Duration of Untreated Prodromal Psychosis and Cognitive Impairments

Abstract

Importance: The possible association between the duration of untreated prodromal symptoms (DUPrS) and cognitive functioning in individuals at clinical high risk (CHR) for psychosis remains underexplored.

Objective: To investigate the intricate interplay between DUPrS, cognitive performance, and conversion outcomes, shedding light on the potential role of DUPrS in shaping cognitive trajectories and psychosis risk in individuals at CHR for psychosis.

Design, setting, and participants: This cohort study of individuals at CHR for psychosis was conducted at the Shanghai Mental Health Center in China from January 10, 2016, to December 29, 2021. Participants at CHR for psychosis typically exhibit attenuated positive symptoms; they were identified according to the Structured Interview for Prodromal Syndromes, underwent baseline neuropsychological assessments, and were evaluated at a 3-year clinical follow-up. Data were analyzed from August 25, 2021, to May 10, 2023.

Exposure: Duration of untreated prodromal symptoms and cognitive impairments in individuals at CHR for psychosis.

Main outcomes and measures: The primary study outcome was conversion to psychosis. The DUPrS was categorized into 3 groups based on percentiles (33rd percentile for short [≤3 months], 34th-66th percentile for median [4-9 months], and 67th-100th percentile for long [≥10 months]). The DUPrS, cognitive variables, and the risk of conversion to psychosis were explored through quantile regression and Cox proportional hazards regression analyses.

Results: This study included 506 individuals (median age, 19 [IQR, 16-21] years; 53.6% [n = 271] women). The mean (SD) DUPrS was 7.8 (6.857) months, and the median (IQR) was 6 (3-11) months. The short and median DUPrS groups displayed poorer cognitive performance than the long DUPrS group in the Brief Visuospatial Memory Test-Revised (BVMT-R) (Kruskal-Wallis χ2 = 8.801; P = .01) and Category Fluency Test (CFT) (Kruskal-Wallis χ2 = 6.670; P = .04). Quantile regression analysis revealed positive correlations between DUPrS rank and BVMT-R scores (<90th percentile of DUPrS rank) and CFT scores (within the 20th-70th percentile range of DUPrS rank). Among the 506 participants, 20.8% (95% CI, 17.4%-24.5%) converted to psychosis within 3 years. Cox proportional hazards regression analysis identified lower educational attainment (hazard ratio [HR], 0.912; 95% CI, 0.834-0.998), pronounced negative symptoms (HR, 1.044; 95% CI, 1.005-1.084), and impaired performance on the Neuropsychological Assessment Battery: Mazes (HR, 0.961; 95% CI, 0.924-0.999) and BVMT-R (HR, 0.949; 95% CI, 0.916-0.984) tests as factors associated with conversion.

Conclusions and relevance: The finding of this cohort study suggest the intricate interplay between DUPrS, cognitive performance, and conversion risk in individuals at CHR for psychosis. The findings emphasize the importance of considering both DUPrS and cognitive functioning in assessing the trajectory of these individuals.

Figure 1.. Distribution of Cognitive Variables Among Individuals at Clinical High Risk for Psychosis With Short (≤3 Months), Median (4-9 Months), and Long (≥10 Months) Duration of Untreated Prodromal Symptoms

Mean z scores of performance tests, with error bars indicating SD. BACS indicates Brief Assessment of Cognition in Schizophrenia symbol coding; BVMT-R, Brief Visuospatial Memory Test–Revised; CPT-IP, Continuous Performance Test–Identical Pairs; HVLT-R, Hopkins Verbal Learning Test–Revised; NAB, Neuropsychological Assessment Battery: Mazes; and WMS-3, Wechsler Memory Scale–Third Edition spatial span.

Figure 2.. Correlations Between Duration of Untreated Prodromal Symptoms (DUPrS) and Cognitive Characteristics, Adjusted by Age, Gender, and Years of Education

F values displayed on the graphs were derived from the nonzero slope tests in linear regression. Shaded areas indicate SD. BACS indicates Brief Assessment of Cognition in Schizophrenia symbol coding; BVMT-R, Brief Visuospatial Memory Test–Revised; CPT-IP, Continuous Performance Test–Identical Pairs; HVLT-R, Hopkins Verbal Learning Test–Revised; NAB, Neuropsychological Assessment Battery: Mazes; and WMS-3, Wechsler Memory Scale–Third Edition spatial span.

Figure 3.. Quantile Regression Plots for Cognitive Performances of Duration of Untreated Prodromal Symptoms (DUPrS) Percentile Ranks P10, P20, P30, P40, P50, P60, P70, P80, and P90

Quantile regression models with cognitive variables including Trail Making Test Part A; Brief Assessment of Cognition in Schizophrenia symbol coding (BACS); Hopkins Verbal Learning Test–Revised (HVLT-R); Wechsler Memory Scale–Third Edition (WMS-3) spatial span; Neuropsychological Assessment Battery (NAB) mazes; Brief Visuospatial Memory Test–Revised (BVMT-R); Category Fluency Test; Continuous Performance Test–Identical Pairs (CPT-IP) as the dependent variables and the DUPrS as the independent variable for the quantiles between 0.1 to 0.9, with increments of 0.1, adjusted for age, sex, education, and positive, negative, disorganized, and general symptoms. Coefficient estimates were calculated with the independent variables in terms of percentiles, and they represent the association with the dependent variable for each 1-decile increase in the independent variable.