Maternal Breathing Dysfunction during Pregnancy Increases Risk for Psychiatric Disorders in Her Offspring: A Paradigm-Shifting Concept

Each year, over half a million women develop sleep disordered breathing (SDB) by the third trimester. SDB is characterized by recurrent partial or complete cessation of breathing during sleep causing pathologic drops in blood oxygen levels, often hundreds of times each night. SDB is a potent inflammatory stimulus, inducing chronic inflammation that, in turn, causes many illnesses in individuals with SDB. There is a growing scientific consensus that maternal inflammation increases susceptibility to autism, which raises a profound question: Is the recent explosion in autism related to the growing incidence of SDB during pregnancy?

How might SDB increase risk for ASD? Fetal brain immune cells, known as microglia, are essential partners in neurodevelopment because they prune excess and imprecise connections in the brain. Shortly after birth, an explosion of connections occurs as the newborn begins to interact with the environment; throughout early childhood, these are gradually trimmed down by microglia to adult levels. This process refines brain connections so that only the most meaningful remain, and superfluous or inefficient connections are removed. ASD is in part a disorder of too many connections, suggesting that normal microglial pruning is disrupted. Since a process known as epigenetics directly links the environment to cell function, we propose that maternal SDB initiates epigenetic alterations in microglia that suppress critical refinement of brain connections.

This project will determine if maternal SDB during pregnancy causes autism-like behavior in the offspring and identify associated epigenetic marks in microglia that impair their pruning activities. These studies will reveal new targets to enable early diagnosis and therapeutic intervention for neurodevelopmental disorders. Because maternal SDB also causes SDB in her offspring, it may also predispose to a multitude of other adult illnesses associated with SDB, including cancer, hypertension, diabetes, obesity, kidney disease, heart disease, stroke, and neurodegenerative disorders.

Principal Investigator

• Tracy Baker
  Associate Professor of Comparative Biosciences
  

Co-Principal Investigator

• Jyoti Watters
  Professor of Comparative Biosciences
  

Co-Investigators

• Michael Cahill
  Assistant Professor of Comparative Biosciences
• Avtar Roopra
  Associate Professor of Neuroscience
  

Collaborator

• Stephen Johnson
  Associate Professor of Comparative Biosciences