Cognitive trajectories of psychosis risk: temporal patterns and association with progression

Cognitive impairment plays a crucial role in the development from clinical high-risk(CHR) to schizophrenia-spectrum psychosis. Understanding its dynamic change trajectories has significant preventive value. This study aims to comprehensively explore the dynamic cognitive trajectories of clinical high-risk(CHR) individuals over a three-year period, compare the trajectories among CHR individuals who convert to psychosis(CHR-C), those who do not(CHR-NC), and healthy controls(HC). This prospective study was part of the Shanghai At Risk for Psychosis(SHARP)-extended program. CHR participants, from psychological counseling outpatient clinics and medication - naive, were followed up at baseline (T1), 2 months ± 1 week (T2), 1 year ± 1 month (T3), 2 years ± 1 month (T4), and 3 years ± 1 month (T5). All participants completed the Chinese version of the MATRICS Consensus Cognitive Battery(MCCB) at these five strictly fixed time points to assess neurocognitive function. Conversion to psychosis was determined as main outcome. A total of 43 CHR(median age, 16[IQR, 15-18] years; 14 men[32.6%]) and 18 HC(median age, 17[IQR, 16-18] years; 8 men[44.4%]) completed five fixed-time cognitive assessments over three years. During the three-year period, CHR individuals were categorized into CHR-C(n = 19) and CHR-NC(n = 24). CHR-C individuals showed more significant cognitive impairments at all time points compared to CHR-NC and HC. The cognitive decline in CHR-C was most prominent in the first year. Growth curve modeling showed that, compared with the HC group, the CHR-C group had a significant negative impact on the composite score of neurocognition(t = -2.809, p = 0.007), and the effect of time is marginally significant(t = -1.911, p = 0.057). The repeated-measures analysis of variance(RMANOVA) indicated significant differences among groups and time-related changes in cognitive scores. Over the entire period, there were highly significant main effects of Time(F = 15.162, p < 0.001, η² = 0.275) and Group(F = 17.896, p < 0.001, η² = 0.472). Moreover, different cognitive domains exhibited distinct change trends across the three groups. The first year after CHR identification is a critical period for observing cognitive changes. These findings emphasize short-term cognitive changes' importance in predicting psychosis and inform early intervention strategies.