Approved Research

Genetic investigation of the relationship of susceptibility to infection with neuropsychiatric illness: a role for C-reactive protein?

Lay summary

Neuropsychiatric illnesses like Alzheimer's disease (AD) and schizophrenia remain an ongoing challenge to treat and there is still much unknown about how these disorders develop. If we can better account for the causal factors in each individual, then we should be able to more effectively treat those affected and potentially even prevent it from occurring with targeted early interventions in those at risk. Previous research suggests that our immune system may be involved in the development of AD and schizophrenia. Whilst infection is thought to increase risk, an overactive response from immune cells to these pathogens is likely to mediate their adverse effect on brain integrity. While this hypothesis is tantalizing, we still do not clearly understand the cause or role of immune dysfunction in the disorder, and what could be done to prevent this dysfunction. C-reactive protein (CRP) is a well-known biomarker of inflammation that may also be functionally relevant in these disorders. The release of CRP by the liver into the blood usually occurs when there is inflammation present, and typically is typically indicative the bodies responds to infection or damage. The CRP molecule itself also responds to infection by helping our white blood cells to fight off invading microbes or viruses. However, CRP is not always just a sign of inflammation. In fact, CRP can also help reduce inflammation and repair damage, depending on its protein structure. This means that CRP is more complicated than generally known, with many different functions. Previous studies in schizophrenia and AD have been conflicting, with some suggesting these disorders are associated with increased CRP, whilst others show the opposite trend. We have recently found evidence that CRP may protect against some psychiatric disorders like schizophrenia and anorexia, whilst paradoxically altering brain structure in ways that are thought to be damaging. These findings highlight the need to further investigate how CRP and the immune system interacts with the brain. In the proposed study we will determine whether elevated CRP increases the likelihood of developing these disorders or if it has a protective effect. This will enable us to better understand the role of CRP in AD and schizophrenia, and whether proinflammatory exposures, such as viral infection may be involved. We will use start-of-the art statistical modelling approaches combined with laboratory tests to investigate these questions. We expect this project to last up to 24 months.