Gestational vitamin D deficiency and autism-related traits: the Generation R Study

Vinkhuyzen, Anna A. E.; Eyles, Darryl W.; Burne, Thomas H. J.; Blanken, Laura M. E.; Kruithof, Claudia J.; Verhulst, Frank C.; Jaddoe, Vincent W. V.; Tiemeier, Henning; McGrath, John J.

doi:10.1038/mp.2016.213

Cited by 138 publications

(125 citation statements)

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“…A recent study of postmortem neural tissue of children with ASD identified local disorganization across different cortical layers suggestive of aberrant prenatal neuronal migration [Stoner et al, ]. Environmental factors, such as maternal thyroid dysfunction or vitamin D deficiency may lead to autism‐like symptoms through restriction of prenatal brain growth [Korevaar et al, ; Román et al, ; Vinkhuyzen et al, ; Whitehouse et al, ]. Alternatively, autistic traits and prenatal HC growth may share a similar genetic background.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of fetal head growth, autistic traits and autism spectrum disorder

et al. 2018

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Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population‐based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism‐Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population‐based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602–612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.Lay SummaryIt is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian, group. No differences in head growth were found in individuals with ASD and controls when the data was combined. Our mixed findings suggest that more research in this area is needed.

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Section: Discussionmentioning

confidence: 99%

A prospective study of fetal head growth, autistic traits and autism spectrum disorder

et al. 2018

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“…Daraki et al investigated the association of maternal 25-hydroxyvitamin D [25(OH) D] levels with multiple neurodevelopmental and cognitive outcomes at 4 years of age in a prospective pregnancy cohort including 487 mother-child pairs [7]. Low gestational maternal vitamin D levels had been previously linked to autism-related neurodevelopmental outcomes in population-representative samples [8]. In the new study, a broad range of behavioural problems and externalizing symptoms, including hyperactivity, impulsivity, and also inattention, were significantly lower in children born to mothers within the high 25(OH) D tertile (> 50.7 nmol/l) as compared to offspring of women in the low 25(OH) D tertile (< 38.4 nmol/l), supporting a protective effect of high maternal vitamin D levels in early * Carmen Moreno cmoreno@hggm.es pregnancy on childhood behavioural outcomes, independent of cognitive factors.…”

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confidence: 99%

Towards understanding and acting on risk factors for developmental psychopathology

Moreno

2018

Eur Child Adolesc Psychiatry

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Most common mental disorders appear before adulthood [1]. Therefore, the ability to identify at-risk children is essential for the design and delivery of prevention programs. Emotional and behavioural dysregulation are key symptomatic expressions of vulnerability in children and important predictors of a broad range of mental outcomes during late adolescence and adult life [2]. The exploration of risk factors leading to this vulnerability represents an important area of research in child psychiatry. This issue of European Child and Adolescent Psychiatry (ECAP) includes several articles focusing on predictive factors for emotional and behavioural dysregulation in childhood or adolescence.In one study, researchers analysed perceived parenting style, as measured by the Parental Bonding Inventory (PBI), as a potential factor modulating psychopathological outcomes in a school-based population of more than a thousand subjects [3]. The cohort was evaluated for emotional and behavioural difficulties at ages 7-9, and again 9 years later, at a mean age of 18 years. The authors found a high correlation between childhood emotional and behavioural traits and adolescent outcomes. They also found that perceived adequate maternal and paternal care had positive effects on socio-emotional development. Positive parent-child relationships had been regarded previously as enhancing resilience towards negative emotional and behavioural outcomes even in the presence of other environmental [4] or genetic risks [5]. However, in the present work, although optimal parenting of both parents was necessary for satisfactory emotional development, the authors found a differential effect. For participants who already displayed behavioural dysregulation during childhood, optimal care by the father, but not by the mother, lowered the risk of developing behavioural problems from pre-puberty to adolescence. This suggests that highly reactive children are especially sensitive to positive paternal care.This ECAP issue also examines the biological underpinnings of emotional dysregulation. For example, van der Knaap et al. used functional MRI to study amygdala responses to negative emotional faces in children aged 6-9 years in the Generation R Study, a population-based sample [6]. They classified children by the presence of maternal depressive symptoms during pregnancy. Those with clinically relevant maternal depressive symptoms presented with increased amygdala hyper-responsivity, indicating neural processing different from that in control children. The findings do not establish the causality of psychopathology at the time of evaluation (6-9 years). In fact, the different groups were not significantly different in their frequency of internalizing or externalizing problems. However, most psychiatric disorders, including affective disorders, typically appear later in life, rendering the use of psychopathology to differentiate the two groups early on as problematic. Instead, the authors suggest that amygdala hyper-responsivity in children may be explored ...

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“…has been implicated with both psychotic and affective disorders [16][17][18][19][20][21][22] and since it acts as an epigenetic regulator during neurodevelopment, it has the potential to integrate intrinsic and environmental signals into the shaping of the maturing brain. Here, we demonstrate that 74 and autism spectrum disorder 75,76 ), and genome wide association of loci harboring the RXRG in bipolar disorder 77 and attention deficit hyperactivity disorder 77 , LXRA in autism spectrum disorder 78 , and NR4A2 in major depressive disorder 79 . Gene set and pathway analyses of GWAS data in major depressive disorder and bipolar disorder additionally reveal enrichment of genes implicated with thyroid hormone and retinoic acid signaling 60 as well as genes containing RAR/RXR consensus sequences 79 .…”

Section: Discussionmentioning

confidence: 60%

The neurobiology of BRD1 implicates sex-biased dysregulation of nuclear receptor signaling in mental disorders

Qvist

et al. 2018

Preprint

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Title:The behavioral and neurobiological effects of reduced Brd1 expression in mice are sex-biased and implicate gender dependent dysregulation of nuclear receptor mediated signaling in mental disorders CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/257170 doi: bioRxiv preprint first posted online Jan. 31, 2018;. CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/257170 doi: bioRxiv preprint first posted online Jan. 31, 2018; Abstract:The schizophrenia and bipolar disorder associated gene, BRD1, encodes a scaffold protein that in complex with epigenetic modifiers regulate gene sets enriched for psychiatric disorder risk. Preclinical evidence from male Brd1 +/-mice has previously implicated BRD1 with phenotypes of translational relevance to schizophrenia. Here we describe the phenotype of female Brd1 +/-mice and report attenuated dendritic architecture and monoaminergic dysregulation accompanied by sex-specific changes in affective behaviors. In accordance, global gene expression profiling reveals regional dysregulation of gene sets enriched with major depressive disorder and schizophrenia risk in female and male Brd1+/-mice, respectively. Independent of sex, however, differentially expressed genes cluster in common functional pathways associated with psychiatric disorders, including mitochondrial dysfunction and oxidative phosphorylation as well as G-protein coupled-, and nuclear receptor mediated signaling. Accordingly, we provide in vitro evidence that BRD1modulates the transcriptional drive of a subset of nuclear receptors (e.g. the vitamin D and glucocorticoid receptors). Moreover, we demonstrate enrichment of psychiatric disorder risk in the target genes of nuclear receptors, sex-biased expression of several nuclear receptor genes in the adult brain of Brd1 +/-mice, and that sex-biased genes in general are enriched with nuclear receptor genes particularly at the earliest developmental stage of the human brain. Overall, our data suggests that the spatio-temporal interaction between BRD1 and subsets of nuclear receptors in the brain is sex-biased and that hampered BRD1 mediated regulation of target genes governed by certain nuclear receptors may significantly contribute to sex differences in psychopathology.

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Gestational vitamin D deficiency and autism-related traits: the Generation R Study

Cited by 138 publications

References 66 publications

A prospective study of fetal head growth, autistic traits and autism spectrum disorder

A prospective study of fetal head growth, autistic traits and autism spectrum disorder

Towards understanding and acting on risk factors for developmental psychopathology

The neurobiology of BRD1 implicates sex-biased dysregulation of nuclear receptor signaling in mental disorders

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