Prenatal antidepressant exposure is associated with in utero changes in cortical thickness in the fetal brain

Approximately 1 in 8 perinatal women have major mood disorders, most commonly major depressive disorder, which is often comorbid with anxiety disorders. Despite well-established risks of untreated mood disorders, many women choose to forgo antidepressant treatment due to concern about effects on the developing fetus, despite unclear evidence of its impact. We examined the association between prenatal maternal antidepressant use and fetal brain cortical thickness.

Retrospective analyses of a cohort of prospectively recruited maternal-fetal pairs that underwent fetal MRI were used to assess the impact of antidepressant exposure. Cortical thickness was measured for 96 structural fetal MRI scans, 48 with and 48 without antidepressant exposure across 82 brain regions at mean gestational ages of 31.0 ± 4.2 and 30.9 ± 4.9 weeks. Using linear mixed effect models, controlling for gestational age at scan, global cortical thickness, and repeat scans, we tested differences between antidepressant exposed and unexposed fetuses. Subsequently, models were repeated with the inclusion of maternal stress to assess its impact on the associations.

Following multiple comparison correction, 11 regions exhibited significant differences between the two groups. Exposed fetuses showed greater cortical thickness in the bilateral superior orbital gyri (p = 0.001) and superior temporal poles (p = 0.002) as well as the right middle (p = 0.001) and inferior (p = 0.004) orbital gyri and right parahippocampal gyrus (p < 0.001). The unexposed infants showed greater cortical thickness in the left postcentral (p < 0.001), angular (p = 0.004), and inferior parietal (p = 0.003) gyri and the right middle cingulate gyrus (p = 0.003). Once maternal stress was accounted for, however, there was significant attenuation of the relationship between exposure and cortical thickness.

In utero exposure to antidepressant medications are associated with changes in cortical thickness in limbic, paralimbic, and sensorimotor regions. Our findings mirror prior work suggesting that antidepressant exposure is associated with increases in structural development of limbic and paralimbic regions observed in those exposed later in life. However, attenuation of findings stemming from the inclusion of maternal stress suggests a more complex relationship between maternal psychopathology, antidepressant use, and fetal development that requires further examination.