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Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure
Kayleigh S J Campbell1,2, Lynne J Williams1, Bruce H Bjornson1,3
1BC Children's Hospital Research Institute, Vancouver, Canada.
Insights
Prenatal exposure to antidepressants like SSRIs may impact infant brain development. This study found sex-specific effects on white matter microstructure in the corpus callosum of neonates exposed to SSRIs.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) may affect white matter (WM) development.
- Previous studies indicate microstructural alterations and reduced connectivity in SSRI-exposed infants.
- Rodent studies show sex-specific disruptions in corpus callosum (CC) axon architecture after perinatal SSRI exposure.
Purpose of the Study:
- To investigate if prenatal SSRI exposure has sex-specific effects on early WM microstructure in human neonates.
- To examine the corpus callosum (CC) as a region of interest for these effects.
Main Methods:
- Diffusion tensor imaging (DTI) was used on postnatal day 7 in SSRI-exposed (n=24) and nonexposed (n=48) neonates.
- Fractional anisotropy (FA) was extracted from CC voxels.
- Multivariate discriminant analysis identified patterns differentiating groups by SSRI exposure and sex.
Main Results:
- Localized variations in CC fractional anisotropy significantly discriminated between neonate groups, with 82% prediction accuracy.
- Observed effects included sex differences in SSRI-exposed neonates (genu, splenium).
- SSRI-related effects independent of sex were found in the genu-to-rostral body, and sex differences were noted in nonexposed neonates (isthmus-splenium, posterior midbody).
Conclusions:
- Prenatal SSRI exposure may lead to sex-specific, localized developmental sensitivities in CC microstructure.
- These findings highlight the potential for differential impacts of SSRIs on brain development based on sex.
Abstract:
Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may influence white matter (WM) development, as previous studies report widespread microstructural alterations and reduced interhemispheric connectivity in SSRI-exposed infants. In rodents, perinatal SSRIs had sex-specific disruptions in corpus callosum (CC) axon architecture and connectivity; yet it is unknown whether SSRI-related brain outcomes in humans are sex specific. In this study, the neonate CC was selected as a region-of-interest to investigate whether prenatal SSRI exposure has sex-specific effects on early WM microstructure. On postnatal day 7, diffusion tensor imaging was used to assess WM microstructure in SSRI-exposed (n = 24; 12 male) and nonexposed (n = 48; 28 male) term-born neonates. Fractional anisotropy was extracted from CC voxels and a multivariate discriminant analysis was used to identify latent patterns differing between neonates grouped by SSRI-exposure and sex. Analysis revealed localized variations in CC fractional anisotropy that significantly discriminated neonate groups and correctly predicted group membership with an 82% accuracy. Such effects were identified across three dimensions, representing sex differences in SSRI-exposed neonates (genu, splenium), SSRI-related effects independent of sex (genu-to-rostral body), and sex differences in nonexposed neonates (isthmus-splenium, posterior midbody). Our findings suggest that CC microstructure may have a sex-specific, localized, developmental sensitivity to prenatal SSRI exposure.
