By Kate Kelland

LONDON, Aug 21 (Reuters) - The delusions and other psychotic symptoms experienced by people with schizophrenia may be caused by a faulty brain "switch" that blurs their ability to distinguish inner thoughts from objective reality, scientists said on Wednesday.

In a study published in the journal Neuron, researchers found the severity of symptoms such as hearing voices and delusions was due to a disconnection between two key regions of the brain - the insula and the lateral frontal cortex.

The finding, they said, could in future lead to the development of better, more targeted treatments for schizophrenia, with fewer side effects.

"In our daily life, we constantly switch between our inner, private world and the outer, objective world," said Lena Palaniyappan, of Nottingham University's psychiatry department, who co-led the study.

"This switching action is enabled by the connections between the insula and frontal cortex. (But) this switch process appears to be disrupted in patients with schizophrenia."

Schizophrenia is one of the most common serious psychiatric disorders affecting around 1 in 100 people worldwide. Scientists are not yet clear what causes it, but believe it could be a combination of a genetic predisposition to the condition combined with environmental factors.

Drug use is known to be a key trigger - people who use cannabis, or stimulant drugs, are three to four times more likely to go on to develop recurrent psychotic symptoms.

Researchers also think underdevelopment of the brain in the womb and in early childhood could play a role in schizophrenia.


SIDE-EFFECTS

Previous studies have found that schizophrenia patients have unusually smooth "folding" patterns of the brain over the insula region - suggesting this brain area may not have developed normally.

In this latest study, Palaniyappan's team used functional magnetic resonance imaging (fMRI) scans to compare the brains of 35 healthy volunteers with those of 38 schizophrenic patients.

The results showed that whereas the majority of healthy people were able to make the switch from inner thoughts to external reality using the connections between the insula and frontal cortex regions, the patients with schizophrenia were less likely to shift to using their frontal cortex.

"This could explain why internal thoughts sometime appear as external objective reality, experienced (by schizophrenia patients) as voices or hallucinations," Palaniyappan said.

She said it could also explain why people with schizophrenia find it hard to take in external material pleasures - for example to enjoy a social event or listening to music.

Palaniyappan said that normally, the insular and frontal cortex form a loop in the brain - with the insular stimulating the frontal cortex while it in turn inhibits the insula - but in patients with schizophrenia this system was found to be flawed.

The study offers clues for the development of more effective treatments for schizophrenia - which for now generally involve a combination of antipsychotic drugs and psychological therapies.

Although antipsychotic drugs can help some patients, many find they do not work and often stop taking them in the longer term because of their side-effects. Experts say that with current treatments, only around 20 percent of patients with schizophrenia achieve complete recovery.

The team is looking at an experimental treatment technique called transcranial magnetic stimulation, or TMS, which uses a magnetic pulse to stimulate malfunctioning brain regions.

Palaniyappan said her results suggested the loop between the insular and the frontal cortex could be targeted with TMS - with a pulse delivered to the frontal lobe aimed at stimulating the insula and resetting the "switching" capability. (Editing by Alison Williams)