O3.7. SMOOTH PURSUIT EYE MOVEMENTS INDICATE BIOLOGICAL DISTINCTION BETWEEN CANNABIS-USING AND NON-USING PATIENTS IN EARLY PSYCHOSIS.

Background Oculomotor abnormalities are among the most widely replicated findings in psychotic disorders with impairments in Smooth Pursuit Eye Movements (SPEM) and Antisaccades (AS) tasks. Cannabis-use may be a clinically relevant demarcating factor in early psychosis seen in around half of FEP patients at presentation and indicative of worse prognosis. No study to date has aimed at differentiating cannabis-using from non-using patients using AS and SPEM. Differences in eye movement measures between groups would indicate altered neurobiology between cannabis-using and non-using patients. We thus aimed to determine whether abnormalities in SPEM and AS are indicative of neurobiological differences between Early Psychosis patients who use cannabis (EPC) and those who do not use cannabis (EPNC). Methods We undertook the EfCiP study (the Effect of Cannabis in Psychosis) consisting of four groups: Early Psychosis patients who used cannabis (EPC) (n=28), Early Psychosis patients who did not use cannabis (EPNC) (n=25), healthy controls who used cannabis (HCC) (n=16) and healthy controls who did not use cannabis (HCNC) (n=22). The smooth pursuit stimulus used a sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz) across a horizontal range. Participants performed 40 antisaccade trials using a horizontal step task with an equal number of left and right stimuli in randomised order. As primary outcomes we tested measures robustly associated with abnormalities in psychosis: maintenance gain to index smooth pursuit and antisaccade percentage errors. We used one-way ANCOVA on four levels (EPC, EPNC, HCC and HCNC) with post-hoc Bonferroni correction. Covariates entered into the model were age, sex, AUDIT and Fagerstrom's scores. Results EPC and EPNC were clinically indistinguishable with no difference across clinical measures: including GAF, PANSS, duration since diagnosis, days spent in hospital, chlorpromazine equivalents, proportion with affective component to psychosis or schizophreniform spectrum disorder. Participants with EPC had higher indices of cannabis use and also scored higher on Fagerstrom's and AUDIT scores to index smoking and alcohol use respectively. Repeated measures ANCOVA revealed a significant effect of task, indicating that mean gain decreased as SPEM frequency increased. There was a significant Group effect (F3,83=3.514, p=0.019, ηp²=0.113). Post-hoc tests revealed significantly reduced mean gain for EPNC vs EPC (p=0.021). There was no significant difference between HCC and HCNC (p=1). There was no significant effect on SPEM gain for any covariate. When controls were combined there was a significant reduction in SPEM gain for EPNC vs EPC (Hedge's g=0.830, p=0.014) and trend level reduced gain for EPNC vs all controls (Hedge's g=0.594, p=0.058) but no difference between EPC and all controls (p=0.998) There was a numerical decrease in antisaccades percentage error rate such that EPC≈EPNC>HCC>HCNC but there was no significant group effect (p>0.35). Discussion This study demonstrates neurobiological distinction between cannabis using and non-using patients. There is evidence of impairment of SPEM in the EPNC group but not in the EPC group, whereas there is no discernable effect of cannabis use on SPEM gain in the healthy situation. This is consistent with lower psychosis liability in EPC than EPNC and suggests an additive component for cannabis use in the EPC group. Differential performance in SPEM and AS may indicate impairments in specific circuitry between groups. Further work should look to delineate the neurobiological substrates for this distinction. [ABSTRACT FROM AUTHOR]