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Psychosis switch points way to improved treatment

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People with psychotic illnesses such as schizophrenia show similar brain changes to those of their immediate family members who present no signs of illness, new research shows.

These brain changes represent a marker of genetic risk of developing a psychotic illness and could open the way to developing new, more specific treatments.

The study, from researchers at Monash University, The University of Melbourne and the University of Cambridge, was published in the journal JAMA Psychiatry.

Lead researcher, Associate Professor Alex Fornito of Monash University, said the genetic markers could be targeted in the development of new treatments that may help to reduce the risk of developing psychotic illness.

“First-degree relatives of people with psychosis are at increased genetic risk of developing a psychotic illness,” Associate Professor Fornito said.

“We have found that people with psychosis and their unaffected first-degree relatives, who otherwise present no signs of illness, show similar brain changes when compared to healthy people.”

Associate Professor Fornito said even at the earliest signs of illness, patients showed altered activity in a specific brain circuit that links a region deep in the brain, called the striatum, with the prefrontal cortex.

This circuit plays an important role in attention, learning and memory.

“The fact that we see the same brain changes in this group, in the absence of any overt signs of illness, points to a neural biomarker of risk for psychosis,” he said.

“Patients who showed more severe changes in this circuit also showed more severe psychotic symptoms, providing a direct link between these brain changes and illness severity.”

The study examined 19 young people experiencing their first episode of psychotic illness and 25 of their unaffected parents or siblings. A group of 26 healthy, unrelated participants was also recruited to draw comparison. The researchers used MRI to map the activity of different brain systems.

The study also found a change in brain activity that was specific to patients experiencing psychosis, but not their relatives.

Associate Professor Fornito said this change may reflect a ‘switch’ that determines whether a person moves from an at-risk state to full-blown illness.

“We know that activity in brain circuits linking the striatum and prefrontal cortex are heavily influenced by the neurotransmitter dopamine, which is a major target for all medications currently used to treat psychosis,” he said.

“The difficulty is that these drugs have rather diffuse effects on the brain, affecting many different systems. They also often have unpleasant side effects.

“Our findings point to a more specific treatment target. We are currently investigating whether we can selectively improve activity patterns in the affected brain circuits using non-invasive magnetic stimulation techniques.

“If successful, using these techniques in at-risk populations may help delay, minimise or prevent the impact of psychosis onset.”

About three in every 100 people will experience a psychotic episode at some point in their life. Psychotic disorders have been estimated to cost the Australian economy more than $2 billion each year.

Debra Vermeer