the 3 groups considered. This study provides psychometric support to the change in the age criterion introduced by DSM-5 and further suggests that the age at onset criterion could be extended to 18 years without changing the psychometric properties of the ADHD symptoms.

Immaturity of Visual Fixations in Dyslexic Children

To our knowledge, behavioral studies recording visual fixations abilities in dyslexic children are scarce. The object of this article is to explore further the visual fixation ability in dyslexics compared to chronological age-matched and reading age-matched non-dyslexic children. Fifty-five dyslexic children from 7 to 14 years old, 55 chronological age-matched non-dyslexic children and 55 reading age-matched non-dyslexic children participated to this study. Eye movements from both eyes were recorded horizontally and vertically by a video-oculography system (EyeBrain® T2). The fixation task consisted in fixating a white-filled circle appearing in the center of the screen for 30 s. Results showed that dyslexic children produced a significantly higher number of unwanted saccades than both groups of non-dyslexic children. Moreover, the number of unwanted saccades significantly decreased with age in both groups of non-dyslexic children, but not in dyslexics. Furthermore, dyslexics made more saccades during the last 15 s of fixation period with respect to both groups of non-dyslexic children. Such poor visual fixation capability in dyslexic children could be due to impaired attention abilities, as well as to an immaturity of the cortical areas controlling the fixation system.

Contributing Factors and Mental Health Outcomes of First Suicide Attempt During Childhood and Adolescence: Results From a Nationally Representative Study

OBJECTIVE To investigate whether risk factors for suicide attempts differ in children and adolescents and to categorize adulthood mental health outcomes of child and adolescent suicide attempters in the general population. METHODS Using a large (N = 34,653), nationally representative US adult sample, the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions, we examined whether individuals who first attempted suicide during childhood (under the age of 13 years) differ from those who first attempted suicide during adolescence (13 through 17 years) in (1) contributing factors for first suicide attempt, including mental disorders and traumatic experiences that occurred before the first suicide attempt, parental history of mental disorders, and family poverty and (2) adulthood mental health outcomes, including lifetime and current prevalence of DSM-IV psychiatric disorders and quality of life measures. RESULTS Suicide attempts during childhood (n = 104) were more strongly related to childhood maltreatment, while suicide attempts during adolescence (n = 415) were more strongly associated with major depressive episode. Compared to first suicide attempts during adolescence, first attempts during childhood were associated with increased risk for multiple suicide attempts (61.3% vs 32.6%), several psychiatric disorders (mania, hypomania, and panic disorder), and poorer social functioning during adulthood (all P values < .05). CONCLUSIONS Suicide attempts in children and adolescents substantially differ in contributing factors and adulthood mental health outcomes. Preventing childhood maltreatment and early intervention for psychiatric disorders may have broad benefits to reduce not only the suffering of these children and adolescents, but also the burden of suicide.

Postural Instability in Children with ADHD Is Improved by Methylphenidate

HIGHLIGHTS Both spatial and temporal analyses of the Center of Pressure demonstrate that children with ADHD have poorer postural control than typically developing sex-, age-, and IQ-matched children. Poor sensory integration in postural control could partially explained the deficits in postural stability in children with ADHD. MPH treatment improves postural performance in both spatial and temporal domains in children with ADHD. MPH improves postural control specifically when visual and proprioceptive inputs are misleading. Such improvement could be due to MPH effects on neurons, facilitating cerebellar processing of postural control. The 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).

Long-term effects of ADHD medication on adult height: results from the NESARC.

To the Editor: Methylphenidate is the most commonly prescribed medication to treat attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. The long-term impact of methylphenidate on adult height remains debated1 because a significant negative impact on children’s growth has been suggested. The Multimodal Treatment Study of ADHD showed that children receiving methylphenidate had heights of 0.17 standard deviations below the population mean at the age of 9 years.2 It has been suggested that height velocity is negatively affected by methylphenidate early in the treatment period, with a normalized growth later on.3 As evidence, Biederman et al4 found no significant association between adult height and methylphenidate in a longitudinal study of 124 patients treated for ADHD during childhood. To our knowledge, this association has never been examined in a larger sample of adult individuals with a lifetime diagnosis of ADHD.