Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

Gobinath, Aarthi R.; Workman, Joanna L.; Chow, Carmen; Lieblich, Stephanie E.; Galea, Liisa A.M.

doi:10.1016/j.neuropharm.2015.09.001

Cited by 64 publications

(60 citation statements)

References 96 publications

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“…2a, b). In our prior study [12] we observed that maternal postpartum CORT, regardless of FLX, decreased density of dorsal DCX-expressing cells in female offspring, and an a priori comparison revealed the same result in this dataset ( p = 0.019, Cohen’s d = 0.91). Maternal postpartum CORT significantly increased the density of DCX-expressing cells in the ventral hippocampus of adolescent males compared with oil ( p = 0.003, Cohen’s d = 1.35; Fig.…”

Section: Resultssupporting

confidence: 69%

“…However, maternal SSRI use has been linked to delayed psychomotor development in infants [9], increased internalizing behavior in children (i.e., behaviors predisposing anxiety and depression; [10]), and a higher risk for autism spectrum disorders in children [11]. These findings may be consistent with preclinical findings from our laboratory that maternal postpartum fluoxetine (FLX) exposure increased anxiety-like behavior in young adult male offspring [12]. However, as in the clinical literature, preclinical research has yielded mixed results regarding maternal SSRI exposure on offspring outcome depending on whether a model of concurrent maternal depression was used, sex of the offspring studied, and age examined (reviewed in [13]).…”

Section: Introductionsupporting

confidence: 59%

“…However, this interaction between prenatal stress and postpartum FLX exposure did not persist to adulthood as maternal postpartum FLX decreased number of DCX-expressing cells in offspring also exposed to prenatal stress, particularly in the males [29]. We recently reported that FLX given to the dam during the postpartum period increased density of DCX-expressing cells in the dorsal hippocampus of adult male offspring but not in adult female offspring [12]. It remains unclear, however, whether maternal postpartum FLX, either alone or in combination with CORT alters hippocampal neurogenesis across development in a rodent model relevant to PPD.…”

Section: Introductionmentioning

confidence: 99%

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Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

et al. 2017

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BackgroundPostpartum depression affects approximately 15% of mothers and represents a form of early life adversity for developing offspring. Postpartum depression can be treated with prescription antidepressants like fluoxetine (FLX). However, FLX can remain active in breast milk, raising concerns about the consequences of neonatal FLX exposure. The hippocampus is highly sensitive to developmental stress, and males and females respond differently to stress at many endpoints, including hippocampal plasticity. However, it is unclear how developmental exposure to FLX alters the trajectory of hippocampal development. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum depression) and concurrent FLX on hippocampal neurogenesis in male and female offspring.MethodsFemale Sprague-Dawley rat dams were treated daily with either CORT or oil and FLX or saline from postpartum days 2–23. Offspring were perfused on postnatal day 31 (pre-adolescent), postnatal day 42 (adolescent), and postnatal day 69 (adult). Tissue was processed for doublecortin (DCX), an endogenous marker of immature neurons, in the dorsal and ventral hippocampus.ResultsMaternal postpartum CORT reduced density of DCX-expressing cells in the dorsal hippocampus of pre-adolescent males and increased it in adolescent males, suggesting that postpartum CORT exposure disrupted the typical progression of the density of DCX-expressing cells. Further, among offspring of oil-treated dams, pre-adolescent males had greater density of DCX-expressing cells than pre-adolescent females, and maternal postpartum CORT prevented this sex difference. In pre-adolescent females, maternal postpartum FLX decreased the density of DCX-expressing cells in the dorsal hippocampus compared to saline. As expected, maternal CORT reduced the density of DCX-expressing cells in adult female, but not male, offspring. The combination of maternal postpartum CORT/FLX diminished density of DCX-expressing cells in dorsal hippocampus regardless of sex or age.ConclusionsThese findings reveal how modeling treatment of postpartum depression with FLX alters hippocampal neurogenesis in developing offspring differently depending on sex, predominantly in the dorsal dentate gyrus and earlier in life.

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Section: Resultssupporting

confidence: 69%

Section: Introductionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

et al. 2017

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“…Although limited, the sex-specific differences of perinatal SSRIs and offspring weight reported by some studies [44,45,47,85,87,95,96] expand literature in serotonin knockout rats (5-HTT) which shows that disruption of 5-HTT homeostasis during critical periods of fetal development results in sex-specific alterations in body weight [13, [97][98][99][100][101]. For example, 5-HTT knockout female rats, who have high levels of serotonin throughout life, appear to be protected against late-onset obesity [100,101] and reduced weight, but higher abdominal fat [102].…”

Section: Animal Studiesmentioning

confidence: 99%

“…Gemmel et al report reduced weight in juvenile female offspring perinatally exposed to SSRIs, regardless of maternal stress [95]. One study showed that postnatal SSRIs in combination with administration of corticosterone postpartum to the dams decreased weight in male, but not female, rat offspring at adulthood [96]. Taken together, animal models are pointing to an effect of perinatal SSRIs on changes in weight.…”

Section: Animal Studiesmentioning

confidence: 99%

Perinatal selective serotonin reuptake inhibitor (SSRI) effects on body weight at birth and beyond: A review of animal and human studies

Hutchison

Mâsse

Pawluski

et al. 2018

Reproductive Toxicology

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. Perinatal selective serotonin reuptake inhibitor (SSRI) effects on body weight at birth and beyond A review of animal and human studies. Reproductive Toxicology, Elsevier, 2018, 77, pp.109-121. 10 Highlights  Our paper reviews our current understanding of the impact of prenatal SSRI exposure on weight and growth using both human and animal findings.  Our review extends the previously published review paper by Grzeskowiak and colleagues in Repro Tox in 2012 by including findings beyond infancy, the impact of maternal mood -pre and post natal, and given that the majority our 5HT is in the gastrointestinal (GI) system we speculate that altering 5HT signaling, via SSRI exposure might have an impact on GI function and later weight gain.  With recent advances in our understanding of the gut-brain axis and the role of 5HT, we raise critical questions about how weight and growth outcomes might be related to SSRI induced changes in the GI microbiome.  Our paper provides an updated review of the literature (e.g., Leuner et al 2014;Nezvalová-Henriksen et al., 2016), with a particular focus on weight related outcomes beyond birth, developmental aspects of SSRI exposure that might also impact weight and growth, as well as provides detailed suggestions for future research. AbstractThe long-term impact of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment during pregnancy and postpartum on offspring outcomes is still not clear. Specifically, perinatal SSRI exposure may have long-term consequences for body weight and related health outcomes in the newborn period and beyond. This review focuses on the impact of perinatal SSRI exposure on weight using human and animal findings. The impact of maternal mood is also explored. We propose potential mechanisms for weight changes, including how early alterations in serotonin signaling may have implications for weight via changes in metabolism and motor development.As the majority of serotonin is in the gastrointestinal (GI) system we also speculate that perinatal SSRI exposure might alter the brain-gut relationship, via the microbiome, leading to changes in feeding behavior and weight.

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Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure

Campbell

Williams

Björnson

et al. 2021

Developmental Psychobiology

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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.

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Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

Cited by 64 publications

References 96 publications

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

Perinatal selective serotonin reuptake inhibitor (SSRI) effects on body weight at birth and beyond: A review of animal and human studies

Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure

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