Maternal Immune Activation Hypotheses for Human Neurodevelopment: Some Outstanding Questions

Overview

Journal Biol Psychiatry Cogn Neurosci Neuroimaging

Specialties Neurology
Psychiatry
Radiology

Date 2021 Oct 24

PMID 34688920

Citations 3

Authors

Thomas G OConnor

Allison A Ciesla

Affiliations

Soon will be listed here.

Abstract

The maternal immune activation hypothesis is a leading model for understanding prenatal influences on individual differences in, and clinical syndromes of, neurodevelopment. Experimental animal and human research has proliferated in recent years, and there is now a sizable research base. Several meta-analyses demonstrate general support for an association between prenatal immune activation and neurodevelopment in human research. However, questions remain about the nature of the immune activation, network of underlying mechanisms involved, and breadth of impact across behavioral phenotypes. Complementing recent reviews of results, the current review places particular emphasis on how a better understanding of mechanisms may be achieved with greater attention to addressing the methodological variation and limitations of existing studies and identifies areas for further clinical research.

Citing Articles

Beyond TORCH: A narrative review of the impact of antenatal and perinatal infections on the risk of disability.

Devaraju M, Li A, Ha S, Li M, Shivakumar M, Li H Neurosci Biobehav Rev. 2023; 153:105390.

PMID: 37708918 PMC: 10617835. DOI: 10.1016/j.neubiorev.2023.105390.

Prenatal air pollution, maternal immune activation, and autism spectrum disorder.

Yu X, Rahman M, Carter S, Lin J, Zhuang Z, Chow T Environ Int. 2023; 179:108148.

PMID: 37595536 PMC: 10792527. DOI: 10.1016/j.envint.2023.108148.

Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants.

Angrand L, Masson J, Rubio-Casillas A, Nosten-Bertrand M, Crepeaux G Toxics. 2022; 10(9).

PMID: 36136483 PMC: 9502677. DOI: 10.3390/toxics10090518.

References

Hill A . THE ENVIRONMENT AND DISEASE: ASSOCIATION OR CAUSATION?. Proc R Soc Med. 1965; 58:295-300. PMC: 1898525. DOI: 10.1177/003591576505800503. View

Piccinni M, Giudizi M, Biagiotti R, Beloni L, Giannarini L, Sampognaro S . Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones. J Immunol. 1995; 155(1):128-33. View

Kraus T, Engel S, Sperling R, Kellerman L, Lo Y, Wallenstein S . Characterizing the pregnancy immune phenotype: results of the viral immunity and pregnancy (VIP) study. J Clin Immunol. 2011; 32(2):300-11. PMC: 7086597. DOI: 10.1007/s10875-011-9627-2. View

Atladottir H, Henriksen T, Schendel D, Parner E . Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study. Pediatrics. 2012; 130(6):e1447-54. PMC: 4451062. DOI: 10.1542/peds.2012-1107. View

Jo H, Schieve L, Sharma A, Hinkle S, Li R, Lind J . Maternal prepregnancy body mass index and child psychosocial development at 6 years of age. Pediatrics. 2015; 135(5):e1198-209. PMC: 4411780. DOI: 10.1542/peds.2014-3058. View

Richard A, Shim B, Kwon Y, Zhang R, Otsuka Y, Schmitt K . AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses. Proc Natl Acad Sci U S A. 2017; 114(8):2024-2029. PMC: 5338370. DOI: 10.1073/pnas.1620558114. View

Goldstein J, Norris S, Aronoff D . DOHaD at the intersection of maternal immune activation and maternal metabolic stress: a scoping review. J Dev Orig Health Dis. 2017; 8(3):273-283. DOI: 10.1017/S2040174417000010. View

Aluvihare V, Kallikourdis M, Betz A . Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol. 2004; 5(3):266-71. DOI: 10.1038/ni1037. View

Stolp H, Ek C, Johansson P, Dziegielewska K, Potter A, Habgood M . Effect of minocycline on inflammation-induced damage to the blood-brain barrier and white matter during development. Eur J Neurosci. 2007; 26(12):3465-74. DOI: 10.1111/j.1460-9568.2007.05973.x. View

10.

Huber S, Kupperman J, Newell M . Hormonal regulation of CD4(+) T-cell responses in coxsackievirus B3-induced myocarditis in mice. J Virol. 1999; 73(6):4689-95. PMC: 112510. DOI: 10.1128/JVI.73.6.4689-4695.1999. View

11.

Croen L, Qian Y, Ashwood P, Zerbo O, Schendel D, Pinto-Martin J . Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development. Autism Res. 2019; 12(10):1551-1561. PMC: 7784630. DOI: 10.1002/aur.2175. View

12.

Choi G, Yim Y, Wong H, Kim S, Kim H, Kim S . The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science. 2016; 351(6276):933-9. PMC: 4782964. DOI: 10.1126/science.aad0314. View

13.

Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen L . Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. J Neuroimmunol. 2008; 204(1-2):149-53. PMC: 2615583. DOI: 10.1016/j.jneuroim.2008.07.006. View

14.

Graham A, Rasmussen J, Rudolph M, Heim C, Gilmore J, Styner M . Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn Amygdala Phenotypes and Subsequent Behavior at 2 Years of Age. Biol Psychiatry. 2017; 83(2):109-119. PMC: 5723539. DOI: 10.1016/j.biopsych.2017.05.027. View

15.

Stolp H, Dziegielewska K, Ek C, Habgood M, Lane M, Potter A . Breakdown of the blood-brain barrier to proteins in white matter of the developing brain following systemic inflammation. Cell Tissue Res. 2005; 320(3):369-78. DOI: 10.1007/s00441-005-1088-6. View

16.

Short S, Lubach G, Karasin A, Olsen C, Styner M, Knickmeyer R . Maternal influenza infection during pregnancy impacts postnatal brain development in the rhesus monkey. Biol Psychiatry. 2010; 67(10):965-73. PMC: 3235476. DOI: 10.1016/j.biopsych.2009.11.026. View

17.

OConnor T, Moynihan J, Caserta M . Annual research review: The neuroinflammation hypothesis for stress and psychopathology in children--developmental psychoneuroimmunology. J Child Psychol Psychiatry. 2013; 55(6):615-31. PMC: 4029900. DOI: 10.1111/jcpp.12187. View

18.

Al-Ayadhi L, Ahmed Mostafa G . Elevated serum levels of interleukin-17A in children with autism. J Neuroinflammation. 2012; 9:158. PMC: 3410815. DOI: 10.1186/1742-2094-9-158. View

19.

Vuolteenaho K, Koskinen A, Kukkonen M, Nieminen R, Paivarinta U, Moilanen T . Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage--mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production. Mediators Inflamm. 2009; 2009:345838. PMC: 2726438. DOI: 10.1155/2009/345838. View

20.

Paolicelli R, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P . Synaptic pruning by microglia is necessary for normal brain development. Science. 2011; 333(6048):1456-8. DOI: 10.1126/science.1202529. View