Brain Morphology In Children Research Articles

Shared and distinct alterations in brain morphology in children with ADHD and obesity: Reduced cortical surface area in ADHD and thickness in overweight/obesity

ObjectiveTo investigate shared versus distinct differences in brain structure among children with ADHD and obesity, we examined the morphology of regions implicated in cognitive control and reward function in a single cross-sectional cohort of children with and without ADHD and overweight/obesity (OV/OB). MethodParticipants included 471 children ages 8–12 years with ADHD (n = 244; 58 OV/OB) and neurotypical (NT) controls (n = 227; 81 OV/OB) classified as healthy-weight (HW; BMI %ile 5th to <85th) vs. having OV/OB (BMI %ile≥85th). Structural MRI was performed to obtain measures of cortical and subcortical morphology and compared across ADHD × BMI groups. ResultsSurface area was generally lower in ADHD vs. NT including in anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), medial (m)PFC, and primary motor (M1) cortex. In contrast, cortical thickness was generally lower in OV/OB vs. HW for ACC, dlPFC, orbitofrontal cortex (OFC), mPFC, and supplementary motor cortex (SMC). Furthermore, ADHD × OV/OB interactions were observed for the ACC and OFC, with the lowest ACC volume in the ADHD + OV/OB group and the highest OFC surface area in the NT + OV/OB group. Subcortical volumes did not differ between groups. ConclusionsOur findings reveal distinct alterations in cortical morphology in association with ADHD and overweight, with cortical surface area reduced in ADHD vs. thickness reduced in OV/OB. Additionally, the findings provide evidence of combined effects of ADHD × OV/OB in brain regions integral to cognition and motivation. Our results support further investigation of causes and correlates of shared and distinct ADHD- and OV/OB-associated differences in developing frontocingulate morphology.

Examining longitudinal associations between prenatal exposure to infections and child brain morphology

BackgroundMaternal infection during pregnancy has been identified as a prenatal risk factor for the later development of psychopathology in exposed offspring. Neuroimaging data collected during childhood has suggested a link between prenatal exposure to maternal infection and child brain structure and function, potentially offering a neurobiological explanation for the emergence of psychopathology. Additionally, preclinical studies utilizing repeated measures of neuroimaging data suggest that effects of prenatal maternal infection on the offspring’s brain may normalize over time (i.e., catch-up growth). However, it remains unclear whether exposure to prenatal maternal infection in humans is related to long-term differential neurodevelopmental trajectories. Hence, this study aimed to investigate the association between prenatal exposure to infections on child brain development over time using repeated measures MRI data. MethodsWe leveraged data from a population-based cohort, Generation R, in which we examined prospectively assessed self-reported infections at each trimester of pregnancy (N = 2,155). We further used three neuroimaging assessments (at mean ages 8, 10 and 14) to obtain cortical and subcortical measures of the offspring’s brain morphology with MRI. Hereafter, we applied linear mixed-effects models, adjusting for several confounding factors, to estimate the association of prenatal maternal infection with child brain development over time. ResultsWe found that prenatal exposure to infection in the third trimester was associated with a slower decrease in volumes of the pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and a faster increase in the middle temporal gyrus. In the temporal pole we observed a divergent pattern, specifically showing an increase in volume in offspring exposed to more infections compared to a decrease in volume in offspring exposed to fewer infections. We further observed associations in other frontal and temporal lobe structures after exposure to infections in any trimester, though these did not survive multiple testing correction. ConclusionsOur results suggest that prenatal exposure to infections in the third trimester may be associated with slower age-related growth in the regions: pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and faster age-related growth in the middle temporal gyrus across childhood, suggesting a potential sensitive period. Our results might be interpreted as an extension of longitudinal findings from preclinical studies, indicating that children exposed to prenatal infections could exhibit catch-up growth. However, given the lack of differences in brain volume between various infection groups at baseline, there may instead be either a longitudinal deviation or a subtle temporal deviation. Subsequent well-powered studies that extend into the period of full brain development (∼25 years) are needed to confirm whether the observed phenomenon is indeed catch-up growth, a longitudinal deviation, or a subtle temporal deviation.

Poverty from fetal life onward and child brain morphology

Poverty is a risk factor for impaired child development, an association possibly mediated by brain morphology. Previous studies lacked prospective poverty assessments during pregnancy and did not stratify by majority/minority status. We investigated the association of household poverty from fetal life forward with brain morphological differences at age 10 years, in 2166 mother–child dyads. Overall, the results showed no associations between any poverty exposure early in life and brain volumes. However, there was the evidence of timing effects: children exposed to poverty in utero had smaller amygdala volumes (B = − 0.18, 95%CI − 0.30; − 0.07, pFDR-adjusted = 0.009). There were also differences in associations by majority/minority status (cerebral white matter: p for interaction = 0.04). Dutch children exposed to childhood poverty showed smaller cerebral white matter volumes than their control (B = − 0.26, 95%CI − 0.45; − 0.06, pFDR-adjusted = 0.035). This association was not observed in the minority population (B = − 0.05, 95%CI − 0.23; 0.12, pFDR-adjusted = 0.542). The smaller cerebral white matter volume mediated the association between childhood poverty and poorer school performance in Dutch children. Our findings point to the importance of poverty exposure in the fetal period and suggest different mechanisms and vulnerabilities across majority/minority groups.

Air pollution exposure during pregnancy and childhood, APOE ε4 status and Alzheimer polygenic risk score, and brain structural morphology in preadolescents

BackgroundAir pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children, and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features. ObjectivesTo evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer's Disease (AD) modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents. MethodsWe included 1186 children from the Generation R Study. Concentrations of fourteen air pollutants were calculated at participants’ home addresses during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9–12 years to assess cortical and subcortical brain volumes. APOE status and PRS for AD were examined as genetic modifiers. Linear regression models were used to conduct single-pollutant and multi-pollutant (using the Deletion/Substitution/Addition algorithm) analyses with a two-way interaction between air pollution and each genetic modifier. ResultsHigher pregnancy coarse particulate matter (PMcoarse) and childhood polycyclic aromatic hydrocarbons exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers (29,485 mm3 (95% CI 6,189; 52,781) and 18,663 mm3 (469; 36,856), respectively). Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD (19436 mm3 (825, 38,046)). DiscussionAPOE status and PRS for AD possibly modify the association between air pollution exposure and brain structural morphology in preadolescents. Higher air pollution exposure is associated with larger cortical volumes in APOE ε4 carriers and children with a high PRS for AD. This is in line with typical brain development, suggesting an antagonistic pleiotropic effect of these genetic features (i.e., protective effect in early-life, but neurodegenerative effect in adulthood). However, we cannot discard chance findings. Future studies should evaluate trajectorial brain development using a longitudinal design.

Air Pollution Exposure during Pregnancy and Childhood, APOE ε4 Status and Polygenic Risk Score for Alzheimer’s Disease, and Brain Structural Morphology in Preadolescents

Background and Aim. Air pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features. We aimed to evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer’s Disease (AD), modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents. Methods. We included 1186 children from the Generation R Study. Concentrations of 14 air pollutants were calculated at the participants’ home address during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9–12 years to assess (sub)cortical brain volumes. APOE status and PRS for AD were examined as effect modifiers. We conducted single-pollutant analyses with a two-way interaction between air pollution and APOE status or PRS for AD and multi-pollutant analyses with the two-way interaction. Results. Higher pregnancy PMcoarse and childhood PAHs exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers (29485 mm3 [95% CI 6189, 52781] and 18663 mm3 [469, 36856], respectively). Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD (19436 mm3 [825, 38046]). Conclusions. APOE status and PRS for AD have a possible modifying effect on the association between air pollution exposure and brain structural morphology in preadolescents. Both seem to modify the association towards the typical development of the brain, with increasing cortical volumes, highlighting the possibility of the antagonistic pleiotropic effect (i.e., protective effect in early life but altered neurodegenerative processes in adulthood). Future studies should research this antagonistic pleiotropic effect and study trajectorial brain development using a longitudinal design. Keywords. environmental pollution, neurodevelopment, neuroimaging, genetic modifiers

Outdoor residential air pollution exposure and the development of brain morphology across childhood: a longitudinal study

Background and aim: Emerging evidence suggests a relationship between exposure to air pollution and brain morphology in children, but little is known about how air pollution exposure influences the development of brain structures throughout childhood. We aim to study the association of air pollution exposure during pregnancy and childhood with the development of brain morphology from age 6-16 years. Methods: We used data from 4,243 children of the Generation R study, a birth cohort in Rotterdam, the Netherlands. We estimated the concentrations of fourteen air pollutants at participant´s home addresses during pregnancy and childhood, using land use regression models. We included structural brain images at three time points, namely at age 6-10 years, 9-12 years, and 13-16 years. We assessed the association between the air pollutants and brain volumes with linear mixed models, fitting an interaction term for age and each pollutant. Models were adjusted for socioeconomic status and lifestyle characteristics. Results: Higher air pollution exposure during pregnancy was associated with a slower decrease of cortical grey matter volume starting at around age 10 and a slower increase of corpus callosum volume (e.g. -12.7 mm3 increase in corpus callosum volume [95%CI -22.0; -3.3] with each year of age per 10 &amp;#x3bc;g/m3 increase in nitrogen dioxide exposure). Childhood exposure was associated with a faster decrease of putamen and caudate nucleus volume, and a slower increase of hippocampus volume. Higher exposure to air pollution during pregnancy and childhood was associated with a slower increase of thalamus volume. Air pollution exposure was not associated with cerebellum, amygdala, nucleus accumbens or globus pallidus volume. Conclusions: Air pollution exposure was associated with region-specific differences in age-related growth trajectories. Air pollution exposure during childhood might affect different brain regions than exposure during pregnancy. Keywords: air pollution, neurodevelopment, children, traffic

Association of Maternal Tobacco Use During Pregnancy With Preadolescent Brain Morphology Among Offspring

Maternal tobacco use during pregnancy has been associated with various health consequences, including suboptimal neurodevelopment in offspring. However, the effect of prenatal exposure to maternal smoking on child brain development has yet to be elucidated. To investigate the association between maternal smoking during pregnancy and offspring brain development in preadolescence as well as the mediating pathways. This prospective, population-based cohort study was embedded in the Generation R Study, Rotterdam, the Netherlands. The Generation R Study was launched in 2002, with follow-up ongoing. Child brain morphology was assessed at 9 to 11 years of age (ie, 10-12 years between exposure and outcome assessment). Data analysis was performed from March 1, 2021, to February 28, 2022, and at the time of manuscript revision. Participants included the singleton children of pregnant women residing in the study area with an expected date of delivery between April 1, 2002, and January 31, 2006; 2704 children with information on maternal smoking during pregnancy and structural neuroimaging at 9 to 11 years of age were included. A subsample of 784 children with data on DNA methylation at birth was examined in the mediation analysis. Information on maternal smoking during pregnancy was collected via a questionnaire in each trimester. As a contrast, paternal smoking was assessed at recruitment. Brain morphology, including brain volumes and surface-based cortical measures (thickness, surface area, and gyrification), was assessed with magnetic resonance imaging. For mediation analysis, DNA methylation at birth was quantified by a weighted methylation risk score. The 2704 participating children (1370 [50.7%] girls and 1334 [49.3%] boys) underwent brain imaging assessment at a mean (SD) age of 10.1 (0.6) years. Compared with nonexposed children (n = 2102), exposure to continued maternal smoking during pregnancy (n = 364) was associated with smaller total brain volume (volumetric difference [b] = -14.5 [95% CI, -25.1 to -4.0] cm3), cerebral gray matter volume (b = -7.8 [95% CI, -13.4 to -2.3] cm3), cerebral white matter volume (b = -5.9 [95% CI, -10.7 to -1.0] cm3), and surface area and less gyrification. These associations were not explained by paternal smoking nor mediated by smoking-associated DNA methylation patterns at birth. Children exposed to maternal smoking only in the first trimester (n = 238) showed no differences in brain morphology compared with nonexposed children. The findings of this cohort study suggest that continued maternal tobacco use during pregnancy was associated with lower brain volumes and suboptimal cortical traits of offspring in preadolescence, which seemed to be independent of shared family factors. Tobacco cessation before pregnancy, or as soon as pregnancy is known, should be recommended to women for optimal brain development of their offspring.

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

ObjectiveAutistic 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.MethodParticipants 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.ResultsCross-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.LimitationsAutistic 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.ConclusionsOur 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.

Prenatal and Childhood Adverse Events and Child Brain Morphology: A Population-Based Study

Prenatal and childhood adverse events have been shown to be related to children’s cognitive and psychological development. However, the influence of early-life adversities on child brain morphology is not well understood, and most studies are based on small samples and often examine only one adversity. Thus, the goal of our study is to examine the relationship between cumulative exposures to prenatal and childhood adversities and brain morphology in a large population-based study. Participants included 2,993 children from the Generation R Study, a cohort of children growing up in Rotterdam, the Netherlands. Recruitment was initiated between 2002 and 2006, and the study is currently performing the 17- to 19-year follow-up wave. Prenatal adversities were reported by mothers at 20–25 weeks of pregnancy, and the child’s lifetime exposure to adversities was reported by mothers when the children were 10 years old. The total brain, gray and white matter volumes, and the volume of the cerebellum, amygdala, and hippocampus were assessed with magnetic resonance imaging when children were 10 years old. In total, 36% of children had mothers who were exposed to at least one adversity during pregnancy and 35% of children were exposed to adversities in childhood. In our study sample, the cumulative number of prenatal adversities was not related to any brain outcome. In contrast, per each additional childhood adverse event, the total brain volume was 0.07 standard deviations smaller (SE = 0.02, p = 0.001), with differences in both gray and white matter volumes. Childhood adversities were not related to the amygdala or hippocampal volumes. Additionally, the link between childhood events and the preadolescent brain was not modified by prenatal events and was not explained by maternal psychopathology. Our results suggest that childhood adversities, but not prenatal adverse events, are associated with smaller global brain volumes in preadolescence. Notably, this is the first large population-based study to prospectively assess the association between the cumulative number of prenatal adversities and the preadolescent brain morphology. The study findings extend the evidence from high-risk samples, providing support for a link between cumulative childhood adverse events and brain morphology in children from the general population.

White matter is increased in the brains of adults with neurofibromatosis 1

BackgroundNeurofibromatosis 1 (NF1) is a rare autosomal dominant disease characterized by increased Schwann cell proliferation in peripheral nerves. Several small studies of brain morphology in children with NF1 have found increased total brain volume, total white matter volume and/or corpus callosum area. Some studies (mostly in children with NF1) also attempted to correlate changes in brain morphology and volume with cognitive or behavioural abnormalities, although the findings were inconsistent. We aimed to characterize alterations in brain volumes by three-dimensional (3D) MRI in adults with NF1 in major intracranial sub-regions. We also aimed to assess the effect of age on these volumes and correlated brain white matter and grey matter volumes with neuropsychometric findings in adults with NF1.MethodsWe obtained brain volume measurements using 3D magnetic resonance imaging for 351 adults with NF1 and, as a comparison group, 43 adults with neurofibromatosis 2 (NF2) or Schwannomatosis. We assessed a subset of 19 adults with NF1 for clinical severity of NF1 features and neurological problems and conducted psychometric testing for attention deficiencies and intelligence quotient. We compared brain volumes between NF1 patients and controls and correlated volumetric measurements to clinical and psychometric features in the NF1 patients.ResultsTotal brain volume and total and regional white matter volumes were all significantly increased in adults with NF1. Grey matter volume decreased faster with age in adults with NF1 than in controls. Greater total brain volume and white matter volume were correlated with lower attention deficits and higher intelligence quotients in adults with NF1.ConclusionOur findings are consistent with the hypothesis that dysregulation of brain myelin production is a cardinal manifestation of NF1 and that these white matter changes may be functionally important in affected adults.

Prenatal and Childhood Adverse Events and Child Brain Morphology: A Population-Based Study

Prenatal and Childhood Adverse Events and Child Brain Morphology: A Population-Based Study

Patterns of Fetal and Infant Growth and Brain Morphology at Age 10 Years

Preterm birth and low birth weight are associated with brain developmental and neurocognitive outcomes in childhood; however, not much is known about the specific critical periods in fetal life and infancy for these outcomes. To examine the associations of fetal and infant growth patterns with brain morphology in children at school age. This population-based, prospective cohort study was conducted from February 1 to April 16, 2021, as a part of the Generation R Study in Rotterdam, the Netherlands. The study included 3098 singleton children born between April 1, 2002, and January 31, 2006. Fetal weight was estimated in the second and third trimesters of pregnancy by ultrasonography. Infant weight was measured at birth and at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in SD scores greater than 0.67 between time points. Infant measurements also included peak weight velocity, and age and body mass index reached at adiposity peak. Brain structure, including global and regional brain volumes, was quantified by magnetic resonance imaging at age 10 years. The study evaluated 3098 children (mean [SD] age at follow-up, 10.1 [0.6] years; 1557 girls [50.3%]; and 1753 Dutch [57.8%]). One SD score-higher weight gain until the second and third trimesters, birth, and 6, 12, and 24 months was associated with larger total brain volume independently of growth during any other age windows (second trimester: 5.7 cm3; 95% CI, 1.2-10.2 cm3; third trimester: 15.3 cm3; 95% CI, 11.0-19.6 cm3; birth: 20.8 cm3; 95% CI, 16.4-25.1 cm3; 6 months: 15.6 cm3; 95% CI, 11.2-19.9 cm3; 12 months: 11.3 cm3; 95% CI, 7.0-15.6 cm3; and 24 months: 11.1 cm3; 95% CI, 6.8-15.4 cm3). Compared with children with normal fetal and infant growth, those with fetal and infant growth deceleration had the smallest total brain volume (-32.5 cm3; 95% CI, -53.2 to -11.9 cm3). Children with fetal weight deceleration followed by infant catch-up growth had similar brain volumes as children with normal growth. Higher peak weight velocity and body mass index reached at adiposity peak were associated with larger brain volumes. Similar results were observed for cerebral and cerebellar gray and white matter volumes. This cohort study's findings suggest that both fetal and infant weight growth might be critical for cerebral and cerebellar brain volumes during childhood. Whether these associations link to neurocognitive outcomes should be further studied.

26.2 Low Family Income from Fetal Life Onward and Child Brain Morphology: Differential Impact by Ethnic Minority and Majority Status in a Population-Based Study

26.2 Low Family Income from Fetal Life Onward and Child Brain Morphology: Differential Impact by Ethnic Minority and Majority Status in a Population-Based Study

Maternal polyunsaturated fatty acids during pregnancy and offspring brain development in childhood

Emerging evidence suggests an association of maternal PUFA concentrations during pregnancy with child cognitive and neuropsychiatric outcomes such as intelligence and autistic traits. However, little is known about prenatal maternal PUFAs in relation to child brain development, which may underlie these associations. We aimed to investigate the association of maternal PUFA status during pregnancy with child brain morphology, including volumetric and white matter microstructure measures. This study was embedded in a prospective population-based study. In total, 1553 mother-child dyads of Dutch origin were included. Maternal plasma glycerophospholipid PUFAs were assessed in midpregnancy. Child brain morphologic outcomes, including total gray and white matter volumes, as well as white matter microstructure quantified by global fractional anisotropy and mean diffusivity, were measured using MRI (including diffusion tensor imaging) at age 9-11 y. Maternal ω-3 (n-3) long-chain PUFA (LC-PUFA) concentrations during pregnancy had an inverted U-shaped relation with child total gray volume (linear term: β: 16.7; 95% CI: 2.0, 31.5; quadratic term: β: -1.1; 95% CI: -2.1, -0.07) and total white matter volume (linear term: β: 15.7; 95% CI: 3.6, 27.8; quadratic term: β: -1.0; 95% CI: -1.8, -0.16). Maternal gestational ω-6 LC-PUFA concentrations did not predict brain volumetric differences in children, albeit the linolenic acid concentration was inversely associated with child total white matter volume. Maternal PUFA status during pregnancy was not related to child white matter microstructure. Sufficient maternal ω-3 PUFAs during pregnancy may be related to more optimal child brain development in the long term. In particular, exposure to lower ω-3 PUFA concentrations in fetal life was associated with less brain volume in childhood. Maternal ω-6 LC-PUFAs were not related to child brain morphology.

Associations of Dietary Patterns With Brain Morphology in Children: Results From a Prospective Population-Based Study

ObjectivesDietary patterns (DPs) in childhood have been associated with neurodevelopmental disorders and cognitive performance in children. However, little is known about the underlying neurobiological mechanisms. We aimed to examine associations of DPs in early and mid-childhood with pre-adolescent brain morphology in a large population-based cohort. MethodsWe studied children’s DPs at ages 1 and 8 and their associations with volumetric (total brain, hippocampus and amygdala) and surface-based brain measures (cortical thickness, surface area and gyrification) at age 10 years in a prospective population-based cohort in the Netherlands. High-resolution T1-weighted magnetic resonance images were collected in 3210 children. Brain measures were extracted using FreeSurfer. Dietary intake was assessed using age-specific food-frequency questionnaires. We derived DPs as diet quality scores based on dietary guidelines and identified Western and Prudent DPs using principal component analyses. We used multiple linear regression and surface-based analyses adjusting for multiple testing (Benjamini-Hochberg method) to examine associations with brain measures. ResultsHigher adherence to a Western DP at age 8 years was associated with a smaller total brain volume (B = –7.84, 95% CI –13.06, –2.61), whereas higher adherence to a Prudent DP at age 8 years was associated with a larger total brain volume (B = 8.45, 95% CI 4.25, 12.65). In addition, children with higher diet quality and better adherence to a Prudent DP showed greater gyrification and larger surface area, mostly clustered in the prefrontal cortex. At age 1 year, no statistically significant associations between DPs and global or surface-based brain measures were observed. No volumetric differences were found in the hippocampus or amygdala at both ages. ConclusionsWe are the first to show in a large population-based setting that dietary patterns in mid-childhood are associated with brain structural alterations, with a prudent diet being linked to a more optimal development. These findings suggest that a healthy diet is important for children’s brain development, which may explain part of the previously demonstrated relation between dietary patterns and psychosocial well-being and cognitive performance in children. Funding SourcesThis project did not receive any funding.

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.

Harsh Parenting and Child Brain Morphology: A Population-Based Study

Evidence suggests that maltreatment shapes the child's brain. Little is known, however, about how normal variation in parenting influences the child neurodevelopment. We examined whether harsh parenting is associated with the brain morphology in 2,410 children from a population-based cohort. Mothers and fathers independently reported harsh parenting at child age 3 years. Structural and diffusion-weighted brain morphological measures were acquired with MRI scans at age 10 years. We explored whether associations between parenting and brain morphology were explained by co-occurring adversities, and whether there was a joint effect of both parents' harsh parenting. Maternal harsh parenting was associated with smaller total gray (β = -0.05 (95%CI = -0.08; -0.01)), cerebral white matter and amygdala volumes (β = -0.04 (95%CI = -0.07; 0)). These associations were also observed with the combined harsh parenting measure and were robust to the adjustment for multiple confounding factors. Similar associations, although non-significant, were found between paternal parenting and these brain outcomes. Maternal and paternal harsh parenting were not associated with the hippocampus or the white matter microstructural metrics. We found a long-term association between harsh parenting and the global brain and amygdala volumes in preadolescents, suggesting that adverse rearing environments common in the general population are related to child brain morphology.

Frequent Bullying Involvement and Brain Morphology in Children.

Background: Over the past few decades, bullying has been recognized as a considerable public health concern. Involvement in bullying is associated with poor long-term social and psychiatric outcomes for both perpetrators and targets of bullying. Despite this concerning prognosis, few studies have investigated possible neurobiological correlates of bullying involvement that may explain the long-term impact of bullying. Cortical thickness is ideally suited for examining deviations in typical brain development, as it has been shown to detect subtle differences in children with psychopathology. We tested associations between bullying involvement and cortical thickness using a large, population-based cohort.Methods: The study sample consisted of 2,602 participants from the Generation R Study. When children were 8 years old, parents and teachers reported on common forms of child bullying involvement (physical, verbal, and relational). Questions ascertained whether a child was involved as a perpetrator (n = 82), a target of bullying (n = 92), as a combined perpetrator and target of bullying (n = 47), or uninvolved in frequent bullying (n = 2,381). High-resolution structural MRI was conducted when children were 10 years of age. Cortical thickness estimates across the cortical mantle were compared among groups.Results: Children classified as frequent targets of bullying showed thicker cortex in the fusiform gyrus compared to those uninvolved in bullying (B = 0.108, pcorrected < 0.001). Results remained consistent when adjusted for socioeconomic factors, general intelligence, and psychiatric symptoms. Children classified as frequent perpetrators showed thinner cortex in the cuneus region; however, this association did not survive stringent correction for multiple testing. Lastly, no differences in cortical thickness were observed in perpetrator–targets.Discussion: Bullying involvement in young children was associated with differential cortical morphology. Specifically, the fusiform gyrus, often involved in facial processing, showed thicker cortex in targets of frequent bullying. Longitudinal data are necessary to demonstrate the temporality of the underlying neurobiology associated with bullying involvement.

Maternal Thyroid Function Before 14 Weeks of Gestation Is Associated with Child Brain Morphology

Clinical ThyroidologyVol. 31, No. 9 Thyroid in PregnancyMaternal Thyroid Function Before 14 Weeks of Gestation Is Associated with Child Brain MorphologyElizabeth N. PearceElizabeth N. PearceSection of Endocrinology, Diabetes, and Nutrition; Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, U.S.A.Search for more papers by this authorPublished Online:10 Sep 2019https://doi.org/10.1089/ct.2019;31.362-364AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 31Issue 9Sep 2019 InformationCopyright 2019 American Thyroid Association, Inc.To cite this article:Elizabeth N. Pearce.Maternal Thyroid Function Before 14 Weeks of Gestation Is Associated with Child Brain Morphology.Clinical Thyroidology.Sep 2019.362-364.http://doi.org/10.1089/ct.2019;31.362-364Published in Volume: 31 Issue 9: September 10, 2019PDF download

Maternal thyroid function during pregnancy and child brain morphology: a time window-specific analysis of a prospective cohort

Adequate thyroid hormone availability during pregnancy is necessary for optimal fetal brain development. During the first 18-20 weeks of gestation, fetal thyroid hormone availability largely depends on the placental transfer of maternal thyroxine. Although various studies have shown that maternal thyroid dysfunction is associated with suboptimal child neurodevelopmental outcomes, the most vulnerable time window remains to be identified. The aim of this study is to examine the association of maternal thyroid function with child brain morphology and to study whether any association depends on the timing of thyroid assessment. This prospective cohort study was part of the Generation R Study in Rotterdam, Netherlands, with a prospective population-based birth cohort. Pregnant women living in Rotterdam with an expected delivery date between April 1, 2002, and Jan 1, 2006, were eligible. Other inclusion criteria were maternal serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) measurement in early or mid-pregnancy (≤18 weeks) and available brain MRI data for child at age 10 years. Exclusion criteria were pre-existing thyroid disorder, thyroid disorder treatment, twin pregnancy, in-vitro fertilisation-induced pregnancy, and suboptimal-quality MRI data or major incidental finding on MRI. The main outcome was the association between maternal TSH and FT4 concentrations with brain MRI outcomes of children. Regression analyses accounted for gestational age at blood sampling, maternal age, ethnicity, education level, smoking, thyroid peroxidase antibody positivity, child sex, age at MRI, and total intracranial volume. Effect modification by gestational age at blood sampling was also investigated. Between Dec 1, 2001, and June 30, 2005, 7069 women were enrolled during early or mid-pregnancy (≤18 weeks of gestation), of whom 5088 were not included because they did not have available data on maternal serum TSH or FT4 concentrations (n=1175), their child did not have brain MRI done (n=3377), or they met exclusion criteria (n=536). Thus, 1981 mother-child pairs were included in the study, with TSH and FT4 concentrations measured during pregnancy at a median of 13·1 weeks of gestation (IQR 12·1-14·5) and offspring brain morphology assessed by MRI at a median age of 9·9 years (9·7-10·2). Maternal TSH had an inverted U-shaped association with offspring total grey matter volume (p=0·007) and with cortical grey matter volume (p=0·022). The association of maternal TSH with child total grey matter volume (pinteraction=0·053) and cortical volume (pinteraction=0·086) differed by the duration of gestation. Analyses stratified for gestational age at blood sampling showed an inverted U-shaped association of maternal TSH with child total grey matter volume and cortical grey matter volume, which was most evident at 8 weeks gestation. After about 14 weeks of gestation, TSH was no longer associated with child brain morphology. Maternal FT4 concentrations were not associated with child total grey matter volume after adjusting for total intracranial volume (p=0·75). Here, we show that both low and high maternal thyroid function are associated with smaller child total grey matter and cortical volume. To the best of our knowledge, this study is the first to show that an association with a neurodevelopmental outcome is most evident when maternal thyroid function is measured early in pregnancy. These novel findings suggest that embryonic brain development is particularly vulnerable to altered maternal thyroid function. Netherlands Organisation for Health Research and Development and the Sophia Children's Hospital Foundation.