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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Psychiatry | doi: 10.3389/fpsyt.2019.00675

Autism spectrum disorders and perinatal complications - is oxidative stress the connection?

 Vanja Mandic-Maravic1, 2, Marija Mitkovic-Voncina1, 2, Marija Pljesa-Ercegovac2, 3, Ana Savic-Radojevic2, 3, Miroslav Djordjevic2, 4,  Tatjana Pekmezovic2, 5,  Roberto Grujicic1,  Marko Ercegovac2, 6, Tatjana Simic2, 3, Dusica Lecic-Tosevski1, 7 and  Milica Pejovic-Milovancevic1, 2*
  • 1Institute of Mental Health (Belgrade), Serbia
  • 2Faculty of Medicine, University of Belgrade, Serbia
  • 3Other, Serbia
  • 4University Children's Hospital, Belgrade, Serbia
  • 5Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Serbia
  • 6Neurology clinic, Clinical Center of Serbia, Serbia
  • 7Serbian Academy of Sciences and Arts (SASA), Serbia

Background: Autism spectrum disorders (ASD) are complex psychiatric disorders, with gene environment interaction being in the basis of their etiology. The association of perinatal complications and ASD is well established. Recent findings suggested that oxidative stress and polymorphism in genes encoding antioxidant enzymes might be involved in the development of ASD. Glutathione transferases (GSTs) have an important role in the antioxidant defense system. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms. Methods: The study included 113 ASD cases and 114 age and sex group-matched healthy controls. All participants were genotyped for GSTA1, GSTM1, GSTT1 and GSTP1 polymorphisms. The questionnaire regarding prenatal and perinatal risk factors and complications was administered for all the subjects in the study. Results: The evaluated perinatal complications as a group significantly increased the risk of ASD (OR=9.415; p=0.000), as well as individual perinatal complications, such as prematurity (OR=11.42; p=0.001), neonatal jaundice (OR=8.774; p=0.000), respiratory distress syndrome (OR=4.835; p=0.047) and the use of any medication during pregnancy (OR=2.413; p=0.03). In logistic regression model, adding GST genotypes did not modify the significant effects found for prematurity and neonatal jaundice as risk factors in ASD. However, there was a significant interaction of GST genotype with medication use during pregnancy and the use of tocolytics during pregnancy, which was predictive of ASD risk only in carriers of GSTM1-null, as opposed to carriers of GSTM1-active genotype. Conclusion: Specific perinatal complications may be significant risk factors for ASD. GSTM1 genotype may serve as a moderator of the effect of some prenatal factors on the risk of ASD such as using medication during pregnancy. It may be speculated that different oxidative stress-related genetic and environmental factors could lead to development of ASD. Apart from etiological mechanisms, possible therapeutic implications in ASD are also discussed.

Keywords: autism, Perinatal complications, Oxidative Stress, GST (glutathione S transferase), prematurity

Received: 07 Mar 2019; Accepted: 21 Aug 2019.

Copyright: © 2019 Mandic-Maravic, Mitkovic-Voncina, Pljesa-Ercegovac, Savic-Radojevic, Djordjevic, Pekmezovic, Grujicic, Ercegovac, Simic, Lecic-Tosevski and Pejovic-Milovancevic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Milica Pejovic-Milovancevic, Institute of Mental Health (Belgrade), Belgrade, Serbia,