Our lab aims to better understand developmental pathways leading to mental health and psychiatric risk. To this end, our research is organized largely along the following main themes:
Examining how early life experiences shape life course mental health
Mental illness is one of the leading causes of disability worldwide, with devastating consequences for many individuals, their families and wider communities. As a result, understanding how mental illness develops in the first place – and thus how best it may be prevented – is of key importance. To rise to this challenge, it is essential to wind back the clock to children’s development. This is because mental disorders typically onset before adulthood (half by age 14), and often first manifest much earlier in life as emotional (e.g. anxiety, depression) and behavioural (e.g. impulsivity, inattention, aggression, rule-breaking) problems. Such evidence suggests that factors occurring early in life can play an important role in shaping an individual’s development, behaviour and long-term health. By knowing what these factors are, we can help devise more effective strategies to intervene early and prevent the occurrence of mental illness.
One stream of our research focuses on understanding how early life experiences shape life course mental health. Specifically, our objectives are to (i) identify factors, both prenatally (e.g. in utero exposure to stressors, toxins, and dietary factors) and across childhood and adolescence (e.g. maltreatment, negative life events and bullying) that influence the development of mental health problems later in life; (ii) examine how the characteristics of these exposures, such as their timing and chronicity, influences psychiatric risk; and (iii) pinpoint factors that help to mitigate risk and foster resilience in children exposed to adversity. We believe that an understanding of both risk and resilience factors is essential in order to develop better strategies to help children thrive and lead healthy lives.
Investigating gene-environment interplay on mental health
A large body of research has shown that mental health problems stem from the interplay of genetic and environmental factors, beginning in utero. Indeed, most mental health problems show moderate to high heritability, reflecting the contribution of many genetic variants with small effect, as well as rare variants of large effect. At the same time, studies have underscored the importance of the social environment, identifying a large number of risk factors for mental illness, including prenatal stress, parental psychopathology, childhood maltreatment, family conflict, and violence exposure. As a result, examining genetic and environmental influences together is essential to gain a better understanding of pathways leading to mental health and mental illness.
A second stream of our research focuses on mapping the complex interplay between our genes and our environments in relation to mental health, including gene-environment correlations (rGE) and interactions (GxE). We do this by applying both molecular approaches (e.g. polygenic risk scores, genome-wide GxE methods) as well as genetically-informed designs (e.g. twin and sibling studies, Mendelian randomization) to chart the independent and joint effects of genetic and environmental influences on mental health. We believe that characterizing these dynamic relationships is important as: (i) environmental factors previously found to associate with mental health problems may be largely genetically confounded, and as such not likely to be effective as intervention targets; (ii) previously identified genetic influences on mental health problems may in turn be environmentally modulated, and as such potentially actionable (e.g. via the implementation of early interventions to curb risk); and (iii) the existence of gene-environment interactions may help to explain large heterogeneity in individual biological and psychological responses to environmental stressors (i.e. with some individuals developing psychiatric problems and others showing resilience), which is currently a major challenge for mental health research and clinical practice.
Identifying biological markers and mediators of psychiatric risk
While it is by now widely accepted that both ‘nature’ and ‘nurture’ play a key role in mental health, how exactly these influences come together at a biological level to shape children’s development and psychiatric risk is much less clear. Studying biology in the context of mental health is important for several reasons. First, it can help us to understand how early life exposures, such as stress in utero or in childhood, can ‘get under the skin’ and increase psychiatric risk even decades after they have occurred – a concept known as ‘biological embedding’. Second, biological research may lead to the identification of novel biomarkers for better risk prediction, early detection, classification, and diagnosis of mental illnesses. Third, biological research may shed light on the molecular mechanisms mediating the effect of genetic and environmental influences on mental health outcomes, which can inform new targets for the prevention and treatment of mental illness.
To this end, a third stream of our research is concerned with studying biological processes associated with mental health problems in children and adolescents, and their determinants. A key focus is on DNA methylation, an epigenetic process that regulates when (in time) and where (in the body) genes are expressed, in response to both genetic and environmental inputs. Drawing on unique cohorts with repeated epigenetic data across development, we are particularly interested in (i) mapping how genome-wide DNA methylation patterns change from birth onward, (ii) identifying what environmental and genetic factors are associated with these changes, and (iii) understanding how these changes in turn relate to individual differences in neurodevelopment, behaviour and mental health. Besides epigenetics, we also examine multiple other biological layers in relation to mental health, bridging molecules to behaviour, including brain structure and function, the immune system and inflammation, the gut microbiome, and neuroendocrine and hormonal function. A growing part of our work is dedicated to finding optimal ways to combine these different layers of biological data via multi-omic integration (e.g. neuroimaging and epigenetics), in order to reach a more complete picture of biological alterations associated with the emergence of mental health problems.