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Deficits in sensorimotor gating or prepulse inhibition (PPI) have been demonstrated repeatedly in patients with schizophrenia or with schizotypal personality disorder, but not consistently in schizotypal non-psychiatric controls. The appearance of normal PPI in this group has been interpreted as reflecting a discontinuous underlying vulnerability to psychosis in high-risk groups. An alternative interpretation is that underlying vulnerability to psychosis is continuously distributed in the normal population (Claridge, 1972, 1987), and therefore that performance on information processing tasks should vary continuously with increasing levels of schizotypy in non-clinical populations. We attempted to examine further the notion of a continuous relationship between PPI and schizotypy in 44 (17 female, 27 male) healthy, non-smoking subjects controlling for menstrual phase. In this selected sample, the findings do not support a continuum model, and suggest that PPI deficits may indeed be the result of a discontinuous neurophysiological change in those with psychotic illness, rather than one continuously distributed in the normal population.

Latent inhibition (LI) refers to a retardation of learning about the consequences of a stimulus when that stimulus has been passively presented a number of times without reinforcement. Acute positive-symptom schizophrenics, normal volunteers who score high on questionnaire measures of schizotypy and non-patients or animals treated with dopamine agonists show reduced LI. Neuroleptic drugs, such as haloperidol, administered at low doses, potentiate LI and effectively reverse disruption of LI induced by dopamine agonists in animals. However, a high dose of haloperidol, administered on its own, has been found to reduce LI. We examined the effects on LI of acute oral administration of an indirect dopamine-agonist, d-amphetamine (5 mg), and a nonselective dopamine receptor antagonist, haloperidol (5 mg), in normal male volunteers, using an associative learning task. Replicating previous reports, we found that d-amphetamine reduced LI; haloperidol also reduced LI, but only in subjects who scored low on the Psychoticism scale of the Eysenck Personality Questionnaire. In a subsequent study, no effect was found of 2 mg oral haloperidol administration on LI. The effect of 5 mg haloperidol on LI is interpreted as similar to that observed with a high dose of haloperidol in rats.

The effect of oral amphetamine administration on the Kamin-blocking effect in healthy volunteer subjects was investigated. Against predictions, Kamin blocking was not disrupted by either a high or low oral dose of D-amphetamine under conditions which have, in previous studies, led to disruption of a related learning phenomenon (latent inhibition). This lack of effect of amphetamine administration upon Kamin blocking weakens hypotheses that this cognitive process is mediated by the same changes in dopaminergic activity which affect latent inhibition. Currently, the only data which show strong comparative associations between Kamin blocking and latent inhibition are when they are applied to schizophrenic populations. These results may suggest that Kamin blocking and latent inhibition may be measuring different aspects of schizophrenic cognitive dysfunction.

It is argued in this article that information-processing models enable us to link psychotic phenomena to their neural bases. The core abnormality is viewed as a disturbance in the integration of sensory input with stored material. The performance of schizophrenic subjects on tasks derived from both animal learning theory and human experimental psychology is consistent with the model. The way in which such a disturbance relates to schizophrenic symptoms is outlined. It may result from an abnormality at one or more points in the neural circuit responsible for generating predictions of subsequent sensory input; in particular the hippocampus and related brain structures are implicated. The potential relevance of the model for psychological intervention is discussed.