Prenatal SSRI Exposure Associated With Fetal Neurodevelopmental Changes

Prenatal selective serotonin reuptake inhibitor (SSRI) exposure has an appreciable effect on fetal brain development, particularly in regions crucial to emotional processing, according to findings published in JAMA Pediatrics.

Researchers conducted a cohort study with 98 infants: 16 with in utero SSRI exposure, 21 with in utero untreated prenatal maternal depression (PMD) exposure, and 61 healthy controls. Gray matter volume estimates were ascertained using structural magnetic resonance imaging (MRI) with voxel-based morphometry; white matter structural connectivity was assessed using diffusion MRI with probalistic tractography. Of the infant dyads, 46 (47%) were boys, 52 (53%) were girls; the mean (standard deviation) age at time of MRI scan was 3.43 (1.50) weeks.

Compared with the PMD and healthy control groups, SSRI-exposed infants showed significant gray matter volume expansion in the right amygdala (Cohen d =.65; 95% CI, 0.06-1.23) and right insula (Cohen d =.86; 95% CI, 0.26-1.14), as well as in the right superior frontal gyrus and the left occipital gyrus (whole-brain corrected P <.05). Compared with the PMD group alone, SSRI-exposed infants showed a significant increase in volume in the right amygdala, right insula, right superior frontal gyrus, and right precuneus (whole-brain corrected P <.05). Compared with healthy control infants alone, SSRI-exposed infants showed a significant increase in volume in the right amygdala, right insula, and right caudate. No gray matter intensity decreases were detected in any region for the SSRI-exposed group (whole-brain corrected P <.05).

The SSRI group also demonstrated a significant increase in white matter structural connectivity between the right amygdala and the right insula (Cohen d =.99; 95% CI, 0.40-1.57) compared with healthy controls and PMD infants (P <.001). Per linear regression of the structural connectome, SSRI-exposed infants also demonstrated an increase in connectivity compared with SSRI-unexposed infants in 4 connections: right amygdala-right insula, left anterior cingulated cortex-left thalamus, right precentral gyrus-right cuneus, and left insula-right precuneus (P <.05). However, network-based statistical analyses showed no significant between-group differences, suggesting similar connectome topology across participants.

These data indicate a potential association between prenatal SSRI exposure and the development of the fetal amygdala-insula circuit, possibly by means of anomalous serotonin signaling. Researchers suggested future randomized, placebo-controlled human studies to affirm the validity of these findings. Such information could potentially inform and improve treatment strategies for psychiatric disorders during pregnancy.

Reference

Lugo-Candelas C, Cha J, Hong S, et al. Associations between brain structure and connectivity in infants and exposure to selective serotonin reuptake inhibitors during pregnancy [published online April 9, 2018]. JAMA Pediatrics. doi:10.1001/jamapediatrics.2017.5227