Psychotropic Medication Prescribing for Children and Adolescents After the Onset of the COVID-19 Pandemic.

Importance: Numerous studies have provided evidence for the negative associations of the COVID-19 pandemic with mental health, but data on the use of psychotropic medication in children and adolescents after the onset of the COVID-19 pandemic are lacking. Objective: To assess the rates and trends of psychotropic medication prescribing before and over the 2 years after the onset of the COVID-19 pandemic in children and adolescents in France. Design, Setting, and Participants: This cross-sectional study used nationwide interrupted time-series analysis of outpatient drug dispensing data from the IQVIA X-ponent database. All 8 839 143 psychotropic medication prescriptions dispensed to children (6 to 11 years of age) and adolescents (12 to 17 years of age) between January 2016 and May 2022 in France were retrieved and analyzed. Exposure: Onset of COVID-19 pandemic. Main outcomes and Measures: Monthly rates of psychotropic medication prescriptions per 1000 children and adolescents were analyzed using a quasi-Poisson regression before and after the pandemic onset (March 2020), and percentage changes in rates and trends were assessed. After the pandemic onset, rate ratios (RRs) were calculated between estimated and expected monthly prescription rates. Analyses were stratified by psychotropic medication class (antipsychotic, anxiolytic, hypnotic and sedative, antidepressant, and psychostimulant) and age group (children, adolescents). Results: In total, 8 839 143 psychotropic medication prescriptions were analyzed, 5 884 819 [66.6%] for adolescents and 2 954 324 [33.4%] for children. In January 2016, the estimated rate of monthly psychotropic medication prescriptions was 9.9 per 1000 children and adolescents, with the prepandemic rate increasing by 0.4% per month (95% CI, 0.3%-0.4%). In March 2020, the monthly prescription rate dropped by 11.5% (95% CI, -17.7% to -4.9%). During the 2 years following the pandemic onset, the trend changed significantly, and the prescription rate increased by 1.3% per month (95% CI, 1.2%-1.5%), reaching 16.1 per 1000 children and adolescents in May 2022. Monthly rates of psychotropic medication prescriptions exceeded the expected rates by 11% (RR, 1.11 [95% CI, 1.08-1.14]). Increases in prescribing trends were observed for all psychotropic medication classes after the pandemic onset but were substantial for anxiolytics, hypnotics and sedatives, and antidepressants. Prescription rates rose above those expected for all psychotropic medication classes except psychostimulants (RR, 1.12 [95% CI, 1.09-1.15] in adolescents and 1.06 [95% CI, 1.05-1.07] in children for antipsychotics; RR, 1.30 [95% CI, 1.25-1.35] in adolescents and 1.11 [95% CI, 1.09-1.12] in children for anxiolytics; RR, 2.50 [95% CI, 2.23-2.77] in adolescents and 1.40 [95% CI, 1.30-1.50] in children for hypnotics and sedatives; RR, 1.38 [95% CI, 1.29-1.47] in adolescents and 1.23 [95% CI, 1.20-1.25] in children for antidepressants; and RR, 0.97 [95% CI, 0.95-0.98] in adolescents and 1.02 [95% CI, 1.00-1.04] in children for psychostimulants). Changes were more pronounced among adolescents than children. Conclusions and Relevance: These findings suggest that prescribing of psychotropic medications for children and adolescents in France significantly and persistently increased after the COVID-19 pandemic onset. Future research should identify underlying determinants to improve psychological trajectories in young people.

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.

Cord serum cytokines at birth and children's trajectories of mood dysregulation symptoms from 3 to 8 years: The EDEN birth cohort.

There is growing evidence that in utero imbalance immune activity plays a role in the development of neurodevelopmental and psychiatric disorders in children. Mood dysregulation (MD) is a debilitating transnosographic syndrome whose underlying pathophysiological mechanisms could be revealed by studying its biomarkers using the Research Domain Criteria (RDoC) model. Our aim was to study the association between the network of cord serum cytokines, and mood dysregulation trajectories in offsprings between 3 and 8 years of age. We used the data of a study nested in the French birth cohort EDEN that took place from 2003 to 2014 and followed mother-child dyads from the second trimester of pregnancy until the children were 8 years of age. The 2002 mother-child dyads were recruited from the general population through their pregnancy follow-up in two French university hospitals. 871 of them were included in the nested cohort and cord serum cytokine levels were measured at birth. Children's mood dysregulation symptoms were assessed with the Strengths and Difficulties Questionnaire Dysregulation Profile at the ages 3, 5 and 8 years in order to model their mood dysregulation trajectories. Out of the 871 participating dyads, 53% of the children were male. 2.1% of the children presented a high mood dysregulation trajectory whereas the others were considered as physiological variations. We found a significant negative association between TNF-α cord serum levels and a high mood dysregulation trajectory when considering confounding factors such as maternal depression during pregnancy (adjusted Odds Ratio (aOR) = 0.35, 95% Confidence Interval (CI) [0.18-0.67]). Immune imbalance at birth could play a role in the onset of mood dysregulation symptoms. Our findings throw new light on putative immune mechanisms implicated in the development of mood dysregulation and should lead to future animal and epidemiological studies.

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.

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.

Abnormal neutrophil-to-lymphocyte ratio in children with autism spectrum disorder and history of maternal immune activation.

Maternal immune activation (MIA), related to autoimmune/inflammatory diseases or acute infections, during the two first trimesters of pregnancy is a risk factor for autism spectrum disorders (ASD) in offspring. In mice, MIA has a long-term impact on offspring's immune equilibrium resulting in a pro-inflammatory phenotype. We therefore hypothesized that children with ASD and a history of MIA could display a similar phenotype specifically assessed by a higher neutrophil to lymphocyte ratio (NLR). In this study, we used a retrospective sample of 231 dyads involving children with ASD and their mothers. Among ASD patients, 12% had a history of MIA. The multivariate analysis revealed a significant association between NLR in children with ASD and maternal history of MIA (F = 2.27, p = 0.03). Using a categorical approach, we observed an abnormal NLR (over 3) in 7.4% of children with ASD MIA+ compared to 1.9% for MIA-. Our study supports the hypothesis suggesting an impact of MIA on the risk of ASD. Further studies could contribute to the development of biomarkers in MIA+ ASD and enable the development of targeted immunomodulatory therapies.

Maternal immune activation during pregnancy is associated with more difficulties in socio-adaptive behaviors in autism spectrum disorder.

Autism spectrum disorder (ASD) are neurodevelopmental conditions characterised by deficits in social communication and interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person's competencies and reflect specifically in ASD, their strengths and difficulties. In this study, we hypothesised that ASD individual with a history of MIA (MIA+) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA-). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used supervised and unsupervised machine learning algorithms. We included 295 mother-child dyads with 14% of them with MIA+. We found that ASD-MIA+ individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA+ directly influenced individual's socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA+ affect persistently the socio-adaptive behavioral trajectories of individuals with ASD. The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results. Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA+ individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of ASD and for the development of specific immunomodulatory strategies.

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.

Antipsychotic use and 28-day mortality in patients hospitalized with COVID-19: A multicenter observational retrospective study.

Prior research has yielded conflicting results about the potential influence of antipsychotics in patients with COVID-19. In this multicenter retrospective study, we examined the association of antipsychotic use at admission with 28-day all-cause mortality in a sample of 59,021 adult patients hospitalized with COVID-19 from January 2020 to November 2021. In a 1:1 ratio matched analytic sample (N=1,454) accounting for age, sex, hospital, hospitalization period, the Elixhauser Comorbidity Index, other psychotropic medications, medications prescribed according to compassionate use or as part of a clinical trial, current diagnoses of psychiatric disorders, and clinical and biological markers of COVID-19 severity, antipsychotic use was not associated with 28-day mortality [23.5% (N=727) versus 18.6% (N=727); OR=1.16; 95%CI=0.89-1.51; p=0.280]. This association remained non-significant in exploratory analyses across all classes of antipsychotics and individual molecules, except for typical antipsychotics and loxapine, which were significantly linked to increased 28-day mortality, associations likely due to residual indication bias. Contrariwise, antipsychotics prescribed at daily doses higher than 200 mg of chlorpromazine-equivalents might be associated with reduced 28-day mortality when compared to patients not taking antipsychotics in the matched analytic sample [10.4% (N=154) versus 18.6% (N=727); AOR=0.56; 95%CI=0.31-0.96; p=0.040]. These results suggest that antipsychotic use, when prescribed at usual doses, are not be associated with 28-day mortality in patients hospitalized with COVID-19.

Characterizing the phenotypic and genetic structure of psychopathology in UK Biobank.

Mental conditions exhibit a higher-order transdiagnostic factor structure which helps to explain the widespread comorbidity observed in psychopathology. However, the phenotypic and genetic structures of psychopathology may differ, raising questions about the validity and utility of these factors. Here, we study the phenotypic and genetic factor structures of ten psychiatric conditions using UK Biobank and public genomic data. Although the factor structure of psychopathology was generally genetically and phenotypically consistent, conditions related to externalizing (e.g., alcohol use disorder) and compulsivity (e.g., eating disorders) exhibited cross-level disparities in their relationships with other conditions, plausibly due to environmental influences. Domain-level factors, especially thought disorder and internalizing factors, were more informative than a general psychopathology factor in genome-wide association and polygenic index analyses. Collectively, our findings enhance the understanding of comorbidity and shared etiology, highlight the intricate interplay between genes and environment, and offer guidance for psychiatric research using polygenic indices.

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.

Major depressive episode and postpartum depression: A network analysis comparison on the IGEDEPP cohort.

INTRODUCTION: Major depression episode (MDE) and postpartum depression (PPD) have the same diagnosis criteria, but dissimilarities may be present regarding the frequency and structure of depressive symptoms. METHODS: We used data from the IGEDEPP Cohort (France) to examine DSM-5 depressive symptoms in two groups of women: 486 with PPD and 871 with a history of non-perinatal MDE. We compare (i) the frequency of each depressive symptom adjusted for the severity of depression, (ii) the global structure of depressive symptom networks, and (iii) the centrality of each symptom in the two networks. RESULTS: Women with PPD were significantly more likely to have appetite disturbance, psychomotor symptoms, and fatigue than those with MDE, while sadness, anhedonia, sleep disturbance, and suicidal ideation were significantly less common. There were no significant differences in the global structure of depressive symptoms of MDE and PPD. However, the most central criterion of the MDE network was "Sadness" while it was "Suicidal ideations" for the PPD network. "Sleep" and "Suicidal ideations" criteria were more central for PPD network, whereas "Culpability" was more important for MDE network than for PPD network. CONCLUSION: We found differences in depressive symptoms expression between PPD and MDE, which justify continuing to clinically distinguish PPD from MDE.

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.

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.

Weight Gain During Antipsychotic Treatment in Children, Adolescents, and Adults: A Disproportionality Analysis in the Global Pharmacovigilance Database, Vigibase®.

INTRODUCTION: While antipsychotic-induced weight gain has been widely described in adults, it has yet to be better characterized in children and adolescents. OBJECTIVE: The aim of this study was to assess antipsychotic-induced weight-gain reporting in children and adolescents as compared to adults, and according to the type of antipsychotic. METHODS: The study is an observational, case-non-case study using individual case safety reports from the WHO global pharmacovigilance database VigiBase® from 1 January 2000 to 2 June 2021. Disproportionality in antipsychotic-related weight-gain reporting in children and adolescents compared to adults was evaluated based on reporting odds ratios (RORs) with corresponding 95% confidence intervals (CIs) through multivariate logistic regression modeling. Analysis was adjusted for sex, region of reporting, year of notification, reporter qualification, concomitant use of antidepressants, and use of more than one antipsychotic. RESULTS: Among 282,224 antipsychotic-related spontaneous reports included in this analysis, we identified 16,881 (6.0%) weight-gain cases. Disproportionality in weight-gain reporting was found in children (adjusted ROR (aROR) 3.6; 95% CI 3.3-3.8) and in adolescents (aROR 2.3; 95% CI 2.2-2.4) compared to adults. Use of risperidone was associated with the highest increase in weight-gain reporting in children (aROR 4.9; 95% CI 3.9-6.1) and adolescents (aROR 3.6; 95% CI 3.1-4.1). CONCLUSIONS: Compared to adults, weight-gain reporting with antipsychotics was disproportionally higher in the pediatric population, especially in children under 12 years of age. Considering the impact of weight gain on global morbidity and mortality, physicians should closely monitor weight gain in young patients, especially children on risperidone.

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.

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.

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.

High intelligence is not associated with a greater propensity for mental health disorders.

BACKGROUND: Studies reporting that highly intelligent individuals have more mental health disorders often have sampling bias, no or inadequate control groups, or insufficient sample size. We addressed these caveats by examining the difference in the prevalence of mental health disorders between individuals with high and average general intelligence (g-factor) in the UK Biobank. METHODS: Participants with g-factor scores standardized relative to the same-age UK population, were divided into two groups: a high g-factor group (g-factor 2 SD above the UK mean; N = 16,137) and an average g-factor group (g-factor within 2 SD of the UK mean; N = 236,273). Using self-report questionnaires and medical diagnoses, we examined group differences in the prevalence of 32 phenotypes, including mental health disorders, trauma, allergies, and other traits. RESULTS: High and average g-factor groups differed across 15/32 phenotypes and did not depend on sex and/or age. Individuals with high g-factors had less general anxiety (odds ratio [OR] = 0.69, 95% CI [0.64;0.74]) and post-traumatic stress disorder (PTSD; OR = 0.67, 95 %CI [0.61;0.74]), were less neurotic (ß = -0.12, 95% CI [-0.15;-0.10]), less socially isolated (OR = 0.85, 95% CI [0.80;0.90]), and were less likely to have experienced childhood stressors and abuse, adulthood stressors, or catastrophic trauma (OR = 0.69-0.90). However, they generally had more allergies (e.g., eczema; OR = 1.13-1.33). CONCLUSIONS: The present study provides robust evidence that highly intelligent individuals do not have more mental health disorders than the average population. High intelligence even appears as a protective factor for general anxiety and PTSD.