Pregnancy-Related Inflammation May Increase Offspring's Anxiety Risk

Recent research from Weill Cornell Medicine highlights how inflammation during pregnancy could influence the long-term mental health of the offspring. The study focuses on the role of maternal infection or stress that triggers an inflammatory response, which can have lasting effects on brain development. Specifically, the researchers examined a brain region known as the ventral dentate gyrus (vDG), part of the hippocampus involved in threat assessment.

Using a mouse model designed to mimic adverse immune activity during pregnancy, scientists observed that genetically normal offspring displayed anxiety-like behaviors such as avoiding open spaces and reacting intensely to stressful situations. These behavioral changes were linked to epigenetic modifications—chemical changes in DNA that regulate gene activity—particularly in neurons of the vDG.

Analyses revealed thousands of sites in the genome where DNA methylation—a key epigenetic marker—was altered, especially in regions controlling synaptic functions. These modifications led to a subset of neurons becoming hyperactive in response to threats, contributing to an exaggerated perception of danger. When exposed to stressful or threatening environments, these neurons exhibited heightened activity that occurred before any behavioral manifestation of anxiety, indicating a reprogramming of threat response circuits.

Further, real-time monitoring showed that in mice affected by prenatal adversity, neuronal activity ramped up prematurely when approaching risky situations, reinforcing the idea that these epigenetic changes prime individuals for heightened anxiety responses.

This pioneering study elucidates a clear mechanistic pathway linking prenatal inflammatory conditions to long-term behavioral outcomes. It underscores the importance of maternal health during pregnancy not only for physical development but also for shaping brain circuits linked to anxiety. Future research may explore whether similar epigenetic signatures can be detected in humans, potentially serving as early biomarkers for anxiety risk and guiding therapeutic interventions.