Cannabis use in healthy individuals and patients with schizophrenia: associations with prepulse inhibition and neurocognitive function

A deficit in prepulse inhibition (PPI) has long been associated with schizophrenia; however, the basis for this deficit is a matter of debate. Interestingly, there is some evidence suggesting that cannabis use in healthy people may be associated with alterations in PPI and cognition similar to those observed in people with schizophrenia. This is particularly striking given the hypothesised association between cannabis use and schizophrenia. The primary aim of this thesis was to investigate whether cannabis use in patients with schizophrenia is associated with further decrements to PPI and cognition, relative to healthy cannabis users and non-using patients with schizophrenia, using novel methodology. PPI and performance on a range of key endophenotypic cognitive tasks were examined in 50 patients with schizophrenia who were not current users of illicit drugs, 22 patients with schizophrenia who were current frequent users of cannabis, 38 healthy controls who were not current users of illicit drugs, and 36 current frequent users of cannabis who were otherwise healthy. PPI was measured across a range of startling stimulus intensities, under two attention set conditions, one in which participants were instructed to ignore the auditory stimuli and focus on a visual task, and one in which they were instructed to attend to the auditory stimuli. Stimulus intensity-response magnitude (SIRM) curves were examined, and a number of parameters were extracted from these curves, each of which reflects a different characteristic of the startle response. PPI of each of these parameters was calculated. When attending to the auditory stimuli, healthy controls exhibited increased sensitivity/potency to startling stimuli and reduced maximum startle capacity, as well as increased PPI of sensitivity/potency and reduced PPI of startle capacity, relative to when they ignored the auditory stimuli. These effects of attention on startle and PPI are ii proposed to be explained by a dual process model of prepulse function, with different prepulse processes occurring as a function of the modality of the attention set condition. All three groups of interest (healthy cannabis users, patients with schizophrenia and cannabis-using patients with schizophrenia) failed to show this pattern of attentional modulation of the reflex parameters. However, the basis for this lack of attentional modulation differed amongst the groups. Relative to healthy controls, non-using patients with schizophrenia showed altered PPI of the response parameters, which reflected an impaired ability to ignore startling stimuli when engaged in a visual task. Healthy cannabis users showed altered PPI of all SIRM reflex parameters, which reflected impairment of sustained attention to the auditory cues; they were, however, able to ignore the auditory stimuli when engaged in the visual task. Cannabis-using patients with schizophrenia exhibited PPI alterations similar to those of the healthy cannabis users, suggesting that cannabis use was associated with improvement of schizophrenia-related PPI alterations, but introduction of cannabis-related alterations. However, both cannabis-using and non-using patients with schizophrenia showed widespread deficits in cognitive performance, whilst cannabis-using controls showed little difference in cognition, relative to non-using controls. In conclusion, cannabis use in patients with schizophrenia was not associated with further decrements to PPI or cognitive functioning.