Hub distribution of the brain functional networks of newborns prenatally exposed to maternal depression and SSRI antidepressants

Abstract

Background: Prenatal maternal depression (PMD) and selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with increased developmental risk in infants. Reports suggest that PMD is associated with hyperconnectivity of the insula and the amygdala, while SSRI exposure is associated with hyperconnectivity of the auditory network in the infant brain. However, associations between functional brain organization and PMD and/or SSRI exposure are not well understood. Methods:We examined the relation between PMD or SSRI exposure and neonatal brain functional organization. Infants of control (n = 17), depressed SSRI-treated (n = 20) and depressed-only (HAM-D ≥ 8) (n = 16) women, underwent resting-state functional magnetic resonance imaging at postnatal Day 6. At 6 months, temperament was assessed using Infant Behavioral Questionnaire (IBQ). We applied GTA and partial least square regression (PLSR) to the resting-state time series to assess group differences in modularity, and connector and provincial hubs.Results: Modularity was similar across all groups. The depressed-only group showed higher connector hub values in the left anterior cingulate, insula, and caudate as well as higher provincial hub values in the amygdala compared to the control group. The SSRI group showed higher provincial hub values in Heschl's gyrus relative to the depressed-only group. PLSR showed that newborns' hub values predicted 10% of the variability in infant temperament at 6 months, suggesting different developmental patterns between groups.Conclusions: Prenatal exposures to maternal depression and SSRIs have differential impacts on neonatal functional brain organization. Hub values at 6 days predict variance in temperament between infant groups at 6 months of age. K E Y W O R D Sdepression, fMRI, infant, prenatal exposure, SSRIs

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

“…As discussed below, gestational SSRI exposure seems to be able to mitigate some of the developmental effects of prenatal stress. It is, however, also able to alter developmental mechanisms and behaviors without counteracting prenatal stress; similar to the human study of Rotem-Kohave et al [145]. That both gestational SSRI exposure and prenatal stress can influence brain development independent of each other is also highlighted in another review focusing specifically on hippocampal plasticity [203].…”

“…Hub values of these regions in neonates of SSRI-depressed mothers did not differ from neonates of healthy mothers. These findings may suggest that SSRIs normalize the depression-induced alterations during brain development [145]. Consequently, both maternal depression and prenatal SSRI-exposure might have overlapping underlying mechanisms, which potentially involves the fetal 5-HT system.…”

“…Indeed, infants prenatally exposed to SSRIs have increased volumes of, and connectivity between, the amygdala and insular cortex [185]. Children prenatally exposed to SSRIs further displayed an increase in connectivity in the right medial frontal orbital gyrus [145]. Moreover, a recent study revealed that newborns prenatally exposed to SSRIs exhibited white matter changes in the basal ganglia and thalamus [186].…”

Serotonin-related rodent models of early-life exposure relevant for neurodevelopmental vulnerability to psychiatric disorders

“…A critical point to be considered when analyzing the risk of exposure to SSRIs in pregnant women is the psychopathological state of the future mother. Evidence indicates that SSRI treatment in depressed mothers can prevent the modifications in brain’s connectivity produced in newborns that are exposed to unmedicated depressive mothers 211 . In addition, other studies have shown that adverse effects produced by prenatal maternal depression on infant’s problematic temperament can be amplified by a concurrent prenatal traumatic stress 212 .…”

Perinatal exposure to fluoxetine and maternal adversity affect myelin-related gene expression and epigenetic regulation in the corticolimbic circuit of juvenile rats

“…Several studies report sex differences 30 , with girls showing stronger associations of prenatal exposure to depressive symptoms with functional connectivity in emotion-regulation networks 31 , right amygdala volume 32 , and cortical thickness 33 than boys. Overall, prenatal exposure to SSRIs and maternal depression affect the developing brain in overlapping-but potentially also in distinct brain regions 34 , with a key role for corticolimbic structures such as the prefrontal cortex and the amygdala 25,35,36 .…”