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Selective serotonin reuptake inhibitors (SSRIs) are the most popular antidepressant medications used to manage perinatal mood disturbances, yet our understanding of how they affect the microbiome‐gut‐brain axis of the mother and offspring is limited. The purpose of this study was to determine how peripartum SSRI treatment may prevent the effects of gestational stress on plasticity in the maternal hippocampus, plasticity in the neonatal brain and related changes in gut microbiota. To do this Sprague–Dawley female rats were left untreated or subjected to unpredictable stress during pregnancy. Half of the females were supplemented daily with fluoxetine. On postpartum day 2 brains were collected for measurement of plasticity (neurogenesis and microglia content) in the maternal hippocampus and in the neonatal brain. Glucocorticoid receptor density was also investigated in the maternal hippocampus. Microbiota composition was analyzed in fecal samples of dams during and after pregnancy, and colon tissue samples from offspring on postnatal day 2. Main findings show there are significant changes to the maternal microbiome‐gut‐brain axis that may be fundamental to mediating plasticity in the maternal hippocampus. In addition, there is significant impact of gestational stress on neonatal gut microbiota and brain microglia density, while the effects of SSRIs are limited. This is the first study to explore the impact of gestational stress and SSRIs on the microbiome‐gut‐brain axis in the mother and neonate. Findings from this study will help inform pathways to intervention strategies including stress reduction techniques and/or microbiota targeted nutritional approaches directed towards improving maternal gut health and outcomes for mother and neonate. [ABSTRACT FROM AUTHOR]

Depression during pregnancy affects 10–15% of women, and 5% of women take antidepressants during pregnancy. Clinical guidelines provide recommendations for selective serotonin reuptake inhibitor (SSRI) drug choice and dose based on CYP2D6 and CYP2C19 genotype; however, they are based on evidence from non-pregnant cohorts. This study aimed to test the hypothesis that women with function-altering variants (increased, decreased, or no function) in these pharmacogenes, taking SSRIs prenatally, would have more depression symptoms than women whose pharmacogenetic variants are associated with normal SSRI metabolism. Comprehensive CYP2D6 and CYP2C19 genotyping using a range of methods, including gene copy number analysis, was performed as secondary analyses on two longitudinal cohorts of pregnant women (N = 83) taking the SSRIs paroxetine, citalopram, escitalopram, or sertraline. The Kruskal–Wallis test compared mean depression scores across four predicted metabolizer groups: poor (n = 5), intermediate (n = 10), normal (n = 53), and ultrarapid (n = 15). There were no significant differences between mean depression scores across the four metabolizer groups (H(3) =.73, p =.87, eta-squared =.029, epsilon-squared =.0089). This is the first study of the relationship in pregnancy between CYP2C19 pharmacogenetic variations and depression symptoms in the context of SSRI use. Findings from this initial study do not support the clinical use of pharmacogenetic testing for SSRI use during the second or third trimesters of pregnancy, but these findings should be confirmed in larger cohorts. There is an urgent need for further research to clarify the utility of pharmacogenetic testing for pregnant women, especially as companies offering direct-to-consumer genetic testing expand their marketing efforts. [ABSTRACT FROM AUTHOR]

Background: Up to 20% of mothers experience antenatal depression and approximately 30% of these women are treated with serotonergic psychotropic pharmacological therapy during pregnancy. Serotonergic antidepressants readily cross the placenta and the fetal blood-brain barrier, altering central synaptic serotonin signaling and potentially altering serotonin levels in the developing fetal brain. Objective: The aim of this study is to assess the impact of prenatal exposure to serotonergic antidepressants, accounting for maternal mood disturbances, on markers of stress regulation during childhood. Methods: We will follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and will search MEDLINE, Embase, CINAHL, PsycINFO, and ClinicalTrials.gov for full-length studies that assessed physiological (eg, cortisol level, heart rate variability, salivary amylase, pupillary size, C-reactive protein) indices of stress regulation in children of pregnant people who were treated with a serotonergic antidepressant at any point during pregnancy. We will assess the quality of observational studies using the Newcastle-Ottawa Scale and the quality of experimental studies using the Cochrane risk-of-bias tool. When possible, we will conduct a random-effects meta-analysis. If meta-analysis is not possible, we will conduct a narrative review. If a sufficient number of studies are found, we will perform subgroup analysis and assess outcomes measured by drug class, dose, trimester of exposure, and child’s age and gender. Results: We registered our review protocol with PROSPERO (International Prospective Register of Systematic Reviews; CRD42021275750), completed the literature search, and initiated title and abstract review in August 2021. We expect to finalize this review by April 2022. Conclusions: Findings should identify the impact of prenatal antidepressant effects on stress regulation and distinguish it from the impact of prenatal exposure to maternal mood disturbances. This review should inform decisions about serotonergic antidepressant use during pregnancy. [ABSTRACT FROM AUTHOR]

Women at the lower end of the socioeconomic distribution have higher rates of depression in pregnancy and lower rates of treatment. In this study, we investigate relationships between income and the use of psychotropic mediciness in pregnancy. This retrospective cohort study using population-based administrative datasets included all women who delivered a live infant in the province of British Columbia, Canada (population of 4.6 million), between April 1, 2000, and December 31, 2009. We compared the socioeconomic distribution in use of psychotropic mediciness in pregnancy. We included 305,984 deliveries among 217,721 women. Women at the low end of the income distribution were significantly more likely to have a diagnosis for all mental health conditions, except anxiety, which was more common in women of highest socioeconomic status. The adjusted odds ratios for psychotropic medicine use indicate that women in the lowest income quintile have lower odds of filling a prescription for a psychotropic medicine after controlling for covariates and diagnoses of mental health conditions. However, they were more likely to fill a prescription for an antipsychotic and were more likely to fill psychotropic medicines from three or more different drug categories during pregnancy. Our findings suggest that women of lower socioeconomic status are less likely to fill a prescription for a psychotropic medicine in pregnancy, a finding largely driven by their decreased likelihood of filling an antidepressant. This is despite overall higher rates of mental illness among women of lower socioeconomic status, suggesting a gap in treatment by socioeconomic status. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Women at the lower end of the socioeconomic distribution have higher rates of depression in pregnancy; however, we know little about the role of socioeconomic status (SES) in determining their treatment. Herein, we investigate the relationships between income and the use of health services for depression in pregnancy. This retrospective cohort study using population-based administrative datasets included all women who delivered a live infant in the province of British Columbia, Canada (population of 4.3 million) between April 1st, 2000 and December 31st, 2009. We restricted to women with an indication of depression during pregnancy and examined their use of health services to treat depression by income quintile. Women in the highest income quintile were significantly more likely to see a psychiatrist for depression during pregnancy and to fill prescriptions for serotonin reuptake inhibitor (SRI) antidepressants than women in the lowest income quintile. Women at the lower end of the income distribution were more likely to have a GP visit for depression. Women at the low end of the income distribution were more likely to end up in hospital for depression or a mental health condition during pregnancy and more likely to receive a benzodiazepine and/or an antipsychotic medication. Our findings suggest a critical gap in access to health services for women of lower income suffering from depression during pregnancy, a time when proper access to effective treatment has the most potential to improve the long-term health of the developing child and the whole family unit. [ABSTRACT FROM AUTHOR]

Background: Many women with depression experience significant difficulty making a decision about whether or not to use antidepressant medication in pregnancy. Patient decision aids (PDAs) are tools that assist patients in making complex health decisions. PDAs can reduce decision-making difficulty and lead to better treatment outcomes. We describe the methods for a pilot randomized controlled trial of an interactive web-based PDA for women who are having difficulty deciding about antidepressant drug use in pregnancy.Methods/design: This is a pilot randomized controlled trial that aims to assess the feasibility of a larger, multi-center efficacy study. The PDA aims to help a woman: (1) understand why an antidepressant is being recommended, (2) be knowledgeable about potential benefits and risks of treatment and non-treatment with antidepressants, and (3) be clear about which benefits and risks are most important to her, with the goal of improving confidence in her decision-making. We include women aged 18 years or older who are: (1) planning a pregnancy or are pregnant (gestational age less than 30 weeks), (2) diagnosed with major depressive disorder, (3) deciding whether or not to use a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) antidepressant in pregnancy, and (4) having at least moderate decision-making difficulty as per a Decisional Conflict Scale (DCS) Score ≥25. Participants are randomized to receive the PDA or an informational resource sheet via a secure website, and have access to the stated allocation until their final study follow-up. The primary outcomes of the pilot study are feasibility of recruitment and retention, acceptability of the intervention, and adherence to the trial protocol. The primary efficacy outcome is DCS score at 4 weeks post randomization, with secondary outcomes including depressive and anxiety symptoms.Discussion: Our PDA represents a key opportunity to optimize the decision-making process for women around antidepressants in pregnancy, leading to effective decision-making and optimizing improved maternal and child outcomes related to depression in pregnancy. The electronic nature of the PDA will facilitate keeping it up-to-date, and allow for widespread dissemination after efficacy is demonstrated.Trial Registration: This trial is registered on ClinicalTrials.Gov under the identifier NCT02308592 (first registered: 2 December 2014). [ABSTRACT FROM AUTHOR]

Purpose To identify specific quantitative and qualitative factors that govern the decision to adhere or decline antidepressant medication in antenatal women with moderate-to-severe mood and anxiety disorders. Methods Fifty women (30 adherers, 20 decliners) were recruited between 18 and 34 weeks gestation in a tertiary care clinic for perinatal mothers. They were prospectively monitored 4 weeks apart up to 1-month postpartum on the: Hamilton Anxiety Scale, Hamilton Depression Scale, Mood Disorders Insight Scale, Antidepressant Compliance Questionnaire, Penn State Worry Questionnaire, and NEO Personality Inventory. Qualitative interviews were conducted at baseline. Hierarchical linear modeling determined illness trajectories of the two groups. Results Significantly different course of illness was observed in adherers versus decliners. Adherers had healthier attitudes toward depression and compliance with medication ( P < .005). Decliners had less illness insight ( P < .001) and cited fear of fetal exposure, and thought medication was unwarranted. Conclusions Pregnant women experienced significantly divergent illness trajectories depending on if they accepted antidepressant medication therapy for their illness. Risk perception, attitudes, and illness insight impacted decisions surrounding adherence and decline. [ABSTRACT FROM AUTHOR]

The Association Between Antidepressant Exposure and Birth Defects - Are We There Yet? Editorial Few moments are more concerning to parents than learning that their infant has a birth defect. Compounding this news is the possibility that the medication used to manage the mother's mood disorder may have increased the risk for her infant developing a birth defect. [Extracted from the article]

Prenatal serotonin reuptake inhibitor exposure is common and neonatal outcomes vary greatly, often leading to confusion about whether to use or even continue antenatal use of these antidepressants. Importantly, some but not all infants are affected, which raises questions about how maternal drug metabolism contributes to fetal drug exposure. To address this key question, our paper reviews the role of key maternal, fetal, and placental pharmacokinetic, metabolic, and genetic factors that affect the extent of fetal drug exposure. Considering the role of these factors may further our understanding of variables that may assist in optimizing maternal psychopharmacotherapy during pregnancy and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Depression in children and youth is common, and requires an understanding of its developmental character and associated comorbid conditions. Initial treatment of mild depression involves active supportive measures with a focus on symptom reduction and improved daily function. Where pharmacotherapy is warranted, evidence supports the use of selective serotonin reuptake inhibitor (SSRI) antidepressants, particularly fluoxetine, to manage moderate/severe depression. SSRI treatment should include a comprehensive management plan in the context of interdisciplinary care, an understanding of its pharmacology and clearly articulated goals for symptom reduction, functional status tracking (school, home and peers) and monitoring for the emergence of suicidal ideation/behaviour. For children with more severe symptoms or complicating factors (comorbid conditions), referral to mental health clinicians should be considered. Use of an SSRI should be associated with family/patient education about medication effects, specific social and health goals that promote self-esteem, improved function and close monitoring for adverse effects. [ABSTRACT FROM AUTHOR]

Aims To compare the disposition of fluoxetine and norfluoxetine enanantiomers in the mother, foetus and infant. Methods Blood from pregnant women taking fluoxetine ( n = 9), during pregnancy was sampled in the third trimester and at delivery (maternal and cord venous blood), and from the infants 48 h after delivery. The subset of these women who were breastfeeding, plus additional subjects recruited in the postpartum period, were studied further, and maternal and infant blood, and breast milk was sampled between 6 days and 11 months ( n = 23). Drug and metabolite concentrations were measured using gas chromatography/mass spectrometry or liquid chromatography, tandem mass spectrometry. Results There was a high correlation between maternal and foetal (cord blood) fluoxetine and norfluoxetine enantiomers ( r2−0.9), the mean foetal/maternal ratios (95% confidence intervals) being 0.91 (0.61, 1.02) and 1.04 (0.93, 1.05), for fluoxetine and norfluoxetine, respectively. In 2 day old infants exposed to the drug in utero, the fluoxetine and norfluoxetine plasma concentrations were the same as in cord blood at delivery. Over the next 2 months, the plasma concentrations in the infants fell progressively. Stereoselective disposition of both the drug and metabolite in the mother, foetus, infant and breast milk was observed. The S : R ratios in the foetus and newborn (∼3) were significantly higher than in the serum (∼2) or breast milk (∼1.9) of the mothers, resulting in greater exposure of the foetus and infants to the biologically active enantiomers, particularly S-norfluoxetine. Conclusions Foetal and infant exposure to fluoxetine and norfluoxetine is enhanced by their stereoselective disposition in the mother, foetus, breast milk and infant. Increased exposure may also result from decreased metabolism of the drug in the foetus and neonate. [ABSTRACT FROM AUTHOR]

Objective: To examine the relation between the mood and anxiety of pregnant, psychiatrically treated women and neonatal health outcomes after birth.Method: We prospectively assessed 46 women treated with psychotropic medications for anxiety and depression during pregnancy. We compared measures of maternal mental health with infant outcomes, in particular, the outcomes of infants with symptoms of poor neonatal adaptation.Results: The mothers of babies who demonstrated poor neonatal adaptation reported higher levels of anxiety and depression at study entry than did the mothers of healthy babies. This relation was not related to the presence or absence of treatment with clonazepam, an anxiolytic used to treat symptoms of anxiety. Further, increased psychiatric comorbidity in the mother was associated with a greater likelihood of transient symptoms in the newborn.Conclusions: Despite psychiatric treatment, the intensity and degree of comorbid symptoms appear to be related to poor transient neonatal health outcome. Our data suggest that, in addition to the impact of pharmacologic factors, maternal psychiatric status influences infant outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants has been associated with delays in early developmental milestones, but there remains uncertainty. Even among a subset of studies examining the Bayley Scales of Infant Development (BSID), some have reported normal mental and psychomotor development while others have suggested a delay in motor development. Given an increasing number of infants exposed to SRIs, furthering our understanding of the possible developmental implications of SRI exposure in utero is critical. Aims: To examine the effects of prenatal serotonin reuptake inhibitor exposure and maternal mood on infant developmental outcomes at 10months of age. Study design: Prospective study of mothers and their 10-month-old infants. Subjects: We examined 31 mother–child pairs exposed prenatally to SRIs and 52 mother–child pairs who were nonexposed. Outcome measure: The Bayley Scales of Infant Development (third edition) scores. Results: Infants exposed prenatally to SRIs scored significantly lower than nonexposed infants on gross motor (P =0.03), social–emotional (P =0.04) and adaptive behavior (P =0.05) subscales of the BSID-III, controlling for pre- and postnatal maternal depressed mood, smoking and alcohol use during pregnancy. No significant differences in any of the BSID-III subscales were observed between infants exposed and infants nonexposed to pre and postnatal maternal depressed mood (P >0.05). Increased levels of maternal positive affect at 10months predicted increased social–emotional scores (P =0.03). Conclusions: Infants prenatally exposed to SRIs score significantly lower on the gross motor, social–emotional and adaptive behavior subscales of the BSID-III, and this was not explained by underlying maternal depression. [Copyright &y& Elsevier]

Motor development underlies many aspects of education and learning. There has been uncertainty about the impact of exposure of antidepressant medication in pregnancy on child motor outcomes. This paper examines whether exposure to antidepressants in utero increases the risk of poorer motor development in two areas: sensorimotor and visuospatial processing. Data were obtained from 195 women and children across 3 groups: women with untreated depression in pregnancy, women treated with antidepressants and control women. Data were collected across pregnancy, postpartum and until 4 years for mother and child. Maternal depression was established at baseline with the Structured Clinical Interview for DSM-IV. Antidepressant exposure, including type, dose and timing, was measured through repeated self-report across pregnancy and the postpartum, medical records at delivery and in cord blood samples collected at delivery. Child sensorimotor and visuospatial outcomes were assessed at 4 years of age with four subtests from the NEPSY-II. Our study found for sensorimotor development, visuomotor precision completion time was associated with better performance for antidepressant-exposed children compared to those with mothers with untreated depression. Yet another measure of sensorimotor development, motor manual sequences, was poorer in those exposed to antidepressants. One subtest for visuospatial processing, block construction, was associated with poorer performance in antidepressant-exposed children who had poor neonatal adaptation and those exposed to a higher dose of antidepressant. These findings suggest an inconsistent association between sensorimotor development and antidepressant use in pregnancy. However, the findings for visuospatial processing would support further exploration of antidepressant associated poor neonatal adaption and later motor development. [ABSTRACT FROM AUTHOR]

• Perinatal SSRIs differentially impact offspring affective behaviors. • Maternal mood symptoms are important to consider in addition to SSRIs. • Sex/gender and age of offspring are important factors affecting outcomes. • Environmental and genetic factors need to be considered. • Further research is needed to determine perinatal SSRI effects on offspring. The developmental impact of selective serotonin reuptake inhibitor (SSRI) and other antidepressant treatments during gestation and postpartum on anxiety and depression behaviors in offspring is unclear. This review focuses on how perinatal exposure to SSRI and other antidepressant may have long term consequences for these affective behaviors during early childhood and beyond. Outcomes vary and consideration is given to methodological factors related to how early SSRI exposure affects developments studied in rodent models such as: a) between pre- and early post-natal SSRI exposure, b) sex, c) experimental models of gestational maternal stress and d) impact of non-SSRI antidepressant medications. We will also review how multiple contextual factors (maternal caregiving and gene x environment interactions) may contribute to the effects of perinatal SSRI exposure and maternal mental illness on affective behaviors in children. [ABSTRACT FROM AUTHOR]

Background: Building on research reports that early and chronic exposure to maternal depressive symptoms (MDS) adversely affects children's developing executive function (EF), this longitudinal study examined whether exposure to MDS and Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant treatment during pregnancy predicted individual differences in EF at school age.Methods: In a longitudinal prospective cohort, maternal report of EF using the Behavior Rating Inventory of EF (BRIEF) was obtained from 139 children (77 females; non-exposed n = 88, SSRI exposed n = 51) at age 6 years. Clinician rated and self reports of MDS were also obtained spanning from the 2nd trimester to 6 years postpartum.Results: Higher levels of MDS, especially at 3 years, were associated with poorer maternal reports of EF skills at 6 years. Associations between prenatal SSRI exposure and EF outcomes were not significant, even when controlling for maternal education and MDS at 3 years.Conclusions: Postnatal exposure to MDS adversely effects developing child EF, even when maternal symptoms were treated with an SSRI antidepressant. [ABSTRACT FROM AUTHOR]

Background Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) is associated with an enhanced risk of preterm birth. Very preterm-born neonates (<32 weeks’ gestation) antenatally-exposed to SSRIs may show altered brain development. Objective To examine whether antenatal-SSRI exposure was associated with adverse neonatal brain microstructural and metabolic development using diffusion tensor and magnetic resonance spectroscopic imaging. Design/Methods Of 177 neonates enrolled, 14 (8%) were antenatally exposed to SSRIs. Neonates were scanned twice (median week 32; interquartile range [IQR]: 30.4–33.6) and again at term-equivalent age (40.1, IQR: 38.6–42.1). Using a region-of-interest approach, N-acetylaspartate to choline ratios (NAA/Cho), lactate to choline ratios, white and gray matter fractional anisotropy (FA), mean, axial, radial diffusivity (MD, AD, RD) values were extracted from white and gray matter subcortical regions. Neurodevelopment was assessed at 18 months, corrected age. Results SSRI-exposed neonates exhibited increased FA and decreased MD, AD and RD values in the superior white matter ( p < 0.05). FA values in the basal ganglia and thalamus were significantly lower in neonates antenatally exposed to SSRIs, compared to non-exposed ( p = 0.004). Lower NAA/Cho values ( p = 0.04) and higher Lactate/Cho values ( p = 0.004) in posterior gray matter were evident in neonates exposed to SSRIs. No association with antenatal-SSRI exposure and neurodevelopment was evident. Conclusions Given the importance of treating depression in mothers at risk for preterm delivery, the impact of antenatal-SSRIs on early brain development requires further attention. Future research is directed at determining the mechanism of this relationship and the contribution of maternal mood. [ABSTRACT FROM AUTHOR]

Highlights: [•] Investigated impact of depression & SRI treatment on early mother–infant interactions. [•] Despite prenatal SRI treatment, depressed mothers interrupt infants more frequently. [•] SRI exposure & higher prenatal depression severity increases infant responsiveness. [•] Without SRI exposure, higher postnatal depression decreases infant responsiveness. [ • ] Infant responsiveness following prenatal SRI exposure may reflect ‘fetal programming’. [Copyright &y& Elsevier]

Summary: Background: Serotonin influences the development of the hypothalamic–pituitary–adrenal (HPA) system; therefore prenatal exposure to selective serotonin reuptake inhibitor antidepressants (SSRIs) may alter HPA axis development and function. To address this, prenatal exposure to SSRIs and maternal mood were examined in relation to neonatal and infant levels of cortisol and its binding protein, corticosteroid-binding globulin (CBG). Methods: Serum cortisol and CBG levels were assayed from SSRI-exposed and non-exposed mothers and their neonates at delivery. Maternal mood symptoms were documented at 36 weeks gestation. To determine the long-term implications of changes in CBG, levels of salivary cortisol were assessed in infants at 3 months of age. Results: Prenatal SSRI exposure significantly increased serum CBG levels in neonates after vaginal delivery (p ≤0.038), even when controlling for maternal depression. Neonatal serum cortisol levels did not vary with SSRI exposure or antenatal maternal mood, but were significantly higher following vaginal delivery (p ≤0.003). Neonatal serum CBG levels were associated with infant salivary levels of evening cortisol (p ≤0.051). In SSRI-exposed infants, increased levels of neonatal CBG predicted a smaller diurnal change in infant salivary cortisol (p ≤0.028), regardless of maternal depression. Conclusions: Prenatal SSRI exposure affects the developing HPA system by altering serum CBG levels in neonates and infant salivary cortisol levels. Further research is warranted on the long-term functional implications of the effect of prenatal SSRI exposure on fetal hepatic CBG gene expression and the developing HPA system. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To address the maternal and neonatal risks of both depression and antidepressant exposure and develop algorithms for periconceptional and antenatal management. Method: Representatives from the American Psychiatric Association, the American College of Obstetricians and Gynecologists and a consulting developmental pediatrician collaborated to review English language articles on fetal and neonatal outcomes associated with depression and antidepressant treatment during childbearing. Articles were obtained from Medline searches and bibliographies. Search keywords included pregnancy, pregnancy complications, pregnancy outcomes, depressive disorder, depressive disorder/dt, abnormalities/drug-induced/epidemiology, abnormalities/drug-induced/et. Iterative draft manuscripts were reviewed until consensus was achieved. Results: Both depressive symptoms and antidepressant exposure are associated with fetal growth changes and shorter gestations, but the majority of studies that evaluated antidepressant risks were unable to control for the possible effects of a depressive disorder. Short-term neonatal irritability and neurobehavioral changes are also linked with maternal depression and antidepressant treatment. Several studies report fetal malformations in association with first trimester antidepressant exposure but there is no specific pattern of defects for individual medications or class of agents. The association between paroxetine and cardiac defects is more often found in studies that included all malformations rather than clinically significant malformations. Late gestational use of selective serotonin reuptake inhibitor antidepressants is associated with transitory neonatal signs and a low risk for persistent pulmonary hypertension in the newborn. Psychotherapy alone is an appropriate treatment for some pregnant women; however, others prefer pharmacotherapy or may require pharmacological treatment. Conclusions: Antidepressant use in pregnancy is well studied, but available research has not yet adequately controlled for other factors that may influence birth outcomes including maternal illness or problematic health behaviors that can adversely affect pregnancy. [Copyright &y& Elsevier]

• Maternal depression is associated with lower infant cortisol reactivity. • Early pregnancy depression is associated with reduced placental NR3C2 DNA methylation. • No association of maternal depression and cortisol with placental or infant buccal NR3C1 DNA methylation. • No association of antidepressant use with cortisol and placental or infant buccal NR3C1 and NR3C2 DNA methylation. • Association between infant cortisol reactivity and maternal depression was suppressed by placental NR3C2 DNA methylation. Understanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early development. Two genes involved in stress response regulation, the glucocorticoid and mineralocorticoid receptors (NR3C1 and NR3C2) have been a focus in understanding stressful exposures and mental health outcomes. Data were obtained from 236 pregnant women from the Mercy Pregnancy Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort, recruited in early pregnancy. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeated measures of the Edinburgh Postnatal Depression Scale (EPDS). Antidepressant use, stressful events and anxiety symptoms were measured. NR3C1 and NR3C2 DNA methylation was measured in placental and infant buccal samples. Infant cortisol was measured in repeat saliva samples across a task. This study found maternal early pregnancy depressive disorder and symptoms were associated with lower DNA methylation at NR3C2 CpG_24 in placental tissue. There were no significant differences for depression or antidepressant use for DNA methylation of NR3C1. Antenatal depression was associated with lower infant cortisol reactivity at 12 months. DNA methylation in CpG_24 site in NR3C2 in placental samples suppressed the relationship between early maternal depressive symptoms and infant cortisol reactivity. These findings show a relationship between antenatal depression, NR3C2 DNA methylation and infant cortisol response providing support for a specific fetal programming pathway. Further research is required to examine the stability of this epigenetic mark across childhood and long-term mental health outcomes. [ABSTRACT FROM AUTHOR]