Maternal Prenatal Depressive Symptoms and Fetal Amygdala-Cerebellum Functional Connectivity

Prenatal maternal depression (PMD) is a common public health concern, affecting up to 20% of pregnancies worldwide. Children exposed to PMD exhibit early self-regulatory and emotional difficulties, although its impact on the developing fetal brain remains largely unexplored. The amygdala and cerebellum are both implicated in emotion regulation and psychiatric vulnerability, are densely interconnected, and undergo rapid maturation in utero. Characterizing the relationship of PMD symptoms to amygdala-cerebellar connectivity before birth offers a unique opportunity to isolate in utero mechanisms of risk.

In a sample of 123 pregnant participants (61% male fetuses, n = 75), PMD symptoms were assessed between the second to third trimester using the Center for Epidemiologic Studies-Depression Scale. Fetuses underwent functional MRI, and region-to-voxel analyses examined amygdala-cerebellar functional connectivity. Statistical tests focused on an emerging hypothesis regarding fetal amygdala-cerebellar connectivity, while also addressing potential amygdala connectivity effects across the full fetal cerebrum.

Higher PMD symptoms were associated with significantly increased functional connectivity between the fetal amygdala and cerebellum. This effect remained significant following small volume correction within the cerebellum and after adjusting for covariates.

This is the first study to demonstrate altered amygdala-cerebellum connectivity in the human fetal brain in relation to prenatal maternal depression. These findings extend models of prenatal programming by addressing the earliest stages of human brain development and by highlighting the cerebellum's role in emotional network development. Enhanced amygdala-cerebellar coupling in utero may represent an early neural marker of risk for later emotional dysregulation.