Approved Research

Genetic correlates of cardiac and brain structure and function in serious mental illness

Lay summary

People with mental illness show an increased risk of dying of heart disease. Our main aims are to test if this is due to genetic factors and the potential role of inflammation.

BACKGROUND

It is known that about a third to half of the risk of having conditions such as schizophrenia, bipolar disorder and depression (serious mental illnesses or SMIs) is due to genetic susceptibility.

Each person with SMI is expected to live shorter than the general population, and over half of this is due to heart conditions. Using heart scans, we previously found that patients with chronic schizophrenia show chunkier and smaller hearts (called 'concentric remodelling'), and some degree of heart scarring ('fibrosis') and inflammation. These changes were found to be independent of established cardiac risk factors, such as old age, male gender, being overweight, smoking and exercising less. However, we don't know what causes these heart changes specifically in schizophrenia, and we don't know if the changes are present in other mental illnesses.

We also know that people suffering from SMI show increases in blood markers of inflammation, and this might be related to heart changes as previous research has found a link between specific inflammatory markers and heart remodelling.

Other studies have found that brain structure and function is changed in schizophrenia and other SMIs. It has been suggested that inflammatory changes may be responsible for brain changes and cognitive symptoms in SMI, and could be a target for new treatments. 

AIMS

This study will show if genetic variants causing increased risk of SMI are associated with heart and brain changes. We will also test if inflammation is linked with these changes.

METHODS

We will calculate the genetic risk for schizophrenia, bipolar disorder and depression for each study participant. Then, using the latest artificial intelligence techniques, we will automatically analyse thousands of participant heart and brain scans.

Then we will statistically test if genetic risk for each SMI is associated with heart and brain abnormalities. We will also test if inflammation is associated with heart and brain abnormalities.

The project will last for approximately 36 months.

IMPACT

This study will investigate the genetic causes of heart and brain changes found in several SMIs. Finding these causes will allow us and others to tackle them in the clinic. For example, if inflammation is found to be implicated, anti-inflammatory medication could be tried to reverse or prevent these heart and brain changes.