Project III

 Mismatch negativity (MMN)
is a measure of neural excitability, a trace, representing a short-term working memory of a change in a given sensory modality. In the auditory modality it is derived by substracting measures of the event-related potential (ERP) recorded at the scalp (i.e. an EEG) after common standard sounds, from the ERP elicited by a deviant rare sound. Initial reports of an amplitude reduction in patients with schizophrenia have been widely replicated, and influences of the state of illness (active symptoms) and illness-traits (including diagnosis) are reported (Oades et al., 1993, 1997). But initial clinical trials with measures soon after admission and shortly before discharge have not shown MMN normalisation to match other symptomatic improvements (Grzella et al., 1997; Schall et al., 1999; Umbricht et al., 1999). Hence this longitudinal study should provide evidence about the sort of patient whose automatic processing capabilities will be sensitive to therapy and the features associated with a less promissing prognosis.

The Negative difference (Nd),
an attentional trace, is derived from the ERP elicited by a neutral stimulus subtracted from that elicited by the same stimulus later during focussed attention, often when it is presented as a target in a discrimination.  Nd shows an unusual scalp topography in patients with schizophrenia compared to that recorded from healthy subjects that may reflect the different routes taken in information processing as one part of the cortex interacts with another (Oades et al., 1994, 1996). Following a better delineation of the sources of Nd in this study, Nd should provide a valuable marker and interesting therapeutic challenge to the improvement of the efficacy of the speed of controlled processing of information (cf. Oades & Jemel, 2001).

We propose, a) a longitudinal examination of the MMN and Nd course at up to four time-points after the initial admission of patients with a first episode of schizophrenia, b) to compare patients with an early illness-onset (adolescents), often associated with a poor prognosis, with those showing a later onset (adults), c) to examine prospectively associations of the development of MMN and Nd with ratings of symptom clusters (subgroups), types of treatment and neuropsychological indicators of frontal and temporal lobe function implicated in the generation of these potentials, d) to examine retrospectively this development in terms of the type of premorbid and prodromal development, and d) to compare these data with calculation of the current dipole sources of the potentials and their accurate location within the brain.

The proposed study has three elements. 1. Tracking the subjects entering the care of child and adolescent psychiatry (prospective element), 2. A co-operative study to contrast the outcome of first-episode adolescent vs. first-episode adult schizophrenia (prospective and retrospective elements) and 3. The progress of patients originally admitted as adolescents, now 16-18 years later (pseudo-long-term study).

In summary the aim is to relate psychophysiological measures of automatic and controlled attentional processing to state and trait features of young first-episode patients with schizophrenia, to relate these measures to their underlying functional neurobiological bases, and to track their development within a good and a poor course of the illness.