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Maternal adversity, inflammation, and neurodevelopment: how intergenerational processes perpetuate disadvantage in a low-resource setting

Grant number: 19/21612-0
Support type:Research Projects - Thematic Grants
Duration: February 01, 2020 - January 31, 2025
Field of knowledge:Health Sciences - Medicine - Psychiatry
Cooperation agreement: National Institutes of Health (NIH)
Principal researcher:Andrea Parolin Jackowski
Grantee:Andrea Parolin Jackowski
Principal researcher abroad: Cristiane Seixas Duarte
Institution abroad: Columbia University in the City of New York, United States
Principal researcher abroad: Jonathan Posner
Institution abroad: Columbia University in the City of New York, United States
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Principal researchers:Ivaldo da Silva ; Síntia Iole Nogueira Belangero
Assoc. researchers: Ana Carolina Coelho Milani ; Andrea de Abreu Feijó de Mello ; Nitamar Abdala
Associated scholarship(s):21/03943-0 - Adverse experiences and family functioning in childhood in a population of pregnant women from basic health units (UBS) in Guarulhos - São Paulo, BP.TT
21/04819-0 - The intergerational impact of maternal exposure to childhood adversities on child cerebral development: regulation and functioning of the hpa axis as a resilience marker, BP.PD
20/15286-0 - The possible association between maternal early life adversities, cortisol levels and the sex of the neonate, BP.IC
+ associated scholarships 20/15407-2 - Types of adverse experiences in childhood most frequent in a population of pregnant women using a Basic health Unit (UBS) in Guarulhos - São Paulo, BP.TT
20/13568-9 - Introduction to scientific research: training on molecular techniques and their application, BP.TT
20/15046-0 - The impact of the early life maternal exposure to adversities on the offspring brain development, BP.IC
20/11246-4 - The frequency of adverse childhood experiences in a population of pregnant women from a basic health unit (UBS) in Guarulhos - São Paulo, BP.TT - associated scholarships

Abstract

Adverse childhood experiences (ACEs) - which includes physical/sexual abuse, neglect or parental mental illness - confer risk for psychiatric dysfunction not only to those directly exposed, but also to the next generation. However, mechanisms underlying these ACE-related intergenerational effects are unclear, significantly limiting a unique prevention opportunity. Our study aims to examine mechanisms by which maternal ACEs influence offspring neurodevelopment, with special focus on prenatal inflammation. Toward this end, we will enroll, in the Brazilian Universal Health Care system (SUS), pregnant women with (n=290) and without (n=290) a history of substantial ACEs and follow their offspring over the first two years of life focused on the neurodevelopment of cognitive control, a cornerstone in the future development of impulsive behaviors. First, we will start by testing associations between maternal ACEs and offspring brain-behavior development using infant MRI and behavioral assessments of cognitive control at 12 and 24 months. Second, we will examine mechanisms underlying these associations, focusing on the role of prenatal inflammation and the placenta using techniques to examine DNA epigenetics and RNA sequencing, while also taking into account genetic influences. As suggested by preclinical research, we hypothesize differential effects of prenatal inflammation in male vs. female pregnancies. In addition, we will explore modifiable post-natal factors and their influence on offspring neurodevelopment, monitoring parental depressive/mood symptoms and conducting two in-home assessments of the family. Revealing mechanisms of intergenerational transmission of adversity, our study will set the stage for high-impact preventive research. We will establish research infrastructure within a Sao Paulo primary care clinic network in a high-risk, low-resource community where preventive effects can have their most substantial impact. (AU)