Cognition and Outcomes in Clinical High-Risk for Psychosis


Does cognition predict outcomes in patients at clinical high-risk for psychosis?


Cognitive deficits are a well-replicated finding across the course of illness, including the psychosis prodrome, in schizophrenia.1,2 There is evidence for cognitive decline in subjects at clinical high-risk for psychosis (CHR) compared to controls, with larger effect sizes in subjects who transition to a psychotic disorder.3 There is also meta-analytic evidence for broad neurocognitive impairments in memory, attention, verbal and visuospatial abilities, social cognition, and executive function in CHR subjects.3 Furthermore, cognitive deficits in CHR are independent predictors of conversion to psychosis and other outcomes.4,5

Cui and colleagues6 aimed to relate baseline cognitive performance to a broad range of clinical outcomes at 1-year follow-up in CHR participants and controls from the ShangHai-At-Risk-for-Psychosis (SHARP) study, which launched in China in 2010. They hypothesized that patients with CHR who converted to psychosis (CHR-C) would have greater cognitive impairments than CHR non-converters (CHR-NC), and both CHR groups would have greater cognitive impairments than healthy controls. They also analyzed outcomes in CHR participants based on clinical status (trichotomized as remission, symptomatic, or poor outcome).

A total of 217 CHR participants and 133 healthy controls from the SHARP study completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and provided complete clinical data.These subjects represent over 90% of the subjects who provided 1-year assessment data.Subjects had a mean age of 18.6 years, 47% were male, and were lifetime psychotropic-naïve at study entry. Subsequently, 80% of CHR subjects received antipsychotic medications.Includes criteria for all subjects were age 13-45, ≥6 years of education, and available legal guardian for subjects age <18. Patients with IQ<70, severe somatic disease, and lifetime substance dependence were excluded. Psychotic disorder or prodromal symptoms were ruled out by structured clinical interview.

Raw cores on the MCCB were converted to Z-scores based on the healthy control scores. The CHR group was divided into CHR-NC (n=155) and CHR-C (n=41) based on the 1-year follow-up assessment.In other analyses, the CHR was trichotomized to 3 clinical outcomes at 1-year: CHR-remission (n=102), CHR-symptomatic (n=37), and CHR-poor outcome (n=57).The CHR-remission group included subjects with spontaneous remission or were improved with antipsychotic medication to mildly impaired ranges or better (SIPS positive symptom scores ≤2) and global function ≥60 at follow-up.The CHR-symptomatic group included medicated subjects with SIPS positive symptom scores of 3-5 and global function ≥60 at follow-up.The CHR-poor outome group included those who converted to psychosis (n=41) and medicated subjects with unremitting positive symptoms (SIPS positive symptom scores of 3-5) and poor global function (<60) at follow-up (n=16). Data were analyzed using multivariate analysis of variation with Bonferroni-adjusted post-hoc pair-wise comparisons between groups for MCCB scores. Effect sizes were calculated using Cohen’s d.

There were no significant differences regarding age, sex, or education between CHR and healthy control groups.Scores were significantly lower than those for healthy controls on all MCCB subsets for all CHR subjects as well as the CHR-C and CHR-NC subgroups.CHR-C subjects performed significantly worse than CHR-NC subjects on the Trail Making Test A (small effect size) and the Brief Visuospatial Memory Test-Revised (medium effect size).

Compared to controls, CHR-remission and CHR-poor outcome scores were lower for all MCCB subsets (medium to large effect sizes for poor outcome), and CHR-symptomatic scores were lower of 6 of 8 MCCB subsets.Furthermore, Brief Visuospatial Memory Test-Revised scores were significantly lower in the CHR-poor outcome versus CHR-remission group.

The authors note that an educated, mostly urban Chinese sample of CHR subjects had cognitive impairments of a similar magnitude to a western prodromal consortium (NAPLS), with evidence for greater impairments in those who converted to psychosis at 1-year follow-up (versus non-converters). Findings increase our understanding of neurocognitive heterogeneity in CHR subjects. The relatively small sample size of some CHR subgroups and 1-year (versus a longer follow-up) duration are noted as potential limitations.

The bottom line

This study demonstrates the feasibility of harmonizing measures across different geographical locations for the reliable and valid assessment of neurocognition in CHR subjects.

Dr Miller is Professor, Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is the Schizophrenia Section Chief for Psychiatric Times. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.


1. Agnew-Blais J, Seidman LJ. Neurocognition in youth and young adults under age 30 at familial risk for schizophrenia: a quantitative and qualitative review. Cogn Neuropsychiatry. 2013;18(1-2):44-82.

2. Gur RC, Calkins ME, Satterthwaite TD, et al. Neurocognitive growth charting in psychosis spectrum youths. JAMA Psychiatry. 2014;71(4):366-374.

3. Fusar-Poli P, Deste G, Smieskova R, et al. Cognitive functioning in prodromal psychosis: a meta-analysis. Arch Gen Psychiatry. 2012;69:562–571.

4. Bolt LK, Amminger GP, Farhall J, et al. Neurocognition as a predictor of transition to psychotic disorder and functional outcomes in ultrahigh risk participants: findings from the NEURAPRO randomized clinical trial. Schizophr Res. 2019;206:67–74.

5. Seidman LJ, Shapiro DI, Stone WS, et al. Association of neurocognition with transition to psychosis: Basline functioning in the second phase of the North American Prodrome Longitudinal Study. JAMA Psychiatry. 2016;73:1239–1248.

6. Cui H, Giuliano AJ, Zhang T, et al. Cognitive dysfunction in a psychotropic medication-naïve, clinical high-risk sample from the ShangHai-At-Risk-for_psychosis (SHARP) study: associations with clinical outcomes. Schizophr Res. 2020.

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