scholarly journals Downstream Effects of Maternal Hypothyroxinemia in Early Pregnancy: Nonverbal IQ and Brain Morphology in School-Age Children

2014 ◽  
Vol 99 (7) ◽  
pp. 2383-2390 ◽  
Author(s):  
Akhgar Ghassabian ◽  
Hanan El Marroun ◽  
Robin P. Peeters ◽  
Vincent W. Jaddoe ◽  
Albert Hofman ◽  
...  
Keyword(s):  
Surface Area ◽  
Cortical Thickness ◽  
Early Pregnancy ◽  
Large Population ◽  
Brain Morphology ◽  
School Age Children ◽  
School Age ◽  
Brain Volumes ◽  
Global Brain ◽  
Volumetric Measures

Context: Although maternal hypothyroxinemia is suggested to be related to various adverse consequences in a child's neurodevelopment, the underlying neurobiology is largely unknown. Objective: The objective of the study was to examine the relationship between maternal hypothyroxinemia in early pregnancy and children's nonverbal intelligence quotient (IQ). Furthermore, we explored whether global brain volumes, cortical thickness, and brain surface area differed between children exposed prenatally to hypothyroxinemia and healthy controls. Design and Setting: The study included a large population-based prospective birth cohort in The Netherlands. Participants: A total of 3727 mother-child pairs with data on prenatal thyroid function at less than 18 weeks of gestation and nonverbal IQ at 6 years participated in the study. In 652 children, brain imaging was performed at 8 years of age. Main Measures: Maternal hypothyroxinemia was defined as free T4 in the lowest 5% of the sample, whereas TSH was in the normal range. At 6 years, children's IQ was assessed using a Dutch test battery. Global brain volumetric measures, cortical thickness, and surface area were assessed using high-resolution structural magnetic resonance imaging. Results: The children of mothers with hypothyroxinemia in early pregnancy scored 4.3 points IQ lower than the children of mothers with normal thyroid status (95% confidence interval −6.68, −1.81; P = .001). After adjustment for multiple testing, we did not find any differences in brain volumetric measures, cortical thickness, and surface area between children exposed prenatally to hypothyroxinemia and controls. Conclusions: Our findings confirm a large adverse effect of maternal hypothyroxinemia on children's nonverbal IQ at school age. However, we found no evidence that maternal hypothyroxinemia is associated with differences in brain morphology in school-age children.

scholarly journals Quantifying the Polygenic Architecture of the Human Cerebral Cortex: Extensive Genetic Overlap between Cortical Thickness and Surface Area

2020 ◽  
Vol 30 (10) ◽  
pp. 5597-5603 ◽  
Author(s):  
Dennis van der Meer ◽  
Oleksandr Frei ◽  
Tobias Kaufmann ◽  
Chi-Hua Chen ◽  
Wesley K Thompson ◽  
...  
Keyword(s):  
Surface Area ◽  
Cortical Thickness ◽  
Large Scale ◽  
Gaussian Mixture ◽  
Total Surface Area ◽  
Brain Morphology ◽  
Genetic Determinants ◽  
Genetic Predictors ◽  
Genetic Overlap ◽  
Causal Variants

Abstract The thickness of the cerebral cortical sheet and its surface area are highly heritable traits thought to have largely distinct polygenic architectures. Despite large-scale efforts, the majority of their genetic determinants remain unknown. Our ability to identify causal genetic variants can be improved by employing brain measures that better map onto the biology we seek to understand. Such measures may have fewer variants but with larger effects, that is, lower polygenicity and higher discoverability. Using Gaussian mixture modeling, we estimated the number of causal variants shared between mean cortical thickness and total surface area, as well as the polygenicity and discoverability of regional measures. We made use of UK Biobank data from 30 880 healthy White European individuals (mean age 64.3, standard deviation 7.5, 52.1% female). We found large genetic overlap between total surface area and mean thickness, sharing 4016 out of 7941 causal variants. Regional surface area was more discoverable (P = 2.6 × 10−6) and less polygenic (P = 0.004) than regional thickness measures. These findings may serve as a roadmap for improved future GWAS studies; knowledge of which measures are most discoverable may be used to boost identification of genetic predictors and thereby gain a better understanding of brain morphology.

Preterm birth and maternal responsiveness during childhood are associated with brain morphology in adolescence

2010 ◽  
Vol 16 (5) ◽  
pp. 784-794 ◽  
Author(s):  
RICHARD E. FRYE ◽  
BENJAMIN MALMBERG ◽  
PAUL SWANK ◽  
KAREN SMITH ◽  
SUSAN LANDRY
Keyword(s):  
Preterm Birth ◽  
Surface Area ◽  
Cortical Thickness ◽  
Mixed Model ◽  
Brain Morphology ◽  
Maternal Responsiveness ◽  
Hemispheric Differences ◽  
Mixed Model Analysis ◽  
Positive Effects ◽  
Supportive Parenting

AbstractAlthough supportive parenting has been shown to have positive effects on development, the neurobiological basis of supportive parenting has not been investigated. Thirty-three adolescents were systemically selected from a longitudinal study on child development based on maternal responsiveness during childhood, a measure of supportive parenting, and whether they were born term or preterm. We analyzed the effect of preterm birth on hemispheric and regional (frontal, temporal, parietal) cortical thickness and surface area using mixed-model analysis while also considering the effect of brain hemisphere (left vs. right). We then determined whether these factors were moderated by maternal responsiveness during childhood. Preterm birth was associated with regional and hemispheric differences in cortical thickness and surface area. Maternal responsiveness during childhood moderated hemispheric cortical thickness. Adolescence with mothers that were inconsistently responsive during childhood demonstrated greater overall cortical thickness and greater asymmetry in cortical thickness during adolescence as compared to adolescence with mothers who were consistently responsive or unresponsive during childhood. Maternal responsiveness and preterm birth did not interact. These data suggest that changes in brain morphology associated with preterm birth continue into adolescence and support the notion that the style of maternal-child interactions during childhood influence brain development into adolescence. (JINS, 2010, 16, 784–794.)

scholarly journals M166. THE EFFECT OF INTELLIGENCE AND EDUCATIONAL ATTAINMENT ON THE BRAIN IN THOSE WITH FAMILIAL HIGH RISK FOR SCHIZOPHRENIA OR BIPOLAR DISORDER: AN ENIGMA–RELATIVES STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S199-S200
Author(s):  
Sonja M C de Zwarte ◽  
Rachel R M Brouwer ◽  
René S Kahn ◽  
Jessica A Turner ◽  
Theo G M van Erp ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Educational Attainment ◽  
Surface Area ◽  
Cortical Thickness ◽  
Multiple Testing ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Effect Sizes ◽  
Brain Volumes ◽  
Iq Test

Abstract Background Schizophrenia (SZ) and bipolar disorder (BD) are both associated with generally lower IQ test results and show overlapping structural brain abnormalities, albeit with lower effect sizes in BD. In contrast, our recent ENIGMA-Relatives meta-analysis showed that patients’ first-degree relatives (FDRs) have divergent patterns of global brain measures (De Zwarte et al. Biol. Psychiatry, 2019). FDRs-BD had larger intracranial volumes (ICV) than matched controls, a pattern not found in FDRs-SZ; when we adjusted for ICV, no differences were detected between FDRs-BD and controls. In contrast, FDRs-SZ had significantly smaller brain volumes, mean cortical thickness and larger ventricle volume than controls. Here, we extend this work by adding measures of local cortical thickness and surface area and by investigating the effect of IQ and educational attainment (EA) on global and local brain measures in FDRs. Methods 6,134 participants from 36 cohorts worldwide were included: N(FDRs-SZ)=1,103, N(FDRs-BD)=867, N(controls)=2,529 (and N(SZ-patients)=942, N(BD-patients)=693). Most cohorts provided information on IQ and/or EA (years completed education in those aged >25 yr.). (Sub-)cortical reconstruction and volumetric segmentations were performed with FreeSurfer. Linear mixed model analyses were performed on brain measures, IQ, and EA within each cohort comparing FDRs to controls (taking family relatedness into account). Cohen’s d effect sizes (95%CI) were calculated. Results FDRs-SZ had a thinner cortex across most cortical regions, compared to controls, with a thinner pars orbitalis surviving correction for multiple testing (left d=– 0.17, right =– 0.16, q<0.05 corrected). FDRs-BD had larger regional surface area in many cortical areas than controls, with a significantly larger cortical surface area in the left transverse temporal, left parahippocampal, right superior temporal, right supramarginal and right transverse temporal regions surviving correction for multiple testing (d’s >+ 0.15, q<0.05, corrected). Mean IQ test scores were lower in both FDRs-SZ (d=–0.42, p<0.001) and FDRs-BD (d=–0.23, p=0.045); while relatives did not differ on EA from controls. The IQ-EA correlation was r=0.39 [0.31–0.47]. When adjusting for IQ or EA, the group differences in brain measures changed, albeit modestly. In FDRs-SZ, controlling for IQ explained part of the effect of familial risk for schizophrenia in total brain, gray and white matter volumes (i.e., reduced effect sizes), while in FDRs-BD IQ correction resulted in a larger average ICV compared to controls. Discussion This study showed differential patterns of cortical thickness and surface area abnormalities in FDRs-SZ and FDRs-BD. While present in both relative groups, cognitive deficits (but only IQ not EA) were more pronounced in FDRs-SZ. We found no evidence that larger ICV in FDRs-BD was related to IQ, suggesting that the differential brain developmental trajectories underlying predisposition for schizophrenia or bipolar disorder may be unrelated to IQ. These large-scale studies inform the debate on whether schizophrenia and bipolar disorder represent truly independent diagnostic categories or whether they fall on a continuum of overlapping symptom profiles.

scholarly journals Quantifying the polygenic architecture of the human cerebral cortex: Extensive genetic overlap between cortical thickness and surface area

2019 ◽  
Author(s):  
Dennis van der Meer ◽  
Oleksandr Frei ◽  
Tobias Kaufmann ◽  
Chi-Hua Chen ◽  
Wesley K. Thompson ◽  
...  
Keyword(s):  
Surface Area ◽  
Cortical Thickness ◽  
Large Scale ◽  
Gaussian Mixture ◽  
Total Surface Area ◽  
Brain Morphology ◽  
Genetic Determinants ◽  
Genetic Predictors ◽  
Genetic Overlap ◽  
Causal Variants

ABSTRACTIntroductionThe thickness of the cerebral cortical sheet and its surface area are highly heritable traits thought to have largely distinct polygenic architectures. Despite large-scale efforts, the majority of their genetic determinants remains unknown. Our ability to identify causal genetic variants can be improved by employing better delineated, less noisy brain measures that better map onto the biology we seek to understand. Such measures may have fewer variants but with larger effects, i.e. lower polygenicity and higher discoverability.MethodsUsing Gaussian mixture modeling, we estimated the number of causal variants shared between mean cortical thickness and total surface area. We further determined the polygenicity and discoverability of regional cortical measures from five often-employed parcellation schemes. We made use of UK Biobank data from 31,312 healthy White European individuals (mean age 55.5, standard deviation (SD) 7.4, 52.1% female).ResultsContrary to previous reports, we found large genetic overlap between total surface area and mean thickness, sharing 4427 out of 7150 causal variants. Regional surface area was more discoverable (p=4.1×10−6) and less polygenic (p=.007) than regional thickness measures. We further found that genetically-informed and less granular parcellation schemes had highest discoverability, with no differences in polygenicity.ConclusionsThese findings may serve as a roadmap for improved future GWAS studies; Knowledge of which measures or parcellations are most discoverable, as well as the genetic overlap between these measures, may be used to boost identification of genetic predictors and thereby gain a better understanding of brain morphology.

Prenatal folate, homocysteine and vitamin B12 levels and child brain volumes, cognitive development and psychological functioning: the Generation R Study

2016 ◽  
Vol 122 (s1) ◽  
pp. S1-S9 ◽  
Author(s):  
Charlotte L. Ars ◽  
Ilse M. Nijs ◽  
Hanan E. Marroun ◽  
Ryan Muetzel ◽  
Marcus Schmidt ◽  
...  
Keyword(s):  
Cognitive Development ◽  
Early Pregnancy ◽  
Psychological Functioning ◽  
Child Behavior Checklist ◽  
Parent Report ◽  
Psychological Problems ◽  
Brain Morphology ◽  
Total Brain Volume ◽  
Brain Volumes ◽  
Spatial Domains

AbstractPrevious studies have suggested that prenatal maternal folate deficiency is associated with reduced prenatal brain growth and psychological problems in offspring. However, little is known about the longer-term impact. The aims of this study were to investigate whether prenatal maternal folate insufficiency, high total homocysteine levels and low vitamin B12 levels are associated with altered brain morphology, cognitive and/or psychological problems in school-aged children. This study was embedded in Generation R, a prospective population-based cohort study. The study sample consisted of 256 Dutch children aged between 6 and 8 years from whom structural brain scans were collected using MRI. The mothers of sixty-two children had insufficient (<8 nmol/l) plasma folate concentrations in early pregnancy. Cognitive development was assessed by the Snijders-Oomen Niet-verbale intelligentietest – Revisie and the NEPSY-II-NL. Psychological problems were assessed at age 6 years using the parent report of the Child Behavior Checklist. Low prenatal folate levels were associated with a smaller total brain volume (B –33·34; 95 % CI –66·7, 0·02; P=050) and predicted poorer performance on the language (B –0·28; 95 % CI –0·52, –0·04; P=0·020) and visuo-spatial domains (B –0·27; 95 % CI –0·50, –0·04; P=0·021). High homocysteine levels (>9·1 µmol/l) predicted poorer performance on the language (B –0·31; 95 % CI –0·56, –0·06; P=0·014) and visuo-spatial domains (B –0·36; 95 % CI –0·60, –0·11; P=0·004). No associations with psychological problems were found. Our findings suggest that folate insufficiency in early pregnancy has a long-lasting, global effect on brain development and is, together with homocysteine levels, associated with poorer cognitive performance.

scholarly journals Maternal early‐pregnancy glucose concentrations and liver fat among school age children

Hepatology ◽  
2021 ◽  
Author(s):  
Madelon L. Geurtsen ◽  
Rama J. Wahab ◽  
Janine F. Felix ◽  
Romy Gaillard ◽  
Vincent W.V. Jaddoe
Keyword(s):  
Early Pregnancy ◽  
Liver Fat ◽  
School Age Children ◽  
School Age

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

2021 ◽  
Author(s):  
Andrea P. Cortes Hidalgo ◽  
Scott W. Delaney ◽  
Stavroula A. Kourtalidi ◽  
Alexander Neumann ◽  
Runyu Zou ◽  
...  
Keyword(s):  
White Matter ◽  
Adverse Events ◽  
Large Population ◽  
Population Based ◽  
Brain Morphology ◽  
Cumulative Number ◽  
Childhood Adversities ◽  
Population Based Study ◽  
Brain Volumes ◽  
Total Brain

AbstractBackgroundPrenatal 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.MethodsParticipants included 2,993 children in whom 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-of-age. The total brain, grey 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.ResultsIn 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 grey 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.ConclusionsOur 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.

scholarly journals Cortical Thickness and Surface Area Networks in Healthy Aging, Alzheimer’s Disease and Behavioral Variant Fronto-Temporal Dementia

2019 ◽  
Vol 29 (06) ◽  
pp. 1850055 ◽  
Author(s):  
Vesna Vuksanović ◽  
Roger T Staff ◽  
Trevor Ahearn ◽  
Alison D Murray ◽  
Claude M Wischik
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Surface Area ◽  
Cortical Thickness ◽  
Healthy Aging ◽  
Large Population ◽  
Structural Basis ◽  
Elderly Subjects ◽  
Modular Organization ◽  
Area Network

Models of the human brain as a complex network of inter-connected sub-units are important in helping to understand the structural basis of the clinical features of neurodegenerative disorders. The aim of this study was to characterize in a systematic manner the differences in the structural correlation networks in cortical thickness (CT) and surface area (SA) in Alzheimer’s disease (AD) and behavioral variant Fronto-Temporal Dementia (bvFTD). We have used the baseline magnetic resonance imaging (MRI) data available from a large population of patients from three clinical trials in mild to moderate AD and mild bvFTD and compared this to a well-characterized healthy aging cohort. The study population comprised 202 healthy elderly subjects, 213 with bvFTD and 213 with AD. We report that both CT and SA network architecture can be described in terms of highly correlated networks whose positive and inverse links map onto the intrinsic modular organization of the four cortical lobes. The topology of the disturbance in structural network is different in the two disease conditions, and both are different from normal aging. The changes from normal are global in character and are not restricted to fronto-temporal and temporo-parietal lobes, respectively, in bvFTD and AD, and indicate an increase in both global correlational strength and in particular nonhomologous inter-lobar connectivity defined by inverse correlations. These inverse correlations appear to be adaptive in character, reflecting coordinated increases in CT and SA that may compensate for corresponding impairment in functionally linked nodes. The effects were more pronounced in the cortical thickness atrophy network in bvFTD and in the surface area network in AD. Although lobar modularity is preserved in the context of neurodegenerative disease, the hub-like organization of networks differs both from normal and between the two forms of dementia. This implies that hubs may be secondary features of the connectivity adaptation to neurodegeneration and may not be an intrinsic property of the brain. However, analysis of the topological differences in hub-like organization CT and SA networks, and their underlying positive and negative correlations, may provide a basis for assisting in the differential diagnosis of bvFTD and AD.

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