Maternal Prenatal Psychological Distress, Poor Nutrition and Atypical Child Development

Many adults in the United Kingdom suffer from psychological distress. Psychological distress can range from worrying a lot, to feeling down, to even more serious problems. Importantly, existing research suggests that adults with psychological difficulties often also have cognitive and behavioural problems as children. Understanding how psychological distress develops is a crucial first step in helping us (i) identify which children are most at risk and (ii) develop targeted strategies to prevent or manage such problems. The reasoning here is that if we can prevent the development of psychological distress in childhood, these children will be less likely to show psychological distress as adults.
We already know that children who show cognitive and behavioural problems tend to come from riskier circumstances. For example, these children can have mothers with psychological difficulties. Moreover, families that have psychological difficulties also tend to eat foods that are of poor nutritional quality (e.g. fast foods, sweets). These two risks (i.e. mother psychological distress and poor diet) are thought to impact development in a range of ways - including on how a child develops in terms of biology. One of the ways the child's biology might be affected is through the nutrition the child is exposed to during pregnancy (i.e., what the mother eats). Therefore, during pregnancy, a developing foetus could be exposed to both psychological distresses in the mother as well as sub-optimal diets. It is important to note that the same is true for after the birth of a child. In fact, our previous research shows that maternal psychological distress and poor nutrition show continuity between pregnancy and after the birth of a child.

To date, however, existing studies have not teased out the specific biological mechanisms that could explain how a particular exposure during pregnancy (or after birth) might relate to increased risk for adjustment problems. One potentially important biological factor of this kind is 'DNA methylation'. DNA methylation allows a way for changes in an individual's environment to influence how their genetic make-up ('genes') affects development. Animal research shows that what a mother eats during pregnancy can change the action of genes important for the development of brain regions involved in how we respond to stress, in emotions and in the control of behaviours and emotions. Importantly, this work also highlights that these DNA influences (and brain changes) are potentially reversible. The very limited number of studies in humans so far shows similar patterns.

In this study we plan to address two key potential limitations of existing research: (1) Existing studies have not examined maternal distress and poor nutrition at the same time. (2) Existing studies have not assessed which biological mechanisms could explain how maternal distress and unhealthy diet might relate to child adjustment problems. (3) Existing studies have not assessed if biological vulnerabilities established in pregnancy can be carried forward after the birth of a child.

This study will address each of these main limitations of the existing research. We are ideally placed to achieve these aims as we have access to psychological, dietary, behavioural and biological data already collected from two very large scale samples of children, extensively studied from before their birth through childhood and into adolescence (The Avon Longitudinal Study of Parents and Children, in Southwest England and Generation R, Rotterdam, The Netherlands).

We hope that results from this research will help answer questions around why some children are more likely to have cognitive and behavioural problems, and guide early intervention for high-risk children to prevent atypical DNA methylation patterns that may underlie them.

The overarching goal of this application is to further understanding of the relationship between pre- and postnatal maternal distress and poor nutrition on child cognitive (attentional) and behavioural (hyperactivity) development. Additionally, we propose to examine a potential biological mechanism through which maternal psychological distress and poor nutrition can affect child mental health - the epigenetic process of DNA methylation. This proposal thus directly contributes to one of the ESRC's main strategic objectives: Understanding human behaviour and its relationship to social determinants. Thus the key groups we anticipate having an impact on are the public, social and health policy makers, and the scientific community. The research proposed here will be of relevance to the general public, since it aims to further our understanding of the ways in which our early experiences are embodied. We will ensure that our findings are communicated to the public through public engagement activities, as detailed in the Pathways to Impact section. Social and health policy makers rely on high quality evidence to inform the design of policies and interventions. Our research will shed light on mechanisms that underlie the long-term consequences of early life adversity. Therefore, our research has the potential to highlight the potential reversibility of the social and biological pathways through which such long-term effects may occur. Our findings will thus be useful to inform the design of policies that aim to reduce or alleviate the harms caused by early life adversity (e.g. nutrition and mental health), and to predict the potential benefits from such interventions. As detailed in the academic beneficiaries section, our research is of relevance to a wide range of academics. Research findings will be published in high quality peer reviewed journals - both biological and social - and presented at a range of conferences. Methodological innovations will be published in a timely manner, including syntax for widely used statistical software (e.g. Mplus or R). Links with other studies, such as Generation R (the Netherlands) will facilitate our broad academic dissemination strategy. Another important form of dissemination is developing the capacity of an early career researcher.

Developing the capacity of an early career researcher. Lotte C Houtepen is Co-I on this application. In June 2016, Dr Houtepen began as a senior research associate on an ESRC funded project (INTERSTELA; PI Laura Howe, Co-I Caroline Relton) on DNA methylation signatures and early-life adversity using the Avon Longitudinal Study of Parents and Children (ALSPAC) resource (more information on the project website). In this application, we propose to further develop the capacity of Dr Houtepen by (i) involving her as a co-I on this application which will initiate a collaboration with Dr Barker and Dr Cecil, (ii) expanding her professional network through a visit to Prof. Tiemeier's group and working with Generation R data, (iii) involving her in the organisation of a 'research day' at the institute of Psychiatry, Psychology and Neuroscience to engage clinicians and policy stakeholders, and (iv) to have training in life course and mediation analyses through three courses ('Analysis of Repeated Measures', 'Mendelian Randomization' and 'Causal Inference in Epidemiology: Concepts and Methods') in the Short Course Programme at Bristol University. These courses will facilitate Dr Houtepen's growing skill set for complex life course modelling in the context of epigenetic analyses.

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