Mechanisms underlying the association between maternal mental illness in pregnancy and adverse offspring outcomes still remain uncertain. Therefore, this study investigated the relationship between maternal antenatal psychopathology and child outcomes in middle childhood, and whether infant development might explain this relationship. 253 women comprising healthy controls, n=103; women with history only Major Depressive Disorder (MDD) (n=32); women with MDD in current pregnancy (n=67); and women at risk of Postpartum Psychosis (PP), n=51, were recruited in pregnancy and followed up, with their children until 6-8 years. Infant development was assessed at 12 months postpartum across all four groups, and children's psychopathology at 6-8 years across all groups except "at risk of PP", who have yet to be assessed. Infants of mothers "at risk of PP" scored lower than "healthy controls" for cognitive development (p=.015), and lower than all groups for motor development (p=.004). Infants of mothers "at risk of PP" also scored lower for language development than "healthy controls" and "MDD in pregnancy" (p=<.001). At 6-8 years, more children of "history-only MDD" had clinically significant peer problems compared to "healthy controls" (34.4% difference). Finally, infant cognitive scores were negatively correlated with clinically significant peer problems at 6-8 years (p=.002). Maternal antenatal psychopathology is associated with less optimal infant development, and more peer problems in middle childhood. Furthermore, infant cognitive development is associated with later psychopathology. Future regression models will test whether these associations represent mechanistic pathways.

We aimed to examine neonatal behaviour and cortisol reactivity in neonates born to women at risk of postpartum psychosis (AR) who had a psychiatric relapse within 4 weeks post-delivery (AR-unwell), compared with neonates of women at risk who stayed well (AR-well) and those born to healthy women (HC). We assessed neonatal behaviour using the Neonatal Behavioral Assessment Scale (NBAS), performed on 105 neonates (AR-unwell=17; AR-well=27; HC=61). Neonatal cortisol was measured pre-, immediately post- and 30-minutes post-NBAS. Neonates born to AR women did not differ from those born to HCs in behaviour or cortisol reactivity. There was also no difference in behaviour between neonates born to AR-unwell women and those born to AR-well women. However, neonates born to AR-unwell women had significantly lower pre-NBAS cortisol compared with neonates of AR-well women (t(38)=2.3, p=.02). Neonates of AR-unwell women also had a greater increase in cortisol from pre- to post-NBAS, though the difference did not reach statistical significance (p=.12), and a greater increase from pre- to 30 minutes post-NBAS (t(32)=2.7, p=.01). Maternal postpartum symptoms appear to disrupt the stress response of neonates whose mothers are at risk of postpartum psychosis.

Antenatal depression is associated with heightened infant stress reactivity, but how long-lasting these changes are, what factors might protect against them, and what the impact is on psychiatric risk is unknown. The Psychiatry Research and Motherhood-Depression study recruited antenatally depressed women, and controls, who are now being followed at child age 7-9 years. Children completed the Depression Self-Rating Scale and the State-Trait Anxiety Inventory. Salivary cortisol output was calculated as AUC from before, to 40 minutes after, the Cold Pressor Task. Children born of antenatally depressed and control mothers did not differ on their self-reported depression (z=0.32, p=0.75), state (z=-1.10, p=0.27) or trait anxiety (z=1.19, p=0.24), or cortisol output (t(39)=-1.82, p=0.076). Cortisol output was significantly correlated with child trait anxiety (r=0.34, p=0.030). These data indicate that, in this cohort, antenatal depression was not associated with child outcomes at 7-9 years. Instead, child cortisol output was associated with concurrent trait anxiety. This may suggest either that age 7-9 is too early, or, more encouragingly, that protective factors are present in this cohort which break the mother-child transmission cycle.

Introduction Antenatal depression is associated with a broad range of suboptimal outcomes in offspring, although the underlying mechanisms are not yet understood. Animal studies propose inflammation and glucocorticoids as mediators of the developmental programming effect of prenatal stress on offspring stress responses, but studies in humans are not yet at this stage. Indeed, to date no single study has examined the effects of a rigorously defined, clinically significant Major Depressive Disorder (MDD) in pregnancy on maternal antenatal inflammatory biomarkers and hypothalamic-pituitary (HPA) axis, as well as on offspring HPA axis, behavior and developmental outcomes in the first postnatal year. Methods: A prospective longitudinal design was used in 106 women (49 cases vs. 57 healthy controls) to study the effect of MDD in pregnancy and associated antenatal biology (inflammatory and cortisol biomarkers), on offspring stress response (cortisol response to immunization, at 8 weeks and 12 months), early neurobehavior (Neonatal Behavioral Assessment Scale, NBAS, at day 6), and cognitive, language and motor development (Bayley Scales of Infant and Toddler Development at 12 months). Results: Compared with healthy controls, women with MDD in pregnancy had raised interleukin (IL) IL-6 (effect size (delta) = 0.53, p = 0.031), IL-10 (delta = 0.53, p = 0.043), tumor necrosis factor alpha (delta = 0.90, p = 0.003) and vascular endothelial growth factor (delta = 0.56, p = 0.008), together with raised diurnal cortisol secretion (delta = 0.89, p = 0.006), raised evening cortisol (delta = 0.64, p = 0.004), and blunted cortisol awakening response (delta = 0.70, p = 0.020), and an 8-day shorter length of gestation (delta = 0.70, p = 0.005). Furthermore, they had neonates with suboptimal neurobehavioral function in four out of five NBAS clusters measured (range of delta = 0.45-1.22 and p = 0.049- < 0.001) and increased cortisol response to stress at one year of age (delta = 0.87, p < 0.001). Lastly, maternal inflammatory biomarkers and cortisol levels were correlated with infant stress response, suggesting a mechanistic link. Conclusion: This study confirms and extends the notion that depression in pregnancy is associated with altered offspring behavior and biological stress response, and demonstrates that changes in maternal antenatal stress related biology are associated with these infant outcomes.

Background Research has shown that maternal mental illness can affect mother–infant interactions with implications for infant outcomes. Severe and chronic mental illness (SMI), particularly schizophrenia, is associated with the greatest risk. Schizophrenia is also associated with impairments in attribution of mental states, ‘theory of mind’ (ToM). Recent attachment research has suggested that maternal mentalizing skills are strongly associated with attachment outcome in infants. To date, no research has explored the relationship between ToM and maternal sensitivity in mothers with SMI using standard tests of ToM. The present study was designed as an exploratory study in order to investigate this. Method A total of 40 women with SMI in the postpartum period were administered a battery of ToM tasks and general neuropsychological tasks. The women were also filmed in an unstructured play session with their infants, which was coded for maternal sensitivity using the Crittenden CARE-Index. Results One ToM task, the Frith–Happé Animations, predicted maternal sensitivity across all diagnoses. There was also an effect of diagnosis, with lower sensitivity observed in women with schizophrenia. ToM impairments did not fully explain the effect of diagnosis on sensitivity. Mothers of girls were rated as being more sensitive than mothers of boys. Conclusions The results suggest that ToM is a significant predictor of maternal sensitivity across all mental health diagnoses, extending the results of studies focusing on healthy populations. Clinical interventions emphasizing the importance of understanding the perspective of the infant may enhance maternal sensitivity.