Cognitive Trouble a 'Robust' Predictor of Psychosis

Megan Brooks

November 11, 2016

Neurocognitive impairment, particularly involving attention and memory, is a "robust" characteristic of individuals at clinical high risk (CHR) for psychosis, especially those who transition to psychosis later on, a landmark study suggests.

"Our findings support theoretical models hypothesizing attention and working memory abilities impairments and, even more strongly, impaired declarative memory abilities as central to the CHR stage," the investigators, with first author Larry J. Seidman, PhD, of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, Massachusetts, write.

The study was published online November 2 in JAMA Psychiatry.

Landmark Study

The analysis included data from the second phase of the North American Prodrome Longitudinal Study (NAPLS-2) and included 689 care-seeking individuals at CHR for psychosis and 264 healthy control persons. Eighty-nine (12.9%) of the CHR individuals developed clinical psychosis within 2 years.

As a group, CHR individuals were significantly impaired compared with control persons with respect to attention and working memory (P < .001) and declarative memory (P < .001) and performed significantly worse on 14 of 19 neuropsychological tests. But the mean effect size (ES) across the 19 neuropsychological tests was small (Cohen d = 0.30).

However, the 89 CHR individuals who experienced conversion to psychosis had large deficits in attention and working memory and declarative memory (Cohen d, approximately 0.80) compared with control persons and performed significantly worse on these measures than CHR individuals who did not experience conversion to psychosis (Cohen d, 0.28 and 0.48, respectively).

These results were not accounted for by general cognitive ability, current depression, or use of medication, alcohol, or cannabis, the researchers say.

"To our knowledge, this is the largest and most definitive study of cognition in the high-risk period before onset of psychosis/schizophrenia," Dr Seidman said in a statement. "This is part of a paradigm shift in the way we are focusing on the earlier, prodromal phase of the disorder in an effort to identify those most likely to develop psychosis."

The distinct profile of performance across domains, especially in those at CHR who subsequently experienced conversion, suggests that "at the incipient psychotic phase, specific forms of neurocognition are affected and are predictive of later psychosis," they add.

"Neurocognitive tests used in concert with other clinical and psychobiological measures may enhance prediction of psychosis or functional outcome," the researchers conclude.

New Reference Point

In an accompanying commentary, Abraham Reichenberg, PhD, Department of Psychiatry, Icahn School of Medicine at Mount Sinai in New York City, and Josephine Mollon, King's College London, United Kingdom, note the study is "a comprehensive and significant report. Yet, unavoidably, the authors only have limited space to present and discuss findings in the article itself.

"The results provide a new reference point for clinicians and researchers by elucidating the profile of neurocognitive deficits associated with the prodrome as well as their potential as risk markers for conversion to clinical psychosis," they write.

"If this Invited Commentary may make one recommendation to readers, it is that the supplementary material should be read with the same level of interest as the main article. This may be one of those rare occasions when the supplementary material is almost as relevant as the article itself," they write.

The study was supported by the National Institute of Mental Health. The study authors and the authors of the commentary have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online November 2, 2016. Abstract, Commentary


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