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Schizophrenia symptoms linked to faulty ‘switch’ in the brain


A study published today in the journal ‘Neuron’ links the symptoms of psychosis experienced by people with schizophrenia to a faulty ‘switch’ within the brain.

The findings reveal that the severity of symptoms such as delusions and hallucinations, which are typical in people with schizophrenia, is caused by a disconnection between two important regions in the brain - the insula and the lateral frontal cortex.

The research could form the basis for better and more targeted treatments for schizophrenia, with fewer side-effects.

The four-year study, led by researchers at the University of Nottingham, centred on the insula region of the brain, a segregated ’island’ that switches between reading information about the internal state of the body and the external world around us.

Dr Lena Palaniyappan, who is a Wellcome Trust Research Fellow at the University of Nottingham and co-led the study, explains: "In our daily life, we constantly switch between our inner, private world and the outer, objective world. This switching action is enabled by the connections between the insula and frontal cortex.

"This switch process appears to be disrupted in patients with schizophrenia. This could explain why internal thoughts sometime appear as external objective reality, experienced as voices or hallucinations in this condition.

“This could also explain the difficulties in ’internalising’ external material pleasures, [such as] enjoying a musical tune or social events, that result in emotional blunting in patients with psychosis. Our observation offers a powerful mechanistic explanation for the formation of psychotic symptoms.”

Several brain regions are engaged when we are lost in thought or, for example, remembering a past event. However, when interrupted by a loud noise or another person speaking, we are able to switch to using our frontal cortex, which processes this external information. With a disruption in the connections from the insula, such switching may not be possible.

The Nottingham scientists used functional MRI (fMRI) imaging, a technique to measure brain activity by monitoring blood flow, to compare the brains of 35 healthy volunteers with those of 38 people with schizophrenia. The results showed that whereas the majority of healthy people were able to make the switch between regions, the people with schizophrenia were less likely to shift to using their frontal cortex.

The insular and frontal cortex form a sensitive ’salience’ loop within the brain - the insula should stimulate the frontal cortex while, in turn, the frontal cortex should inhibit the insula - but in people with schizophrenia, this system was found to be seriously compromised.

The results suggest that detecting the lack of a positive influence from the insula to the frontal cortex using fMRI could have a high degree of predictive value in identifying people with schizophrenia.

Schizophrenia is a serious mental health condition that affects around 1 in 100 people. Onset occurs most commonly in a person’s late teens or early 20s, which can have devastating consequences for their future. The exact causes of schizophrenia remain undefined, but they are thought to be a mixture of inherited genes that increase the risk of developing the condition and social and environmental factors.

Treatment currently involves a combination of antipsychotic medications, psychological therapies and social interventions. However, many people living with the condition in the long term struggle to find a treatment that is 100 per cent effective in managing their condition, and only one in five of them will go on to experience complete recovery.

Palaniyappan L et al. Neural primacy of the salience processing system in schizophrenia. Neuron 2013 (epub ahead of print).


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