Neuropsychological deficits in individuals with an at risk mental state for psychosis — Working memory as a potential trait marker

https://doi.org/10.1016/j.schres.2007.09.003Get rights and content

Abstract

Objective

To investigate the neuropsychological profile of individuals with an at risk mental state for psychosis (ARMS, N = 60) compared to healthy controls (HC, N = 51) and to identify those cognitive domains which discriminate best between groups.

Method

Study subjects and controls were compared using a neuropsychological test battery covering the domains of intelligence (LPS3, MWT-A), executive functions (ToH, WCST, TAP - Go/NoGo), working memory (Tests for Attentional Performance (TAP) - Working Memory), and attention (CPT-OX). A multivariate analysis of variance (MANOVA) comparing ARMS subjects with HC was conducted. A stepwise logit regression procedure was performed in order to determine the subset of measures which best distinguish ARMS subjects from HC.

Results

ARMS subjects revealed deficiencies in intelligence, executive functions, working memory and attention. Verbal intelligence, executive functions, and, in particular, working memory discriminated best between the groups.

Conclusion

Individuals with an at risk mental state for psychosis already show impairment of neuropsychological functions prior to the onset of the first psychotic episode and can best be distinguished from healthy controls on the basis of working memory.

Introduction

The early detection of psychosis and of individuals at risk for psychosis has become a well established goal within the psychiatric health care system. Risk assessment is mainly based on the presence of prodromal symptoms, self-limiting or attenuated psychotic symptoms, and a family history of psychosis in connection with deterioration in social functioning (Yung et al., 2004, Riecher-Rössler et al., 2006). But the risk assessment is not very reliable yet. Only about 20–40% of individuals identified as being at risk in fact progress to frank psychosis within a 12-month observation period (Yung et al., 2004, Riecher-Rössler et al., 2007, for review see Phillips et al., 2005).

On the other hand, studies seem to show that cognitive functioning is not only reduced in frank schizophrenia, but already in individuals with an “at risk mental state” (for review Brewer et al., 2006) and in individuals at genetic risk (for review see Niemi et al., 2003, Keshavan et al., 2005). The assessment of cognitive functioning could thus potentially enhance the predictive power of early detection of psychosis in future.

Several impaired cognitive domains associated with a prodromal state have been reported, such as impaired sustained attention, verbal and logical memory, executive functions, and spatial working memory, performance IQ, premorbid and global IQ (Brewer et al., 2005, Brewer et al., 2006). Complementary findings have recently been obtained by Niendam et al. (2006), who documented evidence for a slowing of information processing speed on the one hand and reduced motor speed on the other hand.

The results of these studies on prodromal subjects are supported by similar findings from earlier studies on subjects at risk for schizophrenia defined by genetic risk only (Cosway et al., 2000, Cornblatt et al., 1999, Reichenberg et al., 2000). Thus, cognitive functioning in relatives of schizophrenic patients showed moderate impairments in abstraction, attention, executive functions, spatial memory, sensory-motor functioning (Staal et al., 2000, Wolf et al., 2002, Erlenmeyer-Kimling et al., 2000) and impaired verbal and non-verbal intelligence, verbal logical, episodic and semantic memory, and language functions (Cosway et al., 2000, Egan et al., 2001, Byrne et al., 2003). Controversial results have been obtained with respect to sustained attention. While Cornblatt et al. (1999) documented a reduction in sustained attention only in those who later transited to psychosis, some other studies failed to provide any evidence of reduced sustained attention in individuals at genetic risk for psychosis (Cosway et al., 2002).

In summary, although there is in meantime a considerable number of studies on the neuropsychological function of individuals at risk for psychosis, only few focus on clinically defined at risk individuals in terms of a current at risk mental state respectively potential prodromal state (Brewer et al., 2006, Lencz et al., 2006, Hawkins et al., 2004, Silverstein et al., 2006, Bartok et al., 2005, Hambrecht et al., 2002). Furthermore, some of these studies so far have not thoroughly controlled for the influence of confounding variables such as age, gender, and education.

Thus, the aim of this study is to further clarify the nature and extent of neuropsychological deficits in individuals with an at risk mental state (ARMS) as compared to healthy control subjects controlling for the influence of confounding factors. The study's specific aim is to identify neuropsychological tests that provide a major contribution towards distinguishing individuals with an at risk mental state from HC.

This study is part of the Basel FePsy study (Früherkennung von Psychosen), which aims to improve the early detection of psychosis. The multi-domain assessment approach used in this study covers psychopathological, neuropsychological, neurophysiological, and neuroimaging investigations (Riecher-Rössler et al., 2007).

Section snippets

Methods

The neuropsychological data reported on here were collected within the research project “Prediction and early detection of schizophrenia — a prospective multilevel approach” at the Psychiatric Department of the University Hospital Basel, Switzerland. The study design and preliminary results of the study have been described in detail elsewhere (Riecher-Rössler et al., 2007, Gschwandtner et al., 2006, Borgwardt et al., 2006, Borgwardt et al., 2007). This report goes beyond previously published

Sample characteristics and confounding factors

Table 1 summarizes the sample characteristics of both groups. Whereas ARMS subjects were approximately four years older than the HC (p = .032), there were no significant differences between the groups concerning, gender, handedness or the number of educational years. However, ARMS subjects showed a larger variance regarding the mean number of educational years (p = .005). ARMS received significantly more often antidepressant medication than HC (p < .001). Current use of cannabis was reported by 19

Discussion

As our results show, ARMS subjects suffer from deficiencies in intelligence, executive functions and working memory compared to HC. These results where independent of whether we only analyzed the ARMS-high risk group according to the definition of Yung et al. (1998) or whether we also included 6 low risk individuals.

Regarding intelligence, our data are in line with the findings of most other authors and show a reduced intellectual capacity in ARMS subjects, especially with respect to verbal

Role of funding source

This project is supported by the Swiss National Science Foundation no. 3200-057216.99, no. 3200-057216.99 and no. PBBSB-106936, the Nora van Meeuwen-Haefliger Stiftung, Basel (CH) and by unconditional grants from the Novartis Foundation, Bristol-Myers Squibb GmbH (CH), Eli Lilly SA (CH), AstraZeneca AG (CH), Janssen-Cilag AG (CH) and Sanofi-Synthelabo AG (CH).

Contributors

Pflueger M and Gschwandtner U contributed equally to this work.

Conflict of interest

See section Role of the funding source.

Acknowledgements

We want to thank Dr. Ch. Schindler (Institute of Social and Preventive Medicine of the University of Basel) for his help with statistical analyses, Prof. Dr. G. Sachs (University Psychiatric Hospital Vienna), Dr. J. Aston, and Dr. G. Berger (both Psychiatric Department of the University Hospital Basel) for their helpful comments and all coworkers of the project for assessing the patients.

References (57)

  • L.T. Niemi et al.

    Childhood developmental abnormalities in schizophrenia: evidence from high-risk studies

    Schizophr. Res.

    (2003)
  • S. Silverstein et al.

    Perceptual organization in first episode schizophrenia and ultra-high-risk states

    Schizophr. Res.

    (2006)
  • W.G. Staal et al.

    Neuropsychological dysfunctions in siblings discordant for schizophrenia

    Psychiatry Res.

    (2000)
  • I. Szendi et al.

    Correlations between clinical symptoms, working memory functions and structural brain abnormalities in men with schizophrenia

    Psychiatry Res.

    (2006)
  • D.R. Weinberger et al.

    Neurobiology of schizophrenia and the role of atypical antipsychotics. Prefrontal neurons and the genetics of schizophrenia

    Soc. Biol. Psychiatry

    (2001)
  • L.E. Wolf et al.

    Wisconsin card sorting deficits in the offspring of schizophrenics in the New York high-risk project

    Schizophr. Res.

    (2002)
  • A.R. Yung et al.

    Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features

    Schizophr. Res.

    (2004)
  • A. Baddeley

    Working memory: looking back and looking forward

    Nat. Rev., Neurosci.

    (2003)
  • S.J. Borgwardt et al.

    Radiological findings in individuals at high risk of psychosis

    J. Neurol. Neurosurg. Psychiatry

    (2006)
  • G.E.P. Box et al.

    An analysis of transformations

    J. R. Stat. Soc., Ser. B (Methodological)

    (1964)
  • W.J. Brewer et al.

    Memory impairments identified in people at ultra-high risk for psychosis who later develop first-episode psychosis

    Am. J. Psychiatry

    (2005)
  • W.J. Brewer et al.

    Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis

    Schizophr. Bull.

    (2006)
  • M. Byrne et al.

    Neuropsychological assessment of young people at high genetic risk for developing schizophrenia compared with controls: preliminary findings of the Edinburgh High Risk Study (EHRS)

    Psychol. Med.

    (1999)
  • M. Byrne et al.

    Neuropsychology, genetic liability, and psychotic symptoms in those at high risk of schizophrenia

    J. Abnorm. Psychology

    (2003)
  • B. Cornblatt et al.

    Global attentional deviance as a marker of risk for schizophrenia: Specificity and predictive validity

    J. Abnorm. Psychology

    (1985)
  • B. Cornblatt et al.

    Cognitive and behavioral precursors of schizophrenia

    Dev. Psychopathol.

    (1999)
  • R. Cosway et al.

    Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study

    Psychol. Med.

    (2000)
  • R. Cosway et al.

    Sustained attention in young people at high risk for schizophrenia

    Psychol. Med.

    (2002)
  • Cited by (80)

    • Working-memory impairment in schizophrenia and schizotypal personality disorder

      2021, Cognitive and Behavioral Dysfunction in Schizophrenia
    View all citing articles on Scopus
    View full text