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A) Clinical studies in first episode and chronic schizophrenia

'Their lives are being ruined twice over – by the illness and by the drugs used to treat it.'
Cliff Prior, Director of the National Schizophrenia Fellowship on the use of typical antipsychotics on people with schizophrenia - August 1999

While some symptoms of schizophrenia can be controlled by the older-style antipsychotics such as haloperidol, many patients have to endure painful and stigmatising side-effects as a consequence of these treatments. In addition, these drugs do not help 30% of people with schizophrenia and they do not improve cognition - our ability to remember, make plans and take decisions - or negative symptoms - the apathy, social withdrawal and lack of emotion found in people with schizophrenia. Recently, newer (or 'atypical') antipsychotic drugs have been developed. These drugs do not have such severe side-effects, and have been shown to improve schizophrenia's cognitive and negative symptoms. The use of these newer drugs in the UK, however, is restricted and there is still a lot to learn about how they affect brain function.

In the Clinical Neuroscience Research Centre, researchers are investigating the effects of newer antipsychotics on symptoms, memory, planning and decision-making skills and the impact of the disease on their family. Recent findings from the Centre's brain imaging research1 into drugs effects on brain function have revealed that newer antipsychotics can restore activity to the crucial part of the brain.

B) Psychological features of schizophrenia - behaviour and thought

Cognition in schizophrenia
Schizophrenia is commonly associated with bizarre thoughts and invisible voices. But, it is now recognised that problems in cognition - reduced attention span, problems with memory and difficulties in reasoning and problem solving - are core features of schizophrenia and are believed the most important factor for poor outcome in people with schizophrenia. Memory is particularly impaired in people with schizophrenia.

Researchers in Clinical Neuroscience Research Centre are investigating the characteristics and the neural correlates of cognitive impairment in people with chronic schizophrenia and those experiencing their first episode of psychosis. 2

Mental state attribution
Normally, we find out information about someone by how they express themselves, not just by what they actually say. People with schizophrenia, however, often fail to detect what someone may be feeling from their expression or from the way they say something. In a study of mental state attribution, people with schizophrenia were required to attribute an emotional state to facial expressions when only the eyes are visible. fMRI scans are performed during these mental state attribution tasks in order to identify the brain regions involved in this deficiency.

Pre-Pulse Inhibition
Our reaction to startling stimuli - termed the startle response - is well established and has been observed in different species for over 50 years. The stimulus is usually a loud noise, but can be a something tactile, like a controlled gush of air on the body. Our response to a stimulus is decreased if a weak signal called a prepulse (shown below) is give just before the main stimulus, and this phenomenon is called Prepulse Inhibition (PPI). The presence of PPI is believed to be an indication of our ability to filter and process information.


PPI Sequence. In Trial 1, only the pulse in given to the study participant, who elicits a full response. In Trial 2, the pulse is preceded by the prepulse. The study participant's response is decreased this time.

PPI is known to be disrupted in schizophrenia. In Clinical Neuroscience Research Centre, research has focussed on how reduced or disrupted PPI relates to cognitive functioning and the severity of schizophrenic symptoms and whether drug treatment affects PPI. 3 The effects of nicotine on PPI is also an area under study in CNRC, and may account for why 75% of people with schizophrenia smoke cigarettes.