TEDS 26: A longitudinal genetic approach to understanding the development and intergenerational transmission of common mental health conditions

The statistics for depression and anxiety in our young people are shocking. Over one-third experience these conditions and rates are rising, particularly in young women. Anxiety and depressive disorders are highly debilitating, disrupt education, reduce normal work capacity and dramatically increase suicide risk. Despite this, <£2 is spent per person per year on research into understanding them. Anxiety and depression also have very complex relationships with physical health conditions, with growing evidence for bidirectional effects, and putative sub-types of depression with specific physical health profiles. This complex picture is made even worse by the stigma which still surrounds these conditions, so many people do not seek help, or if they do, they do so for physical rather than psychological concerns. This backdrop means we know much less than we need to about how anxiety and depression develop, who is most at risk, when and how these conditions influence and are influenced by physical health concerns, and which factors drive treatment seeking and more general health service use.

Furthermore, despite having known for centuries that anxiety and depression "run in families" we know very little about which factors lead to the child of a parent with anxiety or depression developing that condition themselves. This question is of key importance to many young people experiencing anxiety and depression.

Our overarching aim is to transform our ability to predict who is at risk of anxiety and/or depression in their mid-twenties and our understanding of how related traits are transmitted from one generation to the next. Our findings will allow us to specify for whom and when to intervene to disrupt the development and intergenerational cycle of these conditions.

To address this aim, we will undertake three sets of new data collection with participants of the Twins Early Development Study (TEDS). TEDS has followed twins born in England and Wales in 1994-1996 from birth, assessing a wide array of emotional, behavioural, cognitive and language measures. Genome-wide genetic data are also available. Approximately 10,000 families are still active in the study, of whom ~65% consistently respond at each wave of data collection. As they approach their mid-twenties the twins are starting to have children, providing an exciting and unique opportunity to re-engage them and their offspring.

First, we will collect information about current mental health conditions using online assessment at age 26. This will allow us to utilise all our prior information to build models that identify groups at the greatest risk of developing mental health conditions in young adulthood, who could benefit from early prevention efforts. Second, we will connect information from TEDS twins' routine medical records to our dataset, built up over 25 years. This will offer additional external, independent information, including on mental health conditions, physical health conditions and use of medical services, all of which can help refine models of risk. Third, we will recruit and assess the children of TEDS participants, which will allow estimation, beyond the relative contributions of genes and environment, of parent-to-child and child-to-parent effects.

We will use this work to drive a new wave of prevention trials, built on the risk models we devise. Furthermore, we will continue to encourage researchers internationally to access the TEDS data resource to address questions beyond our core focus.

The Twins Early Development Study (TEDS) is the largest longitudinal twin birth cohort in the UK, with 25 years of MRC-funded prospectively assessed data. The focus thus far has been on developmental psychopathology, cognitive development and educational achievement, with physical health and the environment also regularly assessed. We now shift our attention to understanding the development and intergenerational transmission of common mental health conditions.
Young adults suffer from debilitating anxiety and depression at increasing and alarming rates. These conditions affect one third of individuals during their lives, disrupting education and employment, and increasing risk of suicide. Despite their high burden, we know relatively little about how to identify those most at risk to enable early intervention. Our objective is to use genetic, environmental and longitudinal data to transform our ability to predict those at heightened risk of anxiety and depression in their twenties, and to understand the intergenerational transmission of related traits.
To address this objective, we propose three workstreams. First, we will assess mental health outcomes (N~10,000 twins), to undertake longitudinal and multivariate twin and genomic analyses, and to build risk prediction models. Second, we will link medical records to our pre-existing dataset (N~14,400 primary;~24,000 secondary care) to validate self-reported mental health data, explore links with an array of physical health conditions, and undertake genetic analyses of service use. Third, we will recruit ~4,000 children of the TEDS twins, collecting data annually at ages 1-3 in order to undertake intergenerational transmission analyses.

The resulting dataset will offer unrivalled opportunities to explore risk factors for mental health not only by our team but the whole academic community.