The impact of prenatal serotonin reuptake inhibitor (SRI) antidepressant exposure and maternal mood on mother–infant interactions at 3 months of age

https://doi.org/10.1016/j.infbeh.2013.04.001Get rights and content

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’.

Abstract

Exposure to maternal depression increases risks for altered mother–infant interactions. Serotonin reuptake inhibitor (SRI) antidepressants are increasingly prescribed to manage antenatal maternal illness. The impact of SRIs on early mother–infant interactions was unknown. Three-month-old infants of 32 depressed mothers treated with SRI medications during pregnancy and 43 non-medicated mothers were studied. Using an established face-to-face mother–infant interaction paradigm, dyad interactions were studied with and without a toy. Videotaped sessions yielded 4 measures: maternal sensitivity, dyadic organization, infant readiness to interact, and maternal interruptive behaviors. Even with prenatal SRI treatment, depressed mothers interrupted their infants more during toy play. In the absence of prenatal SRI treatment, maternal postnatal depression adversely influenced infant behavior. Higher levels of maternal depression symptoms at 3 months predicted poorer infant readiness to interact during the toy session. Conversely, in the SRI-exposed group, higher prenatal depression scores predicted greater infant readiness to interact at 3 months. Increased infant readiness with SRI exposure suggests a “fetal programming effect” whereby prenatal maternal mood disturbances shaped a future response to a postnatal depressed maternal environment.

Introduction

Interactions between mothers and their infants play a critical role in shaping early social–emotional regulation. Maternal apathy, helplessness and irritability associated with depressed mood adversely influence the cognitive, social and emotional development in early childhood via maladaptive interaction and attachment patterns (Martins & Gaffan, 2000). Maternal mood disturbances are experienced in approximately 10–20% of pregnancies (Oberlander, Warburton, Misri, Aghajanian, & Hertzman, 2006), and increasingly serotonin reuptake inhibitor (SRI)1 antidepressants are used to treat these disorders (Oberlander, Gingrich, & Ansorge, 2009). This raises critical new questions about the impact – whether positive or negative – such treatment may have on the developing infant.

Maternal mood shapes fetal neurobehavioral development in both negative (DiPietro et al., 1996, Tronick and Weinberg, 1997) and positive directions (DiPietro, Novak, Costigan, Atella, & Reusing, 2006). Behavioral reactivity in utero is also altered (Allister et al., 2001, Monk et al., 2000) and the risk for premature birth increases (Glover, 2011, Talge et al., 2007). During the first year of life, prenatal maternal mood predicts infant temperament and attention regulation (Austin and Priest, 2005, Davis et al., 2007, Pluess et al., 2011, Talge et al., 2007), even when accounting for postnatal maternal mood. Well into childhood, prenatal maternal mood still influences cognitive, behavioral and emotional outcomes (Talge et al., 2007) when accounting for obstetric risk, psychosocial disadvantage and postnatal maternal mood. Mechanisms by which prenatal mood influences early brain development remain unclear, yet the magnitude of the effect is clinically significant, with approximately 15% of emotional and behavioral problems in childhood attributable to prenatal mood (Talge et al., 2007).

Infants of depressed mothers show less positive affect and this extends over the first year of life (Abrams et al., 1995, Field et al., 2006). In the postpartum, infants of depressed mothers show fewer positive facial expressions, are less attentive and show increased distress during mother–child interactions (Field, 1984). Early maternal sensitivity (both impaired and typical) in response to her infant's signals has been associated with later mother–infant attachment and subsequent behavioral development during infancy (Ainsworth, 1979, Pederson et al., 1998, Wolff and Ijzendoorn, 1997) and childhood (Murray et al., 1996a, Murray et al., 1996b, Olson et al., 1984).

Beyond mood disturbances, pharmacotherapeutic treatments also influence early infant behavior (Oberlander et al., 2009). SRIs are estimated to be prescribed in 5–13% of pregnancies (Cooper, Willy, Pont, & Ray, 2007), and readily cross the placenta and blood brain barrier (Kim et al., 2006). SRIs block the intrasynatpic reuptake of the neurochemical serotonin which acts as a neurotrophic factor involved in early brain development (Gaspar, Cases, & Maroteaux, 2003). This raises critical questions about the developmental impact of altered central serotonin during critical periods of neurodevelopment (Oberlander et al., 2009). While SRIs are often considered for prenatal therapy with the goal of improving maternal mental health during pregnancy (Gentile, 2005), such treatment has been shown to result in remission of a major depressive disorder in only 37% of patients and an overall cumulative remission rate of 67% (Rush et al., 2006). Thus, beyond gestational SRI exposure, ongoing maternal mood disturbances may place the infant's neurobehavior at continued risk during childhood.

While SRIs are not associated with gross neurological malformations (Bellantuono et al., 2007, Simon et al., 2002), neonatal neurobehavioral disturbances, referred to as “poor neonatal adaptation”, have been widely reported (Moses-Kolko et al., 2005, Nordeng and Spigset, 2005). Currently, very little is known about the impact of prenatal SRI exposure on early social–emotional regulation. In a single study of maternal–infant interactions following prenatal SRI exposure, maternal differences in positive and negative responses were only apparent when the mothers were treated with multiple prenatal psychotropic medications (SRIs and benzodiazepines) (Reebye, Morison, Panikkar, Misri, & Grunau, 2002). Importantly, the impact of prenatal maternal mood was not reported and it remained unclear whether the outcomes were influenced by SRI exposure alone. According to analogous research, prenatal exposure to cocaine (a pharmacological analog to SRIs that acts as a nonselective drug that also inhibits serotonin reuptake) (Barker & Blakely, 1995), has been associated with mothers who were less attentive and interrupted more frequently, and their cocaine exposed infants were less willing to interact (Mayes et al., 1997).

The present study was undertaken to study the impact of SRI treatment on early social–emotional development as reflected by mother–infant interactions, while accounting for both prenatal and postnatal maternal mood. When their infants were 3 months of age, we studied mother–infant interactions in a cohort of mothers who had been depressed and treated with an SRI antidepressant. This group (SRI-exposed) was compared to the dyadic behaviors of mothers who had a range of depression symptoms (including non-depressed and depressed) and had not received an SRI during pregnancy (non-SRI-exposed). Variation in depression symptoms in the non-exposed group allows us to better separate SRI exposure effects from the potential impact of maternal mood. If prenatal exposure to SRI medications has an influence on the development of infant interactive behaviors, we expected infants to show differential responses during our interaction paradigm. Similarly, if SRI treatment changes maternal interaction patterns, we expected mothers treated with SRIs to interact with their infants differently. The impact of maternal mood was controlled for in all analyses in order to determine if interactions between maternal mood and both maternal and infant behavior differed depending on SRI treatment status.

Section snippets

Participants

With approval from the University of British Columbia Research Ethics Board, Children's and Women's Health Centre of British Columbia Research Review Committee, and informed parental consent, mothers were recruited in their second trimester as part of a prospective study of infant development following prenatal antidepressant medication exposure. The mothers had originally been recruited in the second trimester (mean weeks 24.14 (SD = 4.67)). Originally 99 mothers were recruited, 19 moved away or

Maternal and infant characteristics

Mother and infant characteristics are listed in Table 3. In the non-exposed group, maternal depression scores (HAMD) were significantly lower pre and postnatally. Additionally, maternal educational achievements were higher, the infants were more likely to be first born, with greater neonatal 5-min APGAR scores and older gestational ages at birth in the non-exposed group. The variables that were significantly different between groups were used as covariates in the MANCOVAs. Mothers treated

Discussion

This study examined the impact of prenatal SRI antidepressant treatment and maternal mood (both pre and postnatal) on mother–infant interactions at 3 months. Two key findings emerged. First, when controlling for the influence of both pre and postnatal mood, mothers treated with an SRI showed more interruptive and forcing behaviors toward their infants. Secondly, maternal mood had an impact on infant readiness to interact at 3 months. In the non-SRI exposed group, increased maternal symptoms of

Conclusions

Mothers treated prenatally with SRIs appear to interrupt their infants more during mother–infant interactions. Furthermore, increased third trimester maternal depressed mood (in spite of SRI treatment), was associated with an increased infant willingness to interact. In contrast, among non-exposed infants, higher postnatal maternal depressed mood was associated with less willingness to interact. Whether our findings reflect altered fetal serotonin signaling (secondary to SRI exposure) or the

Funding sources

Research funded by March of Dimes Foundation (USA) and the Canadian Institutes of Health Research (TFO (PI), CIHR #MOP 57837). TFO is supported by a HELP (Human Early Learning Partnership) Senior Career Award and is the R. Howard Webster Professor in Brain Imaging and Early Child Development (UBC). WMW was supported by postdoctoral fellowships from CIHR, Michael Smith Foundation for Health Research and funding from the Sunny Hill Foundation. REG holds a Senior Scientist salary award from the

Conflict of interest statement

None of the authors have conflicts of interest, including financial interests that are relevant to the study reported in this manuscript. Study sponsors had no role in study design; data collection, analysis or interpretation; in the writing of the paper; and in the decision to submit the paper for publication.

Acknowledgments

None of this work would have been possible without the mothers and their infants who gave generously of their time, and the thoughtful work of Dr. Shaila Misri and Victoria Nethercott who were central to recruitment and data collection and to Kathy Armstrong and Irik Sielski for Mother-Infant Interaction coding.

References (51)

  • E. Barker et al.

    Norepinephrine and serotonin transporters: Molecular targets of antidepressant drugs

    Psychopharmacology: The Fourth Generation of Progress

    (1995)
  • C. Bellantuono et al.

    Serotonin reuptake inhibitors in pregnancy and the risk of major malformations: A systematic review

    Human Psychopharmacology: Clinical and Experimental

    (2007)
  • S.B. Campbell et al.

    Depression in first-time mothers: Mother–infant interaction and depression chronicity

    Developmental Psychology

    (1995)
  • J.F. Cohn et al.

    Face-to-face interactions, spontaneous and structured, of mothers with depressive symptoms

  • W.O. Cooper et al.

    Increasing use of antidepressants in pregnancy

    American Journal of Obstetrics and Gynecology

    (2007)
  • J.A. DiPietro et al.

    Maternal psychological distress during pregnancy in relation to child development at age two

    Child Development

    (2006)
  • J.A. DiPietro et al.

    Fetal neurobehavioral development

    Child Development

    (1996)
  • B. Egeland et al.

    Maternal intrusiveness in infancy and child maladaptation in early school years

    Development and Psychopathology

    (1993)
  • R. Feldman

    Coding interactive behavior (CIB) manual. Unpublished Manual

    (1998)
  • T. Field et al.

    Behavior-state matching and synchrony in mother–infant interactions of nondepressed versus depressed dyads

    Developmental Psychology

    (1990)
  • T.M. Field

    Early interactions between infants and their postpartum depressed mothers

    Infant Behavior and Development

    (1984)
  • P. Gaspar et al.

    The developmental role of serotonin: News from mouse molecular genetics

    Nature Reviews Neuroscience

    (2003)
  • S. Gentile

    SSRIs in pregnancy and lactation: Emphasis on neurodevelopmental outcome

    CNS Drugs

    (2005)
  • V. Glover

    Annual research review: Prenatal stress and the origins of psychopathology: An evolutionary perspective

    Journal of Child Psychology and Psychiatry

    (2011)
  • P.D. Gluckman et al.

    Early life events and their consequences for later disease: A life history and evolutionary perspective

    American Journal of Human Biology

    (2007)
  • Cited by (35)

    • Perinatal selective serotonin reuptake inhibitor (SSRI) and other antidepressant exposure effects on anxiety and depressive behaviors in offspring: A review of findings in humans and rodent models

      2021, Reproductive Toxicology
      Citation Excerpt :

      While clinical studies are scarce, it has been reported that during free-play and feeding, mothers treated with SSRIs do not differ in negative or positive interaction compared to mothers not treated with SSRIs, yet, mothers treated with SSRIs and Rivotal (a benzodiazepine derivative) show more inconsistent negative and positive messages towards their infants [128]. Another study which controlled for maternal depressive symptoms found that SSRI treated mothers interrupted their infants more than control dyads [129]. Further, maternal depression was related to poorer infant readiness to play in both control and SSRI treated dyads [129], suggesting a complex relationship between SSRIs, maternal mood, and mother-child interactions.

    • Advanced neuroimaging: A window into the neural correlates of fetal programming related to prenatal exposure to maternal depression and SSRIs

      2020, Seminars in Perinatology
      Citation Excerpt :

      The notion of fetal programming has been widely applied to understanding associations between prenatal stress in the context of maternal mood disturbances and adverse infant and child development.1,2 While prenatal depression has been widely linked to biological and behavioral risks3 for decreased birth weight, increased rates of preterm birth,4 elevated levels of cortisol and norepinephrine,5 and socio-emotional,6 and cognitive disturbances,3,7 not all outcomes reflect adverse developmental programming.8,9 We often wonder why some but not all children appear to be differentially susceptible to early adversity.10,11

    • Serotonin and motherhood: From molecules to mood

      2019, Frontiers in Neuroendocrinology
    View all citing articles on Scopus
    View full text