Aim

To assess the potential moderating effects of reactive temperament and 5-HTTLPR genotype on the association between parental depression and child behavioural and emotional outcomes.

Background

Parental depression is a consistent and strong predictor of adverse outcome for children. Work within ALSPAC has established that maternal anxiety during pregnancy, and maternal depression both pre- and post-natally, predict an increased risk of behavioural problems in children. These effects have been shown to persist until at least age 7 years. Paternal depression in the postnatal period has also been shown to be independently associated with similar adverse risks for children.

There has been considerable interest in recent years in the hypothesis that some children are differentially susceptible to environmental influence, for better or for worse. According to this conception, the same group of children (usually identified as having reactive temperament, and sometimes by genotype) show worse outcomes in adverse environments compared to non-reactive children, but also better outcomes in response to positive environmental exposures. We have previously explored this hypothesis in collaboration with ALSPAC in relation to paternal influence on children's behaviour (forthcoming publication in Family Science by Ramchandani, Bakermans-Kranenberg and van IJzendoorn). Findings from other studies have also supported the notion that differential susceptibility may occur in relation to reactive temperament, and also in relation to genes related to serotonergic and dopaminergic functioning (notably 5-HTTLPR and DRD4) (van IJzendoorn & Bakermans-Kranenberg, in press; Pluess et al, 2010).

Work undertaken by Professor Michael Meaney with the MAVAN cohort study has found preliminary evidence of a moderating effect of the serotonin transporter gene on the association between maternal prenatal depression and child outcome. We have come together to propose a further investigation with the ALSPAC team to investigate specific candidate genotype by environmental risk factors, focussing on parental depression. The MAVAN cohort could act as a second confirmatory cohort for any findings emerging from these analyses.

We would like to develop this further, using a conservative approach and testing the serotonergic candidate genes, namely:

1) Serotonin Transporter Gene- Promoter Region Polymorphism (5-HTTLPR)

If evidence of interaction and clear differential susceptibility is found, then we would seek to take a biologically informed approach and confirm findings in other relevant functional polymorphisms in genes related to serotonergic neurotransmission.

Resources required

We do not anticipate significant resource being required, as we have an existing dataset containing the key variables needed, with the main exception of the genotype classifications. The lead applicant (Paul Ramchandani) would undertake the analyses in collaboration with the other applicants.

This proposal is deliberately brief, but we are happy to answer any questions and provide further detail as required.