The brain changes associated with schizophrenia may start in small regions and then expand through the brain over time – but the mechanism behind this is a mystery.
Schizophrenia is a condition that involves hallucinations and paranoid delusions, and is considered to be one of the most severe forms of mental illness. Its underlying cause is unknown. Many previous studies have suggested the condition is linked with slight shrinkage of tissue in several parts of the brain. In total, those affected may have a few per cent less “grey matter”, suggesting loss of brain cells or the connections between cells, called synapses.
To find out if the pattern of shrinkageĚýchanges over time , then at Monash University in Melbourne, Australia, and his colleagues looked at brain scans from four previous studies of people with schizophrenia.
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This included scans from people in the first months after diagnosis, those who had had the condition for longer – up to an average of 18 years – and those without the condition, looking at nearly 900 people in total.
The shrinkage of brain tissue seemed to start in two regions, on each side of the head, called the hippocampi, more commonly known for their role in memory formation.
In the people who had had the condition for several years, there was a loss of grey matter not only in the hippocampi, but also in wider regions, such as the frontal and temporal lobes of the brain, which are involved in many cognitive functions including planning and decision-making.
The progression of the damage over time seemed to follow the major neural routes between brain areas. “This tells us that the exact wiring pattern of the brain is important for shaping volume loss and its potential progression from the hippocampus,” says Chopra.
It is unclear, however, exactly what causes the brain changes to expand, he says. Schizophrenia isn’t thought to be caused by infections, nor by a change in the folding of proteins called prions, which is another way damage can spread through the brain.
“What we’re thinking is spreading is potentially some sort of altered activation of neurons,” says Chopra. “It’s a bit hand-wavy.”
Another idea about schizophreniaĚýis that symptoms are linked with the overactivity of neurons that send signals using the brain chemical dopamine – mainly because the antipsychoticĚýmedicines that reduce symptoms also lower levels of dopamine. “What we’re showing here is not mutually exclusive with the dopamine signalling hypothesis,” says Chopra. “Perhaps that spreading is altered dopamine signalling.”
The findings also shed light on a long-standing question: whether the grey matter loss is caused by schizophrenia itself or as a side effect of the antipsychotic drugs that are taken by most people with the condition.
One group of people in the study had only just been diagnosed and hadn’t yet begun taking antipsychotics, yet they already had grey matter shrinkage in their hippocampi. “We saw this effect in a group of patients who had zero antipsychotic exposure,” says Chopra.
at King’s College London, who wasn’t involved in the research, says the study was designed well and could improve understanding of the condition’s causes. “It gives us a gateway into the biological mechanisms of schizophrenia and could potentially unlock novel targets for drug development,” he says. “But the precise mechanisms driving the spreading will need to be understood.”
JAMA Psychiatry
