Blood brain barrier dysfunction in Schizophrenia; A molecular genetics based approach to prognosis

Schizophrenia has been estimated to affect up to 1 in 100 people in Ireland. Given its prevalence, the underlying causes of the condition are still far from clear. Intriguingly, there exists a chromosomal abnormality termed 22q11 deletion syndrome (22q11DS), where schizophrenia can manifest 20 times more frequently than in the general population.
Each cell of our body contains 23 pairs of chromosomes, and genetically, 22q11DS patients lack approximately 40-60 genes within a small region in one of the pairs of chromosome 22. In effect, 22q11DS patients will have less or indeed dysfunctional expression of a selected number of genes and this is likely the cause of their condition. It has however proven very difficult to pinpoint the exact gene or collection of genes that together cause the clinical features of 22q11DS. It has also proven difficult to determine why some patients develop schizophrenia while others don't.
Here, we wish to explore the role of the molecule claudin-5 in 22q11DS patients and how it may be involved in the development of schizophrenia in certain individuals. Claudin-5 is highly important in regulating the blood-brain and blood retina barriers (BBB/BRB) and decreased levels of the protein product of this gene have been shown by us and others to cause 'leakiness' and developmental defects in the blood vessels associated with the brain and retina. Using genetic, molecular biology and pre-clinical modelling approaches, we wish to establish whether there are variants (mutations) in the remaining claudin-5 gene of a cohort of 22q11DS patients and whether these variants pre-dispose some patients to abnormal brain and retinal blood vessels. The aim is to be in a position to establish a co-ordinated care pathway for patients in the future which will empower patients, their families and the public health system.

Award Date
23 October 2015
Award Value
Principal Investigator
Dr Matthew Campbell
Host Institution
Trinity College Dublin
Health Research Awards