Background: Most studies of neurocognitive functioning in Clinical High Risk (CHR) cohorts have examined group averages, likely concealing heterogeneous subgroups. We aimed to identify neurocognitive subgroups and to explore associated outcomes.
Methods: Data were acquired from 324 participants (mean age 18.4) in the first phase of the North American Prodrome Longitudinal Study (NAPLS-1), a multi-site consortium following individuals for up to 2 1/2 years. We applied Ward's method for hierarchical clustering data to 8 baseline neurocognitive measures, in 166 CHR individuals, 49 non-CHR youth with a family history of psychosis, and 109 healthy controls. We tested whether cluster membership was associated with conversion to psychosis, social and role functioning, and follow-up diagnosis. Analyses were repeated after data were clustered based on independently developed clinical decision rules.
Results: Four neurocognitive clusters were identified: Significantly Impaired (n = 33); Mildly Impaired (n = 82); Normal (n = 145) and High (n = 64). The Significantly Impaired subgroup demonstrated the largest deviations on processing speed and memory tasks and had a conversion rate of 58%, a 40% chance of developing a schizophrenia spectrum diagnosis (compared to 24.4% in the Mildly Impaired, and 10.3% in the other two groups combined), and significantly worse functioning at baseline and 12-months. Data clustered using clinical decision rules yielded similar results, pointing to high convergent validity.
Conclusion: Neurocognitive profiles vary substantially in their severity and are associated with diagnostic and functional outcome, underscoring neurocognition as a predictor of illness outcomes. These findings, if replicated, are a first step toward personalized treatment for individuals at-risk for psychosis.
Keywords: Clinical High Risk; Cluster analysis; Functional outcome; Heterogeneity; Neuropsychology.
Copyright © 2018 Elsevier B.V. All rights reserved.
Conflict of interest statement
Association of Neurocognition With Transition to Psychosis: Baseline Functioning in the Second Phase of the North American Prodrome Longitudinal StudyLJ Seidman et al. JAMA Psychiatry 73 (12), 1239-1248. PMID 27806157.Neurocognitive impairment, especially in attention and working memory abilities and declarative memory abilities, is a robust characteristic of CHR participants, especial …
Neuropsychology of the Prodrome to Psychosis in the NAPLS Consortium: Relationship to Family History and Conversion to PsychosisLJ Seidman et al. Arch Gen Psychiatry 67 (6), 578-88. PMID 20530007.These findings document that CHR individuals have significant neuropsychological difficulties, particularly those who later develop psychosis. This dysfunction is general …
The Relationship of Neurocognition and Negative Symptoms to Social and Role Functioning Over Time in Individuals at Clinical High Risk in the First Phase of the North American Prodrome Longitudinal StudyEC Meyer et al. Schizophr Bull 40 (6), 1452-61. PMID 24550526.The modest overlap among neurocognition, negative symptoms, and social and role functioning indicates that these domains make substantially separate contributions to CHR …
The Impact of Inflammation on Neurocognition and Risk for Psychosis: A Critical ReviewS Kogan et al. Eur Arch Psychiatry Clin Neurosci. PMID 31620871. - ReviewNeurocognitive difficulties are highly prevalent among people with schizophrenia and have been linked to increased inflammation, as well as dysfunction and disability. Po …
Neurocognition in Clinical High Risk Young Adults Who Did or Did Not Convert to a First Schizophrenic Psychosis: A Meta-AnalysisA De Herdt et al. Schizophr Res 149 (1-3), 48-55. PMID 23830855. - ReviewBased on the current meta-analytic data we might conclude that it is possible to differentiate between CHR-C and CHR-NC with respect to working memory and visual learning …
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