COMT Haplotypes Modulate Associations of Antenatal Maternal Anxiety and Neonatal Cortical Morphology

Qiu, Anqi; Tuan, Ta Anh; Ong, Mei Lyn; Li, Yue; Chen, Helen; Rifkin‐Graboi, Anne; Broekman, Birit F.P.; Kwek, Kenneth; Saw, Seang‐Mei; Chong, Yap Seng; Gluckman, Peter D.; Fortier, Marielle V.; Holbrook, Joanna D.; Meaney, Michael J.

doi:10.1176/appi.ajp.2014.14030313

Cited by 88 publications

(91 citation statements)

References 72 publications

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“…Relevant to the current study is evidence that the well-documented association between prenatal maternal anxiety or stress and child outcome cited above may be moderated by the child’s COMT genotype [16]. A report from Singapore on 146 neonates indicated that the association between prenatal maternal anxiety and neonatal cortical morphometry was moderated by genetic variation in COMT [16], with increased thickness of the ventrolateral prefrontal cortex observed in neonates with the val allele.…”

Section: Introductionmentioning

confidence: 65%

Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD

et al. 2017

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Maternal prenatal anxiety is an important risk factor for altered child neurodevelopment but there is uncertainty concerning the biological mechanisms involved and sources of individual differences in children’s responses. We sought to determine the role of functional genetic variation in COMT, which encodes catechol-O-methyltransferase, in the association between maternal prenatal anxiety and child symptoms of ADHD and working memory. We used the prospectively-designed ALSPAC cohort (n = 6,969) for our primary data analyses followed by replication analyses in the PREDO cohort (n = 425). Maternal prenatal anxiety was based on self-report measures; child symptoms of ADHD were collected from 4–15 years of age; working memory was assessed from in-person testing at age 8 years; and genetic variation in COMT at rs4680 was determined in both mothers and children. The association between maternal prenatal anxiety and child attention/hyperactivity symptoms and working memory was moderated by the child’s rs4680 genotype, with stronger effects obtained for the val/val (G:G) genotype relative to val/met (A:G) (all p<0.01) and met/met (A:A) groups (all p<0.05). Similar findings were observed in the PREDO cohort where maternal prenatal anxiety interacted with child rs4680 to predict symptoms of ADHD at 3.5 years of age. The findings, from two cohorts, show a robust gene-environment interaction, which may contribute to inter-individual differences in the effects of maternal prenatal anxiety on developmental outcomes from childhood to mid-adolescence.

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Section: Introductionmentioning

confidence: 65%

Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD

et al. 2017

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“…This was demonstrated in a study of the effects of antenatal maternal anxiety and infant COMT genotypes (Val158Met, rs737865 and rs165599) on neonatal cortical thickness 159 . Neither maternal anxiety nor infant COMT genotype were related to regional cortical thickness individually; however, interaction effects between maternal anxiety and infant genotype were observed in several regions, including the right ventromedial prefrontal cortex, an area involved in the regulation of anxiety and mood.…”

Section: Influences Of Genes and Environmentmentioning

confidence: 86%

Imaging structural and functional brain development in early childhood

2018

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In humans, the period from term birth to ~2 years of age is characterized by rapid and dynamic brain development and plays an important role in cognitive development and risk for disorders such as autism and schizophrenia. Recent imaging studies have begun to delineate the growth trajectories of brain structure and function in the first years after birth and their relationship to cognition and risk for neuropsychiatric disorders. This Review discusses the development of grey and white matter, structural and functional networks, as well as genetic and environmental influences on early childhood brain development. We also discuss initial evidence regarding the usefulness of early imaging biomarkers for predicting cognitive outcomes and risk for neuropsychiatric disorders.

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“…For instance, prenatal anxiety was reported to associate with offsprings' gray matter volume reductions in the prefrontal cortex at 6-9 years of age (Buss et al, 2010). A separate study similarly observed an effect of prenatal maternal anxiety on neonatal frontal cortical thickness that was moderated by functional variants of the catechol-O-methyltransferase (COMT) gene, which regulates catecholamine signaling and is implicated in anxiety, pain, and stress responsivity (Qiu et al, 2014). Furthermore, a strong positive association was observed between postnatal maternal anxiety and offspring right hippocampal growth and a strong negative association between postnatal maternal anxiety and offspring left hippocampal volume at 6 months of age (Pruessner et al, 2008;Qiu et al, 2013).…”

Section: Neuroanatomicalmentioning

confidence: 98%

Intergenerational Transmission of Stress in Humans

Bowers

Yehuda

2015

Neuropsychopharmacol

409

269

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The hypothesis that offspring are affected by parental trauma or stress exposure, first noted anecdotally, is now supported empirically by data from Holocaust survivor offspring cohorts and other populations. These findings have been extended to less extreme forms of stress, where differential physical, behavioral, and cognitive outcomes are observed in affected offspring. Parental stress-mediated effects in offspring could be explained by genetics or social learning theory. Alternatively, biological variations stemming from stress exposure in parents could more directly have an impact on offspring, a concept we refer to here as 'intergenerational transmission', via changes to gametes and the gestational uterine environment. We further extend this definition to include the transmission of stress to offspring via early postnatal care, as animal studies demonstrate the importance of early maternal care of pups in affecting offsprings' long-term behavioral changes. Here, we review clinical observations in offspring, noting that offspring of stress-or trauma-exposed parents may be at greater risk for physical, behavioral, and cognitive problems, as well as psychopathology. Furthermore, we review findings concerning offspring biological correlates of parental stress, in particular, offspring neuroendocrine, epigenetic, and neuroanatomical changes, in an attempt to determine the extent of parental stress effects. Although understanding the etiology of effects in offspring is currently impeded by methodological constraints, and limitations in our knowledge, we summarize current information and conclude by presenting hypotheses that have been prompted by recent studies in the field.

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COMT Haplotypes Modulate Associations of Antenatal Maternal Anxiety and Neonatal Cortical Morphology

Cited by 88 publications

References 72 publications

Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD

Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD

Imaging structural and functional brain development in early childhood

Intergenerational Transmission of Stress in Humans

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