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.

中文翻译：

---

新生儿胼胝体微结构的产前抗抑郁药暴露与性别差异

产前暴露于选择性 5-羟色胺再摄取抑制剂 (SSRI) 抗抑郁药可能会影响白质 (WM) 的发育，因为先前的研究报告了暴露于 SSRI 的婴儿广泛的微观结构改变和大脑半球间连通性降低。在啮齿动物中，围产期 SSRIs 在胼胝体 (CC) 轴突结构和连接方面具有性别特异性破坏；但目前尚不清楚人类 SSRI 相关的大脑结果是否具有性别特异性。在这项研究中，新生儿 CC 被选为感兴趣的区域，以研究产前 SSRI 暴露是否对早期 WM 微观结构具有性别特异性影响。在出生后第 7 天，扩散张量成像用于评估 SSRI 暴露（n  = 24；12 名男性）和未暴露（n = 48; 28 名男性）足月新生儿。从 CC 体素中提取分数各向异性，并使用多变量判别分析来识别按 SSRI 暴露和性别分组的新生儿之间不同的潜在模式。分析揭示了 CC 分数各向异性的局部变化，可显着区分新生儿组并以 82% 的准确度正确预测组成员。这种影响在三个维度上确定，代表 SSRI 暴露新生儿的性别差异（膝部、压部）、与性别无关的 SSRI 相关影响（膝部到喙体）和未暴露新生儿的性别差异（峡部-脾部、后部）中间体）。我们的研究结果表明，CC 微观结构可能对产前 SSRI 暴露具有性别特异性的、局部的、发育敏感性。