Maternal immune activation during pregnancy is associated with more difficulties in socio-adaptive behaviors in autism spectrum disorders.

Author:

Ellul Pierre1,Maruani Anna1,Vantalon Valérie1,Humeau Elise1,Amestoy Anouck2,Anchordoqui Andrea2,Atzori Paola3,Baleyte Jean-Marc4,Benmansour Safiyah4,Bonnot Olivier5,Bouvard Manuel2,Cartigny Ariane1,Coulon Nathalie6,Coutelle Romain7,Fonseca David Da3,Demily Caroline6,Givaudan Marion3,Gollier-Briant Fanny5,Guénolé Fabian8,Koch Andrea1,Leboyer Marion4,Lefebvre Aline1,Lejuste Florian4,Levy Charlotte2,Mendes Eugénie1,Robert Natalia6,Schroder Carmen M7,Speranza Mario6,Zante Elodie6,Peyre Hugo1,Rosenzwajg Michelle9,Klatzmann David9,tchitchek nicolas9,DELORME Richard1

Affiliation:

1. University of Paris Cité

2. Centre Hospitalier Charles-Perrens, Pôle Universitaire de Psychiatrie de L'enfant Et de L'adolescent

3. Salvator University Hospital, Public Assistance-Marseille Hospitals, Aix- Marseille University

4. Univ Paris Est Créteil, INSERM, IMRB, AP-HP, FHU ADAPT

5. CHU & Universite de Nantes

6. Fondation FondaMental

7. Centre Expert TSA-SDI, Université de Strasbourg, Centre Hospitalier de Versailles. UMR1018, Université Paris Saclay, Pasteur Insitute Paris

8. CHU de Caen, Caen Normandy University

9. INSERM U959, Sorbonne University

Abstract

Abstract Background Autism spectrum disorders (ASD) are neurodevelopmental disorders characterised by deficits in social communication or interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person's competencies and reflect specifically in autism, their strengths and difficulties. Methods In this study, we hypothesised that individual with ASD with a history of MIA (MIA+) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used a supervised and unsupervised statistical approach. Results We included 295 mother-child dyads with 14% of them with MIA+. We found that ASD-MIA+ individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA+ directly influenced individual's socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA+ may affected persistently the socio-adaptive behavioral trajectories of individuals with ASD. Limitations The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results Conclusions Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA+ individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of autism and for the development of specific immunomodulatory strategies.

Publisher

Research Square Platform LLC

Reference28 articles.

1. Autism spectrum disorder;Lord C;Nat Rev Dis Primers,2020

2. Maternal immune activation and neuroinflammation in human neurodevelopmental disorders;Han VX;Nat Rev Neurol,2021

3. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring;Choi GB;Science,2016

4. From the genetic architecture to synaptic plasticity in autism spectrum disorder;Bourgeron T;Nat Rev Neurosci,2015

5. Adaptive Behavior [Internet]. AAIDD_CMS. [cited 2022 Dec 15]. Available from: https://www.aaidd.org/intellectual-disability/definition/adaptive-behavior

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