The Association Between Prenatal Infection and Adolescent Behavior: Investigating Multiple Prenatal, Perinatal, and Childhood Second Hits.

OBJECTIVE: Exposure to infections during pregnancy may be a potential risk factor for later psychopathology, but large-scale epidemiological studies investigating associations between prenatal infection and long-term offspring behavioral problems in the general population are scarce. In our study, we aimed to investigate the following: (1) the association between prenatal infection and adolescent behavior, (2) putative underlying pathways (mediation), and (3) "second hits" interacting with prenatal infection to increase the risk of adolescent behavior problems (moderation). METHOD: Our study was embedded in a prospective Dutch pregnancy cohort (Generation R; n = 2,213 mother-child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. At age 13 to 16 years, we assessed total, internalizing, and externalizing problems, and autistic traits using the Child Behavioral Checklist and the Social Responsiveness Scale, respectively. We investigated maternal lifestyle and nutrition, perinatal factors (placental health and delivery outcomes), and child health (lifestyle, traumatic events, infections) as mediators and moderators. RESULTS: We observed associations of prenatal infection with adolescent total behavioral, internalizing, and externalizing problems. The association between prenatal infection and internalizing problems was moderated by higher levels of maternal psychopathology, alcohol and tobacco use, and a higher number of traumatic childhood events. We found no association between prenatal infection and autistic traits. Yet, children exposed to prenatal infections and maternal substance use, and/or traumatic childhood events, had a higher risk of autistic traits in adolescence. CONCLUSION: Prenatal infection may be a risk factor for later psychiatric problems as well as a disease primer making individuals susceptible to other hits later in life. STUDY PREREGISTRATION INFORMATION: Prenatal maternal infection and adverse neurodevelopment: a structural equation modelling approach to downstream environmental hits; https://osf.io/cp85a; cp85a. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants.

Stage 2 Registered Report: The Bidirectional Relationship Between Brain Features and the Dysregulation Profile: A Longitudinal, Multimodal Approach.

OBJECTIVE: Youth with symptoms of emotion dysregulation are at risk for a multitude of psychiatric diagnoses later in life. However, few studies have focused on the underlying neurobiology of emotion dysregulation. This study assessed the bidirectional relationship between emotion dysregulation symptoms and brain morphology throughout childhood and adolescence. METHOD: A combined total of 8,235 children and adolescents drawn from 2 large population-based cohorts, the Generation R Study and Adolescent Brain Cognitive Development (ABCD) Study, were included. Data were acquired in 3 waves in Generation R (mean [SD] age = 7.8 [1.0] wave 1 [W1]; 10.1 [0.6] W2; 13.9 [0.5] W3) and in 2 waves in ABCD (mean [SD] age = 9.9 [0.6] W1; 11.9 [0.6] W2). Cross-lagged panel models were used to determine the bidirectional relationships between emotion dysregulation symptoms and brain morphology. The study was preregistered before performing analyses. RESULTS: In the Generation R sample, emotion dysregulation symptoms at W1 preceded lower hippocampal (ß = -.07, SE = 0.03, p = .017) and temporal pole (ß = -.19, SE = 0.07, p = .006) volumes at W2. Emotion dysregulation symptoms at W2 preceded lower fractional anisotropy in the uncinate fasciculus (ß = -.11, SE = 0.05, p = .017) and corticospinal tract (ß = -.12, SE = 0.05, p = .012). In the ABCD sample, emotion dysregulation symptoms preceded posterior cingulate (ß = .01, SE = 0.003, p = .014) and nucleus accumbens volumes (left hemisphere: ß = -.02, SE = 0.01, p = .014; right hemisphere: ß = -.02, SE = 0.01, p = .003). CONCLUSION: In population-based samples, with relatively low psychopathology symptoms in the majority of children, symptoms of emotion dysregulation can precede differential development of brain morphology. This provides the foundation for future work to assess to what extent optimal brain development can be promoted through early intervention. STUDY REGISTRATION INFORMATION: The Bidirectional Relationship Between Brain Features and the Dysregulation Profile: A Longitudinal, Multimodal Approach; https://doi.org/10.1016/j.jaac.2022.03.008. DIVERSITY & INCLUSION STATEMENT: We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Dietary patterns, brain morphology and cognitive performance in children: Results from a prospective population-based study.

Dietary patterns in childhood have been associated with child neurodevelopment and cognitive performance, while the underlying neurobiological pathway is unclear. We aimed to examine associations of dietary patterns in infancy and mid-childhood with pre-adolescent brain morphology, and whether diet-related differences in brain morphology mediate the relation with cognition. We included 1888 and 2326 children with dietary data at age one or eight years, respectively, and structural neuroimaging at age 10 years in the Generation R Study. Measures of brain morphology were obtained using magnetic resonance imaging. Dietary intake was assessed using food-frequency questionnaires, from which we derived diet quality scores based on dietary guidelines and dietary patterns using principal component analyses. Full scale IQ was estimated using the Wechsler Intelligence Scale for Children-Fifth Edition at age 13 years. Children with higher adherence to a dietary pattern labeled as 'Snack, processed foods and sugar' at age one year had smaller cerebral white matter volume at age 10 (B = -4.3, 95%CI -6.9, -1.7). At age eight years, higher adherence to a 'Whole grains, soft fats and dairy' pattern was associated with a larger total brain (B = 8.9, 95%CI 4.5, 13.3), and larger cerebral gray matter volumes at age 10 (B = 5.2, 95%CI 2.9, 7.5). Children with higher diet quality and better adherence to a 'Whole grains, soft fats and dairy' dietary pattern at age eight showed greater brain gyrification and larger surface area, clustered primarily in the dorsolateral prefrontal cortex. These observed differences in brain morphology mediated associations between dietary patterns and IQ. In conclusion, dietary patterns in early- and mid-childhood are associated with differences in brain morphology which may explain the relation between dietary patterns and neurodevelopment in children.

Cognitive performance in children and adolescents with psychopathology traits: A cross-sectional multicohort study in the general population.

Psychopathology and cognitive development are closely related. Assessing the relationship between multiple domains of psychopathology and cognitive performance can elucidate which cognitive tasks are related to specific domains of psychopathology. This can help build theory and improve clinical decision-making in the future. In this study, we included 13,841 children and adolescents drawn from two large population-based samples (Generation R and ABCD studies). We assessed the cross-sectional relationship between three psychopathology domains (internalizing, externalizing, dysregulation profile (DP)) and four cognitive domains (vocabulary, fluid reasoning, working memory, and processing speed) and the full-scale intelligence quotient. Lastly, differential associations between symptoms of psychopathology and cognitive performance by sex were assessed. Results indicated that internalizing symptoms were related to worse performance in working memory and processing speed, but better performance in the verbal domain. Externalizing and DP symptoms were related to poorer global cognitive performance. Notably, those in the DP subgroup had a 5.0 point lower IQ than those without behavioral problems. Cognitive performance was more heavily affected in boys than in girls given comparable levels of psychopathology. Taken together, we provide evidence for globally worse cognitive performance in children and adolescents with externalizing and DP symptoms, with those in the DP subgroup being most heavily affected.

The longitudinal bidirectional relationship between autistic traits and brain morphology from childhood to adolescence: a population-based cohort study.

OBJECTIVE: Autistic traits are associated with alterations in brain morphology. However, the anatomic location of these differences and their developmental trajectories are unclear. The primary objective of this longitudinal study was to explore the bidirectional relationship between autistic traits and brain morphology from childhood to adolescence. METHOD: Participants were drawn from a population-based cohort. Cross-sectional and longitudinal analyses included 1950 (mean age 13.5) and 304 participants (mean ages 6.2 and 13.5), respectively. Autistic traits were measured with the Social Responsiveness Scale. Global brain measures and surface-based measures of gyrification, cortical thickness and surface area were obtained from T1-weighted MRI scans. Cross-sectional associations were assessed using linear regression analyses. Cross-lagged panel models were used to determine the longitudinal bidirectional relationship between autistic traits and brain morphology. RESULTS: Cross-sectionally, higher levels of autistic traits in adolescents are associated with lower gyrification in the pars opercularis, insula and superior temporal cortex; smaller surface area in the middle temporal and postcentral cortex; larger cortical thickness in the superior frontal cortex; and smaller cerebellum cortex volume. Longitudinally, both autistic traits and brain measures were quite stable, with neither brain measures predicting changes in autistic traits, nor vice-versa. LIMITATIONS: Autistic traits were assessed at only two time points, and thus we could not distinguish within- versus between-person effects. Furthermore, two different MRI scanners were used between baseline and follow-up for imaging data acquisition. CONCLUSIONS: Our findings point to early changes in brain morphology in children with autistic symptoms that remain quite stable over time. The observed relationship did not change substantially after excluding children with high levels of autistic traits, bolstering the evidence for the extension of the neurobiology of autistic traits to the general population.

Hallucinations and Brain Morphology Across Early Adolescence: A Longitudinal Neuroimaging Study.

BACKGROUND: Psychotic disorders have been widely associated with structural brain abnormalities. However, it is unclear whether brain structure predicts psychotic experiences in youth from the general population, owing to an overall paucity of studies and predominantly cross-sectional designs. Here, the authors investigated longitudinal associations between brain morphology and hallucinations from childhood to early adolescence. METHODS: This study was embedded in the population-based Generation R Study. Children underwent structural neuroimaging at age 10 years (N = 2042); a subsample received a second scan at age 14 years (n = 964). Hallucinations were assessed at ages 10 and 14 years and studied as a binary variable. Cross-lagged panel models and generalized linear mixed-effects models were fitted to examine longitudinal associations between brain morphology and hallucinations. RESULTS: Smaller total gray and white matter volumes and total cortical surface area at baseline were associated with a higher occurrence of hallucinations between ages 10 and 14 years. The regions associated with hallucinations were widespread, including the frontal, parietal, temporal, and occipital lobes, as well as the insula and cingulate cortex. Analyses of subcortical structures revealed that smaller baseline hippocampal volumes were longitudinally associated with hallucinations, although this association was no longer significant following adjustment for intracranial volume. No evidence for reverse temporality was observed (i.e., hallucinations predicting brain differences). CONCLUSIONS: The findings from this longitudinal study suggest that global structural brain differences are associated with the development of hallucinations. These results extend findings from clinical populations and provide evidence for a neurodevelopmental vulnerability across the psychosis continuum.

The Bidirectional Relationship Between Brain Features and the Dysregulation Profile: A Longitudinal, Multimodal Approach.

The field of psychiatry increasingly highlights the importance of studying not only the influence of the brain on behavior, but also the long-term influences that the persistence of specific behaviors can have on the brain. A severe behavioral phenotype that puts children at risk for later psychopathology is the Child Behavior Checklist-Dysregulation Profile (CBCL-DP).1 In earlier work, Shaw et al.2 proposed a model in which the amygdala, nucleus accumbens, and orbitofrontal cortex, structures involved in the bottom-up response to emotional stimuli, are related to emotion dysregulation. Additionally, 3 key limbic white matter tracts have also been shown to be associated with CBCL-DP symptoms: the uncinate fasciculus, cingulum bundle, and forceps minor.3,4.

Genetic variants associated with longitudinal changes in brain structure across the lifespan.

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

The long-term impact of elevated C-reactive protein levels during pregnancy on brain morphology in late childhood.

IMPORTANCE: Animal studies show that Maternal Immune Activation (MIA) may have detrimental effects on fetal brain development. Clinical studies provide evidence for structural brain abnormalities in human neonates following MIA, but no study has investigated the long-term effects of MIA (as measured with biomarkers) on human brain morphology ten years after the exposure. OBJECTIVE: Our aim was to evaluate the long-term impact of MIA on brain morphology in 10-year-old children, including the possible mediating role of gestational age at birth. DESIGN: We leveraged data from Generation R, a large-scale prospective pregnancy cohort study. Pregnant women were included between 2002 and 2006, and their children were invited to participate in the MRI study between 2013 and 2015. To be included, mother-child dyads had to have data on maternal C-reactive protein levels during gestation and a good quality MRI-scan of the child's brain at age 10 years. Of the 3,992 children scanned, a total of 2,053 10-year-old children were included in this study. EXPOSURE: Maternal C-reactive protein was measured in the first 18 weeks of gestation. For the analyses we used both a continuous approach as well as a categorical approach based on clinical cut-offs to determine if there was a dose-response relationship. MAIN OUTCOMES AND MEASURES: High-resolution MRI brain morphology measures were used as the primary outcome. Gestational age at birth, established using ultrasound, was included as a mediator using a causal mediation analysis. Corrections were made for relevant confounders and multiple comparisons. Biological sex was investigated as moderator. RESULTS: We found a direct association between continuous MIA and lower cerebellar volume. In girls, we demonstrated a negative indirect association between continuous MIA and total brain volume, through the mediator gestational age at birth. We observed no associations with categorical MIA after multiple testing correction. CONCLUSION AND RELEVANCE: Our results suggest sex-specific long-term effects in brain morphology after MIA. Categorical analyses suggest that this association might be driven by acute infections or other sources of severe inflammation, which is of clinical relevance given that the COVID-19 pandemic is currently affecting millions of pregnant women worldwide.

Neurodevelopmental Trajectories in Children With Internalizing, Externalizing and Emotion Dysregulation Symptoms.

Introduction: Childhood and adolescence are crucial periods for brain and behavioral development. However, it is not yet clear how and when deviations from typical brain development are related to broad domains of psychopathology. Methods: Using three waves of neuroimaging data within the population-based Generation R Study sample, spanning a total age range of 6-16 years, we applied normative modeling to establish typical development curves for (sub-)cortical volume in 37 brain regions, and cortical thickness in 32 brain regions. Z-scores representing deviations from typical development were extracted and related to internalizing, externalizing and dysregulation profile (DP) symptoms. Results: Normative modeling showed regional differences in developmental trajectories. Psychopathology symptoms were related to negative deviations from typical development for cortical volume in widespread regions of the cortex and subcortex, and to positive deviations from typical development for cortical thickness in the orbitofrontal, frontal pole, pericalcarine and posterior cingulate regions of the cortex. Discussion: Taken together, this study charts developmental curves across the cerebrum for (sub-)cortical volume and cortical thickness. Our findings show that psychopathology symptoms, are associated with widespread differences in brain development, in which those with DP symptoms are most heavily affected.

What senior academics can do to support reproducible and open research: a short, three-step guide.

Increasingly, policies are being introduced to reward and recognise open research practices, while the adoption of such practices into research routines is being facilitated by many grassroots initiatives. However, despite this widespread endorsement and support, as well as various efforts led by early career researchers, open research is yet to be widely adopted. For open research to become the norm, initiatives should engage academics from all career stages, particularly senior academics (namely senior lecturers, readers, professors) given their routine involvement in determining the quality of research. Senior academics, however, face unique challenges in implementing policy changes and supporting grassroots initiatives. Given that-like all researchers-senior academics are motivated by self-interest, this paper lays out three feasible steps that senior academics can take to improve the quality and productivity of their research, that also serve to engender open research. These steps include changing (a) hiring criteria, (b) how scholarly outputs are credited, and (c) how we fund and publish in line with open research principles. The guidance we provide is accompanied by material for further reading.

Child mental health problems as a risk factor for academic underachievement: A multi-informant, population-based study.

OBJECTIVE: To investigate whether child mental health problems prospectively associate with IQ-achievement discrepancy (i.e., academic under- and over-achievement) in emerging adolescence. The secondary aims were to test whether these associations are specific to certain mental health problems, to assess potential sex differences, and to examine whether associations are robustly observed across multiple informants (i.e., maternal and teacher-reports). METHODS: This study included 1,577 children from the population-based birth cohort the Generation R Study. Child mental health problems at age 6 were assessed by mothers and teachers using the Child Behavior Checklist and the Teacher's Report Form. The IQ-achievement discrepancy was quantified as the standardized residuals of academic achievement regressed on IQ, where IQ was measured with four tasks from the Wechsler Intelligence Scale for Children-Fifth Edition around age 13 and academic attainment was measured with the Cito test, a national Dutch academic test, at the end of elementary school (12 years of age). RESULTS: Mental health problems at age 6 were associated with IQ-achievement discrepancy at age 12, with more problems associating with greater academic underachievement. When examining specific mental health problems, we found that attention problems was the only mental health problem to independently associate with the IQ-achievement discrepancy (adjusted standardized difference per 1-standard deviation, mother: -0.11, p < 0.001, 95% CI [-0.16, -0.06]; teacher: -0.13, p < 0.001, 95% CI [-0.18, -0.08]). These associations remained after adjusting for co-occurring mental health problems. The overall pattern of associations was consistent across boys and girls and across informants. CONCLUSION: Mental health problems during the transition from kindergarten to elementary school associate with academic underachievement at the end of elementary school. These associations were primarily driven by attention problems, as rated by both mothers and teachers-suggesting that strategies targeting attention problems may be a particularly promising avenue for improving educational performance irrespective of IQ, although this should be established more thoroughly through further research.

Sleep and mental health in childhood: a multi-method study in the general pediatric population.

BACKGROUND: Sleep problems, altered sleep patterns and mental health difficulties often co-occur in the pediatric population. Different assessment methods for sleep exist, however, many studies only use one measure of sleep or focus on one specific mental health problem. In this population-based study, we assessed different aspects of sleep and mother-reported mental health to provide a broad overview of the associations between reported and actigraphic sleep characteristics and mental health. METHODS: This cross-sectional study included 788 children 10-11-year-old children (52.5% girls) and 344 13-14-year-old children (55.2% girls). Mothers and children reported on the sleep of the child and wrist actigraphy was used to assess the child's sleep patterns and 24 h activity rhythm. Mental health was assessed via mother-report and covered internalizing, externalizing and a combined phenotype of internalizing and externalizing symptoms, the dysregulation profile. RESULTS: Higher reported sleep problems were related to more symptoms of mental health problems in 10-11- and 13-14-year-old adolescents, with standardized ß-estimates ranging between 0.11 and 0.35. There was no association between actigraphy-estimated sleep and most mental health problems, but earlier sleep onset was associated with more internalizing problems (ß = - 0.09, SE = 0.03, p-value = 0.002), and higher intra-daily variability of the 24 h activity rhythm was associated with more dysregulation profile symptoms at age 10-11 (ß = 0.11, SE = 0.04, p-value = 0.002). DISCUSSION: Reported sleep problems across informants were related to all domains of mental health problems, providing evidence that sleep can be an important topic to discuss for clinicians seeing children with mental health problems. Actigraphy-estimated sleep characteristics were not associated with most mental health problems. The discrepancy between reported and actigraphic sleep measures strengthens the idea that these two measures tap into distinct constructs of sleep.

Adolescent gender diversity: sociodemographic correlates and mental health outcomes in the general population.

BACKGROUND: Gender diversity in young adolescents is understudied outside of referral clinics. We investigated gender diversity in an urban, ethnically diverse sample of adolescents from the general population and examined predictors and associated mental health outcomes. METHODS: The study was embedded in Generation R, a population-based cohort of children born between 2002 and 2006 in Rotterdam, the Netherlands (n = 5727). At ages 9-11 and 13-15 years, adolescents and/or their parents responded to two questions addressing children's contentedness with their assigned gender, whether they (a) 'wished to be the opposite sex' and (b) 'would rather be treated as someone from the opposite sex'. We defined 'gender-variant experience' when either the parent or child responded with 'somewhat or sometimes true' or 'very or often true'. Mental health was assessed at 13-15 years, using the Achenbach System of Empirically Based Assessment. RESULTS: Less than 1% of the parents reported that their child had gender-variant experience, with poor stability between 9-11 and 13-15 years. In contrast, 4% of children reported gender-variant experience at 13-15 years. Adolescents who were assigned female at birth reported more gender-variant experience than those assigned male. Parents with low/medium educational levels reported more gender-variant experience in their children than those with higher education. There were positive associations between gender-variant experience and symptoms of anxiety, depression, somatic complaints, rule-breaking, and aggressive behavior as well as attention, social, and thought problems. Similar associations were observed for autistic traits, independent of other mental difficulties. These associations did not differ by assigned sex at birth. CONCLUSIONS: Within this population-based study, adolescents assigned females were more likely to have gender-variant experience than males. Our data suggest that parents may not be aware of gender diversity feelings in their adolescents. Associations between gender diversity and mental health symptoms were present in adolescents.

Data sharing and privacy issues in neuroimaging research: Opportunities, obstacles, challenges, and monsters under the bed.

Collaborative networks and data sharing initiatives are broadening the opportunities for the advancement of science. These initiatives offer greater transparency in science, with the opportunity for external research groups to reproduce, replicate, and extend research findings. Further, larger datasets offer the opportunity to identify homogeneous patterns within subgroups of individuals, where these patterns may be obscured by the heterogeneity of the neurobiological measure in smaller samples. However, data sharing and data pooling initiatives are not without their challenges, especially with new laws that may at first glance appear quite restrictive for open science initiatives. Interestingly, what is key to some of these new laws (i.e, the European Union's general data protection regulation) is that they provide greater control of data to those who "give" their data for research purposes. Thus, the most important element in data sharing is allowing the participants to make informed decisions about how they want their data to be used, and, within the law of the specific country, to follow the participants' wishes. This framework encompasses obtaining thorough informed consent and allowing the participant to determine the extent that they want their data shared, many of the ethical and legal obstacles are reduced to just monsters under the bed. In this manuscript we discuss the many options and obstacles for data sharing, from fully open, to federated learning, to fully closed. Importantly, we highlight the intersection of data sharing, privacy, and data ownership and highlight specific examples that we believe are informative to the neuroimaging community.

Direct and Indirect Associations of Widespread Individual Differences in Brain White Matter Microstructure With Executive Functioning and General and Specific Dimensions of Psychopathology in Children.

BACKGROUND: Executive functions (EFs) are important partly because they are associated with risk for psychopathology and substance use problems. Because EFs have been linked to white matter microstructure, we tested the prediction that fractional anisotropy (FA) and mean diffusivity (MD) in white matter tracts are associated with EFs and dimensions of psychopathology in children younger than the age of widespread psychoactive substance use. METHODS: Parent symptom ratings, EF test scores, and diffusion tensor parameters from 8588 9- to 10-year-olds in the ABCD Study (Adolescent Brain Cognitive Development Study) were used. RESULTS: A latent factor derived from EF test scores was significantly associated with specific conduct problems and attention-deficit/hyperactivity disorder problems, with dimensions defined in a bifactor model. Furthermore, EFs were associated with FA and MD in 16 of 17 bilateral white matter tracts (range: ß = .05; SE = .17; through ß = -.31; SE = .06). Neither FA nor MD was directly associated with psychopathology, but there were significant indirect associations via EFs of both FA (range: ß = .01; SE = .01; through ß = -.09; SE = .02) and MD (range: ß = .01; SE = .01; through ß = .09; SE = .02) with both specific conduct problems and attention-deficit/hyperactivity disorder in all tracts except the forceps minor. CONCLUSIONS: EFs in children are inversely associated with diffusion tensor imaging measures in nearly all tracts throughout the brain. Furthermore, variance in diffusion tensor measures that is shared with EFs is indirectly shared with attention-deficit/hyperactivity disorder and conduct problems.

Stability and Change of Psychopathology Symptoms Throughout Childhood and Adolescence.

Assessing stability and change of children's psychopathology symptoms can help elucidate whether specific behaviors are transient developmental variations or indicate persistent psychopathology. This study included 6930 children across early childhood (T1), late childhood (T2) and early adolescence (T3), from the general population. Latent profile analysis identified psychopathology subgroups and latent transition analysis quantified the probability that children remained within, or transitioned across psychopathology subgroups. We identified four psychopathology subgroups; no problems (T1: 85.9%, T2: 79.0%, T3: 78.0%), internalizing (T1: 5.1%, T2: 9.2%, T3: 9.0%), externalizing (T1: 7.3%, T2: 8.3%, T3: 10.2%) and the dysregulation profile (DP) (T1: 1.7%, T2: 3.5%, T3: 2.8%). From T1 to T2, 44.7% of the children remained in the DP. Between T2 and T3, 33.6% remained in the DP; however, 91.4% were classified in one of the psychopathology subgroups. Our findings suggest that for many children, internalizing or externalizing symptoms encompass a transient phase within development. Contrary, the DP resembles a severe at-risk state in which the predictive value for being in one of the psychopathology subgroups increases over time.

Brain morphology, autistic traits, and polygenic risk for autism: A population-based neuroimaging study.

Autism spectrum disorders (ASD) are associated with widespread brain alterations. Previous research in our group linked autistic traits with altered gyrification, but without pronounced differences in cortical thickness. Herein, we aim to replicate and extend these findings using a larger and older sample. Additionally, we examined whether (a) brain correlates of autistic traits were associated with polygenic risk scores (PRS) for ASD, and (b) autistic traits are related with brain morphological changes over time in a subset of children with longitudinal data available. The sample included 2400 children from the Generation R cohort. Autistic traits were measured using the Social Responsiveness Scale (SRS) at age 6 years. Gyrification, cortical thickness, surface area, and global morphological measures were obtained from high-resolution structural MRI scans at ages 9-to-12 years. We performed multiple linear regression analyses on a vertex-wise level. Corresponding regions of interest were tested for association with PRS. Results showed that autistic traits were related to (a) lower gyrification in the lateral occipital and the superior and inferior parietal lobes, (b) lower cortical thickness in the superior frontal region, and (c) lower surface area in inferior temporal and rostral middle frontal regions. PRS for ASD and longitudinal analyses showed significant associations that did not survive correction for multiple testing. Our findings support stability in the relationship between higher autistic symptoms and lower gyrification and smaller surface areas in school-aged children. These relationships remained when excluding ASD cases, providing neurobiological evidence for the extension of autistic traits into the general population. LAY SUMMARY: We found that school-aged children with higher levels of autistic traits had smaller total brain volume, cerebellum, cortical thickness, and surface area. Further, we also found differences in the folding patterns of the brain (gyrification). Overall, genetic susceptibility for autism spectrum disorders was not related to these brain regions suggesting that other factors could be involved in their origin. These results remained significant when excluding children with a diagnosis of ASD, providing support for the extension of the relationship between autistic traits and brain findings into the general population.

Bayesian evidence synthesis in case of multi-cohort datasets: An illustration by multi-informant differences in self-control.

The trend toward large-scale collaborative studies gives rise to the challenge of combining data from different sources efficiently. Here, we demonstrate how Bayesian evidence synthesis can be used to quantify and compare support for competing hypotheses and to aggregate this support over studies. We applied this method to study the ordering of multi-informant scores on the ASEBA Self Control Scale (ASCS), employing a multi-cohort design with data from four Dutch cohorts. Self-control reports were collected from mothers, fathers, teachers and children themselves. The available set of reporters differed between cohorts, so in each cohort varying components of the overarching hypotheses were evaluated. We found consistent support for the partial hypothesis that parents reported more self-control problems than teachers. Furthermore, the aggregated results indicate most support for the combined hypothesis that children report most problem behaviors, followed by their mothers and fathers, and that teachers report the fewest problems. However, there was considerable inconsistency across cohorts regarding the rank order of children's reports. This article illustrates Bayesian evidence synthesis as a method when some of the cohorts only have data to evaluate a partial hypothesis. With Bayesian evidence synthesis, these cohorts can still contribute to the aggregated results.

The association between body mass index and brain morphology in children: a population-based study.

Brain morphology is altered in both anorexia nervosa and obesity. However, it is yet unclear if the relationship between Body Mass Index-Standard Deviation Score (BMI-SDS) and brain morphology exists across the BMI-SDS spectrum, or is present only in the extremes. The study involved 3160 9-to-11 year-old children (50.3% female) who participate in Generation R, a population-based study. Structural MRI scans were obtained from all children and FreeSurfer was used to quantify both global and surface-based measures of gyrification and cortical thickness. Body length and weight were measured to calculate BMI. Dutch growth curves were used to calculate BMI-SDS. BMI-SDS was analyzed continuously and in two categories (median split). The relationship between BMI-SDS (range - 3.82 to 3.31) and gyrification showed an inverted-U shape curve in children with both lower and higher BMI-SDS values having lower gyrification in widespread areas of the brain. BMI-SDS had a positive linear association with cortical thickness in multiple brain regions. This study provides evidence for an association between BMI-SDS and brain morphology in a large sample of children from the general population and suggests that a normal BMI during childhood is important for brain development. Future studies could determine whether lifestyle modifications optimize BMI-SDS result in return to more typical patterns of brain morphology.