Antenatal exposure to antidepressants is associated with altered brain development in very preterm-born neonates

Podrebarac, Samantha K.; Duerden, Emma G.; Chau, Vann; Grunau, Ruth E.; Synnes, Anne; Oberlander, Tim F.; Miller, Steven P.

doi:10.1016/j.neuroscience.2016.11.025

Cited by 31 publications

(22 citation statements)

References 95 publications

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“…Reelin is a glycoprotein which plays a critical role in neuronal migration and positioning during neurodevelopment, again suggesting effects of SSRI exposure on the brain of developing offspring. Recent imaging data has confirmed that prenatal SSRIs do indeed alter the developing brain, with prenatal SSRIs decreasing activity in the basal ganglia and thalamus of preterm neonates (Podrebarac et al, 2016). Reduced activity in key brain regions during infancy as a result of prenatal SSRIs may provide insight into how altered neural development plays a role in mediating behavior.…”

Section: Serotonin Ssris and Brain Developmentmentioning

confidence: 95%

Perinatal selective serotonin reuptake inhibitor medication (SSRI) effects on social behaviors, neurodevelopment and the epigenome

Gemmel

Bögi

Ragan

et al. 2018

Neuroscience & Biobehavioral Reviews

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Recent research has linked early life exposure to selective serotonin reuptake inhibitor medications (SSRIs) to modifications of social behaviors in children. Serotonin is a key regulator of neurodevelopment, social behaviors and mental health, and with the growing use of SSRIs to treat maternal affective disorders during the perinatal period, questions have been raised about the benefits and risks of perinatal SSRI exposure on the developing child. This review will highlight how perinatal SSRIs affect maternal care and neurodevelopmental outcomes related to social affiliative behaviors in offspring; such as play behaviors, social interactions, reproductive behaviors, and maternal care of the next generation. We will also review how early life exposure to SSRIs can alter related neurobiology, and the epigenome. Both clinical research and findings from animal models will be discussed. Understanding the impact of perinatal SSRIs on neurobehavioral outcomes will improve the health and well-being of subsequent generations.

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Section: Serotonin Ssris and Brain Developmentmentioning

confidence: 95%

Perinatal selective serotonin reuptake inhibitor medication (SSRI) effects on social behaviors, neurodevelopment and the epigenome

Gemmel

Bögi

Ragan

et al. 2018

Neuroscience & Biobehavioral Reviews

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“…Prenatal SSRIs decrease S100B, an astroglial-specific Ca2+-binding protein critical for cell growth and differentiation, and reelin, a glycoprotein critical for neuronal migration and positioning, in human neonates at birth (Brummelte et al, 2013;Pawluski et al, 2009). Recent imaging data has confirmed that prenatal SSRIs alter the developing brain, with prenatal SSRI exposure decreasing activity in the basal ganglia and thalamus of preterm neonates (Podrebarac et al, 2016). However, further work is needed to assess the effects of perinatal SSRIs on central markers of neurodevelopment.…”

Section: Introductionmentioning

confidence: 99%

Perinatal fluoxetine prevents the effect of pre-gestational maternal stress on 5-HT in the PFC, but maternal stress has enduring effects on mPFC synaptic structure in offspring

et al. 2018

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Maternal affective disorders are frequently treated with selective serotonin reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed these medications during pregnancy. Infant development depends on the early serotonergic environment, which is altered by perinatal SSRIs, raising concern about how these medications affect neural outcomes. While clinical and preclinical research suggests an impact of SSRIs on the developing brain, more research is needed to determine the effects on neuroplasticity, the serotonergic system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating behavior. The current work investigated the effects of the SSRI, fluoxetine, on the serotonergic system in the prefrontal cortex (PFC) during pre-adolescence, and changes to synaptic markers and glucocorticoid receptor density in the cingulate cortex (medial PFC) of pre-adolescent and adult Sprague-Dawley male and female rats. To model aspects of Perinatal Depression and maternal anxiety, pre-gestational maternal stress was used resulting in male and female offspring from 4 groups: 1) control, 2) perinatal fluoxetine exposed, 3) pre-gestational maternal stress exposed, and 4) pre-gestational maternal stress + fluoxetine. Perinatal fluoxetine prevented the effects of maternal stress on 5-HT levels and 5-HT turnover ratio in the PFC of pre-adolescent offspring, particularly in females. However, pre-gestational stress reduced synaptophysin and PSD-95 densities in the cingulate cortex, effects that were more pronounced in males. Interestingly, perinatal fluoxetine exposure reduced GR density in adult males in this same brain area. Together, results show differential effects of perinatal SSRIs and pre-gestational maternal stress on neurodevelopment in the PFC of males and females.

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“…Associations between prenatal SSRI exposure and brain function and structure during early infancy are also emerging (Jha et al, 2016;Lugo-Candelas et al, 2018;Podrebarac et al, 2017). Lugo-Candelas et al (2018) reported that infants exposed to SSRIs in utero had concomitant increases in amygdala and insula volume correlated with increases in white-matter connectivity relative to infants of untreated depressed mothers and control infants (Lugo-Candelas et al, 2018).…”

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confidence: 99%

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

Rotem-Kohavi

Williams²,

Müller

et al. 2019

Depress Anxiety

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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

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Antenatal exposure to antidepressants is associated with altered brain development in very preterm-born neonates

Cited by 31 publications

References 95 publications

Perinatal selective serotonin reuptake inhibitor medication (SSRI) effects on social behaviors, neurodevelopment and the epigenome

Perinatal selective serotonin reuptake inhibitor medication (SSRI) effects on social behaviors, neurodevelopment and the epigenome

Perinatal fluoxetine prevents the effect of pre-gestational maternal stress on 5-HT in the PFC, but maternal stress has enduring effects on mPFC synaptic structure in offspring

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

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