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Identifying brain dysfunction preceding psychosis

Friday 6 May 2011

New research, led by the Institute of Psychiatry at King’s, has discovered how levels of glutamate in an area of the brain known as the thalamus affect brain function in those at risk of developing psychosis. The work was published this month in Archives of General Psychiatry.

Patients who have an ‘at-risk mental state’ (ARMS) meet criteria for the potential development of a psychotic disorder within two years. Studies of brain activity of those with an ARMS have shown abnormal activity in the prefrontal and temporal areas of the brain.

The aim of the research was to study the relationship between brain activation during tests of cognitive functions - those that control basic functions like memory or motor skills - and central levels of glutamate, the main neurotransmitter found in the brain. Tests were carried out in patients with an ARMS as it is thought that glutamate levels are important during the early stages of psychosis.

The work used fMRI to scan the brains of both those with an ARMS and control volunteers while performing a verbal fluency task. During the task the subject was shown a letter on a screen and had to think of, and speak, a word beginning with that letter. Those in the ARMS group showed greater activation in the middle front gyrus in both sides of the brain than the control group. This area is found in the frontal lobe of the brain.

Levels of glutamate in the brain were also tested using another imaging technique called proton magnetic resonance spectroscopy. This allowed the researchers to directly measure levels of the neurotransmitter. The results of this test showed that levels of the molecule within the thalamus were lower in the ARMS group than the controls.

The lower level of glutamate seen in the ARMS group was directly related to altered brain activation compared to the controls. These results suggest that there is a complex and pathological relationship between glutamate levels and brain function in those with an enhanced risk of psychosis.

Dr Paolo Fusar-Poli, from the IoP and lead author of the study said: ‘This work shows glutamate dysfunction plays a crucial role in the early phases of psychosis - influencing cortical activation and affecting cognitive functions.

‘The identification of neurophysiological markers for those at risk of psychosis will allow for preventive interventions and enable the development of new treatments for patients.’

This work has identified mechanisms that may underlie the increased vulnerability to psychosis of patients with an ARMS. A follow up study of those taking part is being undertaken to determine their long-term clinical outcome.

'Thalamic Glutamate Levels as a Predictor of Cortical Response During Executive Functioning in Subjects at High Risk for Psychosis' is published in the Archives of General Psychiatry.

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