Irish-led study finds link between blood vessels and schizophrenia

Blood vessel abnormalities in the brain may play a major role in the development of schizophrenia, a study led by Irish researchers has concluded.

The discovery is likely to open up a new front in the development of drugs to treat schizophrenia – a debilitating condition that affects around one per cent of people in Ireland.

This could involve treating brain disorders in a similar way to countering cardiovascular disease by treating blood vessels around the heart, according to lead researcher Dr Matthew Campbell, assistant professor in neurovascular genetics at Trinity College Dublin.

The network of blood vessels in the brain is made up of a great many tiny capillaries, forming what is known as the blood-brain barrier (BBB), which regulates the transport of energy and materials in and out of the brain.

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Scientists working in the TCD Smurfit Institute of Genetics and RCSI Department of Psychiatry have discovered that abnormalities in the integrity of the barrier, indicated by leaky capillaries, may be a critical factor in the development of schizophrenia and other brain disorders.

The research is published on Tuesday by the leading journal Molecular Psychiatry in a joint paper with scientists from Cardiff University in the UK, and teams from Stanford and Duke Universities in the US.

The scientists are the first to identify the possibility of a genetic pre-disposition to blood brain barrier abnormalities that is linked to development of schizophrenia.

“Our recent findings have, for the first time, suggested that schizophrenia is a brain disorder associated with abnormalities of brain blood vessels,” explained Dr Campbell. “The concept of tailoring drugs to regulate and treat abnormal brain blood vessels is a novel treatment strategy and offers great potential to complement existing treatments of this debilitating disease.”

He added: “While it is very well accepted that improving cardiovascular health can reduce the risk of stroke and heart attacks, we now believe that drugs aimed at improving cerebrovascular health may be an additional strategy to treating brain diseases in the future.”

This "cardiovascular aspect" is likely to bring a change of emphasis on treatments, Dr Campbell told The Irish Times, especially as current treatments only work for some patients; in some cases there is resistance to the treatment and "compliance is an issue".

Consultant psychiatrist at Beaumont Hospital Prof Kieran Murphy, head of RCSI Department of Psychiatry, said: "We have shown for the first time that dysfunction of the blood-brain barrier may be an important factor in the development of schizophrenia. These findings greatly add to our understanding of this debilitating and socially isolating condition."

Their work has concentrated on people with a genetic abnormality known as 22q11 deletion syndrome – who are 20 times more likely to develop schizophrenia in the course of their lives.

People living with ‘22q’ are missing a portion of a chromosome which carries their genes. A gene called “Claudin-5” is normally located within this region, and it is changes in the levels of this component withing the BBB that are associated with the occurrence of schizophrenia. “Claudin-5 acts like a super glue than ensures good blood flow,” Dr Campbell added.

The ‘22q’ abnormality was not very well known in spite of being the second most common syndrome after Down Syndrome, he said. This was because of its “very, very subtle features” which vary between individuals, but can include heart problems; developmental delay, learning difficulties, high risk of infections, the development of specific facial features, and neuropsychiatric conditions, such as schizophrenia.

The next stage in their research is further investigation of the BBB with a view to preventing symptoms that lead to brain disorders such as schizophrenia, he said, and the development of genetic approaches to re-introduce the gene in animals successfully.