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Original Investigation
June 2018

Associations Between Brain Structure and Connectivity in Infants and Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy

Author Affiliations
  • 1Department of Psychiatry, Columbia University Medical Center, New York, New York
  • 2New York State Psychiatric Institute, New York
  • 3Sackler Institute for Developmental Psychobiology, Columbia University Medical Center, New York, New York
  • 4Department of Pediatrics, Keck School of Medicine, Los Angeles, California
  • 5Department of Psychiatry, Institute for the Developing Mind, Los Angeles, California
JAMA Pediatr. 2018;172(6):525-533. doi:10.1001/jamapediatrics.2017.5227
Key Points

Question  Is prenatal exposure to selective serotonin reuptake inhibitors associated with fetal brain development?

Findings  In this cohort study including 98 infants, significant gray matter volume expansion was noted in the amygdala and insula, as well as an increase in white matter structural connectivity between these same regions in selective serotonin reuptake inhibitor–exposed infants, compared with infants exposed to untreated prenatal maternal depression and healthy controls.

Meaning  In line with prior animal studies, these multimodal brain imaging findings suggest that prenatal selective serotonin reuptake inhibitor exposure has a significant association with fetal brain development.


Importance  Selective serotonin reuptake inhibitor (SSRI) use among pregnant women is increasing, yet the association between prenatal SSRI exposure and fetal neurodevelopment is poorly understood. Animal studies show that perinatal SSRI exposure alters limbic circuitry and produces anxiety and depressive-like behaviors after adolescence, but literature on prenatal SSRI exposure in humans is limited and mixed.

Objective  To examine associations between prenatal SSRI exposure and brain development using structural and diffusion magnetic resonance imaging (MRI).

Design, Setting, and Participants  A cohort study conducted at Columbia University Medical Center and New York State Psychiatric Institute included 98 infants: 16 with in utero SSRI exposure, 21 with in utero untreated maternal depression exposure, and 61 healthy controls. Data were collected between January 6, 2011, and October 25, 2016.

Exposures  Selective serotonin reuptake inhibitors and untreated maternal depression.

Main Outcomes and Measures  Gray matter volume estimates using structural MRI with voxel-based morphometry and white matter structural connectivity (connectome) using diffusion MRI with probabilistic tractography.

Results  The sample included 98 mother (31 [32%] white, 26 [27%] Hispanic/Latina, 26 [27%] black/African American, 15 [15%] other) and infant (46 [47%] boys, 52 [53%] girls) dyads. Mean (SD) age of the infants at the time of the scan was 3.43 (1.50) weeks. Voxel-based morphometry showed significant gray matter volume expansion in the right amygdala (Cohen d = 0.65; 95% CI, 0.06-1.23) and right insula (Cohen d = 0.86; 95% CI, 0.26-1.14) in SSRI-exposed infants compared with both healthy controls and infants exposed to untreated maternal depression (P < .05; whole-brain correction). In connectome-level analysis of white matter structural connectivity, the SSRI group showed a significant increase in connectivity between the right amygdala and the right insula with a large effect size (Cohen d = 0.99; 95% CI, 0.40-1.57) compared with healthy controls and untreated depression (P < .05; whole connectome correction).

Conclusions and Relevance  Our findings suggest that prenatal SSRI exposure has an association with fetal brain development, particularly in brain regions critical to emotional processing. The study highlights the need for further research on the potential long-term behavioral and psychological outcomes of these neurodevelopmental changes.