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Title: Antenatal mood disturbance and infant development : investigating neurobiological mechanisms of risk
Author: Braithwaite, Elizabeth
ISNI:       0000 0004 5346 2970
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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Introduction: Maternal antenatal depression is associated with increased risk of adverse offspring outcomes, which manifest in approximately 20% of infants. However, the mechanisms by which risk is transferred from mother to infant, and the factors determining susceptibility to antenatal mood disturbance, remain poorly understood. Objectives: The primary objectives of this thesis are to investigate whether: (i) Antenatal depression is associated with alterations of the maternal and infant Hypothalamic-Pituitary-Adrenal (HPA) axis. (ii) The infant serotonin transporter genotype (5-HTTLPR) confers susceptibility to antenatal mood disturbance. Methods: This thesis is an analysis of two different cohorts. First, 103 pregnant women were recruited in Oxford, UK. Participants’ self-reported antenatal mood, and salivary cortisol was assessed in response to a stressor and diurnally. 88 participants were visited two months post-birth. Mothers reported postnatal mood and infant temperament. Infant cortisol responses to inoculation were assessed, as was infant DNA methylation. Analysis of this cohort addresses the first objective of this thesis. Next, data from the ALSPAC cohort was analysed to address the second objective. Maternal-reported antenatal mood and infant behaviour up to 7 years was available, as was 5-HTTLPR genotype data for over 4,000 infants. Results: Antenatal depression was not associated with increased maternal cortisol during pregnancy. Neither antenatal depression nor cortisol was associated with infant cortisol reactivity or temperament. Antenatal depression predicted increased NR3C1 DNA methylation in males, and decreased BDNF DNA methylation in male and female infants. Infant 5-HTTLPR genotype did not moderate associations between antenatal mood disturbance and behavioural difficulties. Conclusions: This thesis does not support the theory that antenatal depression exerts influence on infant development via increased activity of the maternal and infant HPA axis; however, changes in infant DNA methylation may be a mediating mechanism. Further, susceptibility to antenatal mood may be more complex than previously thought.
Supervisor: Ramchandani, Paul; Murphy, Susannah Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Child and adolescent psychiatry ; Epidemiology ; prenatal depression ; infant development