Chapter 3. Evidence of Genetic and Epigenetic Risk Components of Autism and Autism Spectrum Disorder

Chapter 3. Evidence of Genetic and Epigenetic Risk Components of Autism and Autism Spectrum Disorder

References

Abu-Taweel GM et al., 2012. Neurobehavioral toxic effects of perinatal oral exposure to aluminum on the developmental motor reflexes, learning, memory and brain neurotransmitters of mice offspring. Pharmacol Biochem Behav. 101(1):49-56. doi: 10.1016/j.pbb.2011.11.003.

Álvarez-Iglesias V. 2011. Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder. BMC Med Genet. 12:50. doi: 10.1186/1471-2350-12-50.

Atilano SR et al., 2015. Mitochondrial DNA variants can mediate methylation status of inflammation, angiogenesis and signaling genes. Hum Mol Genet. 24(16):4491-503. doi: 10.1093/hmg/ddv173.

Atlante A et al., 2001. Glutamate neurotoxicity, oxidative stress and mitochondria. FEBS Lett. 18:497(1):1-5.

Auerbach, BD et al., 2011. Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 480, 63–68.

Avdjieva-Tzavella D et al., 2012. Mitochondrial DNA mutations in two Bulgarian children with autistic spectrum disorders. Balkan J Med Genet. 15(2):47-54. doi: 10.2478/bjmg-2013-0006.

Belgard TG et al. 2014. Population structure confounds autism genetic classifier. Mol Psychiatry. 19(4):405-7.

Belaïd-Nouira Y et al., 2013. A novel insight on chronic AlCl3 neurotoxicity through IL-6 and GFAP expressions: modulating effect of functional food fenugreek seeds. Nutr Neurosci. 16(5):218-24. doi: 10.1179/1476830512Y.0000000048.

Bell ML et al., 2010. Prenatal exposure to fine particulate matter and birth weight: variations by particulate constituents and sources. Epidemiology 21(6):884-91. doi: 10.1097/EDE.0b013e3181f2f405.

Berko ER, Greally JM. et al., 2015. How might epigenetic dysregulation in early embryonic life contribute to autism spectrum disorder? Epigenomics. 7(1):1-4. doi: 10.2217/epi.14.86.

Betancur C. 2011. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Research. 1380:42-77.

Bishop NJ et al., 1997. Aluminum neurotoxicity in preterm infants receiving intravenous-feeding solutions. N Engl J Med. 336(22):1557-1561.

Bishop SL et al., 2013. Subcategories of restricted and repetitive behaviors in children with autism spectrum disorders. J Autism Dev Disord. 43(6):1287-97. doi: 10.1007/s10803-012-1671-0.

Bolton P et al., 1994. A case-control family history study of autism. J Child Psychol Psychiatry. 35(5):877-900.

Bucan M et al., 2009. Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PLoS Genet. 5(6):e1000536. doi: 10.1371/journal.pgen.1000536.

Butler MG et al. 2015. High-resolution chromosome ideogram representation of currently recognized genes for autism spectrum disorders. Int J Mol Sci. 16(3):6464-95. doi: 10.3390/ijms16036464.

Casanova EL et al., 2016. Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression. Mol Autism. 7:18. doi: 10.1186/s13229-016-0082-z.

Chauhan A, et al. 2011. Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. J Neurochem.117(2):209–220.

Chen S et al., 2015. Elevated mitochondrial DNA copy number in peripheral blood cells is associated with childhood autism. BMC Psychiatry. 15:50. doi: 10.1186/s12888-015-0432-y.

Chen Y et al., 2010. ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling. Proc Natl Acad Sci U S A.107(26):12011-6. doi: 10.1073/pnas.0914984107.

Chuchu N et al., 2013. The aluminium content of infant formulas remains too high. BMC Pediatr. 13:162. doi: 10.1186/1471-2431-13-162.

Constantino JN. 2003. Autistic traits in the general population: a twin study. Arch Gen Psychiatry. 60(5):524-30.

Constantino JN 2011. The quantitative nature of autistic social impairment. Pediatr Res. 2011 May;69(5 Pt 2):55R-62R. doi: 10.1203/PDR.0b013e318212ec6e.

Coutant R et al., 2001. Relationships between placental GH concentration and maternal smoking, newborn gender and maternal leptin: possible implications for birth weight. J Clin Endocrinol Metab. 86(10):4854-9.

Cross-Disorder Group of the Psychiatric Genomics Consortium et al., 2013. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 20;381(9875):1371-9. doi: 10.1016/S0140-6736(12)62129-1.

Curran EA et al., 2015. Association between obstetric mode of delivery and autism spectrum disorder: a population-based sibling design study. JAMA Psychiatry.72(9):935-42. doi: 10.1001/jamapsychiatry.2015.0846.

Davis JO 1995. Prenatal development of monozygotic twins and concordance for schizophrenia. Schizophr Bull. ;21(3):357-66.

de Laat P et al., 2015. Obstetric complications in carriers of the m.3243A>G mutation, a retrospective cohort study on maternal and fetal outcome. Mitochondrion. 25:98-103. doi: 10.1016/j.mito.2015.10.005.

De Rubeis et al., 2014. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014 515(7526):209-15. doi: 10.1038/nature13772.

Derom C et al., 2002. The East Flanders Prospective Twin Survey (EFPTS). Twin Res. 2002 Oct;5(5):337-41.

D’Gama AM et al., 2015 Targeted DNA sequencing from autism spectrum disorder brains implicates multiple genetic mechanisms. Neuron. 88(5):910-7. doi: 10.1016/j.neuron.2015.11.009.

Dhillon S et al., 2011. Genetics and mitochondrial abnormalities in autism spectrum disorders: a review. Curr Genomics. 322-32. doi: 10.2174/138920211796429745.

Dickerson AS, 2016. Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic. Environ Monit Assess. 188(7):407. doi: 10.1007/s10661-016-5405-1.

Durand CM et al., 2007. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 39(1):25-7.

Durand CM et al., 2012. SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism. Mol Psychiatry. 17(1):71-84. doi: 10.1038/mp.2011.57.

Eapen V, 2011. Genetic basis of autism: is there a way forward? Curr Opin Psychiatry. 24(3):226-36. doi: 10.1097/YCO.0b013e328345927e.

Ebisu K et al., 2012. Airborne PM2.5 chemical components and low birth weight in the northeastern and mid-Atlantic regions of the United States. Environ Health Perspect. 120(12):1746-52. doi: 10.1289/ehp.1104763.

Efron, B and N Zhang. 2011. False discovery rates and copy number variation. Biometrika, 98, 251 – 271. [Full text]

El Marroun H et al., 2012. Maternal use of selective serotonin reuptake inhibitors, fetal growth and risk of adverse birth outcomes. Arch Gen Psychiatry. 69(7):706-14. doi: 10.1001/archgenpsychiatry.2011.2333.

Elliott HR et al., 2008. Pathogenic mitochondrial DNA mutations are common in the general population. Am J Hum Genet.83(2):254-60. doi: 10.1016/j.ajhg.2008.07.004.

El-Shimy IA, et al., 2015. Minocycline attenuates Aβ oligomers-induced pro-inflammatory phenotype in primary microglia while enhancing Aβ fibrils phagocytosis. Neurosci Lett. 609:36-41. doi: 10.1016/j.neulet.2015.10.024.

Eryigit-Madzwamuse S et al., 2015. Personality of adults who were born very preterm. Arch Dis Child Fetal Neonatal Ed. 100(6):F524-9. doi: 10.1136/archdischild-2014-308007.

Fanni D et al., 2014. Aluminum exposure and toxicity in neonates: a practical guide to halt aluminum overload in the prenatal and perinatal periods. World J Pediatr. 10(2):101-7. doi: 10.1007/s12519-014-0477-x.

Ferger AI et al., 2010. Effects of mitochondrial dysfunction on the immunological properties of microglia. J Neuroinflammation. 7:45. doi: 10.1186/1742-2094-7-45.

Fiumara A et al.,2002. Rett syndrome phenotype following infantile acute encephalopathy. J Child Neurol. 17(9):700-2.

Frazier TW et al., 2015. Quantitative autism symptom patterns recapitulate differential mechanisms of genetic transmission in single and multiple incidence families. Mol Autism.6:58. doi: 10.1186/s13229-015-0050-z.

Fry AE et al., 2016. Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy. BMC Med Genet 17(1):34. doi: 10.1186/s12881-016-0294-2.

Frye RE et al., 2013. Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder. Transl Psychiatry. 3:e220. doi: 10.1038/tp.2012.143.

Frye et al., 2013. Redox metabolism abnormalities in autistic children associated with mitochondrial disease. Transl Psychiatry 3, e273; doi:10.1038/tp.2013.51

Frye, R et al., 2015. Mitochondrial dysfunction may explain symptom variation in Phelan-McDermid Syndrome. Scientific Reports Nature 6:19544 DOI10.1038/srep19544.

Fuccillo, MV. 2014. Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors. Cell. 158(1): 198–212. doi: 10.1016/j.cell.2014.04.045

Gallup GG Jr and DR Hobbs. 2011. Evolutionary medicine: bottle feeding, birth spacing and autism. Med Hypotheses. 77(3):345-6. doi: 10.1016/j.mehy.2011.05.010.

Gai X, et al.,2011. Rare structural variation of synapse and neurotransmission genes in autism. Mol Psychiatry; advance online publication 17(4):402-411.

Gargus JJ and F Imtiaz. Mitochondrial energy-deficient endophenotype in autism. Am J Biochem Biotech. 4(2):198–207.

Gidaya N et al., 2014. In utero exposure to selective serotonin reuptake inhibitors and risk for autism spectrum disorder. J Autism Dev Disord. 44(10):2558-67. doi: 10.1007/s10803-014-2128-4.

Giulivi C et al., 2013. Gestational exposure to a viral mimetic poly(i:C) results in long-lasting changes in mitochondrial function by leucocytes in the adult offspring. Mediators Inflamm 2013:609602. doi: 10.1155/2013/609602.

Giunco CT et al., 2009. Association between APOE polymorphisms and predisposition for autism. Psychiatr Genet. 19(6):338. doi: 10.1097/YPG.0b013e3283328e41

Giulivi C et al., 2010. Mitochondrial dysfunction in autism. JAMA. 304(21):2389-96. doi: 10.1001/jama.2010.1706.

Graf ER et al., 2004. Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell. 119(7):1013-26.

Graf WD et al., 2000. Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation. J Child Neurol. 15(6):357-61.

Gu F et al., 2013. Alterations in mitochondrial DNA copy number and the activities of electron transport chain complexes and pyruvate dehydrogenase in the frontal cortex from subjects with autism. Transl Psychiatry. 3:e299. doi: 10.1038/tp.2013.68.

Guo S et al., 2015. Prevalence of migraine in persons with the 3243A>G mutation in mitochondrial DNA. Eur J Neurol. doi: 10.1111/ene.12832.

Hadley, D. et al. 2014. The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism. Nat Commun. 5, 40174 doi: 10.1038/ncomms5074.

Haas RH 2010. Autism and mitochondrial disease. Dev Disabil Res Rev. 16(2):144-53. doi: 10.1002/ddrr.112.

Horder J et al., 2013. Reduced subcortical glutamate/glutamine in adults with autism spectrum disorders: a [¹H]MRS study. Transl Psychiatry. 3:e279. doi: 10.1038/tp.2013.53.

Hsiao EY, Patterson PH. et al., 2011. Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain Behav Immun. 25(4):604-15. doi: 10.1016/j.bbi.2010.12.017.

James SJ et al., 2004. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 80(6):1611-7.

Jonsson L et al., 2014. Association study between autistic-like traits and polymorphisms in the autism candidate regions RELN, CNTNAP2, SHANK3 and CDH9/10. Mol Autism. 5(1):55. doi: 10.1186/2040-2392-5-55.

Keith LS et al., 2002 Aluminum toxicokinetics regarding infant diet and vaccinations. Vaccine. 20 Suppl 3:S13-7.

Kolevzon, A. et al., 2007. Prenatal and perinatal risk factors for autism. Arch. Pediatr. Adolesc. Med. 161:326-33.

Krumm N et al., 2013 Transmission disequilibrium of small CNVs in simplex autism. Am J Hum Genet. 93(4):595-606. doi: 10.1016/j.ajhg.2013.07.024.

Kumari S et al. 2012. Glutamate induces mitochondrial dynamic imbalance and autophagy activation: preventive effects of selenium. PLoS One. 7(6):e39382. doi: 10.1371/journal.pone.0039382.

Kurita H. 2011. Childhood disintegrative disorder. In: Hollander E, Kolevzon A, Coyle JT, editors. Textbook of autism spectrum disorders. Arlington, VA: American Psychiatric Publishing pp 99-105.

Kurita H. et al., 2004. External validity of childhood disintegrative disorder in comparison with autistic disorder. J Autism Dev Disord 34:355-62.

Kurita, H. and Inoue, K. 2013. How different is early-onset childhood disintegrative disorder from autistic disorder with speech loss? Open Journal of Psychiatry 3:39-45. doi: 10.4236/ojpsych.2013.32A007.

Ladd-Acosta C et al., 2014. Common DNA methylation alterations in multiple brain regions in autism. Mol Psychiatry. 19(8):862-71. doi: 10.1038/mp.2013.114.

Lasalle JM et al., 2013. Autism genes keep turning up chromatin. OA Autism 1(2):14.

Leblond CS et al., 2014. Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments. PLoS Genet. 10(9):e1004580. doi: 10.1371/journal.pgen.1004580.

Majamaa-Voltti K et al., 2008. Causes of death in pedigrees with the 3243A>G mutation in mitochondrial DNA. J Neurol Neurosurg Psychiatry.79(2):209-11. doi: 10.1136/jnnp.2007.122648.

Mantovani JF. 2000. Autistic regression and Landau-Kleffner syndrome: progress or confusion? Dev Med Child Neurol 42:349-53.

Maraschi A et al., 2014. Parkin regulates kainate receptors by interacting with the GluK2 subunit. Nat Commun5:5182. doi: 10.1038/ncomms6182.

Marrale, M. Assessing the impact of copy number variants on miRNA genes in utism by Monte Carlo Simulation PLoS One. 2014; 9(3): e90947. doi:10.1371/journal.pone.0090947

Matsunami N et al., 2013. Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population. PLoS One. 2013;8(1):e52239. doi: 10.1371/journal.pone.0052239.

McGee A et al., 2014. Convergent synaptic and circuit substrates underlying autism genetic risks. Front Biol (Beijing).9(2):137-150.

McPartland, J and FR Volkmar, 2013. Autism and Related Disorders. Handb Clin Neurol. 2012; 106: 10.1016/B978-0-444-52002-9.00023-1. 10.1016/B978-0-444-52002-9.00023-1

Mitkus RJ et al., 2011. Updated aluminum pharmacokinetics following infant exposures through diet and vaccination. Vaccine. 29(51):9538-43. doi: 10.1016/j.vaccine.2011.09.124.

Mousavizadeh K et al.,2013. Association of human mtDNA mutations with autism in Iranian patients. J Res Med Sci. 18(10):926.

NRDC, 2015. ISSUES: HEALTH Healthy Milk, Healthy Baby Chemical Pollution and Mother’s Milk http://www.nrdc.org/breastmilk/lead.asp

Naviaux RK 2008. Mitochondrial control of epigenetics. Cancer Biol Ther. 7(8):1191-3.

Nunnari J and A Suomalainen. 2012. Mitochondria: in sickness and in health. Cell. 148(6):1145-59. doi: 10.1016/j.cell.2012.02.035.

Oksenberg N, Ahituv N. 2013. The role of AUTS2 in neurodevelopment and human evolution. Trends Genet. 29(10):600-8. doi: 10.1016/j.tig.2013.08.001.

Oliveira G 2005. Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Dev Med Child Neurol. 47(3):185-9.

O’Roak BJ et al., 2011. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet 43: 585-589.

O’Roak BJ et al., 2012b. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science 338:1619-22.

Ozgen HM et al., 2009. Copy number changes of the microcephalin 1 gene (MCPH1) in patients with autism spectrum disorders. Clin Genet. 76(4):348-56. doi: 10.1111/j.1399-0004.2009.01254.x.

Palmieri L and AM Persic. 2010. Mitochondrial dysfunction in autism spectrum disorders: cause or effect? Biochim Biophys Acta. 1797(6-7):1130-7. doi: 10.1016/j.bbabio.2010.04.018.

Parker-Athill E. et al., 2009. Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism. J Neuroimmunol. 217(1-2):20-7. doi: 10.1016/j.jneuroim.2009.08.012.

Parker-Athilla, C and J Tana. 2010. Maternal immune activation and autism spectrum disorder: interleukin-6 signaling as a key mechanistic pathway. Neurosignals. 18(2): 113-128. doi:10.1159/000319828.

Pelphry K and A Westphal, 2012. In defense of childhood disintegrative disorder. Spectrum, Opinion/Viewpoint https://spectrumnews.org/opinion/viewpoint/in-defense-of-childhood-disintegrative-disorder/

Pettem KL 2013. Interaction between autism-linked MDGAs and neuroligins suppresses inhibitory synapse development. J Cell Biol. 200(3):321-36. doi: 10.1083/jcb.201206028.

Piven J et al., 1997. Broader autism phenotype: evidence from a family history study of multiple-incidence autism families. Am J Psychiatry. 154(2):185-90.

Poot M 2013. Towards identification of individual etiologies by resolving genomic and biological conundrums in patients with autism spectrum disorders. Mol Syndromol. 4(5):213-26. doi: 10.1159/000350041.

Pons R et al., 2004. Mitochondrial DNA abnormalities and autistic spectrum disorders. J Pediatr. 144(1):81-5.

Purcell AE et al., 2001. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology. 57(9):1618-28.

Ramanathan S et al., 2004. A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R. BMC Med Genet. 5:10.

Ramoz N et al. 2004. Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. Am J Psychiatry. 161(4):662-9.

Rebolledo-Jaramillo B et al., 2014. Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA. Proc Natl Acad Sci U S A. 111(43):15474-9. doi: 10.1073/pnas.1409328111.

Reed T et al., 2002. Influences of chorion type on measurements of the corpus callosum in adult monozygotic male twins? Am J Hum Biol. 14(3):338-46.

Reiner O et al., 2015. Regulation of neuronal migration, an emerging topic in autism spectrum disorders (ASD). J Neurochem. doi: 10.1111/jnc.13403.

Ronald, A et al., 2006b. Phenotypic and genetic overlap between autistic traits at the extremes of the general population. J. Am. Acad. Child Adolesc. Psychiatry 45(10):1206-14.

Ronald, A. et al., 2005. The genetic relationship between individual differences in social and nonsocial behaviours characteristic of autism. Dev. Sci. 8:444-458

Ronald, A. et al.,2006a Genetic heterogeneity between the three components of the autism spectrum: a twin study. J. Am. Acad. Child Adolesc. Psychiatry 45, 691-699 (2006).

Rosander C 2015. Dravet syndrome in Sweden: a population-based study. Dev Med Child Neurol. doi: 10.1111/dmcn.12709.

Rose et al., 2014. Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLOS One 9(1): e85436. doi:10.1371/journal.pone.0085436

Rose, S. et al., 2015. Increased susceptibility to ethylmercury-induced mitochondrial dysfunciton in a subset of autism lymphoblastoid cell lines. J of Toxicology Article ID 573701, 13pp http://dx.doi.org/10.1155/2015/573701

Rossignol DA and Frye RE 2012. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 17:290-314. doi: 10.1038/mp.2010.136.

Sandhu JK et al., 2003. Molecular mechanisms of glutamate neurotoxicity in mixed cultures of NT2-derived neurons and astrocytes: protective effects of coenzyme Q10. J Neurosci Res. 72(6):691-703.

Sato D et al., 2012. SHANK1 deletions in males with autism spectrum disorder. Am J Hum Genet. 90(5):879-87. doi: 10.1016/j.ajhg.2012.03.017.

Scheller J et al., 2011. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 1813(5):878-88. doi: 10.1016/j.bbamcr.2011.01.034.

Schmeisser MJ et al., 2012. Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature. 486(7402):256-60. doi: 10.1038/nature11015.

Sebat J. 2007. Strong association of de novo copy number mutations with autism. Science. 316(5823):445-9.

Segurado R et al. 2005. Confirmation of association between autism and the mitochondrial aspartate/glutamate carrier SLC25A12 gene on chromosome 2q31. Am J Psychiatry. 162(11):2182-4.

Serajee FJ, Zhang H, Huq A. 2006. Prevalence of common mitochondrial point mutations in autism. Neuropediatrics. 37(Suppl 1):S127

Shoffner J et al., 2010. Fever plus mitochondrial disease could be risk factors for autistic regression. J Child Neurol 25(4):429-34.

Sokol DK 1995. Intrapair differences in personality and cognitive ability among young monozygotic twins distinguished by chorion type. Behav Genet. 25(5):457-66.

Silverman JM et al. 2008. Autism-related routines and rituals associated with a mitochondrial aspartate/glutamate carrier SLC25A12 polymorphism. Am J Med Genet B Neuropsychiatr Genet. 2008 147(3):408-10.

Smith M, et al. 2012. Mitochondrial and ion channel gene alterations in autism. Biochim Biophys Acta. 1817(10):1796–1802.

Smith QR 2000 Transport of glutamate and other amino acids at the blood-brain barrier. J Nutr. 130(4S Suppl):1016S-22S.

Steinman G, Mankuta D. et al., 2013 Breastfeeding as a possible deterrent to autism–a clinical perspective. Med Hypotheses. 81(6):999-1001. doi: 10.1016/j.mehy.2013.09.013.

Tang G et al., 2013. Mitochondrial abnormalities in temporal lobe of autistic brain. Neurobiol Dis. 54:349-61. doi: 10.1016/j.nbd.2013.01.006.

Tomljenovic L, Shaw CA. 2011. Aluminum vaccine adjuvants: are they safe? Curr Med Chem. 18(17):2630-7.

Towbin KE. 2005. Pervasive Developmental Disorder Not Otherwise Specified. In: Volkmar FR, Klin A, Paul R, Cohen DJ, editors. Handbook of Autism and Pervasive Developmental Disorders. Wiley; Hoboken, NJ.

Ure AM 2015. Neonatal brain abnormalities associated with autism spectrum disorder in children born very preterm. Autism Res. doi: 10.1002/aur.1558.

Uzunova, G. et al., 2014. The role of ionotropic glutamate receptors in childhood neurodevelopmental disorders: Autism Spectrum Disorders and Fragile X Syndrome. Current Neuropharmacology 12:71-98

Vaishnavi et al;., 2014. Mining the 3′UTR of Autism-implicated Genes for SNPs Perturbing MicroRNA Regulation. Genomics, Proteomics and Bioinformatics. 12:92-104.

Van Acker R, Loncola J, Van Acker E. Rett Syndrome: A pervasive developmental disorder. In: Volkmar FR, Paul R, Klin A, Cohen D, editors. Handbook of Autism and Pervasive Developmental Disorders. John Wiley & Sons; Hoboken, NJ: 2005.

Vannucchi G et al.,2014. Bipolar disorder in adults with Asperger’s Syndrome: a systematic review. J Affect Disord. 168:151-60. doi: 10.1016/j.jad.2014.06.042.

van Daalen E et al., 2011. Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism. Neurogenetics. 12(4):315-23. doi: 10.1007/s10048-011-0297-2.

Volk L et al., 2015. Glutamate synapses in human cognitive disorders. Annu Rev Neurosci38:127-49. doi: 10.1146/annurev-neuro-071714-033821.

Wang Y et al., 2013. STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor. Proc Natl Acad Sci U S A. 110(42):16975-80. doi: 10.1073/pnas.1315862110.

Wang Z et al., 2014. Reelin gene variants and risk of autism spectrum disorders: an integrated meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 165B(2):192-200. doi: 10.1002/ajmg.b.32222.

Wei H, et al., 2011. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation. 8:52

Wei H et al., 2012. Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim Biophys Acta. 1822:831-42

Wei H et al., 2013. Brain IL-6 and autism. Neuroscience. 2013 252:320-5. doi: 10.1016/j.neuroscience.2013.08.025.

Weissman JR et al., 2008. Mitochondrial disease in autism spectrum disorder patients: a cohort analysis. PLoS One. 3(11):e3815. doi: 10.1371/journal.pone.0003815.

Wenger TL et al., 2016. The role of mGluR copy number variation in genetic and environmental forms of syndromic autism spectrum disorder. Sci Rep.6:19372. doi: 10.1038/srep19372.

Whittaker RG. 2015. Epilepsy in adults with mitochondrial disease: A cohort study. Ann Neurol. 2015 Sep 18. doi: 10.1002/ana.24525.

Yi F et al. Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons. Science. 352(6286):aaf2669. doi: 10.1126/science.aaf2669.

Yuan H et al., 2015. Ionotropic GABA and glutamate receptor mutations and human neurologic diseases. Mol Pharmacol. 88(1):203-17. doi: 10.1124/mol.115.097998.

Zaidi, S et al., 2013. De novo mutations in histone modifying genes in congenital heart disease. Nature. 498(7453): 220-223. doi: 10.1038/nature12141.

Zeisel SH. 2009. Epigenetic mechanisms for nutrition determinants of later health outcomes. Am J Clin Nutr. 89(5):1488S-1493S. doi: 10.3945/ajcn.2009.27113B.

Zhang B et al. 2010. Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children. J Neuroinflammation. 7:80. doi: 10.1186/1742-2094-7-80.

Zielke,. HR et al., 1993. A glutamatergic mechanism for aluminum toxicity in astrocytes. Molecular and Chemical Neuropathology 19(3): 219-233.

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