Neurocognitive dysfunctioning may help predict future psychosis risk: JAMA study

Indicated prevention in young people at clinical high risk for psychosis (CHR-P) is a promising avenue for enhancing clinical outcomes. Findings from a meta-analysis conducted by Catalan et al and published today in JAMA psychiatry suggest that neurocognitive dysfunction can serve as a potential detection and prognostic biomarker in individuals at CHR-P.

The risk of developing full-blown psychosis in individuals at CHR-P is 30% at 4 years' follow-up which is approximately 50-fold higher than that of the general population. Therefore early identification of these individuals can go a long way in delivering timely preventive care and subsequent treatment to this relatively young population subset.

The main aim of the present study is to provide a meta-analytical examination of the consistency and magnitude of neurocognitive functioning in individuals at CHR-P. Independent researchers extracted the data, clustering the neurocognitive tasks according to 7 Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and 8 CHR-P domains.

The primary effect size measure was Hedges g of neurocognitive functioning in individuals at CHR-P (1) compared with healthy control (HC) individuals or (2) compared with individuals with first-episode psychosis (FEP) or (3) stratified for the longitudinal transition to psychosis.

The principle findings of this meta-analysis of 78 studies were:

1. Compared with HC individuals, individuals at CHR-P showed medium to large deficits on the Stroop color word reading task, Hopkins Verbal Learning Test–Revised, digit symbol coding test, Brief Assessment of Cognition Scale Symbol Coding, University of Pennsylvania Smell Identification Test, Hinting Task, Rey Auditory Verbal Learning Test, California Verbal Learning Test (CVLT), and National Adult Reading Test.

2. Individuals at CHR-P were less impaired than individuals who had already encountered a FEP.

3. Longitudinal transition to psychosis from a CHR-P state was associated with medium to large deficits in the CVLT task.

4. Younger age was associated with increased neurocognitive impairments between individuals at CHR-P and HC individuals, while more years of education were related to decreased differences.

These findings suggest that there is widespread impairment of neurocognitive functioning in individuals at CHR-P compared with HC individuals, encompassing all neurocognitive domains, albeit to varying degrees.

The neurocognitive tasks that are more likely to predict psychosis onset among individuals at CHR-P encompass the CVLT (medium to large effect sizes) and, to a lesser extent, the TMT-A, CPT-IP, and IQ (small to medium effect sizes). These potential prognostic biomarkers are ideal candidates to refine existing individualized multivariable prediction models that integrate multimodal domains (eg, clinical, neuroimaging, electrophysiological, and neurocognitive).

A further downstream clinical impact of these findings may be to present an opportunity for refining preventive interventions. Findings from this meta-analysis support neurocognitive dysfunction as a potential detection and prognostic biomarker in individuals at CHR-P. These findings characterize the neurocognitive features of psychosis risk states and can advance clinical research and inform multivariable prediction and preventive approaches.

Source: JAMA Psychiatry: doi:10.1001/jamapsychiatry.2021.1290