Prenatal depression, fetal neurobehavior, and infant temperament: Novel insights on early neurodevelopment from a socioeconomically disadvantaged Indian cohort.

This article extends the research focusing on the early origins of psychopathology into the prenatal period, by exploring the association between maternal prenatal depression and offspring (fetal and infant) neurobehavior. The sample is recruited from a rural population in South India where women in the third trimester of pregnancy were assessed for depression and the heart rate responses of their fetuses to extrinsically applied vibroacoustic stimuli were studied. At 2 months postbirth, infant temperament and cortisol responsivity to immunization were assessed. The association between maternal prenatal depression and fetal responsivity to vibroacoustic stimulation, and infant responsivity to immunization, was U shaped with higher levels of responsivity noted in the offspring of mothers with very high and very low depression scores, and lower levels noted in the offspring of mothers with moderate depression scores. Maternal prenatal depression was not associated with infant temperament. The findings highlight the importance of environmental influences in the developmental origins of neurobehavior, suggesting that such differences, not evident at baseline, may emerge upon exposure to stressors. The study also emphasizes the need for further investigation in low- and middle-income contexts by providing preliminary evidence of the differing patterns of association observed between high- and low-income populations.

Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3.

BACKGROUND: Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression. METHOD: A diagnosis of depression during pregnancy was recorded from Manchester cohort participants' medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression. RESULTS: In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively). CONCLUSIONS: This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.

Foetal exposure to maternal depression predicts cortisol responses in infants: findings from rural South India.

BACKGROUND: Maternal depression during pregnancy is associated with an increased risk of adverse child outcomes. One potential mechanism is the influence of antenatal depression on the foetal hypothalamic-pituitary-adrenal axis. This can be observed as disturbances in baseline cortisol secretion during childhood. The influence of antenatal depression on infant cortisol reactivity to a stressor may provide further insight into this association. In addition, the dose-response relationship between foetal exposure to antenatal depression and infant cortisol reactivity is unclear. METHODS: A consecutive sample of 133 pregnant women in their third trimester was recruited from an antenatal clinic in Karnataka, South India. Women were assessed for depression before and after birth on the Edinburgh Postnatal Depression Scale (EPDS) and the Kessler 10 Scale. Salivary cortisol response to immunization was measured in 58 infants at 2 months of age. We aimed (i) to investigate the association between antenatal depression and infant cortisol reactivity to immunization and (ii) to explore whether the relationship is dose-dependent. RESULTS: Exposure to antenatal depression independently predicted elevated infant cortisol responses to immunization (ß = 0.53, P = 0.04). The association was found to be U-shaped, for antenatal depression measured on the EPDS, with the infants exposed to the highest and lowest levels of maternal antenatal EPDS scores during intra-uterine life showing elevated cortisol responses to immunization (R(2) = 0.20, P = 0.02). Infants exposed to moderate levels of maternal antenatal depression showed the lowest cortisol response to immunization. CONCLUSIONS: These findings suggest that the association between antenatal depression and infant cortisol reactivity is dose-dependent and U-shaped, implying that infants exposed to both low and high levels of maternal depression showed greater reactivity. The study provides the first evidence of such an association from a low-income setting.

Expressed emotion as an assessment of family environment with mothers and fathers of 1-year-old children.

BACKGROUND: High levels of expressed emotion (EE) in parents have been found to put children at risk for emotional and behavioural problems. However, the majority of existing studies have focused on mothers of school-aged children and adolescents rather than younger children, and have only rarely included fathers. METHODS: The present study examined the reliability of EE in mothers and fathers of 1-year old children. It also investigated whether depression and marital problems in the postnatal period predicted EE toward the child at 12 months. EE was assessed with the Preschool Five Minute Speech Sample in 163 families. RESULTS: The rater-interrater and code-recode reliability was high for most EE dimensions. Mothers and fathers were found to display quite similar EE scores. Regression analyses showed that depression and couple relationship significantly predicted EE in mothers, but not fathers. CONCLUSIONS: The findings suggest that EE provides a reliable and useful assessment of the family environment in families of young children.

Depressed fathers' speech to their 3-month-old infants: a study of cognitive and mentalizing features in paternal speech.

BACKGROUND: Depression in fathers in the postnatal period is associated with an increased risk of child behaviour problems. A key potential pathway of risk transmission is exposure of the child to negative cognitions and affect in the context of early parenting. This study examines paternal speech during face-to-face father-infant interactions at 3 months. METHOD: Currently depressed (n=19) and non-depressed (n=19) fathers were individually matched on age and education. Speech was coded for cognitive biases and mentalizing statements using a modified version of previous measures of maternal speech. Paternal depression was diagnosed using a structured psychiatric interview. RESULTS: Depression in fathers was associated with more speech focused on the paternal experience and less on the infants' experience. Depressed fathers' speech comprised more negative and critical utterances, compared with non-depressed fathers. CONCLUSIONS: Important differences emerge in the speech of fathers who experience depression. Examining negative cognitions in the speech of these fathers as early as 3 months may help in understanding children's risk in relation to paternal psychopathology.

Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation.

Prenatal maternal psychological distress increases risk for adverse infant outcomes. However, the biological mechanisms underlying this association remain unclear. Prenatal stress can impact fetal epigenetic regulation that could underlie changes in infant stress responses. It has been suggested that maternal glucocorticoids may mediate this epigenetic effect. We examined this hypothesis by determining the impact of maternal cortisol and depressive symptoms during pregnancy on infant NR3C1 and BDNF DNA methylation. Fifty-seven pregnant women were recruited during the second or third trimester. Participants self-reported depressive symptoms and salivary cortisol samples were collected diurnally and in response to a stressor. Buccal swabs for DNA extraction and DNA methylation analysis were collected from each infant at 2 months of age, and mothers were assessed for postnatal depressive symptoms. Prenatal depressive symptoms significantly predicted increased NR3C1 1F DNA methylation in male infants (ß = 2.147, P = 0.044). Prenatal depressive symptoms also significantly predicted decreased BDNF IV DNA methylation in both male and female infants (ß = -3.244, P = 0.013). No measure of maternal cortisol during pregnancy predicted infant NR3C1 1F or BDNF promoter IV DNA methylation. Our findings highlight the susceptibility of males to changes in NR3C1 DNA methylation and present novel evidence for altered BDNF IV DNA methylation in response to maternal depression during pregnancy. The lack of association between maternal cortisol and infant DNA methylation suggests that effects of maternal depression may not be mediated directly by glucocorticoids. Future studies should consider other potential mediating mechanisms in the link between maternal mood and infant outcomes.

Prenatal risk factors for depression: a critical review of the evidence and potential mechanisms.

Exposure to adverse experiences in early life increases the risk of depression during adulthood. Recent findings have highlighted that exposure of a fetus to an adverse intrauterine environment may also have implications for later offspring depression. This review considers the status of the evidence for these associations and the potential mechanisms underlying prenatal developmental risks for later depression, addressing the challenging possibility that environmental predisposition to depression may begin before birth.

Maternal depression and foetal responses to novel stimuli: insights from a socio-economically disadvantaged Indian cohort.

Maternal stress during pregnancy has pervasive effects on stress responsivity in children. This study is the first to test the hypothesis that maternal prenatal depression, as observed in South India, may be associated with how foetuses respond to a potentially stressful stimulus. We employed measures of foetal heart rate at baseline, during exposure to a vibroacoustic stimulus, and post-stimulation, to study patterns of response and recovery in 133 third trimester foetuses of depressed and non-depressed mothers. We show that the association between maternal depression and foetal stress responsivity is U-shaped with foetuses of mothers with high and low depression scores demonstrating elevated responses, and poorer recovery, than foetuses of mothers with moderate levels. The right amount of intra-uterine stimulation is important in conditioning foetuses towards optimal regulation of their stress response. Our results imply that, in certain environmental contexts, exposure to moderate amounts of intra-uterine stress may facilitate this process.

Disruption to the development of maternal responsiveness? The impact of prenatal depression on mother-infant interactions.

Both prenatal and postnatal maternal depression are independently associated with an increased risk of adverse infant development. The impact of postnatal depression on infants may be mediated through the effect of depression in reducing maternal responsiveness. However, the mechanisms underlying the effect of prenatal depression are unclear. Using longitudinal data from over 900 mother-infant pairs in a UK birth cohort (ALSPAC), we found that women with high depressive symptom scores during mid pregnancy, but NOT when their infants were 8 months, had a 30% increased risk of low maternal responsiveness when the infant was 12 months compared to women with consistently low depression. This may provide a mechanism to explain the independent association between prenatal depression and poorer infant development.

The association between observed non-verbal maternal responses at 12 months and later infant development at 18 months and IQ at 4 years: a longitudinal study.

BACKGROUND: An infant's early environment has an important influence on their development. For example, the sensitivity and warmth of a mother's responses towards her infant is associated with the infant's later socio-emotional development. However, it is less clear whether maternal responses are associated with the infant's later cognitive development. METHOD: We used data from a large UK cohort study to investigate the association between non-verbal maternal responses and later infant development and IQ. Maternal responses were rated at 12 months during an observed mother-infant interaction. Infant development was assessed using the Griffiths scales at 18 months and IQ at 4 years was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Data on the infant's developmental level at 6 months (prior to the maternal response ratings) was also available. The complete case sample comprised 732 mother-infant pairs. RESULTS: There was evidence for an association between positive maternal responses and infant development at 18 months. After adjusting for infant developmental level at 6 months and other confounders, we found a difference of 0.25 standard deviations (coef 2.0, 95% CI (0.8-3.2), p=0.002) on the Griffiths scales between infant's whose mothers showed positive compared to neutral non-verbal responses at 12 months. However, an association between positive maternal responses and IQ at 4 years diminished following adjustment for maternal educational attainment. CONCLUSION: The results provide evidence that positive maternal responses are associated with improved development in infants at 18 months. However, the association between maternal response and IQ at 4 years may be explained by higher educational attainment in mothers who show positive responses. Future studies are needed to explore the influence of maternal responses on different aspects of infant development as well as the role of maternal factors such as education.

Risk factors for recurrence of maltreatment: a systematic review.

BACKGROUND: Children who have been maltreated are at increased risk of further maltreatment. Competent identification of those at highest risk of further maltreatment is an important part of safe and effective practice, but is a complex and demanding task. AIM: To systematically review the research base predicting those children at highest risk of recurrent maltreatment. METHODS: Systematic review of cohort studies investigating factors associated with substantiated maltreatment recurrence in children. RESULTS: Sixteen studies met the inclusion criteria. The studies were heterogeneous. A variety of forms of maltreatment were considered. Four factors were most consistently identified as predicting future maltreatment: number of previous episodes of maltreatment; neglect (as opposed to other forms of maltreatment); parental conflict; and parental mental health problems. Children maltreated previously were approximately six times more likely to experience recurrent maltreatment than children who had not previously been maltreated. The risk of recurrence was highest in the period soon after the index episode of maltreatment (within 30 days), and diminished thereafter. CONCLUSIONS: There are factors clearly associated with an increased risk of recurrent maltreatment, and these should be considered in professional assessments of children who have been maltreated. A comprehensive approach to risk assessment, including but not solely based on these factors, is likely to lead to interventions which offer greater protection to children.