Early systemic inflammation induces neurodevelopmental disorders: results from ARTEMIS, a French multicenter study of juvenile rheumatisms and systemic autoimmune and auto-inflammatory disorders and meta-analysis.

Prenatal immune-mediated events are known risk factors for neurodevelopmental disorders in the offspring (NDD). Although the brain continues to develop for years after birth and many postnatal factors alter the regular trajectory of neurodevelopment, little is known about the impact of postnatal immune factors. To fill this gap we set up ARTEMIS, a cohort of juvenile rheumatisms and systemic autoimmune and auto-inflammatory disorders (jRSAID), and assessed their neurodevelopment. We then complemented our results with a systematic review and meta-analysis. In ARTEMIS, we used unsupervised and supervised analysis to determine the influence of jRSAID age at onset (AO) and delay in introduction of disease-modifying therapy (DMT) on NDD (NCT04814862). For the meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, Cochrane, and Web of Science up to April 2022 without any restrictions on language, or article type for studies investigating the co-occurence of jRSAID and NDD (PROSPERO- CRD42020150346). 195 patients were included in ARTEMIS. Classification tree isolated 3 groups of patients (i) A low-risk group (AO > 130 months (m)) with 5% of NDD (ii) A medium-risk group (AO < 130 m and DMT < 2 m) with 20% of NDD (iii) and a high-risk-group (AO < 130 m and DMT > 2 m) with almost half of NDD. For the meta-analysis, 18 studies encompassing a total of (i) 46,267 children with jRSAID; 213,930 children with NDD, and 6,213,778 children as controls were included. We found a positive association between jRSAID and NDD with an OR = 1.44 [95% CI 1.31; 1.57] p < 0.0001, [I2 = 66%, Tau2 = 0.0067, p < 0.01]. Several sensitivity analyses were performed without changing the results. Metaregression confirmed the importance of AO (p = 0.005). Our study supports the association between jRSAID and NDD. AO and DMT have pivotal roles in the risk of developing NDD. We plead for systematic screening of NDD in jRSAID to prevent the functional impact of NDD.

Associations of screen use with cognitive development in early childhood: the ELFE birth cohort.

BACKGROUND: The associations of screen use with children's cognition are not well evidenced and recent, large, longitudinal studies are needed. We aimed to assess the associations between screen use and cognitive development in the French nationwide birth cohort. METHODS: Time and context of screen use were reported by parents at ages 2, 3.5 and 5.5. Vocabulary, non-verbal reasoning and general cognitive development were assessed with the MacArthur-Bates Communicative Development Inventory (MB) at age 2, the Picture Similarities subtest from the British Ability Scales (PS) at age 3.5 and the Child Development Inventory (CDI) at ages 3.5 and 5.5. Outcome variables were age-adjusted and standardized (mean = 100, SD = 15). Multiple imputations were performed among children (N = 13,763) with ≥1 screen use information and ≥1 cognitive measures. Cross-sectional and longitudinal associations between screen use and cognitive development were assessed by linear regression models adjusted for sociodemographic and birth factors related to the family and children, and children's lifestyle factors competing with screen use. Baseline cognitive scores were further considered in longitudinal analysis. RESULTS: TV-on during family meals at age 2, not screen time, was associated with lower MB scores at age 2 (ß [95% CI] = -1.67 [-2.21, -1.13]) and CDI scores at age 3.5 (-0.82 [-1.31, -0.33]). In cross-sectional analysis, screen time was negatively associated with CDI scores at ages 3.5 (-0.67 [-0.94, -0.40]) and 5.5 (-0.47 [-0.77, -0.16]), and, in contrast, was positively associated with PS scores (0.39 [0.07, 0.71]) at age 3.5. Screen time at age 3.5 years was not associated with CDI scores at age 5.5 years. CONCLUSIONS: Our study found weak associations of screen use with cognition after controlling for sociodemographic and children's birth factors and lifestyle confounders, and suggests that the context of screen use matters, not solely screen time, in children's cognitive development.

Do early musical impairments predict later reading difficulties? A longitudinal study of pre-readers with and without familial risk for dyslexia.

The present longitudinal study investigated the hypothesis that early musical skills (as measured by melodic and rhythmic perception and memory) predict later literacy development via a mediating effect of phonology. We examined 130 French-speaking children, 31 of whom with a familial risk for developmental dyslexia (DD). Their abilities in the three domains were assessed longitudinally with a comprehensive battery of behavioral tests in kindergarten, first grade, and second grade. Using a structural equation modeling approach, we examined potential longitudinal effects from music to literacy via phonology. We then investigated how familial risk for DD may influence these relationships by testing whether atypical music processing is a risk factor for DD. Results showed that children with a familial risk for DD consistently underperformed children without familial risk in music, phonology, and literacy. A small effect of musical ability on literacy via phonology was observed, but may have been induced by differences in stability across domains over time. Furthermore, early musical skills did not add significant predictive power to later literacy difficulties beyond phonological skills and family risk status. These findings are consistent with the idea that certain key auditory skills are shared between music and speech processing, and between DD and congenital amusia. However, they do not support the notion that music perception and memory skills can serve as a reliable early marker of DD, nor as a valuable target for reading remediation. RESEARCH HIGHLIGHTS: Music, phonology, and literacy skills of 130 children, 31 of whom with a familial risk for dyslexia, were examined longitudinally. Children with a familial risk for dyslexia consistently underperformed children without familial risk in musical, phonological, and literacy skills. Structural equation models showed a small effect of musical ability in kindergarten on literacy in second grade, via phonology in first grade. However, early musical skills did not add significant predictive power to later literacy difficulties beyond phonological skills and family risk status.

Brain volumes, thicknesses, and surface areas as mediators of genetic factors and childhood adversity on intelligence.

Although genetic and environmental factors influence general intelligence (g-factor), few studies examined the neuroanatomical measures mediating environmental and genetic effects on intelligence. Here, we investigate the brain volumes, cortical mean thicknesses, and cortical surface areas mediating the effects of the g-factor polygenic score (gPGS) and childhood adversity on the g-factor in the UK Biobank. We first examined the global and regional brain measures that contribute to the g-factor. Most regions contributed to the g-factor through global brain size. Parieto-frontal integration theory (P-FIT) regions were not more associated with the g-factor than non-PFIT regions. After adjusting for global brain size and regional associations, only a few regions predicted intelligence and were included in the mediation analyses. We conducted mediation analyses on global measures, regional volumes, mean thicknesses, and surface areas, separately. Total brain volume mediated 7.04% of the gPGS' effect on the g-factor and 2.50% of childhood adversity's effect on the g-factor. In comparison, the fraction of the gPGS and childhood adversity's effects mediated by individual regional volumes, surfaces, and mean thicknesses was 10-15 times smaller. Therefore, genetic and environmental effects on intelligence may be mediated to a larger extent by other brain properties.

Investigating the increased risk of schizophrenia and bipolar disorders in relatives of ADHD probands using colocalization analysis of common genetic variants.

BACKGROUND: Relatives of ADHD probands are known to be at increased risk of schizophrenia and bipolar disorder, suggesting shared genetic factors. In this study, we aim to identify shared common risk variants (i.e., Single-Nucleotide Polymorphisms, SNPs) between ADHD and schizophrenia, and between ADHD and bipolar disorder. METHODS: With the summary data from three GWAS, one on ADHD (20,183 cases with ADHD and 35,191 controls), another on schizophrenia (76,755 cases with schizophrenia and 243,649 controls) and another on bipolar disorder (41,917 cases with bipolar disorder and 371,549 controls), we used colocalization analysis to identify SNPs shared by ADHD and schizophrenia, and SNPs shared by ADHD and bipolar disorder. Functional genomic analyses were then conducted on these two sets of shared common genetic variants. RESULTS: We found that three of the 12 SNPs associated with ADHD colocalized with schizophrenia SNPs and one of the 12 SNPs associated with ADHD colocalized with bipolar disorder. Only 0.4% of the SNPs associated with schizophrenia (2 out of 431) and 2.3% of the SNPs associated with bipolar disorder (2 out of 86), colocalized with ADHD SNPs. Some genes mapped to these shared genetic variants (SCN2A and UNC5D) are involved in the development of the nervous system. CONCLUSIONS: Using colocalization analysis, the present study uncovers shared genetic variants associated with ADHD and schizophrenia as well as ADHD and bipolar disorder, and may at least partially explain the increased risk of schizophrenia and bipolar disorder in relatives of ADHD probands.

Association of difficulties in motor skills with longitudinal changes in social skills in children with autism spectrum disorder: findings from the ELENA French Cohort.

Developmental coordination disorder is a frequently co-occurring condition with autism spectrum disorder (ASD). Several cross-sectional studies have reported that children with difficulties in motor skills have a higher severity of ASD symptoms. This study aims to examine the association of difficulties in motor skills with longitudinal changes in social skills in children with ASD. Participants were drawn from the ELENA cohort, a French longitudinal cohort of children with ASD. Motor skills were assessed using the Movement Assessment Battery for Children at baseline, while social skills were measured using the Autism Diagnostic Observation Schedule (ADOS-2) and the Vineland Adaptive Behavior Scales (VABS-II) at both the baseline and a follow-up assessment conducted 3 years later. A composite score of social skills was created at baseline and at both time points. Linear regression models were performed to assess the association between difficulties in motor skills and changes in social skills, considering potential confounders such as IQ, age, and gender. The sample included 162 children with ASD. Children with difficulties in global motor skills (N = 114) showed less favorable trajectories in social skills compared to those without motor difficulties. The results were consistent when examining the ADOS-2 and the VABS-II separately. This study provides evidence for the negative impact of difficulties in motor skills on the longitudinal development of social skills in children with ASD. Interventions targeting motor difficulties may have broader benefits, extending beyond motor function to improve socialization.

CARECOS study: Medical students' empathy as assessed with the CARE measure by examiners versus standardized patients during a formative Objective and Structured Clinical Examination (OSCE) station.

PURPOSE: To assess the Consultation And Relational Empathy (CARE) measure as a tool for examiners to assess medical students' empathy during Objective and Structured Clinical Examinations (OSCEs), as the best tool for assessing empathy during OSCEs remains unknown. METHODS: We first assessed the psychometric properties of the CARE measure, completed simultaneously by examiners and standardized patients (SP, either teachers - SPteacher - or civil society members - SPcivil society), for each student, at the end of an OSCE station. We then assessed the qualitative/quantitative agreement between examiners and SP. RESULTS: We included 129 students, distributed in eight groups, four groups for each SP type. The CARE measure showed satisfactory psychometric properties in the context of the study but moderate, and even poor inter-rater reliability for some items. Considering paired observations, examiners scored lower than SPs (p < 0.001) regardless of the SP type. However, the difference in score was greater when the SP was a SPteacher rather than a SPcivil society (p < 0.01). CONCLUSION: Despite acceptable psychometric properties, inter-rater reliability of the CARE measure between examiners and SP was unsatisfactory. The choice of examiner as well as the type of SP seems critical to ensure a fair measure of empathy during OSCEs.

A General Cognitive Ability Factor for the UK Biobank.

UK Biobank participants do not have a high-quality measure of intelligence or polygenic scores (PGSs) of intelligence to simultaneously examine the genetic and neural underpinnings of intelligence. We created a standardized measure of general intelligence (g factor) relative to the UK population and estimated its quality. After running a GWAS of g on UK Biobank participants with a g factor of good quality and without neuroimaging data (N = 187,288), we derived a g PGS for UK Biobank participants with neuroimaging data. For individuals with at least one cognitive test, the g factor from eight cognitive tests (N = 501,650) explained 29% of the variance in cognitive test performance. The PGS for British individuals with neuroimaging data (N = 27,174) explained 7.6% of the variance in g. We provided high-quality g factor estimates for most UK Biobank participants and g factor PGSs for UK Biobank participants with neuroimaging data.

The influence of sibship composition on language development at 2 years of age in the ELFE birth cohort study.

The number of older siblings a child has is negatively correlated with the child's verbal skills, an effect that is well known in the literature. However, few studies have examined the effect of older siblings' sex, of the age gap between siblings, of having foreign-speaking parents, as well as the mediating role of parental interaction. Using data from 12,296 children (49.3% female) from the French ELFE birth cohort, we analyzed the effect of these characteristics of the siblings and their family on children's expressive vocabulary measured using the French MacArthur-Bates Communicative Development Inventory. Children's vocabulary at age 2 years was negatively associated with the number of older siblings (-0.08 SD per additional sibling), and this effect was partly mediated by parental interactions. In analyses restricted to children with one older sibling, the vocabulary score was negatively correlated with the age gap between the target child and their older sibling. The vocabulary score was not correlated to their sibling's sex, contrary to the result of a previous study. In addition, the effect of the number of siblings was less negative in foreign speaking families that in French speaking families, suggesting that older siblings might partly compensate for the effect of having foreign-speaking parents. Overall, our results are consistent with the resource dilution (stating that parents have limited resources to distribute among their children) and inconsistent with the confluence model (stating that a child's cognitive ability is correlated to the mean cognitive ability of the family). RESEARCH HIGHLIGHTS: Our results are consistent with the resource dilution model and inconsistent with the confluence model The negative effect of the number of siblings on expressive vocabulary is partly mediated by parental interactions Larger age gaps between a child and their older sibling are associated with lower expressive vocabulary score.

Preschool language and visuospatial skills respectively predict multiplication and addition/subtraction skills in middle school children.

A converging body of evidence from neuroimaging, behavioral, and neuropsychology studies suggests that different arithmetic operations rely on distinct neuro-cognitive processes: while addition and subtraction may rely more on visuospatial reasoning, multiplication would depend more on verbal abilities. In this paper, we tested this hypothesis in a longitudinal study measuring language and visuospatial skills in 358 preschoolers, and testing their mental calculation skills at the beginning of middle school. Language skills at 5.5 years significantly predicted multiplication, but not addition nor subtraction scores at 11.5 years. Conversely, early visuospatial skills predicted addition and subtraction, but not multiplication scores. These results provide strong support for the existence of a double dissociation in mental arithmetic operations, and demonstrate the existence of long-lasting links between language/visuospatial skills and specific calculation abilities.

Prenatal and childhood exposure to ambient air pollution and cognitive function in school-age children: Examining sensitive windows and sex-specific associations.

BACKGROUND: Combined effect of both prenatal and early postnatal exposure to ambient air pollution on child cognition has rarely been investigated and periods of sensitivity are unknown. This study explores the temporal relationship between pre- and postnatal exposure to PM10, PM2.5, NO2 and child cognitive function. METHODS: Using validated spatiotemporally resolved exposure models, pre- and postnatal daily PM2.5, PM10 (satellite based, 1 km resolution) and NO2 (chemistry-transport model, 4 km resolution) concentrations at the mother's residence were estimated for 1271 mother-child pairs from the French EDEN and PELAGIE cohorts. Scores representative of children's General, Verbal and Non-Verbal abilities at 5-6 years were constructed based on subscale scores from the WPPSI-III, WISC-IV or NEPSY-II batteries, using confirmatory factor analysis (CFA). Associations of both prenatal (first 35 gestational weeks) and postnatal (60 months after birth) exposure to air pollutants with child cognition were explored using Distributed Lag Non-linear Models adjusted for confounders. RESULTS: Increased maternal exposure to PM10, PM2.5 and NO2, during sensitive windows comprised between the 15th and the 33rd gestational weeks, was associated with lower males' General and Non-verbal abilities. Higher postnatal exposure to PM2.5 between the 35th and 52nd month of life was associated with lower males' General, Verbal and Non-verbal abilities. Some protective associations were punctually observed for the very first gestational weeks or months of life for both males and females and the different pollutants and cognitive scores. DISCUSSION: These results suggest poorer cognitive function at 5-6 years among males following increased maternal exposure to PM10, PM2.5 and NO2 during mid-pregnancy and child exposure to PM2.5 around 3-4 years. Apparent protective associations observed are unlikely to be causal and might be due to live birth selection bias, chance finding or residual confounding.

Early-onset restrictive food intake disorders in children: a latent class analysis.

The two most frequent early-onset restrictive food intake disorders are early-onset anorexia nervosa (EOAN) and avoidant/restrictive food intake disorders (ARFID). Although the core symptoms of EOAN (i.e., fear of gaining weight and disturbed body image) are not present in ARFID, these symptoms are difficult to assess during the initial phase of hospitalisation. Our aim was  to identify restrictive food intake disorder subtypes in children using latent class analysis (LCA) based on the information available at admission to hospital, and to determine the agreement between the subtypes identified using LCA and the final diagnosis: EOAN or ARFID. We retrospectively included 97 children under 13 years old with severe eating disorders (DSM-5) at their first hospitalisation in a specialised French paediatric unit. LCA was based on clinical information, growth chart analyses and socio-demographic parameters available at admission. We then compared the probabilities of latent class membership with the diagnosis (EOAN or ARFID) made at the end of the hospitalisation. The most parsimonious LCA model was a 2-class solution. Children diagnosed with EOAN at the end of hospitalisation had a 100% probability of belonging to class 1 while children diagnosed with ARFID had an 8% probability of belonging to class 1 based on parameters available at admission. Our results indicate that clinical and socio-demographic characteristics other than the core symptoms of EOAN may be discriminating for a differential diagnosis.

Comparing brain asymmetries independently of brain size.

Studies examining cerebral asymmetries typically divide the l-R Measure (e.g., Left-Right Volume) by the L + R Measure to obtain an Asymmetry Index (AI). However, contrary to widespread belief, such a division fails to render the AI independent from the L + R Measure and/or from total brain size. As a result, variations in brain size may bias correlation estimates with the AI or group differences in AI. We investigated how to analyze brain asymmetries in to distinguish global from regional effects, and report unbiased group differences in cerebral asymmetries in the UK Biobank (N = 40, 028). We used 306 global and regional brain measures provided by the UK Biobank. Global gray and white matter volumes were taken from Freesurfer ASEG, subcortical gray matter volumes from Freesurfer ASEG and subsegmentation, cortical gray matter volumes, mean thicknesses, and surface areas from the Destrieux atlas applied on T1-and T2-weighted images, cerebellar gray matter volumes from FAST FSL, and regional white matter volumes from Freesurfer ASEG. We analyzed the extent to which the L + R Measure, Total Cerebral Measure (TCM, e.g., Total Brain Volume), and l-R TCM predict regional asymmetries. As a case study, we assessed the consequences of omitting each of these predictors on the magnitude and significance of sex differences in asymmetries. We found that the L + R Measure, the TCM, and the l-R TCM predicted the AI of more than 89% of regions and that their relationships were generally linear. Removing any of these predictors changed the significance of sex differences in 33% of regions and the magnitude of sex differences across 13-42% of regions. Although we generally report similar sex and age effects on cerebral asymmetries to those of previous large-scale studies, properly adjusting for regional and global brain size revealed additional sex and age effects on brain asymmetry.

Sleep complaints are associated with increased suicide risk independently of psychiatric disorders: results from a national 3-year prospective study.

Prior research suggests that sleep disturbances are associated with increased risk of suicide. However, sleep disturbances are associated with a wide range of psychiatric disorders, and it is unknown whether this association is independent of psychopathology. In a large nationally representative prospective survey, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we used structural equation modeling to examine the shared and specific effects of three sleep complaints (i.e., trouble falling asleep, early morning awakening, and hypersomnia) on the 3-year occurrence of attempting suicide. Because psychiatric disorders increase the risk of suicide attempt almost exclusively through a general psychopathology factor representing their shared effect, covariates included that factor, prior history of suicide attempt, and a wide range of sociodemographic and clinical characteristics. The 3-year prevalence rate of suicide attempt was 0.6% (n = 241). Compared with participants who did not attempt suicide between the two waves, those who did reported significantly more frequently having trouble falling asleep (44.6% vs. 16.6%), early morning awakening (38.9% vs. 12.7%), and hypersomnia (35.0% vs. 10.7%). Following adjustments, effects of sleep complaints on this risk were significant and exerted almost exclusively through a general sleep complaints factor representing the shared effect across all sleep complaints. There were no residual associations of any individual sleep complaint with attempting suicide above that association. Sleep complaints are associated with an increased risk of attempting suicide independently of psychopathology, and should be included in suicide risk assessments as these symptoms may provide targets for reducing the risks of suicidal behaviors.

Poor visuo-spatial orientation and path memorization in children with dyslexia.

PURPOSE: Given the importance of spatial representation and navigation in the natural environment and the presence of sensory motor integration impairment in dyslexic children the aim of this study was to explore the capability in spatial orientation task in dyslexic children. MATERIALS AND METHODS: We included forty children: 26 dyslexic children (mean age: 10.1 ± 0.3 years old) and 14 typically developing (TD) children (mean age: 10.1 ± 0.4 years old). Children have to walk on an unguided isosceles rectangle triangle of 3 meters that was marked on the ground of a room, during two visual conditions: eyes open and eyes closed. Their paths were recorded using the HTC Vive system (Base + Trackers) with a refresh rate of 90 Hz with accuracy < 0.05 mm. RESULTS: Results underlined that both groups of children reported poor performance during eyes closed condition. Moreover, dyslexic children, reported poor spatial orientation capabilities in the most difficult conditions, that is during reproduction of hypotenuse and angle of 45 deg. CONCLUSIONS: We suggested that visual information is important during walking; the poor body orientation observed in dyslexic children could be due to a deficient integration of the sensorial inputs (visual, vestibular and proprioceptive). Further studies testing vestibular/cerebellar rehabilitation could be useful for these kinds of children.HighlightsChildren with dyslexia showed poor spatial orientation capabilities compared to typically developing children, particularly when visual inputs are not available and in the most difficult conditions (like rotation of the body).Poor motor abilities reported by children with dyslexia could be due to cerebrocerebellar pathways impairments.

Neuroanatomical norms in the UK Biobank: The impact of allometric scaling, sex, and age.

Few neuroimaging studies are sufficiently large to adequately describe population-wide variations. This study's primary aim was to generate neuroanatomical norms and individual markers that consider age, sex, and brain size, from 629 cerebral measures in the UK Biobank (N = 40,028). The secondary aim was to examine the effects and interactions of sex, age, and brain allometry-the nonlinear scaling relationship between a region and brain size (e.g., total brain volume)-across cerebral measures. Allometry was a common property of brain volumes, thicknesses, and surface areas (83%) and was largely stable across age and sex. Sex differences occurred in 67% of cerebral measures (median |ß| = .13): 37% of regions were larger in males and 30% in females. Brain measures (49%) generally decreased with age, although aging effects varied across regions and sexes. While models with an allometric or linear covariate adjustment for brain size yielded similar significant effects, omitting brain allometry influenced reported sex differences in variance. Finally, we contribute to the reproducibility of research on sex differences in the brain by replicating previous studies examining cerebral sex differences. This large-scale study advances our understanding of age, sex, and brain allometry's impact on brain structure and provides data for future UK Biobank studies to identify the cerebral regions that covary with specific phenotypes, independently of sex, age, and brain size.

Combining multivariate genomic approaches to elucidate the comorbidity between autism spectrum disorder and attention deficit hyperactivity disorder.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two highly heritable neurodevelopmental disorders. Several lines of evidence point towards the presence of shared genetic factors underlying ASD and ADHD. We conducted genomic analyses of common risk variants (i.e. single nucleotide polymorphisms, SNPs) shared by ASD and ADHD, and those specific to each disorder. METHODS: With the summary data from two GWAS, one on ASD (N = 46,350) and another on ADHD (N = 55,374) individuals, we used genomic structural equation modelling and colocalization analysis to identify SNPs shared by ASD and ADHD and SNPs specific to each disorder. Functional genomic analyses were then conducted on shared and specific common genetic variants. Finally, we performed a bidirectional Mendelian randomization analysis to test whether the shared genetic risk between ASD and ADHD was interpretable in terms of reciprocal relationships between ASD and ADHD. RESULTS: We found that 37.5% of the SNPs associated with ASD (at p < 1e-6) colocalized with ADHD SNPs and that 19.6% of the SNPs associated with ADHD colocalized with ASD SNPs. We identified genes mapped to SNPs that are specific to ASD or ADHD and that are shared by ASD and ADHD, including two novel genes INSM1 and PAX1. Our bidirectional Mendelian randomization analyses indicated that the risk of ASD was associated with an increased risk of ADHD and vice versa. CONCLUSIONS: Using multivariate genomic analyses, the present study uncovers shared and specific genetic variants associated with ASD and ADHD. Further functional investigation of genes mapped to those shared variants may help identify pathophysiological pathways and new targets for treatment.

Early postnatal growth and subsequent neurodevelopment in children delivered at term: The ELFE cohort study.

BACKGROUND: Despite the limited evidence, accelerated early postnatal growth (EPG) is commonly believed to benefit neurodevelopment for term-born infants, especially those small for gestational age. OBJECTIVES: To investigate the existence of critical time windows in the association of EPG with neurodevelopment, considering birth size groups. STUDY DESIGN: In the French ELFE birth cohort, 12,854 term-born neonates were classified as small, appropriate or large for gestational age (SGA, AGA, LGA, respectively). Parents reported their child's development by using the Child Development Inventory (CDI-score) at age 12 months and the MacArthur-Bates Development Inventory (MAB-score; 100 score units) assessing language ability at age 24 months. Predictions of individual weight, body mass index (BMI), length, and head circumference (HC) from birth to age 24 months were obtained from repeated measurements fitted with the Jenss-Bayley mixed-effects model. For each infant, conditional gains (CG) in these growth parameters were generated at four-time points (3, 6, 12 and 24 months) representing specific variations in growth parameters during 0-3, 3-6, 6-12, 12-24 months, independent of previous measures. Using multivariable linear regression models, we provided the estimate differences of the neurodevelopmental scores according to variation of each growth parameter CG, by birth size group. RESULTS: For SGA infants, the MAB-score differed by 5.8 (95% confidence interval [CI] -0.2, 11.8), 6.7 (95% CI -0.1, 13.3), and 9.7 (95% CI 1.9, 17.5) score units when CG in BMI, weight, and HC at 3 months varied from -2 to 1 standard deviation, respectively. For all infants, MAB-score was linearly and positively associated with length conditional gains at 12 months, with stronger magnitude for SGA infants. Results for the CDI-score were overall consistent with those for MAB-score. CONCLUSIONS: For term-born SGA infants, moderate catch-up in HC, BMI and weight within the first 3 months of life may benefit later neurodevelopment, which could guide clinicians to monitor EPG.

Religiosity and prevalence of suicide, psychiatric disorders and psychotic symptoms in the French general population.

We aimed to examine the association between religious beliefs and observance and the prevalence of psychiatric disorders, psychotic symptoms and history of suicide attempts in the French general population. The cross-sectional survey interviewed 38,694 subjects between 1999 and 2003, using the MINI. Current religious beliefs and observance were identified by means of two questions: "are you a believer?" and "are you religiously observant?". We studied the association between religiosity and psychiatric outcomes using a multivariable logistic regression model adjusted for sociodemographic characteristics, including migrant status. Religious beliefs were positively associated with psychotic symptoms and disorders [OR = 1.37, 95% CI (1.30-1.45) and OR = 1.38, 95% CI (1.20-1.58)], unipolar depressive disorder [OR = 1.15, 95% CI (1.06-1.23)] and generalized anxiety disorder [OR = 1.13, 95% CI (1.06-1.21)], but negatively associated with bipolar disorder [OR = 0.83, 95% CI (0.69-0.98)], alcohol use disorders [OR = 0.69, 95% CI (0.62-0.77)], substance use disorders [OR = 0.60, 95% CI (0.52-0.69)] and suicide attempts [OR = 0.90, 95% CI (0.82-0.99)]. Religious observance was positively associated with psychotic symptoms and disorders [OR = 1.38, 95% CI (1.20-1.58) and OR = 1.25, 95% CI (1.07-1.45)], but negatively associated with social anxiety disorder [OR = 0.87, 95% CI (0.76-0.99)], alcohol use disorders [OR = 0.60, 95% CI (0.51-0.70)], substance use disorders [OR = 0.48, 95% CI (0.38-0.60)] and suicide attempts [OR = 0.80, 95% CI (0.70-0.90)]. Among believers, religious observance was not associated with psychotic outcomes. Religiosity appears to be a complex and bidirectional determinant of psychiatric symptoms and disorders. In this respect, religiosity should be more thoroughly assessed in epidemiological psychiatric studies, as well as in clinical practice.

Mechanical complications of cerebrospinal fluid shunt. Differences between adult and pediatric populations: myths or reality?

OBJECTIVE: Shunt malfunctions seem more frequent in children (44 to 81%) than in adults (18 to 29%). Because of discrepancies between studies, it is not possible to affirm this disparity. The objective was to verify whether the incidence of cerebrospinal fluid (CSF) shunt malfunctions is higher in children than adults. METHODS: We present a retrospective series of child and adult patients who underwent CSF shunt placement between 2000 and 2013 with a Sophysa SM8® valve. RESULTS: 599 adults and 98 children (sex ratio 1.28) underwent CSF shunt placement. Age at first surgery ranged between 1 day of life and 90 years (mean of 55.8 years, SD 25.8, median 64.8 years). The mean follow-up was 4 years (SD 4.264, 0-16; median 3 years). The cumulative complication rate was 25.5% (178/697). Mechanical complications were disconnection (25.1%), migration (11.8%), intracranial catheter obstruction (8.9%) and malposition (8.4%). The mean delay for the first revision was 1.90 years (0-13.9), (SD 2.73, median 0.5). The probability of shunt failure was 65% at 10 years in the child group and 36% at 10 years in the adult group. Moreover, in the child group, 33% of revisions occurred during the first year after shunt placement versus 17% in the adult group. Thus, the probability of shunt failure was higher in children than in adults (log-rank test, p < 0.001). CONCLUSIONS: This is the first retrospective study, comparing children and adults undergoing CSF shunt using the same valve, able to confirm the higher rate of complications in children.