Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study

Abstract

The aim of this propensity-matched cohort study was to evaluate the impact of prenatal SSRI exposure and a history of maternal depression on neonatal brain volumes and white matter microstructure. SSRI-exposed neonates (n=27) were matched to children of mothers with no history of depression or SSRI use (n=54). Additionally, neonates of mothers with a history of depression, but no prenatal SSRI exposure (n=41), were matched to children of mothers with no history of depression or SSRI use (n=82). Structural magnetic resonance imaging and diffusion weighted imaging scans were acquired with a 3T Siemens Allegra scanner. Global tissue volumes were characterized using an automatic, atlas-moderated expectation maximization segmentation tool. Local differences in gray matter volumes were examined using deformation-based morphometry. Quantitative tractography was performed using an adaptation of the UNC-Utah NA-MIC DTI framework. SSRI-exposed neonates exhibited widespread changes in white matter microstructure compared to matched controls. Children exposed to a history of maternal depression but no SSRIs showed no significant differences in brain development compared to matched controls. No significant differences were found in global or regional tissue volumes. Additional research is needed to clarify whether SSRIs directly alter white matter development or whether this relationship is mediated by depressive symptoms during pregnancy.

Keywords: Antidepressant; Depression; Diffusion tensor imaging; Fetal development; Infant, Newborn; Magnetic resonance imaging.

Figure 1

Sagittal view. 11 projection pathways (bilateral, left hemisphere segments not shown). CF-PFC, corticofugal prefrontal cortex; CF-PMC, corticofugal premotor cortex; CF-MC, corticofugal motor cortex; CF-PC, corticofugal parietal cortex; CT-PFC, corticothalamic prefrontal cortex; CT-PMC, corticothalamic premotor cortex; CT-MC, corticothalamic motor cortex; CT-PC, corticothalamic parietal cortex; OT, optic tract; ML, medial lemniscus. 7 callosal pathways. CC-OFC, corpus callosum: orbitofrontal cortex (rostrum); CC-PFC, corpus callosum: prefrontal cortex (genu); CC-PMC, corpus callosum: premotor cortex; CC-MC, corpus callosum: motor cortex; CC-PC, corpus callosum: parietal cortex; CC-OC, corpus callosum: occipital cortex (splenium); CC-TC, corpus callosum: temporal cortex (tapetum). 9 association pathways (bilateral, right hemisphere segments not shown). UNC, uncinate; AF-fp, Arcuate frontoparietal segment; AF-ft, Arcuate frontotemporal segment; AF-tp, Arcuate temporoparietal segment; SLF, superior longitudinal fasciculus; CCG, cingulum cingulate gyrus segment; CH, cingulum: hippocampal segment; IFOF, inferior fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus; Fx, fornix

Figure 2

Local differences in anisotropy and diffusivity along the corticofugal tracts. Beta plots show diffusion parameter values along the arc length of each fiber. Positive beta values correspond to higher diffusion or anisotropy in SSRI-exposed neonates and negative beta values correspond to lower diffusion or anisotropy in SSRI-exposed neonates. Colored circles indicate regions of significance post FDR correction. Significant points are also visualized on the fiber itself for each parameter. Magenta indicates significant positive beta values. Yellow indicates significant negative beta values. Black regions were not analyzed due to increased subject variability.

Figure 3

Local differences in anisotropy and diffusivity along the corticothalamic tracts. Beta plots show diffusion parameter values along the arc length of each fiber. Positive beta values correspond to higher diffusion or anisotropy in SSRI-exposed neonates and negative beta values correspond to lower diffusion or anisotropy in SSRI-exposed neonates. Colored circles indicate regions of significance post FDR correction. Significant points are also visualized on the fiber itself for each parameter. Magenta indicates significant positive beta values. Yellow indicates significant negative beta values. Black regions were not analyzed due to increased subject variability.