Could Cognitive Assessments Enhance Ability to Detect Transition to Psychosis?

Cognitive problems are a hallmark feature of schizophrenia, and many of these deficits are present in milder forms during the prodromal phase of psychosis.

A study of the largest and most diverse sample of individuals considered to be clinically high risk for psychosis suggests that working memory and declarative memory deficits are most strongly associated with subsequent psychosis. These differences may help researchers better identify the roughly 30 percent of high-risk patients most likely to transition to psychosis. The findings were published in the December 2016 issue of JAMA Psychiatry.

The participants included 689 individuals in the clinical high-risk (CHR) period of psychosis and 264 matched controls who were a part of the multisite North American Prodrome Longitudinal Study second phase (NAPLS2). All participants underwent a series of 19 neuropsychological tests that covered four principal factors of cognition: executive and visuospatial abilities, verbal abilities, attention and working memory, and declarative memory.

“We found that people at high risk for psychosis had a broad range of cognitive deficits, though areas of working memory and declarative memory were most strongly associated with subsequent psychosis,” said lead author Larry Seidman, Ph.D., a professor in the Department of Psychiatry at Harvard Medical School and vice chair of the Public Psychiatry Division at Beth Isreal Deaconess Medical Center.

In particular, the 89 CHR individuals who eventually transitioned to psychosis within two years performed significantly worse in two tasks compared with the 600 CHR individuals who did not transition. These tests were the Brief Visuospatial Memory Test–Revised (BVMTR) and Paired Associate Memory (PAM) test.

Seidman cautioned that while these test scores on average were significantly different between the groups, any test by itself would not be predictive at an individual level. However, including a cognitive test in a set of diagnostic assessments might help identify those at greatest risk.

The NAPLS2 group recently developed an individualized risk calculator for patients with prodromal psychosis that included both verbal memory and attention scores as components of the algorithm. A description of this calculator, which could distinguish psychosis converters from nonconverters about 70 percent of the time, was published in the October 2016 issue of the American Journal of Psychiatry. (The study was one of the AJP editor’s top picks for 2016.

Scott Clark, Ph.D., M.B.B.S., a researcher at the University of Adelaide in Australia who studies early detection of psychosis, told Psychiatric News that the results of the JAMA Psychiatry study further support the use of cognitive assessments in high-risk individuals for psychosis.

Clark and his colleagues are currently working on their own protocol for psychosis risk assessments. Their approach is to administer specific tests one at a time in a stepwise fashion until a high-risk patient can be confidently classified as a converter or nonconvertor.

The tests, which include clinical rating scales, family history, and biological measurements, are arranged to try and reserve tests that may be time consuming or expensive toward the end of the protocol, so they would be needed only in rare cases.

Clark has tested various permutations of this stepwise algorithm—with and without cognitive assessments—and found multiple ways to achieve good accuracy (similar to the 70 percent seen in the NAPLS2 calculator). Regardless of the combination of assessments, Clark’s group has found that at least three separate measurements are needed to reach this threshold. “From a practical standpoint, having flexibility in what tests you need is valuable since clinics vary in their resources and clinician expertise,” he said. “It’s a case of letting each center do the best with what they got.”

In that pragmatic fashion, Clark thinks Seidman’s findings could have potential use in a stepwise prediction algorithm. “The PAM, in particular, only takes around 10 minutes to conduct, so it could be an efficient element of a risk calculator in a busy setting,” Clark said.

Beyond diagnosis, Seidman is hopeful that delineating the cognitive defects in CHR individuals may lead to the design of tailored cognitive-enhancement therapies.

“The question is, can we prevent psychosis? Or can we prevent only cognitive comorbidity when psychosis manifests?” Seidman asked.

Even if just the latter question proves true, it still will offer tremendous help to psychosis patients, he said.

“We think of curing or preventing a disease as a goal, but another important goal is to treat disability. And when it comes to schizophrenia, poor cognition is the most disabling aspect. If we can identify and target cognitive problems, we can help these people get back to work, get back to school, get back to their lives.” ■

“Association of Neurocognition With Transition to Psychosis: Baseline Functioning in the Second Phase of the North American Prodrome Longitudinal Study” can be accessed here. “An Individualized Risk Calculator for Research in Prodromal Psychosis” is available here.