Neuropsychology of the prodrome to psychosis in the NAPLS Consortium: Relationship to family history and conversion to psychosis

Context: Early detection and prospective evaluation of clinical high-risk (CHR) individuals who may develop schizophrenia or other psychotic disorders is critical for predicting psychosis onset and for testing preventive interventions. Objectives: To elucidate the neuropsychology of the CHR syndrome, to determine the association of neuropsychological function with conversion to psychosis and family history of psychosis, and to examine whether baseline neuropsychological functioning predicts subsequent psychosis. Design: Longitudinal study with 21?2 years of follow-up. Setting: Eight centers participating in the North American Prodrome Longitudinal Study. Participants: Three hundred four prospectively identified CHR individuals meeting Structured Interview for Prodromal Syndromes criteria, 52 non-CHR persons with a family history of psychosis in first- or second-degree relatives (family high-risk group), and 193 normal controls with neither a family history of psychosis nor a CHR syndrome, all of whom underwent baseline neuropsychological evaluations. Main Outcome Measures: A neurocognitive composite score, 8 individual neuropsychological measures, an IQ estimate, and high-risk status. Results: Global ("composite") neuropsychological functioning was comparably impaired in the CHR and family high-risk groups compared with controls, but profiles differed significantly between groups. Neuropsychological functioning in the CHR group was significantly lower in persons who progressed to psychosis than in those who did not and was worst in the subgroup with a family history of psychosis. Tests of processing speed and verbal learning and memory were most sensitive in discriminating CHR individuals from controls, although reductions were less severe than in established schizophrenia. Neuropsychological functioning did not contribute uniquely to the prediction of psychosis beyond clinical criteria, but worse verbal memory predicted more rapid conversion. Conclusions: These findings document that CHR individuals have significant neuropsychological difficulties, particularly those who later develop psychosis. This dysfunction is generally of moderate severity but less than in first-episode schizophrenia, suggesting that further decline may occur after baseline CHR assessment.This study was supported by the National Institute of Mental Health (grants R18 MH 43518, U01 MH081928, and P50 MH080272 to Dr Seidman; grant U01 MH066134 to Dr Addington; grants R01 MH60720 and K24 MH76191 to Dr Cadenhead; grant R01 MH65079 to DrCannon; grant K05MH01654 to DrMcGlashan; grants U01 MH066069 and P50 MH064065 to Dr Perkins; grant R18 MH 43518 to Dr Tsuang; grants RO1MH062066 and 5 U01MH081988 to DrWalker; grants U01MH74356, U01 MH082022, and R41 MH083436 to Dr Woods; and grant R01 MH061523 to Dr Cornblatt)