The impact of prenatal maternal infection and inflammation on human brain development and psychopathology during adolescence

Active Project Grant Awarded Last action

Award ID
R01MH124776
Recipient
Awarding agency
Obligated
$7,291,046

Award facts

Assistance listing
93.242 Mental Health Research Grants
Completion date 90% complete
Originally
Funding
  • $6,517,756.00 Federal
  • $773,290.00 Non-federal
Place of performance
New York, NY 10029, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Maternal immune activation (MIA) refers to the triggering of the maternal immune system during pregnancy by infections or chronic conditions. This leads to a series of immunologic alterations in the fetus, which can have an impact on brain development. Large-scale, population-based studies have implicated MIA in a number of neuropsychiatric disorders, including autism spectrum disorders, bipolar disorder and schizophrenia. Moreover, studies in rodents have consistently demonstrated that MIA during early phases of pregnancy leads to structural and functional brain abnormalities and behavioral dysfunction in the offspring. In humans, recent imaging studies reported similar effects of MIA on child brain structure and behavior. However, these studies were limited by modest sample sizes and relatively short follow-up periods. The overall aim of this study is to investigate the impact of maternal immune activation during pregnancy on adolescent neurodevelopment. We will use the only cohort in the world, generation r, with both sufficient sample size and longitudinal follow-up to combine (i) detailed information on infection and inflammation during pregnancy, with (II) offspring brain imaging and (III) behavioral and psychiatric outcomes. In aim 1A we will define our exposure variable maternal immune activation (MIA). We will use detailed trimester-specific information on infections and determine the type of infection, as well as severity. We will measure a panel of well-known pro- inflammatory markers (CRP, IL-1SS, IL-6, IL-8, TNF-a) to calculate an inflammatory index of chronic low-grade inflammation in serum at 13 and 20 weeks of gestation. In aim 1B we will investigate the association between MIA, fetal growth and gestational age at birth. In aim 2, we will investigate the impact of MIA on offspring brain structure and connectivity at age 14 years. To test the hypothesis that MIA leads to atypical cortical development, we will include MRI measures available and ready to use for 3,757 adolescents. These include total brain, white matter, cortical gray and subcortical volumes. In aim 3 we will determine whether MIA increases the risk for cognitive deficits, behavioral impairments and psychopathology also at age 14 years. This project will provide a comprehensive definition of maternal immune activation, including specific aspects of infection such as type and timing, examine its effects on neurodevelopment, and elucidate putative mechanisms for these effects in the largest birth cohort to date. Collectively, these outputs will suggest targets for prevention and aid the efforts towards early identification of high-risk pregnancies.

Transactions

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Original award $773,290 $773,290
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Subawards

Subrecipient Amount Awarded
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC) The Erasmus University Medical Center (EMC) team will participate actively in all three scientific aims of this proposal under the direction of Drs. White,… $143,589
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC) $697,982

Quick answers

Who received award R01MH124776?

R01MH124776 was awarded to Icahn School Of Medicine At Mount Sinai by National Institute of Mental Health (National Institutes of Health) on August 11, 2021.

How much is award R01MH124776 worth?

$7,291,046 has been obligated on R01MH124776: $6,517,756 in federal funding and $773,290 in non-federal funding.

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