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Original Investigation
December 2016

Association of Neurocognition With Transition to PsychosisBaseline Functioning in the Second Phase of the North American Prodrome Longitudinal Study

Author Affiliations
  • 1Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • 2Department of Psychiatry, Harvard Medical School at Massachusetts General Hospital, Boston
  • 3Department of Psychiatry, Zucker Hillside Hospital, Queens, New York
  • 4Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
  • 5Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles
  • 6Department of Psychology, University of California, Los Angeles
  • 7Department of Psychiatry, University of California, San Diego
  • 8Department of Psychology, Yale University, New Haven, Connecticut
  • 9Department of Psychiatry, Yale University, New Haven, Connecticut
  • 10Department of Psychiatry, University of California, San Francisco
  • 11San Francisco Veterans Affairs Medical Center, San Francisco, California
  • 12Department of Psychiatry, The University of North Carolina at Chapel Hill
  • 13Department of Psychology, Emory University, Atlanta, Georgia
  • 14Department of Psychiatry, Emory University, Atlanta, Georgia
JAMA Psychiatry. 2016;73(12):1239-1248. doi:10.1001/jamapsychiatry.2016.2479
Key Points

Questions  What are the core neurocognitive dysfunctions associated with the clinical high-risk state of psychosis, and which functions are associated with individuals who transition to full psychosis?

Findings  In this multisite, case-control study and standardized assessment across 8 sites, clinical high-risk individuals were significantly impaired in virtually all neurocognitive dimensions compared with controls, especially in those who later transitioned to psychosis. Verbal abilities and declarative memory abilities were associated with time to conversion to psychosis, in association with age, site, and unusual thought content and suspiciousness.

Meaning  Interventions targeting the enhancement of neurocognitive functioning are warranted in those at clinical high risk for psychosis.

Abstract

Importance  Neurocognition is a central characteristic of schizophrenia and other psychotic disorders. Identifying the pattern and severity of neurocognitive functioning during the “near-psychotic,” clinical high-risk (CHR) state of psychosis is necessary to develop accurate risk factors for psychosis and more effective and potentially preventive treatments.

Objectives  To identify core neurocognitive dysfunctions associated with the CHR phase, measure the ability of neurocognitive tests to predict transition to psychosis, and determine if neurocognitive deficits are robust or explained by potential confounders.

Design, Setting, and Participants  In this case-control study across 8 sites, baseline neurocognitive data were collected from January 2009 to April 2013 in the second phase of the North American Prodrome Longitudinal Study (NAPLS 2). The dates of analysis were August 2015 to August 2016. The setting was a consortium of 8 university-based, outpatient programs studying the psychosis prodrome in North America. Participants were 264 healthy controls (HCs) and 689 CHR individuals, aged 12 to 35 years.

Main Outcomes and Measures  Neurocognitive associations with transition to psychosis and effects of medication on neurocognition. Nineteen neuropsychological tests and 4 factors derived from factor analysis were used: executive and visuospatial abilities, verbal abilities, attention and working memory abilities, and declarative memory abilities.

Results  This study included 264 HCs (137 male and 127 female) and 689 CHR participants (398 male and 291 female). In the HCs, 145 (54.9%) were white and 119 (45.1%) were not, whereas 397 CHR participants (57.6%) were white and 291 (42.3%) were not. In the HCs, 45 (17%) were of Hispanic origin, whereas 127 CHR participants (18.4%) were of Hispanic origin. The CHR individuals were significantly impaired compared with HCs on attention and working memory abilities and declarative memory abilities. The CHR converters had large deficits in attention and working memory abilities and declarative memory abilities (Cohen d, approximately 0.80) compared with controls and performed significantly worse on these dimensions than nonconverters (Cohen d, 0.28 and 0.48, respectively). These results were not accounted for by general cognitive ability or medications. In Cox proportional hazards regression, time to conversion in those who transitioned to psychosis was significantly predicted by high verbal (premorbid) abilities (β = 0.40; hazard ratio [HR], 1.48; 95% CI, 1.08-2.04; P = .02), impaired declarative memory abilities (β = −0.87; HR, 0.42; 95% CI, 0.31-0.56; P < .001), age (β = −0.10; HR, 0.90; 95% CI, 0.84-0.97; P = .003), site, and a combined score of unusual thought content or delusional ideas and suspiciousness or persecutory ideas items (β = 0.44; HR, 1.56; 95% CI, 1.36-1.78; P < .001).

Conclusions and Relevance  Neurocognitive impairment, especially in attention and working memory abilities and declarative memory abilities, is a robust characteristic of CHR participants, especially those who later develop psychosis. Interventions targeting the enhancement of neurocognitive functioning are warranted in this population.

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