Longitudinal change in neurocognition and its relation to symptomatic and functional changes over 2 years in individuals at clinical high-risk for psychosis

Background: Negative symptoms and functional disability represent the core of schizophrenia and both are associated with cognitive impairments. We explored the course of cognitive change and its relation to symptomatic and functional changes in individuals at clinical high-risk (CHR) for psychosis to identify cognitive indicators of long-term course. Such attempts may offer insight into the pathological changes associated with the development of illness in the prodromal state. Methods: Forty-seven CHR individuals completed neurocognitive, clinical, and functional assessments at baseline and 2-year follow-up; twenty-eight healthy controls were assessed for neurocognitive and functional measures at baseline and 2-year follow-up. The delta values of CHR individuals in neurocognitive, clinical, and functional domains were determined from differences between baseline and follow-up scores to estimate the degree of change. Results: Although overall longitudinal cognitive performance of CHR individuals improved, the magnitude of improvement was not statistically different from that of normal controls at the group level. However, the individual data yielded two groups of CHR subjects showing opposite trajectories of cognitive change in semantic fluency (i.e., improvement or decline), which was significantly associated with changes in negative symptoms and functioning. Moreover, the relationships between negative symptoms and functioning were more strengthened over time than baseline. Conclusions: Our findings show that semantic fluency seems to be a neurocognitive indicator reflecting clinical courses in CHR individuals. The longitudinal relationship of negative symptoms and functioning with semantic fluency may represent ongoing pathological processes in neural systems involving aberrant fronto-temporal interaction in the early phase of schizophrenia.