Physical and mental health multimorbidity across the lifespan (LIfespaN multimorbidity research Collaborative (LINC)).

Lead Research Organisation: Cardiff University
Department Name: School of Medicine

Abstract

Multimorbidity (MM) happens when two or more different diseases are present at the same time in an individual. This is common between physical and psychiatric diseases with almost half of people with a psychiatric disease also having a physical disease. As well as about a third of people with a physical disease also having a psychiatric disease. These patients have worse quality of life than those with a single disease, they often struggle to get the best care and are at risk of living less long. A common and serious type of MM is between internalizing diseases (depression and anxiety) and cardiovascular disease (ICV-MM). Still, very little is understood as to how ICV-MM develops and why it happens. We do know however that both internalizing disease and cardiovascular risk (e.g., obesity, cholesterol) tend to begin before adulthood.

To really understand how ICV risk develops, we need large studies of people of all ages whose health has been followed over time. Studies of children are crucial because they can tell us about early risks for development of ICV-MM later in life. This is important for developing better plans to prevent at-risk children developing ICV-MM.

We know that genes influence risk of both internalizing and cardiovascular disease and that some people are at high genetic risk. We also know that certain conditions that start early in life (neurodevelopmental conditions) such as intellectual disability, autism and ADHD increase risk of developing ICV MM later. Children's environments can also increase this risk, for example, stressful experiences such as poverty and physical or sexual abuse. But how exactly genes, neurodevelopmental conditions and early environmental risks influence the development of ICV-MM over the lifespan is still not understood.

Certain groups are known to be at increased risk of ICV-MM, such as people of South Asian heritage and women, but we don't know why this is. Better understanding of how ICV-MM develops in different groups in society will help doctors give patients care that is matched to their specific needs. It will also help doctors, governments and schools prevent ICV-MM in at-risk children in ways that work best for them.

To really understand the complexities of ICV-MM development, a team of researchers with a wide range of expertise is needed who together understand physical and psychiatric diseases as well as how genetics, neurodevelopmental conditions and the environments people live in influence them throughout their lives.
Our LIfespaN multimorbidity research Collaborative (LINC) combines wide-ranging medical and research expertise in physical and psychiatric diseases. We have brought together five very large studies in which the health of many people has been followed over time. Rich medical data is available, including from medical records. Genetic information is also available for these people. Other important information has also been collected such as on people's living environments, life events and lifestyles.

These studies follow the health over time of children, adolescents and adults. We can therefore study how internalizing and cardiovascular disease happen together in adulthood. Importantly we can then also study early risk factors in the children before they develop these conditions. Because our child and adult samples differ in ethnicity and economic situation, we can also study how the development of ICV-MM differs for different groups in society. Finally, because we have genetic data, we can study how genes influence ICV-MM development in people at risk.

Our study will help us understand how ICV-MM develops and which circumstances influence this. What we learn will be important for the prevention of ICV-MM in children who are at risk because of genetics, their sex, or ethnic or economic reasons. We will work with patients, doctors and charities to develop specific health advice in order to reduce ICV-MM in at risk groups in the future.

Technical Summary

One in two individuals with mental health disorders have poor physical health and, conversely, one in three of those with physical health disorders have mental health disorders. The social and economic cost of this physical and mental health multimorbidity (PMH MM) is substantial. Targeted interventions to reduce this risk are needed urgently.
A particularly common example of PMH MM is Internalizing disorders (anxiety and depression) co-occurring with CardioMetabolic diseases (ICM MM). Internalizing and cardiometabolic disorders typically originate in childhood. Yet the role in ICM MM development played by risk factors that are present from an early age onwards (genetics, neurodevelopmental disorders (NDDs) and adverse childhood experiences (ACE)) remains unclear.
To examine PMH MM across the lifespan, we have established the LIfespaN multimorbidity research Collaborative (LINC) comprising a multidisciplinary team, and an incredible resource of five large longitudinal population-based cohorts, with rich data on health and social environment, early-life factors and genomics. Our resource includes three young cohorts and four adult cohorts and is ethnically and socioeconomically diverse.
We will examine the effects of key shared genetic and environmental factors on the development of ICM MM. For genetic factors, we will include polygenic scores for relevant traits as well as rare variants (Copy Number Variants and Rare Coding Variants). We will investigate the role of NDDs and environmental risk factors, including ACE (deprivation, maltreatment). We will examine effects of sex and ethnicity heritage on ICM MM development.
Our findings will provide insights to inform tailored interventions. We will disseminate rapidly to the research community, and work in concert with policymakers to develop multiple-stakeholder interventions to better support those at elevated risk of ICM MM.

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