Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Prenatal Stress and Maternal Immune Dysregulation in Autism Spectrum Disorders: Potential Points for Intervention

Author(s): David Q. Beversdorf*, Hanna E. Stevens, Kara Gross Margolis and Judy Van de Water

Volume 25, Issue 41, 2019

Page: [4331 - 4343] Pages: 13

DOI: 10.2174/1381612825666191119093335

Price: $65

Abstract

Background: Genetics is a major etiological contributor to autism spectrum disorder (ASD). Environmental factors, however, also appear to contribute. ASD pathophysiology due to gene x environment is also beginning to be explored. One reason to focus on environmental factors is that they may allow opportunities for intervention or prevention.

Methods and Results: Herein, we review two such factors that have been associated with a significant proportion of ASD risk, prenatal stress exposure and maternal immune dysregulation. Maternal stress susceptibility appears to interact with prenatal stress exposure to affect offspring neurodevelopment. We also explore how maternal stress may interact with the microbiome in the neurodevelopmental setting. Additionally, understanding of the impact of maternal immune dysfunction on ASD has recently been advanced by recognition of specific fetal brain proteins targeted by maternal autoantibodies, and identification of unique mid-gestational maternal immune profiles. This might also be interrelated with maternal stress exposure. Animal models have been developed to explore pathophysiology targeting each of these factors.

Conclusion: We are beginning to understand the behavioral, pharmacopathological, and epigenetic effects related to these interactions, and we are beginning to explore potential mitigating factors. Continued growth in understanding of these mechanisms may ultimately allow for the identification of multiple potential targets for prevention or intervention for this subset of environmental-associated ASD cases.

Keywords: Autism spectrum disorder, prenatal stress, immune dysregulation, maternal antibodies, microbiome, pathophysiology.

« Previous Next »
[1]
Szatmari P, Paterson AD, Zwaigenbaum L, et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 2007; 39(3): 319-28.
[http://dx.doi.org/10.1038/ng1985] [PMID: 17322880]
[2]
Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011; 68(11): 1095-102.
[http://dx.doi.org/10.1001/archgenpsychiatry.2011.76] [PMID: 21727249]
[3]
Sandin S, Lichtenstein P, Kuja-Halkola R, Hultman C, Larsson H, Reichenberg A. Heritability of autism spectrum disorder. JAMA 2017; 318(12): 1182-4.
[http://dx.doi.org/10.1001/jama.2017.12141] [PMID: 28973605]
[4]
Bai D, Yip BHK, Windham GC, et al. Association of genetic and environmental factors with autism in a 5-country cohort. JAMA Psychiatry 2019. Epub ahead of print
[http://dx.doi.org/10.1001/jamapsychiatry.2019.1411] [PMID: 31314057]
[5]
Gage SH, Munafò MR, Davey Smith G. Causal inference in developmental origins of health and disease (DOHaD) research. Annu Rev Psychol 2016; 67: 567-85.
[http://dx.doi.org/10.1146/annurev-psych-122414-033352] [PMID: 26442667]
[6]
Beversdorf DQ, Stevens HE, Jones KL. Prenatal stress, maternal immune dysregulation, and their association with autism spectrum disorders. Curr Psychiatry Rep 2018; 20(9): 76.
[http://dx.doi.org/10.1007/s11920-018-0945-4] [PMID: 30094645]
[7]
Volk HE, Kerin T, Lurmann F, Hertz-Picciotto I, McConnell R, Campbell DB. Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene. Epidemiology 2014; 25(1): 44-7.
[http://dx.doi.org/10.1097/EDE.0000000000000030] [PMID: 24240654]
[8]
von Ehrenstein OS, Aralis H, Cockburn M, Ritz B. In utero exposure to toxic air pollutants and risk of childhood autism. Epidemiology 2014; 25(6): 851-8.
[http://dx.doi.org/10.1097/EDE.0000000000000150] [PMID: 25051312]
[9]
Raz R, Roberts AL, Lyall K, et al. Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case-control analysis within the Nurses’ health study II cohort. Environ Health Perspect 2015; 123(3): 264-70.
[http://dx.doi.org/10.1289/ehp.1408133] [PMID: 25522338]
[10]
Kalkbrenner AE, Windham GC, Serre ML, et al. Particulate matter exposure, prenatal and postnatal windows of susceptibility, and autism spectrum disorders. Epidemiology 2015; 26(1): 30-42.
[http://dx.doi.org/10.1097/EDE.0000000000000173] [PMID: 25286049]
[11]
Ornoy A. Valproic acid in pregnancy: how much are we endangering the embryo and fetus? Reprod Toxicol 2009; 28(1): 1-10.
[http://dx.doi.org/10.1016/j.reprotox.2009.02.014] [PMID: 19490988]
[12]
Connors SL, Crowell DE, Eberhart CG, et al. β2-adrenergic receptor activation and genetic polymorphisms in autism: data from dizygotic twins. J Child Neurol 2005; 20(11): 876-84.
[http://dx.doi.org/10.1177/08830738050200110401] [PMID: 16417856]
[13]
Lyall K, Schmidt RJ, Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. Int J Epidemiol 2014; 43(2): 443-64.
[http://dx.doi.org/10.1093/ije/dyt282] [PMID: 24518932]
[14]
Rossignol DA, Genuis SJ, Frye RE. Environmental toxicants and autism spectrum disorders: a systematic review. Transl Psychiatry 2014; 4 e360
[http://dx.doi.org/10.1038/tp.2014.4] [PMID: 24518398]
[15]
Surén P, Roth C, Bresnahan M, et al. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA 2013; 309(6): 570-7.
[http://dx.doi.org/10.1001/jama.2012.155925] [PMID: 23403681]
[16]
D’Onofrio BM, Rickert ME, Frans E, et al. Paternal age at childbearing and offspring psychiatric and academic morbidity. JAMA Psychiatry 2014; 71(4): 432-8.
[http://dx.doi.org/10.1001/jamapsychiatry.2013.4525] [PMID: 24577047]
[17]
Cheslack-Postava K, Suominen A, Jokiranta E, et al. Increased risk of autism spectrum disorders at short and long interpregnancy intervals in Finland. J Am Acad Child Adolesc Psychiatry 2014; 53(10): 1074-81.e4.
[http://dx.doi.org/10.1016/j.jaac.2014.06.009] [PMID: 25245351]
[18]
Abdullah MM, Ly AR, Goldberg WA, et al. Heavy metal in children’s tooth enamel: related to autism and disruptive behaviors? J Autism Dev Disord 2012; 42(6): 929-36.
[http://dx.doi.org/10.1007/s10803-011-1318-6] [PMID: 21735299]
[19]
Roberts AL, Lyall K, Rich-Edwards JW, Ascherio A, Weisskopf MG. Maternal exposure to intimate partner abuse before birth is associated with autism spectrum disorder in offspring. Autism 2016; 20(1): 26-36.
[http://dx.doi.org/10.1177/1362361314566049] [PMID: 25662292]
[20]
Beversdorf DQ, Manning SE, Hillier A, et al. Timing of prenatal stressors and autism. J Autism Dev Disord 2005; 35(4): 471-8.
[http://dx.doi.org/10.1007/s10803-005-5037-8] [PMID: 16134032]
[21]
Kinney DK, Miller AM, Crowley DJ, Huang E, Gerber E. Autism prevalence following prenatal exposure to hurricanes and tropical storms in Louisiana. J Autism Dev Disord 2008; 38(3): 481-8.
[http://dx.doi.org/10.1007/s10803-007-0414-0] [PMID: 17619130]
[22]
Meltzer A, Van de Water J. The role of the immune system in autism spectrum disorder. Neuropsychopharmacology 2017; 42(1): 284-98.
[http://dx.doi.org/10.1038/npp.2016.158] [PMID: 27534269]
[23]
Jones KL, Pride MC, Edmiston E, et al. Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism. Mol Psychiatry 2018. Epub ahead of print
[http://dx.doi.org/10.1038/s41380-018-0126-1] [PMID: 29955164]
[24]
Dawson G, Ashman SB, Carver LJ. The role of early experience in shaping behavioral and brain development and its implications for social policy. Dev Psychopathol 2000; 12(4): 695-712.
[http://dx.doi.org/10.1017/S0954579400004089] [PMID: 11202040]
[25]
Niederhofer H, Reiter A. Maternal stress during pregnancy, its objectivation by ultrasound observation of fetal intrauterine movements and child’s temperament at 6 months and 6 years of age: a pilot study. Psychol Rep 2000; 86(2): 526-8.
[http://dx.doi.org/10.2466/pr0.2000.86.2.526] [PMID: 10840907]
[26]
van Os J, Selten JP. Prenatal exposure to maternal stress and subsequent schizophrenia. The May 1940 invasion of The Netherlands. Br J Psychiatry 1998; 172: 324-6.
[http://dx.doi.org/10.1192/bjp.172.4.324] [PMID: 9715334]
[27]
Ward AJ. A comparison and analysis of the presence of family problems during pregnancy of mothers of “autistic” children and mothers of typically developing children. Child Psychiatry Hum Dev 1990; 20: 279-88.
[http://dx.doi.org/10.1007/BF00706020] [PMID: 2376213]
[28]
Ward AJ. Prenatal stress and childhood psychopathology. Child Psychiatry Hum Dev 1991; 22(2): 97-110.
[http://dx.doi.org/10.1007/BF00707788] [PMID: 1800027]
[29]
Ward HE, Johnson EA, Salm AK, Birkle DL. Effects of prenatal stress on defensive withdrawal behavior and corticotropin releasing factor systems in rat brain. Physiol Behav 2000; 70(3-4): 359-66.
[http://dx.doi.org/10.1016/S0031-9384(00)00270-5] [PMID: 11006435]
[30]
Weinstock M. Does prenatal stress impair coping and regulation of hypothalamic-pituitary-adrenal axis? Neurosci Biobehav Rev 1997; 21(1): 1-10.
[http://dx.doi.org/10.1016/S0149-7634(96)00014-0] [PMID: 8994205]
[31]
Walder DJ, Laplante DP, Sousa-Pires A, Veru F, Brunet A, King S. Prenatal maternal stress predicts autism traits in 61/2 year-old children: Project Ice Storm. Psychiatry Res 2014; 219(2): 353-60.
[http://dx.doi.org/10.1016/j.psychres.2014.04.034] [PMID: 24907222]
[32]
Varcin KJ, Alvares GA, Uljarević M, Whitehouse AJO. Prenatal maternal stress events and phenotypic outcomes in Autism Spectrum Disorder. Autism Res 2017; 10(11): 1866-77.
[http://dx.doi.org/10.1002/aur.1830] [PMID: 28681538]
[33]
Li J, Vestergaard M, Obel C, et al. A nationwide study on the risk of autism after prenatal stress exposure to maternal bereavement. Pediatrics 2009; 123(4): 1102-7.
[http://dx.doi.org/10.1542/peds.2008-1734] [PMID: 19336368]
[34]
Larsson HJ, Eaton WW, Madsen KM, et al. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol 2005; 161(10): 916-25.
[http://dx.doi.org/10.1093/aje/kwi123] [PMID: 15870155]
[35]
Class QA, Abel KM, Khashan AS, et al. Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress. Psychol Med 2014; 44(1): 71-84.
[http://dx.doi.org/10.1017/S0033291713000780] [PMID: 23591021]
[36]
Manzari N, Matvienko-Sikar K, Baldoni F, O’Keeffe GW, Khashan AS. Prenatal maternal stress and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis. Soc Psychiatry Psychiatr Epidemiol 2019; 54(11): 1299-309.
[http://dx.doi.org/10.1007/s00127-019-01745-3] [PMID: 31324962]
[37]
Murphy DL, Lerner A, Rudnick G, Lesch KP. Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv 2004; 4(2): 109-23.
[http://dx.doi.org/10.1124/mi.4.2.8] [PMID: 15087484]
[38]
Heils A, Teufel A, Petri S, et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996; 66(6): 2621-4.
[http://dx.doi.org/10.1046/j.1471-4159.1996.66062621.x] [PMID: 8632190]
[39]
Lesch KP, Bengel D, Heils A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274(5292): 1527-31.
[http://dx.doi.org/10.1126/science.274.5292.1527] [PMID: 8929413]
[40]
Prasad HC, Zhu CB, McCauley JL, et al. Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase. Proc Natl Acad Sci USA 2005; 102(32): 11545-50.
[http://dx.doi.org/10.1073/pnas.0501432102] [PMID: 16055563]
[41]
Bondy B, Buettner A, Zill P. Genetics of suicide. Mol Psychiatry 2006; 11(4): 336-51.
[http://dx.doi.org/10.1038/sj.mp.4001803] [PMID: 16462816]
[42]
Beversdorf DQ, Carpenter AL, Alexander JK, et al. Influence of serotonin transporter SLC6A4 genotype on the effect of psychosocial stress on cognitive performance: an exploratory pilot study. Cogn Behav Neurol 2018; 31(2): 79-85.
[http://dx.doi.org/10.1097/WNN.0000000000000153] [PMID: 29927798]
[43]
Hariri AR, Mattay VS, Tessitore A, et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002; 297(5580): 400-3.
[http://dx.doi.org/10.1126/science.1071829] [PMID: 12130784]
[44]
Hennessey T, Andari E, Rainnie DG. RDoC-based categorization of amygdala functions and its implications in autism. Neurosci Biobehav Rev 2018; 90: 115-29.
[http://dx.doi.org/10.1016/j.neubiorev.2018.04.007] [PMID: 29660417]
[45]
McCauley JL, Olson LM, Dowd M, et al. Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid-compulsive subset of autism. Am J Med Genet B Neuropsychiatr Genet 2004; 127B(1): 104-12.
[http://dx.doi.org/10.1002/ajmg.b.20151] [PMID: 15108191]
[46]
Muller CL, Anacker AMJ, Veenstra-VanderWeele J. The serotonin system in autism spectrum disorder: from biomarker to animal models. Neuroscience 2016; 321: 24-41.
[http://dx.doi.org/10.1016/j.neuroscience.2015.11.010] [PMID: 26577932]
[47]
Brune CW, Kim SJ, Salt J, Leventhal BL, Lord C, Cook EH Jr. 5-HTTLPR genotype-specific phenotype in children and adolescents with autism. Am J Psychiatry 2006; 163(12): 2148-56.
[http://dx.doi.org/10.1176/ajp.2006.163.12.2148] [PMID: 17151167]
[48]
Cook EH Jr, Courchesne R, Lord C, et al. Evidence of linkage between the serotonin transporter and autistic disorder. Mol Psychiatry 1997; 2(3): 247-50.
[http://dx.doi.org/10.1038/sj.mp.4000266] [PMID: 9152989]
[49]
Losh M, Sullivan PF, Trembath D, Piven J. Current developments in the genetics of autism: from phenome to genome. J Neuropathol Exp Neurol 2008; 67(9): 829-37.
[http://dx.doi.org/10.1097/NEN.0b013e318184482d] [PMID: 18716561]
[50]
Zhong N, Ye L, Ju W, Brown WT, Tsiouris J, Cohen I. 5-HTTLPR variants not associated with autistic spectrum disorders. Neurogenetics 1999; 2(2): 129-31.
[http://dx.doi.org/10.1007/s100480050064] [PMID: 10369890]
[51]
Jones KL, Smith RM, Edwards KS, Givens B, Tilley MR, Beversdorf DQ. Combined effect of maternal serotonin transporter genotype and prenatal stress in modulating offspring social interaction in mice. Int J Dev Neurosci 2010; 28(6): 529-36.
[http://dx.doi.org/10.1016/j.ijdevneu.2010.05.002] [PMID: 20470877]
[52]
Hecht PM, Hudson M, Connors SL, Tilley MR, Liu X, Beversdorf DQ. Maternal serotonin transporter genotype affects risk for ASD with exposure to prenatal stress. Autism Res 2016; 9(11): 1151-60.
[http://dx.doi.org/10.1002/aur.1629] [PMID: 27091118]
[53]
Murphy DL, Maile MS, Vogt NM. 5HTTLPR: white knight or dark blight? ACS Chem Neurosci 2013; 4(1): 13-5.
[http://dx.doi.org/10.1021/cn3002224] [PMID: 23336038]
[54]
Abbott PW, Gumusoglu SB, Bittle J, Beversdorf DQ, Stevens HE. Prenatal stress and genetic risk: how prenatal stress interacts with genetics to alter risk for psychiatric illness. Psychoneuroendocrinology 2018; 90: 9-21.
[http://dx.doi.org/10.1016/j.psyneuen.2018.01.019] [PMID: 29407514]
[55]
Smith-Hicks CL. GABAergic dysfunction in pediatric neuro-developmental disorders. Front Cell Neurosci 2013; 7: 269.
[http://dx.doi.org/10.3389/fncel.2013.00269] [PMID: 24391546]
[56]
Fine R, Zhang J, Stevens HE. Prenatal stress and inhibitory neuron systems: implications for neuropsychiatric disorders. Mol Psychiatry 2014; 19(6): 641-51.
[http://dx.doi.org/10.1038/mp.2014.35] [PMID: 24751963]
[57]
Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz SC, Realmuto GR. Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psychiatry 2002; 52(8): 805-10.
[http://dx.doi.org/10.1016/S0006-3223(02)01430-0] [PMID: 12372652]
[58]
Yip J, Soghomonian JJ, Blatt GJ. Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications. Acta Neuropathol 2007; 113(5): 559-68.
[http://dx.doi.org/10.1007/s00401-006-0176-3] [PMID: 17235515]
[59]
Gaetz W, Bloy L, Wang DJ, et al. GABA estimation in the brains of children on the autism spectrum: measurement precision and regional cortical variation. Neuroimage 2014; 86: 1-9.
[http://dx.doi.org/10.1016/j.neuroimage.2013.05.068] [PMID: 23707581]
[60]
Rojas DC, Singel D, Steinmetz S, Hepburn S, Brown MS. Decreased left perisylvian GABA concentration in children with autism and unaffected siblings. Neuroimage 2014; 86: 28-34.
[http://dx.doi.org/10.1016/j.neuroimage.2013.01.045] [PMID: 23370056]
[61]
Harada M, Taki MM, Nose A, et al. Non-invasive evaluation of the GABAergic/glutamatergic system in autistic patients observed by MEGA-editing proton MR spectroscopy using a clinical 3 tesla instrument. J Autism Dev Disord 2011; 41: 447-54.
[62]
Lussier SJ, Stevens HE. Delays in GABAergic interneuron development and behavioral inhibition after prenatal stress. Dev Neurobiol 2016; 76(10): 1078-91.
[http://dx.doi.org/10.1002/dneu.22376] [PMID: 26724783]
[63]
Stevens HE, Su T, Yanagawa Y, Vaccarino FM. Prenatal stress delays inhibitory neuron progenitor migration in the developing neocortex. Psychoneuroendocrinology 2013; 38(4): 509-21.
[http://dx.doi.org/10.1016/j.psyneuen.2012.07.011] [PMID: 22910687]
[64]
Stevens H, Lussier S, Michaelson J, Radhakrishna S, Elser B. Embryonic GABAergic proliferation as a contributing mechanism of sex differences in prenatal stress effects on brain and behavior. Neuropsychopharmacology 2017; 43: S497.
[65]
Bale TL. Sex differences in prenatal epigenetic programming of stress pathways. Stress 2011; 14(4): 348-56.
[http://dx.doi.org/10.3109/10253890.2011.586447] [PMID: 21663536]
[66]
Howerton CL, Morgan CP, Fischer DB, Bale TL. O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development. Proc Natl Acad Sci USA 2013; 110(13): 5169-74.
[http://dx.doi.org/10.1073/pnas.1300065110] [PMID: 23487789]
[67]
Millan MJ. MicroRNA in the regulation and expression of serotonergic transmission in the brain and other tissues. Curr Opin Pharmacol 2011; 11(1): 11-22.
[http://dx.doi.org/10.1016/j.coph.2011.01.008] [PMID: 21345728]
[68]
Bai M, Zhu XZ, Zhang Y, et al. Anhedonia was associated with the dysregulation of hippocampal HTR4 and microRNA Let-7a in rats. Physiol Behav 2014; 129: 135-41.
[http://dx.doi.org/10.1016/j.physbeh.2014.02.035] [PMID: 24582667]
[69]
Elton TS, Selemon H, Elton SM, Parinandi NL. Regulation of the MIR155 host gene in physiological and pathological processes. Gene 2013; 532(1): 1-12.
[http://dx.doi.org/10.1016/j.gene.2012.12.009] [PMID: 23246696]
[70]
Monteleone MC, Adrover E, Pallarés ME, Antonelli MC, Frasch AC, Brocco MA. Prenatal stress changes the glycoprotein GPM6A gene expression and induces epigenetic changes in rat offspring brain. Epigenetics 2014; 9(1): 152-60.
[http://dx.doi.org/10.4161/epi.25925] [PMID: 23959066]
[71]
Singh NP, Singh UP, Guan H, Nagarkatti P, Nagarkatti M. Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression. PLoS One 2012; 7(9) e45054
[http://dx.doi.org/10.1371/journal.pone.0045054] [PMID: 23024791]
[72]
Babenko O, Kovalchuk I, Metz GA. Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health. Neurosci Biobehav Rev 2015; 48: 70-91.
[http://dx.doi.org/10.1016/j.neubiorev.2014.11.013] [PMID: 25464029]
[73]
Sjaarda CP, Hecht P, McNaughton AJM, et al. Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development. Sci Rep 2017; 7(1): 8735.
[http://dx.doi.org/10.1038/s41598-017-07405-3] [PMID: 28821725]
[74]
Zucchi FC, Yao Y, Ward ID, et al. Maternal stress induces epigenetic signatures of psychiatric and neurological diseases in the offspring. PLoS One 2013; 8(2) e56967
[http://dx.doi.org/10.1371/journal.pone.0056967] [PMID: 23451123]
[75]
Issler O, Haramati S, Paul ED, et al. MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity. Neuron 2014; 83(2): 344-60.
[http://dx.doi.org/10.1016/j.neuron.2014.05.042] [PMID: 24952960]
[76]
Baudry A, Mouillet-Richard S, Schneider B, Launay JM, Kellermann O. miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science 2010; 329(5998): 1537-41.
[http://dx.doi.org/10.1126/science.1193692] [PMID: 20847275]
[77]
Moya PR, Wendland JR, Salemme J, Fried RL, Murphy DL. miR-15a and miR-16 regulate serotonin transporter expression in human placental and rat brain raphe cells. Int J Neuropsychopharmacol 2013; 16(3): 621-9.
[http://dx.doi.org/10.1017/S1461145712000454] [PMID: 22564678]
[78]
Arisawa T, Tahara T, Fukuyama T, et al. Genetic polymorphism of pri-microRNA 325, targeting SLC6A4 3′-UTR, is closely associated with the risk of functional dyspepsia in Japan. J Gastroenterol 2012; 47(10): 1091-8.
[http://dx.doi.org/10.1007/s00535-012-0576-1] [PMID: 22438098]
[79]
Hu VW, Frank BC, Heine S, Lee NH, Quackenbush J. Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes. BMC Genomics 2006; 7: 118.
[http://dx.doi.org/10.1186/1471-2164-7-118] [PMID: 16709250]
[80]
Nguyen A, Rauch TA, Pfeifer GP, Hu VW. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J 2010; 24(8): 3036-51.
[http://dx.doi.org/10.1096/fj.10-154484] [PMID: 20375269]
[81]
Griffiths BB, Hunter RG. Neuroepigenetics of stress. Neuroscience 2014; 275: 420-35.
[http://dx.doi.org/10.1016/j.neuroscience.2014.06.041] [PMID: 24976514]
[82]
Matsui F, Hecht P, Yoshimoto K, et al. DHA mitigates autistic behaviors accompanied by dopaminergic change on a gene/prenatal stress mouse model. Neuroscience 2018; 371: 407-19.
[http://dx.doi.org/10.1016/j.neuroscience.2017.12.029] [PMID: 29288796]
[83]
Matrisciano F, Tueting P, Dalal I, et al. Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology 2013; 68: 184-94.
[http://dx.doi.org/10.1016/j.neuropharm.2012.04.013] [PMID: 22564440]
[84]
Bale TL. Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci 2015; 16(6): 332-44.
[http://dx.doi.org/10.1038/nrn3818] [PMID: 25921815]
[85]
Rodgers AB, Morgan CP, Bronson SL, Revello S, Bale TL. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J Neurosci 2013; 33(21): 9003-12.
[http://dx.doi.org/10.1523/JNEUROSCI.0914-13.2013] [PMID: 23699511]
[86]
Rodgers AB, Morgan CP, Leu NA, Bale TL. Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. Proc Natl Acad Sci USA 2015; 112(44): 13699-704.
[http://dx.doi.org/10.1073/pnas.1508347112] [PMID: 26483456]
[87]
Pisu MG, Boero G, Garau A, et al. Are preconceptional stressful experiences crucial elements for the aetiology of autism spectrum disorder? Insights from an animal model. Neuropharmacology 2019; 157 107686
[http://dx.doi.org/10.1016/j.neuropharm.2019.107686] [PMID: 31247268]
[88]
Roberts AL, Lyall K, Rich-Edwards JW, Ascherio A, Weisskopf MG. Maternal exposure to childhood abuse is associated with elevated risk of autism. JAMA Psychiatry 2013; 70: 508-15.
[http://dx.doi.org/10.1001/jamapsychiatry.2013.447] [PMID: 23553149]
[89]
Chan JC, Nugent BM, Bale TL. Parental advisory: maternal and paternal stress can impact offspring neurodevelopment. Biol Psychiatry 2018; 83(10): 886-94.
[http://dx.doi.org/10.1016/j.biopsych.2017.10.005] [PMID: 29198470]
[90]
Rao M, Gershon MD. The bowel and beyond: the enteric nervous system in neurological disorders. Nat Rev Gastroenterol Hepatol 2016; 13(9): 517-28.
[http://dx.doi.org/10.1038/nrgastro.2016.107] [PMID: 27435372]
[91]
Israelyan N, Margolis KG. Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders. Pharmacol Res 2018; 132: 1-6.
[http://dx.doi.org/10.1016/j.phrs.2018.03.020] [PMID: 29614380]
[92]
Margolis KG. A role for the serotonin reuptake transporter in the brain and intestinal features of autism spectrum disorders and developmental antidepressant exposure. J Chem Neuroanat 2017; 83-84: 36-40.
[http://dx.doi.org/10.1016/j.jchemneu.2017.02.001] [PMID: 28213183]
[93]
Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013; 155(7): 1451-63.
[http://dx.doi.org/10.1016/j.cell.2013.11.024] [PMID: 24315484]
[94]
Sampson TR, Mazmanian SK. Control of brain development, function, and behavior by the microbiome. Cell Host Microbe 2015; 17(5): 565-76.
[http://dx.doi.org/10.1016/j.chom.2015.04.011] [PMID: 25974299]
[95]
Kelly JR, Minuto C, Cryan JF, Clarke G, Dinan TG. Cross talk: the microbiota and neurodevelopmental disorders. Front Neurosci 2017; 11: 490.
[http://dx.doi.org/10.3389/fnins.2017.00490] [PMID: 28966571]
[96]
Kabouridis PS, Pachnis V. Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system. J Clin Invest 2015; 125(3): 956-64.
[http://dx.doi.org/10.1172/JCI76308] [PMID: 25729852]
[97]
Wang Y, Kasper LH. The role of microbiome in central nervous system disorders. Brain Behav Immun 2014; 38: 1-12.
[http://dx.doi.org/10.1016/j.bbi.2013.12.015] [PMID: 24370461]
[98]
Carlson AL, Xia K, Azcarate-Peril MA, et al. Infant gut microbiome associated with cognitive development. Biol Psychiatry 2018; 83(2): 148-59.
[http://dx.doi.org/10.1016/j.biopsych.2017.06.021] [PMID: 28793975]
[99]
Mayer EA, Knight R, Mazmanian SK, Cryan JF, Tillisch K. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci 2014; 34(46): 15490-6.
[http://dx.doi.org/10.1523/JNEUROSCI.3299-14.2014] [PMID: 25392516]
[100]
Hoban AE, Stilling RM, Ryan FJ, et al. Regulation of prefrontal cortex myelination by the microbiota. Transl Psychiatry 2016; 6 e774
[http://dx.doi.org/10.1038/tp.2016.42] [PMID: 27045844]
[101]
Ong IM, Gonzalez JG, McIlwain SJ, et al. Gut microbiome populations are associated with structure-specific changes in white matter architecture. Transl Psychiatry 2018; 8(1): 6.
[http://dx.doi.org/10.1038/s41398-017-0022-5] [PMID: 29317592]
[102]
Aatsinki A-K, Lahti L, Uusitupa H-M, et al. Gut microbiota composition is associated with temperament traits in infants. Brain Behav Immun 2019; 80: 849-58.
[http://dx.doi.org/10.1016/j.bbi.2019.05.035] [PMID: 31132457]
[103]
Jašarević E, Rodgers AB, Bale TL. A novel role for maternal stress and microbial transmission in early life programming and neurodevelopment. Neurobiol Stress 2015; 1: 81-8.
[http://dx.doi.org/10.1016/j.ynstr.2014.10.005] [PMID: 25530984]
[104]
Zijlmans MAC, Korpela K, Riksen-Walraven JM, de Vos WM, de Weerth C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology 2015; 53: 233-45.
[http://dx.doi.org/10.1016/j.psyneuen.2015.01.006] [PMID: 25638481]
[105]
Hechler C, Borewicz K, Beijers R, et al. Association between psychosocial stress and fecal micobiota in pregnant women. Sci Rep 2019; 9(1): 4463.
[http://dx.doi.org/10.1038/s41598-019-40434-8] [PMID: 30872645]
[106]
Kim S, Kim H, Yim YS, et al. Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature 2017; 549(7673): 528-32.
[http://dx.doi.org/10.1038/nature23910] [PMID: 28902840]
[107]
Lammert CR, Frost EL, Bolte AC, et al. Cutting edge: critical roles for microbiota-mediated regulation of the immune system in a prenatal immune activation model of autism. J Immunol 2018; 201(3): 845-50.
[http://dx.doi.org/10.4049/jimmunol.1701755] [PMID: 29967099]
[108]
Isaksson J, Pettersson E, Kostrzewa E, Diaz Heijtz R, Bölte S. Brief report: association between autism spectrum disorder, gastrointestinal problems and perinatal risk factors within sibling pairs. J Autism Dev Disord 2017; 47(8): 2621-7.
[http://dx.doi.org/10.1007/s10803-017-3169-2] [PMID: 28536957]
[109]
Hornig M, Bresnahan MA, Che X, et al. Prenatal fever and autism risk. Mol Psychiatry 2018; 23(3): 759-66.
[http://dx.doi.org/10.1038/mp.2017.119] [PMID: 28607458]
[110]
Mahic M, Mjaaland S, Bøvelstad HM, et al. Maternal immunoreactivity to herpes simplex virus 2 and risk of autism spectrum disorder in male offspring. MSphere 2017; 2(1): e00016-7.
[http://dx.doi.org/10.1128/mSphere.00016-17] [PMID: 28251181]
[111]
Jiang HY, Xu LL, Shao L, et al. Maternal infection during pregnancy and risk of autism spectrum disorders: a systematic review and meta-analysis. Brain Behav Immun 2016; 58: 165-72.
[http://dx.doi.org/10.1016/j.bbi.2016.06.005] [PMID: 27287966]
[112]
Goines P, Van de Water J. The immune system’s role in the biology of autism. Curr Opin Neurol 2010; 23(2): 111-7.
[http://dx.doi.org/10.1097/WCO.0b013e3283373514] [PMID: 20160651]
[113]
Connolly N, Anixt J, Manning P. Ping-I Lin D, Marsolo KA, Bowers K. Maternal metabolic risk factors for autism spectrum disorder - An analysis of electronic medical records and linked birth data. Autism Res 2016; 9: 829-37.
[http://dx.doi.org/10.1002/aur.1586] [PMID: 26824581]
[114]
Buffington SA, Di Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M. Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell 2016; 165(7): 1762-75.
[http://dx.doi.org/10.1016/j.cell.2016.06.001] [PMID: 27315483]
[115]
McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics 2014; 133(5): 872-83.
[http://dx.doi.org/10.1542/peds.2013-3995] [PMID: 24777214]
[116]
Luna RA, Oezguen N, Balderas M, et al. Distinct microbiome-neuroimmune signatures correlated with functional abdominal pain in children with autism spectrum disorder. Cell Mol Gastroenterol Hepatol 2016; 3(2): 218-30.
[http://dx.doi.org/10.1016/j.jcmgh.2016.11.008] [PMID: 28275689]
[117]
Foster JA, Rinaman L, Cryan JF. Stress & the gut-brain axis: regulation by the microbiome. Neurobiol Stress 2017; 7: 124-36.
[http://dx.doi.org/10.1016/j.ynstr.2017.03.001] [PMID: 29276734]
[118]
Ferguson BJ, Marler S, Altstein LL, et al. Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder. Brain Behav Immun 2016; 58: 57-62.
[http://dx.doi.org/10.1016/j.bbi.2016.05.009] [PMID: 27181180]
[119]
Burokas A, Arboleya S, Moloney RD, et al. Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry 2017; 82(7): 472-87.
[http://dx.doi.org/10.1016/j.biopsych.2016.12.031] [PMID: 28242013]
[120]
Frank MG, Fonken LK, Dolzani SD, et al. Immunization with Mycobacterium vaccae induces an anti-inflammatory milieu in the CNS: attenuation of stress-induced microglial priming, alarmins and anxiety-like behavior. Brain Behav Immun 2018; 73: 352-63.
[http://dx.doi.org/10.1016/j.bbi.2018.05.020] [PMID: 29807129]
[121]
Clarke G, Grenham S, Scully P, et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 2013; 18(6): 666-73.
[http://dx.doi.org/10.1038/mp.2012.77] [PMID: 22688187]
[122]
Sylvia KE, Demas GE. A gut feeling: microbiome-brain-immune interactions modulate social and affective behaviors. Horm Behav 2018; 99: 41-9.
[http://dx.doi.org/10.1016/j.yhbeh.2018.02.001] [PMID: 29427583]
[123]
Ding HT, Taur Y, Walkup JT. Gut microbiota and autism: key concepts and findings. J Autism Dev Disord 2017; 47(2): 480-9.
[http://dx.doi.org/10.1007/s10803-016-2960-9] [PMID: 27882443]
[124]
Li Q, Han Y, Dy ABC, Hagerman RJ. The gut microbiota and autism spectrum disorders. Front Cell Neurosci 2017; 11: 120.
[http://dx.doi.org/10.3389/fncel.2017.00120] [PMID: 28503135]
[125]
Li Q, Zhou J-M. The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum disorder. Neuroscience 2016; 324: 131-9.
[http://dx.doi.org/10.1016/j.neuroscience.2016.03.013] [PMID: 26964681]
[126]
Mulle JG, Sharp WG, Cubells JF. The gut microbiome: a new frontier in autism research. Curr Psychiatry Rep 2013; 15(2): 337.
[http://dx.doi.org/10.1007/s11920-012-0337-0] [PMID: 23307560]
[127]
Vuong HE, Hsiao EY. Emerging roles for the gut microbiome in autism spectrum disorder. Biol Psychiatry 2017; 81(5): 411-23.
[http://dx.doi.org/10.1016/j.biopsych.2016.08.024] [PMID: 27773355]
[128]
Liu Y, Fatheree NY, Mangalat N, Rhoads JM. Human-derived probiotic Lactobacillus reuteri strains differentially reduce intestinal inflammation. Am J Physiol Gastrointest Liver Physiol 2010; 299(5): G1087-96.
[http://dx.doi.org/10.1152/ajpgi.00124.2010] [PMID: 20798357]
[129]
Sgritta M, Dooling SW, Buffington SA, et al. Mechanisms underlying microbial-mediated changes in socail behavior in mouse modesl of autism spectrum disorder. Neuron 2019; 101(2): 246-59.e6.
[http://dx.doi.org/10.1016/j.neuron.2018.11.018] [PMID: 30522820]
[130]
Arnold LE. Probiotics for Quality of Life in Autism Spectrum Disorders Available at: https://clinicaltrials.gov/ct2/show/NCT02903030
[131]
Kang D-W, Adams JB, Gregory AC, et al. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 2017; 5(1): 10.
[http://dx.doi.org/10.1186/s40168-016-0225-7] [PMID: 28122648]
[132]
Kang D-W, Adams JB, Coleman DM, et al. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep 2019; 9(1): 5821.
[http://dx.doi.org/10.1038/s41598-019-42183-0] [PMID: 30967657]
[133]
Navarro F, Liu Y, Rhoads JM. Can probiotics benefit children with autism spectrum disorders? World J Gastroenterol 2016; 22(46): 10093-102.
[http://dx.doi.org/10.3748/wjg.v22.i46.10093] [PMID: 28028357]
[134]
Jeste SS, Geschwind DH. Disentangling the heterogeneity of autism spectrum disorder through genetic findings. Nat Rev Neurol 2014; 10(2): 74-81.
[http://dx.doi.org/10.1038/nrneurol.2013.278] [PMID: 24468882]
[135]
Sun GY, Simonyi A, Fritsche KL, et al. Docosahexaenoic acid (DHA): an essential nutrient and a nutraceutical for brain health and diseases. Prostaglandins Leukot Essent Fatty Acids 2018; 136: 3-13.
[http://dx.doi.org/10.1016/j.plefa.2017.03.006] [PMID: 28314621]
[136]
Sun GY, Li R, Yang B, et al. Quercetin potentiates docosahexaenoic acid to suppress lipopolysaccharide-induced oxidative/inflammatory responses, alter lipid peroxidation products, and enhance the adaptive stress pathways in BV-2 microglial cells. Int J Mol Sci 2019; 20(4): 932.
[http://dx.doi.org/10.3390/ijms20040932] [PMID: 30795510]
[137]
Bittle J, Menezes EC, McCormick ML, Spitz DR, Dailey M, Stevens HE. The role of redox regulation in the effects of prenatal stress on embryonic interneuron migration. Cereb Cortex 2019.
[http://dx.doi.org/10.1093/cercor/bhz052]
[138]
Kiecolt-Glaser JK, Belury MA, Porter K, Beversdorf DQ, Lemeshow S, Glaser R. Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older adults. Psychosom Med 2007; 69(3): 217-24.
[http://dx.doi.org/10.1097/PSY.0b013e3180313a45] [PMID: 17401057]
[139]
Chaouat G. The Th1/Th2 paradigm: still important in pregnancy? Semin Immunopathol 2007; 29(2): 95-113.
[http://dx.doi.org/10.1007/s00281-007-0069-0] [PMID: 17626305]
[140]
Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 1993; 14(7): 353-6.
[http://dx.doi.org/10.1016/0167-5699(93)90235-D] [PMID: 8363725]
[141]
Atladóttir HÓ, Henriksen TB, Schendel DE, Parner ET. Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study. Pediatrics 2012; 130(6): e1447-54.
[http://dx.doi.org/10.1542/peds.2012-1107] [PMID: 23147969]
[142]
Atladóttir HO, Thorsen P, Østergaard L, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord 2010; 40(12): 1423-30.
[http://dx.doi.org/10.1007/s10803-010-1006-y] [PMID: 20414802]
[143]
Chess S. Autism in children with congenital rubella. J Autism Child Schizophr 1971; 1(1): 33-47.
[http://dx.doi.org/10.1007/BF01537741] [PMID: 5172438]
[144]
Deykin EY, MacMahon B. Viral exposure and autism. Am J Epidemiol 1979; 109(6): 628-38.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a112726] [PMID: 222139]
[145]
Lee BK, Magnusson C, Gardner RM, et al. Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders. Brain Behav Immun 2015; 44: 100-5.
[http://dx.doi.org/10.1016/j.bbi.2014.09.001] [PMID: 25218900]
[146]
Zerbo O, Iosif AM, Walker C, Ozonoff S, Hansen RL, Hertz-Picciotto I. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (Childhood Autism Risks from Genetics and Environment) study. J Autism Dev Disord 2013; 43(1): 25-33.
[http://dx.doi.org/10.1007/s10803-012-1540-x] [PMID: 22562209]
[147]
Croen LA, Qian Y, Ashwood P, et al. Infection and fever in pregnancy and autism spectrum disorders: findings from the study to explore early development. Autism Res 2019; 12(10): 1551-61.
[http://dx.doi.org/10.1002/aur.2175] [PMID: 31317667]
[148]
Deverman BE, Patterson PH. Cytokines and CNS development. Neuron 2009; 64(1): 61-78.
[http://dx.doi.org/10.1016/j.neuron.2009.09.002] [PMID: 19840550]
[149]
Mehler MF, Kessler JA. Cytokines in brain development and function. Adv Protein Chem 1998; 52: 223-51.
[http://dx.doi.org/10.1016/S0065-3233(08)60437-4] [PMID: 9917922]
[150]
Samuelsson AM, Jennische E, Hansson HA, Holmäng A. Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning. Am J Physiol Regul Integr Comp Physiol 2006; 290(5): R1345-56.
[http://dx.doi.org/10.1152/ajpregu.00268.2005] [PMID: 16357100]
[151]
Zaretsky MV, Alexander JM, Byrd W, Bawdon RE. Transfer of inflammatory cytokines across the placenta. Obstet Gynecol 2004; 103(3): 546-50.
[http://dx.doi.org/10.1097/01.AOG.0000114980.40445.83] [PMID: 14990420]
[152]
Ashdown H, Dumont Y, Ng M, Poole S, Boksa P, Luheshi GN. The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia. Mol Psychiatry 2006; 11(1): 47-55.
[http://dx.doi.org/10.1038/sj.mp.4001748] [PMID: 16189509]
[153]
Hauguel-de Mouzon S, Guerre-Millo M. The placenta cytokine network and inflammatory signals. Placenta 2006; 27(8): 794-8.
[http://dx.doi.org/10.1016/j.placenta.2005.08.009] [PMID: 16242770]
[154]
Goines PE, Croen LA, Braunschweig D, et al. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: a case-control study. Mol Autism 2011; 2: 13.
[http://dx.doi.org/10.1186/2040-2392-2-13] [PMID: 21810230]
[155]
Jones KL, Croen LA, Yoshida CK, et al. Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation. Mol Psychiatry 2017; 22(2): 273-9.
[http://dx.doi.org/10.1038/mp.2016.77] [PMID: 27217154]
[156]
Shimaoka Y, Hidaka Y, Tada H, et al. Changes in cytokine production during and after normal pregnancy. Am J Reprod Immunol 2000; 44(3): 143-7.
[http://dx.doi.org/10.1111/j.8755-8920.2000.440303.x] [PMID: 11028900]
[157]
Denney JM, Nelson EL, Wadhwa PD, et al. Longitudinal modulation of immune system cytokine profile during pregnancy. Cytokine 2011; 53(2): 170-7.
[http://dx.doi.org/10.1016/j.cyto.2010.11.005] [PMID: 21123081]
[158]
Brown AS. The environment and susceptibility to schizophrenia. Prog Neurobiol 2011; 93(1): 23-58.
[http://dx.doi.org/10.1016/j.pneurobio.2010.09.003] [PMID: 20955757]
[159]
Hsiao EY. Immune dysregulation in autism spectrum disorder. Int Rev Neurobiol 2013; 113: 269-302.
[http://dx.doi.org/10.1016/B978-0-12-418700-9.00009-5] [PMID: 24290389]
[160]
Malkova NV, Yu CZ, Hsiao EY, Moore MJ, Patterson PH. Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav Immun 2012; 26(4): 607-16.
[http://dx.doi.org/10.1016/j.bbi.2012.01.011] [PMID: 22310922]
[161]
Patterson PH. Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness. Curr Opin Neurobiol 2002; 12(1): 115-8.
[http://dx.doi.org/10.1016/S0959-4388(02)00299-4] [PMID: 11861174]
[162]
Gumusoglu SB, Stevens HE. Preclinical evidence for Inflammation/Immunology in prenatal programming of psychiatric disorders. Biol Psychiatry 2019; 85(2): 107-21.
[http://dx.doi.org/10.1016/j.biopsych.2018.08.008] [PMID: 30318336]
[163]
Meyer U, Feldon J, Schedlowski M, Yee BK. Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia. Neurosci Biobehav Rev 2005; 29(6): 913-47.
[http://dx.doi.org/10.1016/j.neubiorev.2004.10.012] [PMID: 15964075]
[164]
Meyer U, Feldon J, Yee BK. A review of the fetal brain cytokine imbalance hypothesis of schizophrenia. Schizophr Bull 2009; 35(5): 959-72.
[http://dx.doi.org/10.1093/schbul/sbn022] [PMID: 18408229]
[165]
Zuckerman L, Weiner I. Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring. J Psychiatr Res 2005; 39(3): 311-23.
[http://dx.doi.org/10.1016/j.jpsychires.2004.08.008] [PMID: 15725430]
[166]
Boksa P. Effects of prenatal infection on brain development and behavior: a review of findings from animal models. Brain Behav Immun 2010; 24(6): 881-97.
[http://dx.doi.org/10.1016/j.bbi.2010.03.005] [PMID: 20230889]
[167]
Brown AS, Surcel H-M, Hinkka-Yli-Salomäki S, Cheslack-Postava K, Bao Y, Sourander A. Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort. Prog Neuropsychopharmacol Biol Psychiatry 2015; 57: 86-92.
[http://dx.doi.org/10.1016/j.pnpbp.2014.10.010] [PMID: 25445476]
[168]
Edmiston E, Ashwood P, Van de Water J. Autoimmunity, autoantibodies, and autism spectrum disorder. Biol Psychiatry 2017; 81(5): 383-90.
[http://dx.doi.org/10.1016/j.biopsych.2016.08.031] [PMID: 28340985]
[169]
Short SJ, Lubach GR, Karasin AI, et al. Maternal influenza infection during pregnancy impacts postnatal brain development in the rhesus monkey. Biol Psychiatry 2010; 67(10): 965-73.
[http://dx.doi.org/10.1016/j.biopsych.2009.11.026] [PMID: 20079486]
[170]
Connor CM, Dincer A, Straubhaar J, Galler JR, Houston IB, Akbarian S. Maternal immune activation alters behavior in adult offspring, with subtle changes in the cortical transcriptome and epigenome. Schizophr Res 2012; 140(1-3): 175-84.
[http://dx.doi.org/10.1016/j.schres.2012.06.037] [PMID: 22804924]
[171]
Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral DG, Van de Water J. Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders. Brain Behav Immun 2009; 23(1): 64-74.
[http://dx.doi.org/10.1016/j.bbi.2008.07.007] [PMID: 18706993]
[172]
Braunschweig D, Krakowiak P, Duncanson P, et al. Autism-specific maternal autoantibodies recognize critical proteins in developing brain. Transl Psychiatry 2013; 3 e277
[http://dx.doi.org/10.1038/tp.2013.50] [PMID: 23838888]
[173]
Brimberg L, Sadiq A, Gregersen PK, Diamond B. Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder. Mol Psychiatry 2013; 18(11): 1171-7.
[http://dx.doi.org/10.1038/mp.2013.101] [PMID: 23958959]
[174]
Simister NE. Placental transport of immunoglobulin G. Vaccine 2003; 21(24): 3365-9.
[http://dx.doi.org/10.1016/S0264-410X(03)00334-7] [PMID: 12850341]
[175]
Tincani A, Bompane D, Danieli E, Doria A. Pregnancy, lupus and antiphospholipid syndrome (Hughes syndrome). Lupus 2006; 15(3): 156-60.
[http://dx.doi.org/10.1191/0961203306lu2279rr] [PMID: 16634369]
[176]
Soares Rolim AM, Castro M, Santiago MB. Neonatal antiphospholipid syndrome. Lupus 2006; 15(5): 301-3.
[http://dx.doi.org/10.1191/0961203306lu2295cr] [PMID: 16761506]
[177]
Fu J, Jiang Y, Liang L, Zhu H. Risk factors of primary thyroid dysfunction in early infants born to mothers with autoimmune thyroid disease. Acta Paediatr 2005; 94(8): 1043-8.
[http://dx.doi.org/10.1111/j.1651-2227.2005.tb02043.x] [PMID: 16188847]
[178]
Braunschweig D, Ashwood P, Krakowiak P, et al. Autism: maternally derived antibodies specific for fetal brain proteins. Neurotoxicology 2008; 29(2): 226-31.
[PMID: 18078998]
[179]
Croen LA, Braunschweig D, Haapanen L, et al. Maternal mid-pregnancy autoantibodies to fetal brain protein: the early markers for autism study. Biol Psychiatry 2008; 64(7): 583-8.
[http://dx.doi.org/10.1016/j.biopsych.2008.05.006] [PMID: 18571628]
[180]
Braunschweig D, Duncanson P, Boyce R, et al. Behavioral correlates of maternal antibody status among children with autism. J Autism Dev Disord 2012; 42(7): 1435-45.
[http://dx.doi.org/10.1007/s10803-011-1378-7] [PMID: 22012245]
[181]
Singer HS, Morris CM, Gause CD, Gillin PK, Crawford S, Zimmerman AW. Antibodies against fetal brain in sera of mothers with autistic children. J Neuroimmunol 2008; 194(1-2): 165-72.
[http://dx.doi.org/10.1016/j.jneuroim.2007.11.004] [PMID: 18093664]
[182]
Zimmerman AW, Connors SL, Matteson KJ, et al. Maternal antibrain antibodies in autism. Brain Behav Immun 2007; 21(3): 351-7.
[http://dx.doi.org/10.1016/j.bbi.2006.08.005] [PMID: 17029701]
[183]
Heuer L, Braunschweig D, Ashwood P, Van de Water J, Campbell DB. Association of a MET genetic variant with autism-associated maternal autoantibodies to fetal brain proteins and cytokine expression. Transl Psychiatry 2011; 1 e48
[http://dx.doi.org/10.1038/tp.2011.48] [PMID: 22833194]
[184]
Brimberg L, Mader S, Jeganathan V, et al. Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD-like phenotype in mice. Mol Psychiatry 2016; 21(12): 1663-71.
[http://dx.doi.org/10.1038/mp.2016.165] [PMID: 27698429]
[185]
Martin LA, Ashwood P, Braunschweig D, Cabanlit M, Van de Water J, Amaral DG. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain Behav Immun 2008; 22(6): 806-16.
[http://dx.doi.org/10.1016/j.bbi.2007.12.007] [PMID: 18262386]
[186]
Bauman MD, Iosif A-M, Ashwood P, et al. Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey. Transl Psychiatry 2013; 3 e278
[http://dx.doi.org/10.1038/tp.2013.47] [PMID: 23838889]
[187]
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005; 57(1): 67-81.
[http://dx.doi.org/10.1002/ana.20315] [PMID: 15546155]
[188]
Campbell DB, D’Oronzio R, Garbett K, et al. Disruption of cerebral cortex MET signaling in autism spectrum disorder. Ann Neurol 2007; 62(3): 243-50.
[http://dx.doi.org/10.1002/ana.21180] [PMID: 17696172]
[189]
Cabanlit M, Wills S, Goines P, Ashwood P, Van de Water J. Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder. Ann N Y Acad Sci 2007; 1107: 92-103.
[http://dx.doi.org/10.1196/annals.1381.010] [PMID: 17804536]
[190]
Goines P, Haapanen L, Boyce R, et al. Autoantibodies to cerebellum in children with autism associate with behavior. Brain Behav Immun 2011; 25(3): 514-23.
[http://dx.doi.org/10.1016/j.bbi.2010.11.017] [PMID: 21134442]
[191]
Rossi CC, Van de Water J, Rogers SJ, Amaral DG. Detection of plasma autoantibodies to brain tissue in young children with and without autism spectrum disorders. Brain Behav Immun 2011; 25(6): 1123-35.
[http://dx.doi.org/10.1016/j.bbi.2011.02.011] [PMID: 21420487]
[192]
Wills S, Rossi CC, Bennett J, et al. Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism. Mol Autism 2011; 2: 5.
[http://dx.doi.org/10.1186/2040-2392-2-5] [PMID: 21521495]
[193]
Rossi CC, Fuentes J, Van de Water J, Amaral DG. Brief Report: antibodies reacting to brain tissue in basque Spanish children with autism spectrum disorder and their mothers. J Autism Dev Disord 2013; 44: 459-65.
[http://dx.doi.org/10.1007/s10803-013-1859-y] [PMID: 24022729]
[194]
Bennett JM, Glaser R, Malarkey WB, Beversdorf DQ, Peng J, Kiecolt-Glaser JK. Inflammation and reactivation of latent herpesviruses in older adults. Brain Behav Immun 2012; 26(5): 739-46.
[http://dx.doi.org/10.1016/j.bbi.2011.11.007] [PMID: 22155500]
[195]
Okada S, Hori N, Kimoto K, Onozuka M, Sato S, Sasaguri K. Effects of biting on elevation of blood pressure and other physiological responses to stress in rats: biting may reduce allostatic load. Brain Res 2007; 1185: 189-94.
[http://dx.doi.org/10.1016/j.brainres.2007.09.030] [PMID: 17945207]
[196]
Gumusoglu SB, Fine RS, Murray SJ, Bittle JL, Stevens HE. The role of IL-6 in neurodevelopment after prenatal stress. Brain Behav Immun 2017; 65: 274-83.
[http://dx.doi.org/10.1016/j.bbi.2017.05.015] [PMID: 28546058]
[197]
Peters JL, Cohen S, Staudenmayer J, Hosen J, Platts-Mills TA, Wright RJ. Prenatal negative life events increases cord blood IgE: interactions with dust mite allergen and maternal atopy. Allergy 2012; 67(4): 545-51.
[http://dx.doi.org/10.1111/j.1398-9995.2012.02791.x] [PMID: 22309645]
[198]
Coe CL, Crispen HR. Social stress in pregnant squirrel monkeys (Saimiri boliviensis peruviensis) differentially affects placental transfer of maternal antibody to male and female infants. Health Psychol 2000; 19(6): 554-9.
[http://dx.doi.org/10.1037/0278-6133.19.6.554] [PMID: 11129358]
[199]
Baganz NL, Blakely RD. A dialogue between the immune system and brain, spoken in the language of serotonin. ACS Chem Neurosci 2013; 4(1): 48-63.
[http://dx.doi.org/10.1021/cn300186b] [PMID: 23336044]
[200]
Andoh M, Shibata K, Okamoto K, et al. Exercise reverses behavioral and synaptic abnormalitites after maternal inflammation. Cell Rep 2019; 27(10): 2817-25.e5.
[http://dx.doi.org/10.1016/j.celrep.2019.05.015] [PMID: 31167129]
[201]
Zinöcker MK, Lindseth IA. The western diet-microbiome-host interaction and its role in metabolic disease. Nutrients 2018; 10(3): 365.
[http://dx.doi.org/10.3390/nu10030365] [PMID: 29562591]
[202]
Beversdorf DQ, Wang P, Barnes G, et al. Phenotyping, etiological factors, and biomarkers: toward precision medicine in autism spectrum disorder. J Dev Behav Pediatr 2016; 37(8): 659-73.
[http://dx.doi.org/10.1097/DBP.0000000000000351] [PMID: 27676697]

Rights & Permissions Print Cite
Article Metrics
22
2
© 2024 Bentham Science Publishers | Privacy Policy