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https://www.readbyqxmd.com/read/28322282/maternal-immune-activation-dysregulation-of-the-fetal-brain-transcriptome-and-relevance-to-the-pathophysiology-of-autism-spectrum-disorder
#1
M V Lombardo, H M Moon, J Su, T D Palmer, E Courchesne, T Pramparo
Maternal immune activation (MIA) via infection during pregnancy is known to increase risk for autism spectrum disorder (ASD). However, it is unclear how MIA disrupts fetal brain gene expression in ways that may explain this increased risk. Here we examine how MIA dysregulates rat fetal brain gene expression (at a time point analogous to the end of the first trimester of human gestation) in ways relevant to ASD-associated pathophysiology. MIA downregulates expression of ASD-associated genes, with the largest enrichments in genes known to harbor rare highly penetrant mutations...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28316773/vitamin-d-treatment-during-pregnancy-prevents-autism-related-phenotypes-in-a-mouse-model-of-maternal-immune-activation
#2
Stephanie Vuillermot, Wei Luan, Urs Meyer, Darryl Eyles
BACKGROUND: Prenatal exposure to infection is a recognized environmental risk factor for neuropsychiatric disorders of developmental origins such as autism or schizophrenia. Experimental work in animals indicates that this link is mediated by maternal immune activation (MIA) involving interactions between cytokine-associated inflammatory events, oxidative stress, and other pathophysiological processes such as hypoferremia and zinc deficiency. Maternal administration of the viral mimic polyriboinosinic-polyribocytidylic acid (poly(I:C)) in mice produces several behavioral phenotypes in adult offspring of relevance to autism spectrum disorder (ASD) and other neurodevelopmental disorders...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28260505/copy-number-variations-with-isolated-fetal-ventriculomegaly
#3
P Hu, Y Wang, R Sun, L Cao, X Chen, C Liu, C Luo, D Ma, W Wang, X Fu, W Shi, S Yi, K Zhang, H Liu, Z Xu
BACKGROUND: Copy Number Variations (CNVs) are an important genetic cause of a number of neurodevelopmental disorders (NDs). However, the association between CNVs and the development and prognosis of isolated fetal ventriculomegaly (IMV) is unclear. OBJECTIVES: To investigate possible associations between CNVs and the development of fetal IMV. METHODS: This retrospective study recruited 154 subjects with ultrasound-confirmed fetal IMV and 190 subjects in a control cohort who underwent a high-risk prenatal serum screening program...
March 3, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28251181/maternal-immunoreactivity-to-herpes-simplex-virus-2-and-risk-of-autism-spectrum-disorder-in-male-offspring
#4
Milada Mahic, Siri Mjaaland, Hege Marie Bøvelstad, Nina Gunnes, Ezra Susser, Michaeline Bresnahan, Anne-Siri Øyen, Bruce Levin, Xiaoyu Che, Deborah Hirtz, Ted Reichborn-Kjennerud, Synnve Schjølberg, Christine Roth, Per Magnus, Camilla Stoltenberg, Pål Surén, Mady Hornig, W Ian Lipkin
Maternal infections during pregnancy are associated with risk of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Proposed pathogenetic mechanisms include fetal infection, placental inflammation, and maternal cytokines or antibodies that cross the placenta. The Autism Birth Cohort comprises mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaire screening, referrals, and linkages to a national patient registry, 442 mothers of children with ASD were identified, and 464 frequency-matched controls were selected...
January 2017: MSphere
https://www.readbyqxmd.com/read/28249166/varying-intolerance-of-gene-pathways-to-mutational-classes-explain-genetic-convergence-across-neuropsychiatric-disorders
#5
Shahar Shohat, Eyal Ben-David, Sagiv Shifman
Genetic susceptibility to intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ) often arises from mutations in the same genes, suggesting that they share common mechanisms. We studied genes with de novo mutations in the three disorders and genes implicated in SCZ by genome-wide association study (GWAS). Using biological annotations and brain gene expression, we show that mutation class explains enrichment patterns more than specific disorder. Genes with loss-of-function mutations and genes with missense mutations were associated with different pathways across disorders...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28235828/independent-maternal-and-fetal-genetic-effects-on-mid-gestational-circulating-levels-of-environmental-pollutants
#6
Michela Traglia, Lisa A Croen, Kristen Lyall, Gayle C Windham, Marty Kharrazi, Gerald N DeLorenze, Anthony R Torres, Lauren A Weiss
Maternal exposure to environmental pollutants could affect fetal brain development and increase autism spectrum disorder (ASD) risk in conjunction with differential genetic susceptibility. Organohalogen congeners measured in maternal mid-pregnancy blood samples have recently shown significant, but negative associations with offspring ASD outcome. We report the first large scale maternal and fetal genetic study of the mid-pregnancy serum levels of a set of 21 organohalogens in a subset of 790 genotyped women and 764 children collected in California by the Early Markers for Autism (EMA) Project...
February 24, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28211989/timothy-syndrome-1-genotype-without-syndactyly-and-major-extracardiac-manifestations
#7
Róbert Sepp, Lidia Hategan, Attila Bácsi, Judit Cseklye, László Környei, János Borbás, Márta Széll, Tamás Forster, István Nagy, Zoltán Hegedűs
Timothy syndrome 1 (TS1) is a rare genetic disorder characterized by multisystem abnormalities including QT prolongation, congenital heart defects, facial dysmorphism, episodic hypoglycemia, and neurological symptoms. A morphological hallmark of TS1 is syndactyly, present in all cases. TS1 is caused by the canonical p.Gly406Arg mutation in the alternatively spliced exon 8A in the CACNA1C gene, encoding for the main cardiac L-type calcium channel. A variant case of TS1 is reported. The proband had intermittent fetal bradycardia with heart rate of 72 bpm...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28209774/methyl-donor-supplementation-alters-cognitive-performance-and-motivation-in-female-offspring-from-high-fat-diet-fed-dams
#8
Sarah E McKee, Nicola M Grissom, Christopher T Herdt, Teresa M Reyes
During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28199771/thyroid-dysfunction-in-children-with-autism-spectrum-disorder-is-associated-with-folate-receptor-alpha-autoimmune-disorder
#9
Richard E Frye, Rebecca Wynne, Shannon Rose, John Slattery, Leanna Delhey, Marie Tippett, Stephen G Kahler, Sirish C Bennuri, Stepan Melnyk, Jeffrey M Sequeira, Edward Quadros
Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in Autism Spectrum Disorder (ASD). FRAAs disrupt folate transport across the blood-brain barrier by binding to the FRα. Thyroid dysfunction is frequently found in children with ASD. We measured blocking and binding FRAAs and thyroid stimulating hormone (TSH), free T4 (FT4), total T3 (TT3), reverse T3 (rT3), thyroid releasing hormone (TRH) and other metabolites in 87 children with ASD, 84 of whom also underwent behavior and cognition testing and in 42 of whom FRAAs, TSH and FT4 were measured at two time points...
February 15, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28168960/sex-specific-neurodevelopmental-programming-by-placental-insulin-receptors-on-stress-reactivity-and-sensorimotor-gating
#10
Stefanie L Bronson, Jennifer C Chan, Tracy L Bale
BACKGROUND: Diabetes, obesity, and overweight are prevalent pregnancy complications that predispose offspring to neurodevelopmental disorders, including autism, attention-deficit/hyperactivity disorder, and schizophrenia. Although male individuals are three to four times more likely than female individuals to develop these disorders, the mechanisms driving the sex specificity of disease vulnerability remain unclear. Because defective placental insulin receptor (InsR) signaling is a hallmark of pregnancy metabolic dysfunction, we hypothesized that it may be an important contributor and novel mechanistic link to sex-specific neurodevelopmental changes underlying disease risk...
December 30, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28163867/umbilical-cord-blood-androgen-levels-and-asd-related-phenotypes-at-12-and-36%C3%A2-months-in-an-enriched-risk-cohort-study
#11
Bo Y Park, Brian K Lee, Igor Burstyn, Loni P Tabb, Jeff A Keelan, Andrew J O Whitehouse, Lisa A Croen, Margaret D Fallin, Irva Hertz-Picciotto, Owen Montgomery, Craig J Newschaffer
BACKGROUND: Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28141706/attached-to-a-diagnosis-the-quandary-of-social-deficits-and-reactive-attachment-disorder
#12
Randall Phelps, Debra Eisert, Susan Schulz, Marilyn Augustyn
Alex is a 9-year-old boy brought to you, his primary care provider, for a "fifth opinion." You have cared for Alex since he was adopted from a Romanian orphanage at 3 years of age. He has been physically healthy with normal growth parameters and no evidence of fetal alcohol syndrome. Alex has long-standing history of social difficulties, impulsivity, lying, controlling, manipulative behaviors, violent outbursts at home with subsequent lack of remorse, and excessive chatter. You referred Alex to an interdisciplinary child development clinic 2 years ago, where he was diagnosed with reactive attachment disorder (RAD) and attention deficit hyperactivity disorder (ADHD)...
February 2017: Journal of Developmental and Behavioral Pediatrics: JDBP
https://www.readbyqxmd.com/read/28137374/maternal-immune-activation-and-autism-spectrum-disorder-from-rodents-to-nonhuman-and-human-primates
#13
REVIEW
Milo Careaga, Takeshi Murai, Melissa D Bauman
A subset of women who are exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental or neuropsychiatric disorder. Although epidemiology studies have primarily focused on the association between maternal infection and an increased risk of offspring schizophrenia, mounting evidence indicates that maternal infection may also increase the risk of autism spectrum disorder. A number of factors, including genetic susceptibility, the intensity and timing of the infection, and exposure to additional aversive postnatal events, may influence the extent to which maternal infection alters fetal brain development and which disease phenotype (autism spectrum disorder, schizophrenia, other neurodevelopmental disorders) is expressed...
March 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28127411/protein-restricted-diet-during-pregnancy-after-insemination-alters-behavioral-phenotypes-of-the-progeny
#14
Tamio Furuse, Kunio Miyake, Takashi Kohda, Hideki Kaneda, Takae Hirasawa, Ikuko Yamada, Tomoko Kushida, Misho Kashimura, Kimio Kobayashi, Fumitoshi Ishino, Takeo Kubota, Shigeharu Wakana
BACKGROUND: Epidemiological studies suggest that hyponutrition during the fetal period increases the risk of mental disorders such as attention deficit hyperactivity disorder and autism-spectrum disorder, which has been experimentally supported using animal models. However, previous experimental hyponutrition or protein-restricted (PR) diets affected stages other than the fetal stage, such as formation of the egg before insemination, milk composition during lactation, and maternal nursing behavior...
2017: Genes & Nutrition
https://www.readbyqxmd.com/read/28088314/is-advanced-paternal-age-a-health-risk-for-the-offspring
#15
REVIEW
Anne-Marie Nybo Andersen, Stine Kjaer Urhoj
In this article we review the epidemiologic evidence for adverse health effects in offspring of fathers of advanced age. First the evidence regarding fetal survival is addressed, and afterward we review the evidence regarding morbidity in children with older fathers. The adverse conditions most consistently associated with increased paternal age are stillbirths, musculo-skeletal syndromes, cleft palate, acute lymphoblastic leukemia and retinoblastoma, and neurodevelopmental disorders in the autism spectrum and schizophrenia...
February 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28067728/advances-in-developmental-neuropsychiatry-autism-spectrum-disorder-cornelia-de-lange-syndrome-self-injurious-behavior-down-syndrome-fetal-alcohol-spectrum-disorder-and-borderline-intellectual-functioning
#16
https://www.readbyqxmd.com/read/28042822/enduring-sexually-dimorphic-impact-of-in-utero-exposure-to-elevated-levels-of-glucocorticoids-on-midbrain-dopaminergic-populations
#17
REVIEW
Glenda E Gillies, Kanwar Virdee, Ilse Pienaar, Felwah Al-Zaid, Jeffrey W Dalley
Glucocorticoid hormones (GCs) released from the fetal/maternal glands during late gestation are required for normal development of mammalian organs and tissues. Accordingly, synthetic glucocorticoids have proven to be invaluable in perinatal medicine where they are widely used to accelerate fetal lung maturation when there is risk of pre-term birth and to promote infant survival. However, clinical and pre-clinical studies have demonstrated that inappropriate exposure of the developing brain to elevated levels of GCs, either as a result of clinical over-use or after stress-induced activation of the fetal/maternal adrenal cortex, is linked with significant effects on brain structure, neurological function and behaviour in later life...
December 30, 2016: Brain Sciences
https://www.readbyqxmd.com/read/28034801/testing-the-correlation-between-experimentally-induced-hypothyroidism-during-pregnancy-and-autistic-like-symptoms-in-the-rat-offspring
#18
Francesca Melancia, Michela Servadio, Sara Schiavi, Patrizia Campolongo, Alexandre Giusti-Paiva, Viviana Trezza
Thyroid hormones are important for the development of the central nervous system. Since the fetal thyroid gland is not functioning until mid-gestation, transport of maternal thyroid hormones across the placenta is essential during the early phases of gestation. Maternal thyroid deficiency has been associated with a higher incidence of neurodevelopmental disorders in the newborns. The relationship between maternal hypothyroidism and the onset of autism spectrum disorders (ASD) in the offspring, however, is still debated...
March 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28031963/folic-acid-supplementation-what-is-new-fetal-obstetric-long-term-benefits-and-risks
#19
REVIEW
Hind N Moussa, Susan Hosseini Nasab, Ziad A Haidar, Sean C Blackwell, Baha M Sibai
The association between folic acid supplementation, prior to conception and/or during pregnancy and pregnancy outcomes, has been the subject of numerous studies. The worldwide recommendation of folic acid is at least 0.4 mg daily for all women of reproductive age, and 4-5 mg in high-risk women. In addition, evidence shows that folic acid supplementation could modulate other adverse pregnancy outcomes, specifically, in pregnancies complicated by seizure disorders, preeclampsia, anemia, fetal growth restriction and autism...
June 2016: Future Science OA
https://www.readbyqxmd.com/read/28031961/fetal-origins-of-autism-spectrum-disorders-the-non-associated-maternal-factors
#20
REVIEW
Hind N Moussa, Anand Srikrishnan, Sean C Blackwell, Pramod Dash, Baha M Sibai
AIM: Several population-based studies have been conducted to determine whether maternal exposures are involved in the pathophysiology of autism spectrum disorder (ASD). We review these studies and describe the factors not associated with increased risk for ASD development. METHODS: We identified studies describing associations between maternal exposures and ASD development. These studies include the Childhood Autism Risks from Genetics and the Environment, Nurses' Health Study II, and the Swedish population registry...
June 2016: Future Science OA
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