Prenatal and perinatal risk factors in a twin study of autism spectrum disorders

Froehlich-Santino, Wendy; Tobón, Amalia Londoño; Cleveland, Sue; Torres, Andrea; Phillips, Jennifer M.; Cohen, Brianne; Torigoe, Tiffany; Miller, Julie E.; Fedele, Angie; Collins, J.S.H.; Smith, Karen; Lotspeich, Linda; Croen, Lisa; Ozonoff, Sally J; Lajonchere, Clara; Grether, Judith K.; O’Hara, Ruth; Hallmayer, Joachim

doi:10.1016/j.jpsychires.2014.03.019

Cited by 76 publications

(59 citation statements)

References 47 publications

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“…While disaggregating perinatal complications from ASD is challenging because susceptibility might have led to perinatal complications and ASD, they point to two hypotheses:

Hypoxia: Obstetrical complications related to hypoxia pose significant risk in meta-analyses (90). This is supported by a recent twin study indicating that respiratory distress and other markers of hypoxia increased ASD risk (91). Relationships between brain hypoxia and social behavior deficits warrant further attention.

Immunologic: Studies link maternal infections during pregnancy to ASD in offspring (89, 90).

…”

Section: Genetic Epidemiology In Asdsupporting

confidence: 64%

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Genetic Epidemiology and Insights into Interactive Genetic and Environmental Effects in Autism Spectrum Disorders

Kim¹,

Leventhal²

2015

Biological Psychiatry

202

130

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Understanding the pathogenesis of Neurodevelopmental Disorders (NDDs) has proven to be challenging. Using Autism Spectrum Disorder (ASD) as a paradigmatic NDD, this paper reviews the existing literature on the etiologic substrates of ASD and explores how genetic epidemiology approaches including gene-environment interactions (GxE) can play roles in identifying factors associated with ASD etiology. New genetic and bioinformatics strategies have yielded important clues to ASD genetic substrates. Next steps for understanding ASD pathogenesis require significant effort to focus on how genes and environment interact with one another in typical development and its perturbations. Along with larger sample sizes, future study designs should include sample ascertainment that is epidemiologic and population-based to capture the entire ASD spectrum with both categorical and dimensional phenotypic characterization, environmental measurement with accuracy, validity and biomarkers, statistical methods to address population stratification, multiple comparisons and GxE of rare variants, animal models to test hypotheses and, new methods to broaden the capacity to search for GxE, including genome-wide and environment-wide association studies, precise estimation of heritability using dense genetic markers and consideration of GxE both as the disease cause and a disease course modifier. While examination of GxE appears to be a daunting task, tremendous recent progress in gene discovery opens new horizons for advancing our understanding the role of GxE in the pathogenesis of, and ultimately identifying the causes, treatments and even prevention for ASD and other NDDs.

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“…While disaggregating perinatal complications from ASD is challenging because susceptibility might have led to perinatal complications and ASD, they point to two hypotheses:

Immunologic: Studies link maternal infections during pregnancy to ASD in offspring (89, 90).

…”

Section: Genetic Epidemiology In Asdsupporting

confidence: 64%

“…This is supported by a recent twin study indicating that respiratory distress and other markers of hypoxia increased ASD risk (91). Relationships between brain hypoxia and social behavior deficits warrant further attention.…”

Section: Genetic Epidemiology In Asdsupporting

confidence: 64%

Genetic Epidemiology and Insights into Interactive Genetic and Environmental Effects in Autism Spectrum Disorders

Kim¹,

Leventhal²

2015

Biological Psychiatry

202

130

View full text Add to dashboard Cite

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“…Few studies have examined whether offspring sex is a factor for exposures and autism risk. A study of 194 twins found that respiratory distress and hypoxia increased the risk of ASD in males, while jaundice was associated with its increased risk in female offspring [76]. They hypothesized that males may be more prone to hypoxic brain injury (HI) than females as testosterone can potentiate HI and progesterone and allopregnanolone can be protective in animal models.…”

Section: Prenatal Programming Of Neuropsychiatric Disordersmentioning

confidence: 99%

Prenatal Programming of Mental Illness: Current Understanding of Relationship and Mechanisms

Kim

Bale

Epperson

2015

Curr Psychiatry Rep

186

130

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The British epidemiologist Dr. David J. Barker documented the relationship between infant birth weight and later onset of hypertension, coronary heart disease, insulin resistance, and type II diabetes. A stressful in utero environment can cause long-term consequences for offspring through prenatal programming. Prenatal programming most commonly occurs through epigenetic mechanisms and can be dependent on the type and timing of exposure as well as the sex of the fetus. In this review, we highlight the most recent evidence that prenatal programming is implicated in the development of psychiatric disorders in offspring exposed to maternal stress during pregnancy. Methodological differences between studies contribute to unavoidable heterogeneity in study findings. Current data suggest that fetal exposure to maternal hypothalamic-pituitary-adrenal axis dysregulation, excessive glucocorticoids, and inflammation with resulting epigenetic changes at both the placental and fetal levels are important areas of continued investigation.

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“…One explanation is that autistic miRNA patterns may represent a permanent response to an early environmental insult, such as perinatal hypoxia (61). In this scenario, miRNA regulation could be disrupted by a layer of epigenetic machinery such as DNA methylation.…”

Section: Introductionmentioning

confidence: 99%

A Comparative Review of microRNA Expression Patterns in Autism Spectrum Disorder

Hicks

Middleton²

2016

Front. Psychiatry

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a wide spectrum of deficits in social interaction, communication, and behavior. There is a significant genetic component to ASD, yet no single gene variant accounts for >1% of incidence. Posttranscriptional mechanisms such as microRNAs (miRNAs) regulate gene expression without altering the genetic code. They are abundant in the developing brain and are dysregulated in children with ASD. Patterns of miRNA expression are altered in the brain, blood, saliva, and olfactory precursor cells of ASD subjects. The ability of miRNAs to regulate broad molecular pathways in response to environmental stimuli makes them an intriguing player in ASD, a disorder characterized by genetic predisposition with ill-defined environmental triggers. In addition, the availability and extracellular stability of miRNAs make them an ideal candidate for biomarker discovery. Here, we discuss 27 miRNAs with overlap across ASD studies, including 3 miRNAs identified in 3 or more studies (miR-23a, miR-146a, and miR-106b). Together, these 27 miRNAs have 1245 high-confidence mRNA targets, a significant number of which are expressed in the brain. Furthermore, these mRNA targets demonstrate over-representation of autism-related genes with enrichment of neurotrophic signaling molecules. Brain-derived neurotrophic factor, a molecule involved in hippocampal neurogenesis and altered in ASD, is targeted by 6 of the 27 miRNAs of interest. This neurotrophic pathway represents one intriguing mechanism by which perturbations in miRNA signaling might influence central nervous system development in children with ASD.

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Prenatal and perinatal risk factors in a twin study of autism spectrum disorders

Cited by 76 publications

References 47 publications

Genetic Epidemiology and Insights into Interactive Genetic and Environmental Effects in Autism Spectrum Disorders

Genetic Epidemiology and Insights into Interactive Genetic and Environmental Effects in Autism Spectrum Disorders

Prenatal Programming of Mental Illness: Current Understanding of Relationship and Mechanisms

A Comparative Review of microRNA Expression Patterns in Autism Spectrum Disorder

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