Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

Bourke, Chase H.; Stowe, Zachary N.; Owens, Michael J.

doi:10.1124/pr.111.005207

Cited by 33 publications

(32 citation statements)

References 307 publications

(326 reference statements)

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“…Alterations to 5-HT systems following prenatal exposure to antidepressants have been reported previously (Cabrera-Vera and Battaglia, 1998; Bourke et al, 2014). In the current study, the effect of escitalopram was specific to the inhibitory, G i -coupled 5-Ht 1a receptor, as no effect of prenatal escitalopram was observed on expression of the excitatory, G s -coupled 5-Ht 7 .…”

Section: Discussionsupporting

confidence: 67%

“…While prenatal exposure to antidepressants has been investigated for possible links to cardiovascular malformations (Malm, 2012), hypertension (Grigoriadis et al, 2014), and autism spectrum disorders (Sørensen et al, 2013), little risk has been documented (Bourke et al, 2014). The changes reported here in terms of serotonin receptor expression are transient as they were not noted in adulthood.…”

Section: Discussionmentioning

confidence: 99%

“…Depression affects approximately 11% of expectant mothers (Gaynes et al, 2005) and a disproportionate percentage of women in the general population (Mitchell et al, 2011; Parker and Brotchie, 2010). Despite these findings, few preclinical studies have documented the impact of clinically relevant in utero antidepressant exposure on offspring, and fewer have studied the impact on female offspring (Bourke et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

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Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

Ehrlich¹,

Neigh

Bourke³

et al. 2015

Neuropharmacology

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Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

Ehrlich¹,

Neigh

Bourke³

et al. 2015

Neuropharmacology

Self Cite

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“…Alternatively, antidepressants could have affected the outcomes separately from the effect of severe depression. For example, selective serotonin reuptake inhibitors, the most frequently prescribed class of antidepressant, that prevent serotonin uptake into the presynaptic neuron and consequently, alter body functions such as cardiovascular and respiratory functions and arousal may have led to severe neonatal morbidity in the treated group . Both mechanisms may function to differing degrees in different women.…”

Section: Commentmentioning

confidence: 99%

“…Most of the previous studies examined perinatal outcomes in a group of women exposed to antidepressants compared to a group of women with no depression or a group of women who were not exposed to antidepressants. [14][15][16][17][18][20][21][22] This type of analysis is problematic, as the underlying condition itself (depression) independently increases the risk of adverse pregnancy outcomes. Furthermore, history of depression, pre-conception antidepressant use, and adherence to antidepressants during pregnancy, which are linked to perinatal outcomes, may also influence the risk of adverse outcomes associated with antidepressant use during pregnancy.…”

Section: Backg Rou N Dmentioning

confidence: 99%

Risk of adverse perinatal outcomes among women with pharmacologically treated and untreated depression during pregnancy: A retrospective cohort study

Adhikari

Patten

Lee

et al. 2019

Paediatric Perinatal Epid

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Background The association between antidepressant use during pregnancy and adverse perinatal outcomes is unclear. The association without taking into consideration the independent effect of depression leads to a confounding of the effects of antidepressants with those of the underlying reason for the use of those medications. Additionally, a history of depression and antidepressant use may also influence this association. Objective This study examined the risks of adverse perinatal outcomes associated with antidepressant use during pregnancy. Methods This retrospective cohort study used population‐based data in Alberta, Canada, for women who delivered between 2012 and 2015 (n = 158486). Women with depression were identified using a validated case definition, and the receipt of antidepressants was identified using Anatomical Therapeutic Chemical codes. Adverse perinatal outcomes such as severe maternal/neonatal morbidity, preterm birth, and neonatal intensive care unit admission were assessed. Multivariable log‐binomial regression was used to estimate the risk of adverse perinatal outcomes associated with antidepressants, adjusting for age and parity. Results In total, 9.1% women had depression and 2.5% women received antidepressants during pregnancy. The relative risk of severe neonatal morbidity/mortality was 1.25 (95% confidence interval 1.17, 1.33) times higher for women with depression alone compared to women without depression. The risk of severe neonatal morbidity/mortality was 1.51 (95% confidence interval 1.36, 1.66) times higher for women who used antidepressants compared to women with depression alone—however, the risk differed between the women with and without a history of antidepressant use. A similar risk pattern was observed for preterm birth and neonatal intensive care unit admission. Conclusions Both depression and antidepressant use were independently associated with the risk of adverse perinatal outcomes; however, the risk associated with antidepressants was higher over and above the risk associated with depression. This may reflect the biological effects of antidepressants, greater severity of depression in those treated, or both.

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Placental Transport and Metabolism: Implications for the Developmental Effects of Selective Serotonin Reuptake Inhibitors (SSRI) Antidepressants

Velasquez

Bonnin

2016

Neuromethods

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Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

Cited by 33 publications

References 307 publications

Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

Risk of adverse perinatal outcomes among women with pharmacologically treated and untreated depression during pregnancy: A retrospective cohort study

Placental Transport and Metabolism: Implications for the Developmental Effects of Selective Serotonin Reuptake Inhibitors (SSRI) Antidepressants

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