Using Neurocognitive Profiles to Predict Conversion to Psychosis in High-Risk Patients

The study exhibited an overall conversion rate of 35% to a psychotic disorder.

Patient neurocognition profiles may be effective diagnostic tools for identifying functional outcomes among patients with high risk for psychosis, suggested research published in Schizophrenia Research.

Researchers recruited 324 participants (mean age, 18.4 years) currently in the first phase of the North American Prodrome Longitudinal Study. The study cohort comprised 166 individuals at Clinical High Risk (CHR) for psychosis, 49 non-CHR youths with a family history of psychosis, and 109 healthy control participants. Participants were followed for 2.5 years, with study visits every 6 months to assess social functioning and clinical symptoms of psychosis per the Structure Interview for Prodromal Symptoms. 

At baseline, patient neurocognition was assessed across several domains, including verbal comprehension, visual-perceptual organization, working memory, speed of processing, verbal fluency, executive functioning, and verbal learning and memory. Researchers defined 4 neurocognitive clusters among the study cohort: Significantly Impaired (n=33), Mildly Impaired (n=82), Normal (n=145), and High Normal (n=64). Primary outcome measures included confirmed relationship between cluster membership and conversion to psychosis, as well as changes in social and role functioning and clinical diagnosis at the study endpoint.

During the study period, 166 CHR patients, 54 (32.5%) converted to a psychotic disorder; the study exhibited an overall conversion rate of 35%. Patients in the Significantly Impaired cluster had a 58% conversion rate to psychosis. Greater neurocognitive impairment was predictive of conversion to psychosis after controlling for sex, age, and baseline positive symptoms (hazard ratio [HR] 1.62; 95% CI, 1.18-2.22). At follow-up, diagnoses varied significantly between neurocognitive clusters (P =.041); individuals in the Significantly Impaired cluster had a 40% chance of developing schizophrenia spectrum diagnosis compared with just 24.4% of individuals in the Mildly Impaired and 10.3% of individuals in the Normal and High Normal subgroups, combined. The Significantly Impaired cluster also demonstrated the greatest deviations in processing speed (P <.001) and declarative memory (P <.001) compared with cognitively normal control participants. At month 12, the Significantly Impaired group had much lower scores than the Mildly Impaired cluster (P =.012) and the Normal and High clusters (P <.001).

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These data illustrate the variation in neurocognitive profiles among individuals and support an association between neurocognition cluster and functional outcome. Further research on individual neurocognitive profiling is necessary to validate its efficacy as a diagnostic tool and personalized treatment option.


Velthorst E, Meyer EC, Giuliano AJ, et al. Neurocognitive profiles in the prodrome to psychosis in NAPLS-1 [published online August 2, 2018]. Schizophr Res. doi:10.1016/j.schres.2018.07.038