Summary:

The proposed project will investigate the impact of foetal exposure to maternal depression on the intergenerational transmission of adverse childhood experiences (ACE) and psychopathology in a prospective longitudinal cohort study: the Avon Longitudinal Study of Parents and Children (ALSPAC). The overarching goal of this project is to elucidate key psychosocial pathways that underpin the intergenerational transmission of risk for childhood adversity (ACE, psychopathology, inflammation). The identification of such pathways would be of great clinical utility: targeted interventions early on could provide preventative strategies to limit these transgenerational cycles.

Background:

Childhood maltreatment is a major public health issue. Currently, over 50,000 children in England are on the child protection register (Department for Education, 2011). The National Society for Prevention of Cruelty to Children (NSPCC) identifies childhood maltreatment as any exposure to physical abuse, sexual abuse, physical neglect, emotional neglect or domestic violence. For research purposes, the term "adverse childhood experiences" (ACE), "victimisation" or "trauma" has been applied in a more generic manner to refer to such forms of maltreatment, as well as to other negative childhood experiences such as peer bullying and exposure to major traumatic life events. For the purpose of this proposal we refer to ACE as a means to encapsulate all such types of detrimental experiences.

ACE have repeatedly been shown to be associated with severe psychiatric illness in adulthood and adolescence, such as depression, psychosis and personality disorders (Fisher et al. 2012; McLaughlin et al. 2012; Nanni et al. 2012; Reed et al. 2013) as well as adulthood inflammation (Danese et al 2007, 2008). There is also a robust relationship between offspring exposure to maternal prenatal stress in utero and later psychopathology (O'Connor et al. 2002; Pawlby et al. 2009; Hay et al. 2010; Rice et al. 2010). Moreover, in our recent work we have demonstrated a strong association between an offspring's exposure to intrauterine stress (maternal depression) and their increased likelihood to experience ACE in middle childhood (Pawlby et al. 2011). Similar associations have since been reported in other samples, specifically the ALSPAC cohort, whereby offspring exposed to maternal depression/anxiety in utero were found to be at an increased risk for peer victimisation in middle childhood (Lereya et al. 2012). These data suggest two important points: i) exposure to depression in utero and ACE are likely part of the same putative pathway that links early life insults with an increased risk for persistent psychiatric disorders, and ii) exposure to maternal prenatal stress is a key risk factor for ACE.

ACE tend to be correlated across generations. Indeed, in both US and UK samples - namely the ALSPAC cohort - a mother's history of maltreatment in her own childhood predicts an increased probability for her offspring to be exposed to maltreatment (Sidebotham et al. 2006; Berlin et al. 2011). In our own sample - the South London Child Development Study (Sharp et al. 1995) - we have recently demonstrated the synergistic effects of maternal prenatal stress on the intergenerational transmission of ACE and psychopathology (Plant et al. 2013). Our findings indicate that maternal history of ACE and depression during pregnancy are key risk factors that interact, whereby the occurrence of both insults results in the greatest risk for offspring being exposed to childhood maltreatment and subsequent adolescent disruptive behaviour disorders. This data suggests that prenatal stress is a key risk factor for the intergenerational transmission of ACE and its sequelae. Whilst investigations into the intergenerational transmission of maltreatment have been conducted previously in the ALSPAC sample (see Sidebotham et al. 2001, 2006), to our knowledge, there has been no direct test of the impact of offspring exposure to maternal stress in utero on the transgenerational transmission of ACE and psychopathology. We thus propose to test this putative pathway for the intergenerational transmission of ACE and psychopathology in the ALSPAC sample, which will allow for a more robust and dynamic investigation of this model and its intricacies that were not so permitted in our existing analyses given our smaller size (n = 125).