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Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Children's versions of the Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) were developed and administered to n = 1,256 parents of typically developing children, aged 4-11 years. Both measures showed good test-retest reliability and high internal consistency. As predicted, girls scored significantly higher on the EQ-C, and boys scored significantly higher on the SQ-C. A further sample of n = 265 children with Autism Spectrum Conditions (ASC) scored significantly lower on the EQ-C, and significantly higher on the SQ-C, compared to typical boys. Empathy and systemizing in children show similar patterns of sex differences to those observed in adults. Children with ASC tend towards a 'hyper-masculinized' profile, irrespective of sex. [ABSTRACT FROM AUTHOR]

This article is an author response to three previous commentaries on 'Fetal testosterone and autistic traits.' [ABSTRACT FROM AUTHOR]

Studies of amniotic testosterone in humans suggest that fetal testosterone (fT) is related to specific (but not all) sexually dimorphic aspects of cognition and behaviour. It has also been suggested that autism may be an extreme manifestation of some male-typical traits, both in terms of cognition and neuroanatomy. In this paper, we examine the possibility of a link between autistic traits and fT levels measured in amniotic fluid during routine amniocentesis. Two instruments measuring number of autistic traits (the Childhood Autism Spectrum Test (CAST) and the Child Autism Spectrum Quotient (AQ-Child)) were completed by these women about their children (N ¼ 235), ages 6-10 years. Intelligence Quotient (IQ) was measured in a subset of these children (N ¼ 74). fT levels were positively associated with higher scores on the CAST and AQ-Child. This relationship was seen within sex as well as when the sexes were combined, suggesting this is an effect of fTrather than of sex per se.No relationships were found between overall IQ and the predictor variables, or between IQ and CASTor AQ-Child. These findings are consistent with the hypothesis that prenatal androgen exposure is related to children exhibiting more autistic traits. These results need to be followed up in a much larger sample to test if clinical cases of ASC have elevated fT. [ABSTRACT FROM AUTHOR]

The Autism Spectrum Quotient-Children's Version (AQ-Child) is a parent-report questionnaire that aims to quantify autistic traits in children 4-11 years old. The range of scores on the AQ-Child is 0-150. It was administered to children with an autism spectrum condition (ASC) ( n = 540) and a general population sample ( n = 1,225). Results showed a significant difference in scores between those with an ASC diagnosis and the general population. Receiver-operating-characteristic analyses showed that using a cut-off score of 76, the AQ-Child has high sensitivity (95%) and specificity (95%). The AQ-Child showed good test-retest reliability and high internal consistency. Factor analysis provided support for four of the five AQ-Child design subscales. Future studies should evaluate how the AQ-C performs in population screening. [ABSTRACT FROM AUTHOR]

There are average differences in prenatal sex steroid hormone levels, as higher levels of fetal testosterone (FT) are needed for male sexual differentiation. Previous research has shown that FT was associated with gray matter (GM) brain regions that show on average volumetric sex differences in prepubertal development. On average, in 8-11 year old children, GM volume in right temporal parietal junction posterior superior temporal sulcus was greater for boys compared to girls and, as expected, positively predicted by FT. On the other hand, GM in the planum temporal/parietal operculum was greater in girls compared to boys and was negatively predicted by FT. Here we will discuss whether FT differently affectsmale and female brain development in a typically developing cohort. We will examine (1) if and how FT is associated with thickness and surface area in the male and female adolescent brain and (2) if there is overlap between FT associations and overall sex developmental differences in an independent cohort, matched on age and pubertal status. [ABSTRACT FROM AUTHOR]

Abstract Background Studies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children. Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old. Finding fT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores. Conclusions These preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life.

Abstract Background Autism spectrum conditions have a strong genetic component. Atypical sensory sensitivities are one of the core but neglected features of autism spectrum conditions. GABRB3 is a well-characterised candidate gene for autism spectrum conditions. In mice, heterozygous Gabrb3 deletion is associated with increased tactile sensitivity. However, no study has examined if tactile sensitivity is associated with GABRB3 genetic variation in humans. To test this, we conducted two pilot genetic association studies in the general population, analysing two phenotypic measures of tactile sensitivity (a parent-report and a behavioural measure) for association with 43 SNPs in GABRB3. Findings Across both tactile sensitivity measures, three SNPs (rs11636966, rs8023959 and rs2162241) were nominally associated with both phenotypes, providing a measure of internal validation. Parent-report scores were nominally associated with six SNPs (P Conclusions This is the first human study to show an association between GABRB3 variation and tactile sensitivity. This provides support for the evidence from animal models implicating the role of GABRB3 variation in the atypical sensory sensitivity in autism spectrum conditions. Future research is underway to directly test this association in cases of autism spectrum conditions.

Abstract Background Autism spectrum conditions have been characterised as an extreme presentation of certain male-typical psychological traits. In addition, several studies have established a link between prenatal exposure to testosterone and cognitive sex differences in later life, and one study found that foetal testosterone (FT) is positively correlated to autistic traits in 6 to 10 year-old children. In this study, we tested whether FT is positively correlated with autistic traits in toddlers aged 18-24 months. Methods Levels of FT were analysed in amniotic fluid and compared with autistic traits, measured using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in 129 typically developing toddlers aged between 18 and 24 months (mean ± SD 19.25 ± 1.52 months). Results Sex differences were observed in Q-CHAT scores, with boys scoring significantly higher (indicating more autistic traits) than girls. In addition, we confirmed a significant positive relationship between FT levels and autistic traits. Conclusions The current findings in children between 18 and 24 months of age are consistent with observations in older children showing a positive association between elevated FT levels and autistic traits. Given that sex steroid-related gene variations are associated with autistic traits in adults, this new finding suggests that the brain basis of autistic traits may reflect individual differences in prenatal androgens and androgen-related genes. The consistency of findings in early childhood, later childhood and adulthood suggests that this is a robust association.

Abstract Background The Autism Spectrum Quotient (AQ) is a self-report questionnaire for quantifying autistic traits. This study tests whether the AQ can differentiate between parents of children with an autism spectrum condition (ASC) and control parents. In this paper, the use of the AQ to define the broader, medium and narrow autism phenotypes (BAP, MAP, NAP) is reported, and the proportion of parents with each phenotype is compared between the two groups. Methods A sample of 571 fathers and 1429 mothers of children with an ASC completed the AQ, along with 349 fathers and 658 mothers of developing typically children. Results Both mothers and fathers of the diagnosed children scored higher than the control parents on total AQ score and on four out of five of the subscales. Additionally, there were more parents of diagnosed children with a BAP, MAP or NAP. Conclusions The AQ provides an efficient method for quantifying where an individual lies along the dimension of autistic traits, and extends the notion of a broader phenotype among first-degree relatives of those with ASC. The AQ is likely to have many applications, including population and clinical screening, and stratification in genetic studies.

Objective: Frontline health professionals need a "red flag" tool to aid their decision making about whether to make a referral for a full diagnostic assessment for an autism spectrum condition (ASC) in children and adults. The aim was to identify 10 items on the Autism Spectrum Quotient (AQ) (Adult, Adolescent, and Child versions) and on the Quantitative Checklist for Autism in Toddlers (Q-CHAT) with good test accuracy.Method: A case sample of more than 1,000 individuals with ASC (449 adults, 162 adolescents, 432 children and 126 toddlers) and a control sample of 3,000 controls (838 adults, 475 adolescents, 940 children, and 754 toddlers) with no ASC diagnosis participated. Case participants were recruited from the Autism Research Centre's database of volunteers. The control samples were recruited through a variety of sources. Participants completed full-length versions of the measures. The 10 best items were selected on each instrument to produce short versions.Results: At a cut-point of 6 on the AQ-10 adult, sensitivity was 0.88, specificity was 0.91, and positive predictive value (PPV) was 0.85. At a cut-point of 6 on the AQ-10 adolescent, sensitivity was 0.93, specificity was 0.95, and PPV was 0.86. At a cut-point of 6 on the AQ-10 child, sensitivity was 0.95, specificity was 0.97, and PPV was 0.94. At a cut-point of 3 on the Q-CHAT-10, sensitivity was 0.91, specificity was 0.89, and PPV was 0.58. Internal consistency was >0.85 on all measures.Conclusions: The short measures have potential to aid referral decision making for specialist assessment and should be further evaluated. [ABSTRACT FROM AUTHOR]

Qualitative semi-structured interviews were conducted with service providers regarding the current healthcare provision and education services for children with Autism Spectrum Conditions (ASC) and their families in mainland China. 10 service providers described the current policy and identified unmet needs within current practice. Providers perceived that children with ASC were an important but under-served group in mainland China. Two levels of service provision related to ASC were identified: (1) healthcare services mainly provided by government authorities; (2) education services mainly provided by the parents of children with ASC. Little cooperation was reported between the two types of providers. The structure of service provision for ASC is under-developed. There is an important need to establish coherent healthcare and education policies to support children with ASC and their families. [ABSTRACT FROM AUTHOR]

Background: Prenatal infections are associated with childhood developmental outcomes such as reduced cognitive abilities, emotional problems and other developmental vulnerabilities. However, there is currently a lack of research examining whether this arises due to potential intermediary variables like low birth weight or preterm birth, or due to some other mechanisms of maternal immune activation arising from prenatal infections., Methods: Administrative data from the National Health Service health board of Greater Glasgow & Clyde, Scotland, were used, linking birth records to hospital records and universal child health review records for 55 534 children born from 2011 to 2015, and their mothers. Causal mediation analysis was conducted to examine the extent to which low birth weight and preterm birth mediate the relationship between hospital-diagnosed prenatal infections and having developmental concern(s) identified by a health visitor during 6-8 weeks or 27-30 months child health reviews., Results: Model estimates suggest that 5.18% (95% CI 3.77% to 7.65%) of the positive association observed between hospital-diagnosed prenatal infections and developmental concern(s) was mediated by low birth weight, while 7.37% (95% CI 5.36 to 10.88%) was mediated by preterm birth., Conclusion: Low birth weight and preterm birth appear to mediate the relationship between prenatal infections and childhood development, but only to a small extent. Maternal immune activation mechanisms unrelated to low birth weight and preterm birth remain the most likely explanation for associations observed between prenatal infections and child developmental outcomes, although other factors (for example, genetic factors) may also be involved., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Previous research has linked prenatal maternal infections to later childhood developmental outcomes and socioemotional difficulties. However, existing studies have relied on retrospectively self-reported survey data, or data on hospital-recorded infections only, resulting in gaps in data collection., Methods: This study used a large linked administrative health dataset, bringing together data from birth records, hospital records, prescriptions and routine child health reviews for 55,856 children born in Greater Glasgow & Clyde, Scotland, 2011-2015, and their mothers. Logistic regression models examined associations between prenatal infections, measured as both hospital-diagnosed prenatal infections and receipt of infection-related prescription(s) during pregnancy, and childhood developmental concern(s) identified by health visitors during 6-8 week or 27-30 month health reviews. Secondary analyses examined whether results varied by (a) specific developmental outcome types (gross-motor-skills, hearing-communication, vision-social-awareness, personal-social, emotional-behavioural-attention and speech-language-communication) and (b) the trimester(s) in which infections occurred., Results: After confounder/covariate adjustment, hospital-diagnosed infections were associated with increased odds of having at least one developmental concern (OR: 1.30; 95% CI: 1.19-1.42). This was broadly consistent across all developmental outcome types and appeared to be specifically linked to infections occurring in pregnancy trimesters 2 (OR: 1.34; 95% CI: 1.07-1.67) and 3 (OR: 1.33; 95% CI: 1.21-1.47), that is the trimesters in which foetal brain myelination occurs. Infection-related prescriptions were not associated with any clear increase in odds of having at least one developmental concern after confounder/covariate adjustment (OR: 1.03; 95% CI: 0.98-1.08), but were associated with slightly increased odds of concerns specifically related to personal-social (OR: 1.12; 95% CI: 1.03-1.22) and emotional-behavioural-attention (OR: 1.15; 95% CI: 1.08-1.22) development., Conclusions: Prenatal infections, particularly those which are hospital-diagnosed (and likely more severe), are associated with early childhood developmental outcomes. Prevention of prenatal infections, and monitoring of support needs of affected children, may improve childhood development, but causality remains to be established., (© 2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Parental stress occurs when parenting demands exceed the resources available to cope with parenting. Previous research has identified household wealth, educational level, marital status, age, and number of dependent children as predictors of parental stress. However, limited evidence exists from sub-Saharan Africa. This study investigated the sociodemographic predictors of parenting stress among mothers in Kenya and Zambia. This cross-sectional study utilised baseline secondary data from parenting intervention programs implemented in Kisumu County (rural Kenya), Nairobi County (Urban Kenya), and Chisamba District (rural Zambia). Out of 913 caregivers recruited for the parenting program, 844 with complete data were included in the analysis. The mean age was 1.0 (SD = 0.7) years. Parental stress was measured using the Parental Stress Score (PSS) tool and demographic questionnaires were used to collect demographic information. Mean PSS were compared across study sites, and a multiple linear regression model was used to examine associations between sociodemographic predictors (household income, educational level, marital status, maternal age, child age, and number of children aged < 5 years) and PSS, adjusting for clustering and other predictors. From the results, the mean PSS in rural Kenya was 37.6 [SD = 11.8], in urban Kenya was 48.4 [SD = 4.2], and in rural Zambia was 43.0 [SD = 9.1]. In addition, the significant association between PSS and mothers' income and educational level was only observed in Kenyan study sites (income: Kenya rural β = -0.40, p < 0.001**; Kenya urban, β = - 0.33, p = .02 * ; Zambia rural, β = - 0.01, p = 0.7) education: Kenya rural, β = - 0.25, p = .005 ** ; Kenya urban, β = - 0.14, p = 0.07; Zambia rural, β = 0.04, p = 0.3). However, marital status, mother's age, child's age, and the number of children below five years were not associated with PSS. The results revealed that mothers' income and education level were negatively associated with PSS, indicating that higher socioeconomic status can buffer the effects of parental stress.Trial registration Pan African Clinical Trials Registry ( https://pactr.samrc.ac.za/ ) database (ID Number: PACTR20180774832663 Date: 26/July/2018; (ID number: PACTR201905787868050 Date: 06/May/2019., (© 2024. The Author(s).)

Higher rates of depression and of depressed mood are associated with autistic traits, and both are associated with social interaction factors, such as social self-efficacy, social motivation and loneliness. This study examined whether these social factors explain the association between autistic traits and depression. 658 participants (527 women) completed an online survey with measures of autistic traits (AQ), social self-efficacy (Social Self-Efficacy Scale), social motivation (Social Striving Assessment Scale), loneliness (UCLA Loneliness Scale) and depressive symptoms (Beck Depression Inventory-II). A mediation analysis found the relationship between autistic traits and depressive symptoms was fully mediated by the other three factors (β[indirect] = .005, z = 2.63, p < .01; β[direct] = .05, z = 1.58, p > .05), forming a pathway from autistic traits, to social self-efficacy, to social motivation, to loneliness and finally to depressive symptoms. These results suggest that targeting social self-efficacy may break this pathway and disrupt this relationship. Interventions targeting supporting positive social interaction should be considered., (© 2024. The Author(s).)

Adolescence is characterised by a peak in sensation seeking accompanied by gradually developing self-control skills. Adolescents typically show steeper delay discounting performance than other age groups; a feature that is transdiagnostically related to a variety of mental health disorders. However, delay discounting performance is not a singular mental process but involves both risk/reward and future orientation elements, usually operationalised as probability/risk and time discounting tasks, respectively. To clarify the specific relations between the risk/reward and future orientation elements of delay discounting and different types of mental health problems, two bi-factor models and a series of structural equation models (SEMs) were fitted to multi-informant (parent and adolescent self-reported) mental health data from a large UK study. A transdiagnostic promotive role of future orientation was found using bi-factor modelling to separate general and dimension-specific mental health variation; however, this was limited to parent reports. In addition, future orientation was negatively associated with conduct problems and ADHD symptoms, but positively associated with emotional problems. Risk aversion was negatively associated with conduct problems, but positively associated with emotional and peer problems. The findings highlight that risk/reward and future orientation elements of delay discounting play partly distinct roles in different mental health problems and can serve both promotive and risk roles during adolescence. Findings also illuminate which elements of delay discounting should be intervention targets for different mental health concerns., (© 2023. Crown.)

Objective: People with amnestic mild cognitive impairment (aMCI) or dementia often exhibit a decline in their social abilities, but few tests of social cognition exist that are suitable for clinical use. Moreover, the relationship between changes in behavior and impairments in social cognition is poorly understood. We examined the utility of the Edinburgh Social Cognition Test (ESCoT) in people with aMCI/dementia and explored associations between social cognition performance and behavior changes., Method: We administered the ESCoT and two established social cognition tests (the Reading the Mind in the Eyes and the Social Norms Questionnaire) to 28 people with aMCI or dementia and 28 age and sex matched cognitively healthy controls. Behavior change was measured using a semistructured interview which assesses behavioral abnormalities found in frontotemporal dementia., Results: People with aMCI/dementia were impaired on the ESCoT affective theory of mind, ESCoT total score and the Reading the Mind in the Eyes. Behavior changes in the domains of apathy, loss of sympathy/empathy, perseveration, and psychotic symptoms were associated with poorer affective theory of mind scores. Disinhibition, loss of sympathy/empathy and hyperorality or altered food preferences were associated with cognitive theory of mind. All behaviors were significantly associated with poorer performance on ESCoT total score, but were not associated with performance on the Reading the Mind in the Eyes or the Social Norms Questionnaire., Conclusions: The ESCoT was sensitive to social cognition impairments in people with aMCI/dementia and it relates to behavior change in aMCI/dementia unlike established tests. Different subtests of the ESCoT were related to different behavior changes. These findings suggest that the ESCoT may be a clinically valuable tool when examining social cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Parental stress often arises when parenting demands exceed the expected and actual resources available for parents to succeed in the parenting role. Parental stress is an important contributor to parent-child relationships. This, in turn, affects opportunities to engage their children in stimulating activities which could improve their development outcomes. However, limited evidence exists from sub-Saharan Africa (SSA) on the association between parental stress, caregiving practices, and child developmental outcomes., Methods: The findings reported in this paper were derived from data collected through previous longitudinal work on nurturing care evaluation studies in Kisumu and Nairobi Counties in Kenya, and Chisamba District in Zambia. A total of 341 caregivers and their children who participated in the three rounds of data collection were included in this study. The children's mean age was 9.3 (SD = 8.2) months pre-intervention, 25.5 (SD = 8.6) months in mid-intervention, and 36 (SD = 10.0) months post-intervention. The Ages and Stages Questionnaire (ASQ), Parental Stress Scale (PSS), and caregiving tools were used to assess children's developmental outcomes, parental stress, and stimulation practices, respectively. A Random Intercept Cross-Lagged Panel model (RI-CLPM) was used to determine the association between caregivers' parenting stress, child stimulation practices, and child developmental outcomes., Results: The findings showed that caregiver stimulation practices were positively associated with developmental outcomes. Findings on the associations between parental stress and caregivers' stimulation practices and children's developmental outcomes were not universally supported., Conclusion: The findings show that improved caregiver stimulation practices are likely to improve children's developmental outcomes. The policy implications of the findings from this study focus on improving parenting practices by addressing the predictors of parental stress. This includes subsidising childcare services to reduce costs., Trial Registration: Pan African Clinical Trials Registry ( https://pactr.samrc.ac.za/ ) database (ID number: PACTR20180774832663 Date: 26/July/2018., (© 2024. The Author(s).)

The current study investigated the effects of metacognitive and executive function (EF) training on childhood EF (inhibition, working memory [WM], cognitive flexibility, and proactive/reactive control) and academic skills (reading, reasoning, and math) among children from disadvantaged backgrounds. Children ( N = 134, M = 8.70 years) were assigned randomly to the three training groups: (a) metacognitive training of basic EF processes (meta-EF), (b) training of basic EF processes (basic-EF), and (c) active controls (active control). They underwent 16 training sessions over the course of 2 months. No effects of EF and/or metacognitive training were found for academic outcomes. However, both meta-EF and basic-EF groups demonstrated greater gains than the active control group on proactive control engagement and WM, suggesting that EF training promotes a shift to more mature ways of engaging EF. Our findings suggest minimal near- and far-transfer effects of metacognitive training but highlight that proactive engagement of EF can be promoted through EF training in children. (PsycInfo Database Record (c) 2023 APA, all rights reserved).age = 8.70 years) were assigned randomly to the three training groups: (a) metacognitive training of basic EF processes (meta-EF), (b) training of basic EF processes (basic-EF), and (c) active controls (active control). They underwent 16 training sessions over the course of 2 months. No effects of EF and/or metacognitive training were found for academic outcomes. However, both meta-EF and basic-EF groups demonstrated greater gains than the active control group on proactive control engagement and WM, suggesting that EF training promotes a shift to more mature ways of engaging EF. Our findings suggest minimal near- and far-transfer effects of metacognitive training but highlight that proactive engagement of EF can be promoted through EF training in children. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Strengths and Difficulties Questionnaire (SDQ) has been widely used to study children's psychosocial development longitudinally; however, such analyses assume longitudinal measurement invariance, that is, they presuppose that symptom manifestations are measured comparably across different ages. Violations of this assumption could bias longitudinal analyses and should therefore be empirically tested. This study tested longitudinal measurement invariance within a confirmatory factor analysis framework in the U.K.-based Avon Longitudinal Study of Parents and Children ( N = 13,988). Results indicated that SDQ scores showed configural, metric, scalar, and residual invariance across ages 7, 8, 9, 11, 13, and 16, supporting its use for comparing variances, covariances, and means over time within a latent variable model as well as using observed scores. At age 4, configural invariance was not supported, indicating that mental health symptoms as measured by the SDQ manifest differently at this age, thus necessitating caution when comparing symptoms as measured by SDQ scores at this age to later ages.

Background: Poor maternal cardiometabolic health in pregnancy is associated with negative effects on child health outcomes, but there is limited literature on child and adolescent socioemotional outcomes. The study aimed to investigate associations between maternal cardiometabolic markers during pregnancy with child and adolescent socioemotional trajectories., Methods: Growth curve models were run to examine how maternal cardiometabolic markers in pregnancy affected child socioemotional trajectories from ages 4 to 16. Models were adjusted for all pregnancy trimesters and maternal, child, and socioeconomic covariates. This study used the Avon Longitudinal Study of Parents and Children (United Kingdom) cohort. Participants consisted of mother-child pairs ( N  = 15,133). Maternal predictors of fasting glucose, triglycerides, high-density lipoprotein, low-density lipoprotein, and body mass index were taken from each pregnancy trimester (T1, T2, T3). Child outcomes included emotional problems, conduct problems, and hyperactivity problems from the Strengths and Difficulties Questionnaire., Results: Fully adjusted models showed significant associations between elevated T1 fasting glucose and increased conduct problems, higher T1 body mass index and increased hyperactivity problems, lowered T1 high-density lipoprotein and decreased hyperactivity problems, and elevated T2 triglycerides and increased hyperactivity problems., Conclusions: Maternal cardiometabolic risk is associated with conduct and hyperactivity outcomes from ages 4 to 16. This study suggests that maternal markers of fasting glucose, low-density lipoprotein, high-density lipoprotein, and triglycerides during pregnancy could be added as supplements for clinical measures of risk when predicting child and adolescent socioemotional trajectories., (© 2023 The Authors.)

Objectives: To examine neonates in Scotland aged 0-27 days with SARS-CoV-2 infection confirmed by viral testing; the risk of confirmed neonatal infection by maternal and infant characteristics; and hospital admissions associated with confirmed neonatal infections., Design: Population-based cohort study., Setting and Population: All live births in Scotland, 1 March 2020-31 January 2022., Results: There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100 000 live births (141/92 009, 0.15%). Among infants born to women with confirmed infection around the time of birth, the confirmed neonatal infection rate was 1812 per 100 000 live births (15/828, 1.8%). Two-thirds (92/141, 65.2%) of neonates with confirmed infection had an associated admission to neonatal or (more commonly) paediatric care. Six of these babies (6/92, 6.5%) were admitted to neonatal and/or paediatric intensive care; however, none of these six had COVID-19 recorded as their main diagnosis. There were no neonatal deaths among babies with confirmed infection., Implications and Relevance: Confirmed neonatal SARS-CoV-2 infection was uncommon over the first 23 months of the pandemic in Scotland. Secular trends in the neonatal confirmed infection rate broadly followed those seen in the general population, although at a lower level. Maternal confirmed infection at birth was associated with an increased risk of neonatal confirmed infection. Two-thirds of neonates with confirmed infection had an associated admission to hospital, with resulting implications for the baby, family and services, although their outcomes were generally good. Ascertainment of confirmed infection depends on the extent of testing, and this is likely to have varied over time and between groups: the extent of unconfirmed infection is inevitably unknown., Competing Interests: Competing interests: CG and JJK are lead investigators for the British Paediatric Surveillance Unit study 'Neonatal complications of COVID-19' and coinvestigators for the 'SARS-CoV-2 infection in neonates or in pregnancy: outcomes at 18 months (SINEPOST)' study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: There is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children's developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother-child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators., Methods: Maternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age., Results: In mediation models, significant total effects were found for MetS associations with children's development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child's COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models., Conclusions: The results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children's LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child's cord blood markers (total indirect effects)., (© 2023. The Author(s).)

Caregivers of a child with a neurodevelopmental disability are more vulnerable to mental health difficulties. These difficulties are influenced by the child's challenging behaviours, and the caregiver's coping strategies; factors impacted by the COVID-19 pandemic. An online mixed methods survey was conducted on caregivers of children with neurodevelopmental disabilities (n = 43) and children who are typically developing (n = 67). The results showed that presence of challenging behaviours related to neurodevelopmental disability, and caregiver coping strategies predicted caregiver psychological distress during lockdown. Themes that emerged included 'confusing messages and guidance', 'loss of freedom' and 'unsupported and forgotten'. The results demonstrate the pressing need for the implementation of appropriate support to protect the mental health of caregivers across the UK., (© 2021. The Author(s).)

Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy., (© 2023. The Author(s).)

Background: Evidence suggests that the SARS-CoV-2 omicron (B.1·1.529) is associated with lower risks of adverse outcomes than the delta (B.1.617.2) variant among the general population. However, little is known about outcomes after omicron infection in pregnancy. We aimed to assess and compare short-term pregnancy outcomes after SARS-CoV-2 delta and omicron infection in pregnancy., Methods: We did a national population-based cohort study of women who had SARS-CoV-2 infection in pregnancy between May 17, 2021, and Jan 31, 2022. The primary maternal outcome was admission to critical care within 21 days of infection or death within 28 days of date of infection. Pregnancy outcomes were preterm birth and stillbirth within 28 days of infection. Neonatal outcomes were death within 28 days of birth, and low Apgar score (<7 of 10, for babies born at term) or neonatal SARS-CoV-2 infection in births occurring within 28 days of maternal infection. We used periods when variants were dominant in the general Scottish population, based on 50% or more of cases being S-gene positive (delta variant, from May 17 to Dec 14, 2021) or S-gene negative (omicron variant, from Dec 15, 2021, to Jan 31, 2022) as surrogates for variant infections. Analyses used logistic regression, adjusting for maternal age, deprivation quintile, ethnicity, weeks of gestation, and vaccination status. Sensitivity analyses included restricting the analysis to those with first confirmed SARS-CoV-2 infection and using periods when delta or omicron had 90% or more predominance., Findings: Between May 17, 2021, and Jan 31, 2022, there were 9923 SARS-CoV-2 infections in 9823 pregnancies, in 9817 women in Scotland. Compared with infections in the delta-dominant period, SARS-CoV-2 infections in pregnancy in the omicron-dominant period were associated with lower maternal critical care admission risk (0·3% [13 of 4968] vs 1·8% [89 of 4955]; adjusted odds ratio 0·25, 95% CI 0·14-0·44) and lower preterm birth within 28 days of infection (1·8% [37 of 2048] vs 4·2% [98 of 2338]; 0·57, 95% CI 0·38-0·87). There were no maternal deaths within 28 days of infection. Estimates of low Apgar scores were imprecise due to low numbers (5 [1·2%] of 423 with omicron vs 11 [2·1%] of 528 with delta, adjusted odds ratio 0·72, 0·23-2·32). There were fewer stillbirths in the omicron-dominant period than in the delta-dominant period (4·3 [2 of 462] per 1000 births vs 20·3 [13 of 639] per 1000) and no neonatal deaths during the omicron-dominant period (0 [0 of 460] per 1000 births vs 6·3 [4 of 626] per 1000 births), thus numbers were too small to support adjusted analyses. Rates of neonatal infection were low in births within 28 days of maternal SARS-CoV-2 infection, with 11 cases of neonatal SARS-CoV-2 in the delta-dominant period, and 1 case in the omicron-dominant period. Of the 15 stillbirths, 12 occurred in women who had not received two or more doses of COVID-19 vaccination at the time of SARS-CoV-2 infection in pregnancy. All 12 cases of neonatal SARS-CoV-2 infection occurred in women who had not received two or more doses of vaccine at the time of maternal infection. Findings in sensitivity analyses were similar to those in the main analyses., Interpretation: Pregnant women infected with SARS-CoV-2 were substantially less likely to have a preterm birth or maternal critical care admission during the omicron-dominant period than during the delta-dominant period., Funding: Wellcome Trust, Tommy's charity, Medical Research Council, UK Research and Innovation, Health Data Research UK, National Core Studies-Data and Connectivity, Public Health Scotland, Scottish Government Health and Social Care, Scottish Government Chief Scientist Office, National Research Scotland., Competing Interests: Declaration of interests AS and CR were members of the Scottish Government's COVID-19 Advisory Group and are members of the New and Emerging Respiratory Virus Threats Advisory Group risk stratification subgroup and the Scottish Government's Committee on Pandemic Preparedness (unremunerated roles). CR is a member of the Scientific Pandemic Influenza Group on Modelling (unremunerated role). AS is a member of AstraZeneca's Thrombotic Thrombocytopenic Advisory Group (unremunerated role). SVK was co-chair of Scottish Government's Expert Reference Group on Ethnicity and COVID-19 (unremunerated role). All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Maternal prenatal infections have been linked to children's neurodevelopment and cognitive outcomes. It remains unclear, however, whether infections occurring during specific vulnerable gestational periods can affect children's cognitive outcomes. The study aimed to examine maternal infections in each trimester of pregnancy and associations with children's developmental and intelligence quotients. The ALSPAC birth cohort was used to investigate associations between maternal infections in pregnancy and child cognitive outcomes., Methods: Infection data from mothers and cognition data from children were included with the final study sample size comprising 7,410 mother-child participants. Regression analysis was used to examine links between maternal infections occurring at each trimester of pregnancy and children's cognition at 18 months, 4 years, and 8 years., Results: Infections in the third trimester were significantly associated with decreased verbal IQ at age 4 (p < .05, adjusted R 2  = 0.004); decreased verbal IQ (p < .01, adjusted R 2  = 0.001), performance IQ (p < .01, adjusted R 2  = 0.0008), and total IQ at age 8 (p < .01, adjusted R 2  = 0.001)., Conclusion: Results suggest that maternal infections in the third trimester could have a latent effect on cognitive development, only emerging when cognitive load increases over time, though magnitude of effect appears to be small. Performance IQ may be more vulnerable to trimester-specific exposure to maternal infection as compared to verbal IQ. Future research could include examining potential mediating mechanisms on childhood cognition, such as possible moderating effects of early childhood environmental factors, and if effects persist in future cognitive outcomes., (© 2022. The Author(s).)

A significant proportion of the personal and economic burden of schizophrenia can be attributed to the late diagnosis or misdiagnosis of the disorder. A novel, objective diagnostic approaches could facilitate the early detection and treatment of schizophrenia and improve patient outcomes. In the present study, we aimed to identify robust schizophrenia-specific blood biomarkers, with the goal of developing an accurate diagnostic model. The levels of selected serum and peripheral blood mononuclear cell (PBMC) markers relevant to metabolic and immune function were measured in healthy controls (n = 26) and recent-onset schizophrenia patients (n = 36) using multiplexed immunoassays and flow cytometry. Analysis of covariance revealed significant upregulation of insulin receptor (IR) and fatty acid translocase (CD36) levels in T helper cells (F = 10.75, P = 0.002, Q = 0.024 and F = 21.58, P = 2.8 × 10 -5 , Q = 0.0004, respectively), as well as downregulation of glucose transporter 1 (GLUT1) expression in monocytes (F = 21.46, P = 2.9 × 10 -5 , Q = 0.0004). The most robust predictors, monocyte GLUT1 and T helper cell CD36, were used to develop a diagnostic model, which showed a leave-one-out cross-validated area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI: 0.66-0.92). The diagnostic model was validated in two independent datasets. The model was able to distinguish first-onset, drug-naïve schizophrenia patients (n = 34) from healthy controls (n = 39) with an AUC of 0.75 (95% CI: 0.64-0.86), and also differentiated schizophrenia patients (n = 22) from patients with other neuropsychiatric conditions, including bipolar disorder, major depressive disorder and autism spectrum disorder (n = 68), with an AUC of 0.83 (95% CI: 0.75-0.92). These findings indicate that PBMC-derived biomarkers have the potential to support an accurate and objective differential diagnosis of schizophrenia., (© 2022. The Author(s).)

Data on the safety of COVID-19 vaccines in early pregnancy are limited. We conducted a national, population-based, matched cohort study assessing associations between COVID-19 vaccination and miscarriage prior to 20 weeks gestation and, separately, ectopic pregnancy. We identified women in Scotland vaccinated between 6 weeks preconception and 19 weeks 6 days gestation (for miscarriage; n = 18,780) or 2 weeks 6 days gestation (for ectopic; n = 10,570). Matched, unvaccinated women from the pre-pandemic and, separately, pandemic periods were used as controls. Here we show no association between vaccination and miscarriage (adjusted Odds Ratio [aOR], pre-pandemic controls = 1.02, 95% Confidence Interval [CI] = 0.96-1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92-1.38). We undertook additional analyses examining confirmed SARS-CoV-2 infection as the exposure and similarly found no association with miscarriage or ectopic pregnancy. Our findings support current recommendations that vaccination remains the safest way for pregnant women to protect themselves and their babies from COVID-19., (© 2022. The Author(s).)

Oxytocin is hypothesized to promote social interactions by enhancing the salience of social stimuli. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to face stimuli in autistic men, effects in autistic women remain unclear. In this study, the influence of intranasal oxytocin on activation and functional connectivity of the basolateral amygdala-the brain's 'salience detector'-while processing emotional faces vs shapes was tested in 16 autistic and 21 non-autistic women by functional magnetic resonance imaging in a placebo-controlled, within-subject, cross-over design. In the placebo condition, minimal activation differences were observed between autistic and non-autistic women. However, significant drug × group interactions were observed for both basolateral amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35-voxel cluster, Montreal Neurological Institute (MNI) coordinates of peak voxel = -22 -10 -28; mean change = +0.079%, t = 3.159, PTukey = 0.0166) but not among non-autistic women (mean change = +0.003%, t = 0.153, PTukey = 0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not in non-autistic women, attenuating group differences in the placebo condition. Taken together, these findings extend evidence of oxytocin's effects on the amygdala to specifically include autistic women and specify the subregion of the effect., (© The Author(s) 2022. Published by Oxford University Press.)

Adolescence is a critical period in the development of mental health with nearly 1 in 5 adolescents suffering from mental health problems and more than 40 percent of these experiencing at least one co-occurring mental health disorder. This study investigates whether there are differences in the relations between key dimensions of child and adolescent mental health in adolescence compared to childhood. Mental health and related socio-emotional traits were measured longitudinally at ages 4, 7, 8, 9, 11, 13, and 16 in the Avon Longitudinal Study of Parents and Children (N = 11279) using the Strengths and Difficulties Questionnaires. Graphical Vector Autoregression models were used to analyse the temporal within-person relations between conduct problems, emotional problems, hyperactivity/inattention, peer problems and prosociality across childhood (ages 4 to 9) and adolescence (11 to 16). Results suggest that adolescence is characterised by an increase in the number and strength of temporal relations between socio-emotional difficulties. In particular, in adolescence there were bidirectional connections between peer problems and emotional problems, between conduct problems and hyperactivity/inattention and between prosociality and conduct problems as well as hyperactivity/inattention. In childhood, conduct problems and prosociality were reciprocally related. Results also suggested peer problems as a potential mediating factor between conduct and emotional problems in childhood. Overall, this study suggests that different domains of socio-emotional development influence each other over development. Adolescence is characterised by an increase in temporal connections, which may be one factor underlying the increased vulnerability to the onset of mental health problems during that period., (© 2022. The Author(s).)

We aimed to validate the Children's Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) in Mainland China, which can reflect the profiles of empathizing and systemizing, and describing specific characteristics of autism spectrum disorder (ASD) and gender-typical behaviors in general population. A total of 800 typically developing (TD) children, aged 4-12 years was recruited initially with whose parents/guardians complete the measurements, and 782 TD children who met inclusion criteria were finally included. A 23-item three-factor EQ-C and a 22-item four-factor SQ-C was developed with good internal consistency (Omega total values of 0.87 and 0.86) and test-retest reliability (Pearson correlation coefficients of 0.82 and 0.69). In TD children, girls scored significantly higher on EQ-C (31.4 ± 7.8 vs. 28.2 ± 7.7) but there were no gender differences in SQ-C scores. TD children showed different cognitive styles (empathizing-dominant for girls with 42.6% identified as Type E; systemizing-dominant for boys with 40.7% identified as Type S). A further sample of 222 children with ASD indicated that they scored lower on EQ/SQ-C compared to TD children (13.2 ± 5.1 vs. 29.7 ± 7.9, 12.4 ± 5.8 vs. 23.5 ± 8.3) and were generally systemizing-dominant (Type S: 50.8% for boys and 64.0% for girls). Autistic children scored higher on the SQ-C in those without intellectual disability and with higher paternal education level and family income (14.2 ± 6.1 vs. 10.9 ± 5.0, 13.3 ± 6.2 vs. 11.5 ± 5.1, 13.7 ± 5.6 vs. 11.9 ± 5.8), while there were no differences in the EQ-C. This study indicated good reliability and validity of the Chinese version of EQ/SQ-C, which can be used in Chinese children with and without ASD. LAY SUMMARY: We developed the Chinese version of the Children's Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) in 782 typically developing (TD) children aged 4-12 years in Mainland China, yielding a 23-item, 3-factor EQ-C and a 22-item, 4-factor SQ-C with good psychometric properties. In TD children, we found gender difference only in scores of EQ-C. Further analyses of 222 autistic children indicated that differences were found in scores of SQ-C when considering their gender, intelligence and socio-economic status., (© 2022 International Society for Autism Research and Wiley Periodicals LLC.)