by Charlotte Cecil
Mental illness is one of the leading causes of disability around the world, affecting one in three people every year in Europe alone – at an estimated cost of over €460 billion. It is hugely disruptive to the lives of individuals, their families and to wider communities.
If we are to successfully rise to the challenge of understanding how mental health disorders develop – and therefore how best they may be prevented – we must wind back the clock to children’s early development. More than half of all diagnosable mental health problems start before the age of 14, and often manifest earlier in childhood as emotional and behavioural problems, such as anxiety, depression, aggression or hyperactivity.
Like most of our individual characteristics, such as height or weight, mental health is thought to be largely determined by our genes as well as our environment, beginning in the womb. In combination with genetic predispositions, events that happen as early as during pregnancy and childhood can shape future health and behaviour, including risk of developing mental disorders later in life.
But why do mental health issues happen at a biological level? In other words – how do our genes and environment actually ‘communicate’ with one another? And how is it that events that happen early in life can get under the skin and leave a biological mark, affecting a person’s development, health and behaviour decades later? Rapid advances in biosocial research are beginning to shed new light on this old nature-nurture conundrum, and epigenetics in particular is increasingly recognised as the potential ‘missing piece’ to this puzzle.
Epigenetic processes regulate how genes are expressed – in other words, how they are switched on and off. Whereas our DNA sequence remains mostly unchanged over the lifespan, epigenetic processes are dynamic and dictate which bits of this genetic sequence should be read (or ignored) at different times in our life and across different cells in our body. These epigenetic ‘switches’ are fundamental for healthy development and for our bodies to work correctly day-after-day. They also coordinate much wider biological functions, such as hormonal, metabolic, immune, and neural changes across our lifespan.
It is perhaps unsurprising, then, that when these epigenetic switches are disrupted, it can have negative consequences for our health. Indeed, epigenetic disruptions have been linked to many diseases, such as cancer and autoimmune disorders – but also, increasingly, to mental health disorders. Crucially, because epigenetic patterns seem to be determined not only by a person’s genes but also by their environment, they represent a possible mechanism explaining how nature and nurture jointly influence a person’s development and health.
Studies have found that exposure to risk factors such as toxins, stress and unhealthy diets are associated with epigenetic changes; and, in turn, that epigenetic changes are associated with mental health problems. However, much of the evidence to date has been based on adults who are already experiencing poor mental health, asking about their childhood experiences retrospectively, and looking at epigenetic information only at one point in time. Therefore, it has been difficult to establish to what extent experiences in early life really influence epigenetic regulation across childhood, and whether these epigenetic changes contribute to psychiatric problems.
To address this gap, I was awarded a three-year ESRC Future Research Leaders fellowship with the aim of investigating the epigenetic ‘signature’ of child mental health problems, based on longitudinal data from two large birth cohorts (ALSPAC in the UK and Generation R in the Netherlands) spanning birth to adolescence. The availability of data at repeated time points across development offered the unique opportunity to examine associations between early environmental risks beginning in pregnancy, epigenetic patterns in early life (before the onset of symptoms) and later mental health outcomes.
This work has so far led to the first set of studies to characterise epigenetic patterns across the genome associated with the development of common behavioural problems in children, including hyperactivity, behavioural problems and adolescent substance use. We have found, for example, that children with high ADHD symptoms show early epigenetic differences in genes involved in fatty acid metabolism and fetal growth, and that an early onset of antisocial behaviour is linked to epigenetic differences in a gene involved in pain perception. We have also found that maternal smoking in pregnancy is associated with epigenetic changes to genes important for neurodevelopment in the child at birth, which in turn was associated with a higher risk of substance use in adolescence.
Overall, our findings support the idea that genes and the environment jointly influence the development of mental health problems in childhood, and that this can happen partly via epigenetic changes happening early in life. However, our results are still preliminary and more work will be needed to replicate findings in larger samples as well as to establish the extent to which these associations are truly causal. Because the relationship between nature, nurture and epigenetics is highly complex, we are only beginning to see part of a much bigger picture. Developments in knowledge, methodology and research in this area will offer exciting opportunities to study the role of epigenetics in mental health, with potentially widespread implications for the way that we understand, prevent, and perhaps in future even treat mental health disorders.
Charlotte Cecil is an ESRC Future Research Leaders fellow at the Institute of Psychiatry, Psychology and Neuroscience, King’s College London. Her work focuses on the impact of early adversity on children’s emotions, behaviour and mental health.
In particular, her aim is to identify how, at a biological level, stressful experiences ‘get under the skin’ to influence children’s development, so as to improve current strategies for helping children and their families.