Neurobiology of selective information processing in the course of treatment of schizophrenia in the early stages of the illness, compared with obsessive-compulsive disorder.

Patients with schizophrenia when faced with a number of stimuli frequently perform inadequately in the selection of the relevant ones for response, or in the suppression of response to the irrelevant stimuli. One of the mechanisms contributing to an appropriate stimulus selection is called sensory-gating. Gating mechanisms can occur early in information processing and may be 'automatic', others may occur later as part the process of selective attention and be subject to control. Some of these cognitive filtering processes may involve function of the frontal lobe and mesocortical transmitter function, and appear to be more or less disturbed in some patients with schizophrenia and obessive-compulsive disorder.

One of the ways to study sensory filtering is with prepulse inhibition (PPI) of the response to a second stimulus that normally evokes a response - in some protocols this is a startle response and in others this is the P50 component of the event-related potential (ERP) recorded in the electroencephalogram (EEG). We adapt this procedure (where the stimulus has no particular consequence) to a Go/No-Go procedure where one of the stimuli presented is the target of a discrimination. Thus we examine the interaction between potentially automatic sensory filtering and controlled information selection. In parallel, subjects perform in situations emphasizing the early and later stages of processing (e.g., deviance detection with mismatch negativity, the planning/solving of problems). As well as studying neuropsychological (Tower-of-London, Covert Orienting of Attention) and psychophysiological measures of response adequacy we look for relationships with plasma indicators of dopamine, noradrenaline and serotonin metabolism and binding.

Most importantly this is a long-term prospective study with measures taken at three time points from patients over a course of two years of treatment. The question is to what extent do the experimental measures of information selection and indicators of neurotransmitter activity parallel the clinical ratings (patient subgroups) and reflect the treatment and outcome?