M68. COGNITIVE IMPAIRMENT IN NEVER-TREATED SCHIZOPHRENIA SPECTRUM INDIVIDUALS

BACKGROUND: Cognitive impairment is a key feature of schizophrenia. While one recent study suggested that individuals with psychosis experience a progressive decline in certain cognitive domains during the first 10 years of their illness, other clinical and functional MRI-based studies have proposed that most cognitive deficits are present during the first episode and remain stable over time, possibly as a result of medication response. To examine the temporal nature of cognitive deficits in the schizophrenia spectrum, we examined cognition in never-medicated individuals at different stages of the illness. METHODS: We recruited three groups of patients: 1) individuals at clinical high-risk (CHR) for psychosis (n=87), 2) individuals experiencing their first-episode of a non-affective psychosis (FEP) (n=64) (defined by a duration of untreated psychosis < 74 weeks), and 3) individuals with chronic schizophrenia (n=40) (CSz – duration of untreated psychosis > 74 weeks). All three groups were antipsychotic-naïve. Patients with any comorbid disorders or current substance abuse disorders were excluded from this study. We also recruited matched healthy control subjects (n=102). All subjects were recruited at the Instituto Nacional de Neurología y Neurocirugía in Mexico City. The study was approved by the institutional review board. Adults provided written informed consent and minors provided assent with written consent provided by both parents. Cognition was assessed with the MATRICS Consensus Cognitive Battery. Differences between groups were analyzed using a repeated measures analysis of variance (RM-ANOVA) with cognitive domain as inter-subject factor and Bonferroni correction for post hoc pairwise comparisons. Statistical significance was set at p ≤ .05. RESULTS: Since age, gender, and parental education were significantly different between the groups, they were included as covariates in the RM-ANOVA. In this revised model, there was no main effect of age (p = 0.69) nor any interaction between age and any cognitive domain. Therefore, age was removed from the final model. We observed a significant main effect of group (p <.001); All patient groups were significantly impaired compared to the control group (CHR mean difference (MD) = 6.12; FEP MD = 16.46; CSz MD = 16.37; p <.001 in all cases), individuals with both FEP and CSz had significantly more cognitive impairment than the CHR group (FEP MD = 10.34; CSz MD = 10.25; p <.001 in both cases). No significant differences were observed between FEP and CSz groups (MD = .09, p >.99). We also found a significant group by cognitive domain interaction (p <.001). Namely, all patient groups were cognitively impaired compared to the control group, except in the Verbal and Visual Learning domains in which there were no significant differences between the control and CHR groups. No significant differences were found between the FEP and CSz groups in any domain. Moreover, the CHR group was not significantly different from the other clinical groups in the Social Cognition domain. Within the FEP and CSz groups, no significant correlations were observed between duration of untreated psychosis and any cognitive domain. DISCUSSION: We observed significant cognitive deficits since at-risk stages of the schizophrenia spectrum. Patients with FEP were as impaired as those with CSz, while cognitive functioning observed in CHR individuals was intermediate between controls and patients with syndromal psychosis. These results emphasize the importance of pre-syndromal detection and prediction of burgeoning psychotic illness. Future research on strategies to mitigate the decline in cognitive function between presyndromal and first-episode psychosis is warranted.