Examining Cognition With Function in Patients Ultrahigh Risk for Psychosis

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Above baseline cognition, trajectories, and component-based analyses can identify psychosis and nonremission from illness.

At baseline, patients who are ultrahigh risk for psychosis showed cognitive deficits, but 2 years later, individuals who showed cognitive improvements had a lower risk for psychosis, according to a study published in JAMA Psychiatry.

Individuals who are ultrahigh risk for psychosis (n=173) and healthy controls (n=384) were evaluated for conversion to psychosis every 6 months for 24 months. For data analysis, individuals who are ultrahigh risk for psychosis were grouped as converters (those who were diagnosed with psychosis at some point over the course of the study), nonconverters (those who were not diagnosed with psychosis), remitters (those no longer meeting the criteria for ultrahigh risk for psychosis), or nonremitters (those who still met criteria for ultrahigh risk for psychosis). Evaluations included a series of both psychosis and cognitive assessments.

The results showed an association between baseline cognitive deficits and converters (mean odds ratio [OR] 1.66; combined 95% CI, 1.08-2.83; P= .04) and nonremitters (mean OR 1.67; combined 95% CI, 1.09-2.95; P=.04). A principal component analysis compared cognitive component structure changes and found social cognition, attention, verbal fluency, general cognitive function, and perception to be responsible for variances at baseline for 63.3% of healthy controls, 74.1% of remitters, and 71.2% of nonremitters, and at 24 months for 62.8% of healthy controls, 75.7% of remitters, and 84.4% of nonremitters. At baseline, remitters scored similarly to nonremitters for social cognition, attention, and general cognitive function, but by 24 months, remitters scored more similarly to healthy controls in these areas. Time played a role in the change of function of the healthy controls, remitters, and nonremitters. General cognitive function (F = 12.23; η2 = 0.047; P<.001) and perception (F = 8.33; η2=0.032; P<.001) had a significant group by time interaction.

Cognitive deficits at baseline differentiated each classification category. Underlying cognitive architecture may affect converters and nonremitters over time, and cognitive component structure changes could help evaluate patients with ultrahigh risk for psychosis. Overall, cognitive function improved over time, but this was most apparent in the remitters group. 

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Future studies need to increase sample sizes and age range to evaluate the effect of age on cognitive trajectories, to evaluate subtle changes in cognitive components to separate remitters and nonremitters, and to increase the time of follow-up to analyze long-term changes.

Researchers conclude that cognition deficits are present prior to psychosis, cognitive architecture changes might influence nonremitters, and remitters trend toward characteristics of health controls over time.  They wrote, “Although predominantly a trait, cognitive architecture shows subtle changes over time in nonremitting individuals at [ultrahigh risk] for psychosis. These cognitive architecture changes are associated with functional outcomes and may herald a conversion to psychosis and a cognitive architecture similar to schizophrenia.”

This study was funded by the National Research Foundation Singapore of the National Medical Research Council Translational and Clinical Research Flagship Program. Please refer to reference for a complete list of authors’ disclosures.


Lam M, Lee J, Rapisarda A, et al. Longitudinal cognitive changes in young individuals at ultrahigh risk for psychosis [published online July 25, 2018]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2018.1668