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Associations Between Brain Structure and Connectivity in Infants and Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy.
Lugo-Candelas, Claudia PhD 1,2; Cha, Jiook PhD 1,2; Hong, Susie BS 1,2; Bastidas, Vanessa BS 1,2; Weissman, Myrna PhD 1,2,3; Fifer, William P. PhD 1,2,3; Myers, Michael PhD 1,2,3; Talati, Ardesheer PhD 1,2,3; Bansal, Ravi PhD 4,5; Peterson, Bradley S. MD 4,5; Monk, Catherine PhD 1,2,3; Gingrich, Jay A. MD; PhD 1,2,3; Posner, Jonathan MD 1,2,3
[Article] JAMA Pediatrics. 172(6):525-533, June 2018.

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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.