Attentional set-shifting ability in first-episode and established schizophrenia: Relationship to working memory

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Abstract

Patients with established schizophrenia perform poorly on attentional set-shifting tasks, due to a failure of inhibitory control and/or perseverative errors. However, attentional set-shifting is also dependent on working memory capacity, which is additionally impaired in schizophrenia. No studies in first-episode psychosis have specifically examined the contribution of working memory to set-shifting ability in schizophrenia.

We investigated 48 first-episode schizophreniform psychosis/schizophrenia (FE) and 40 chronic schizophrenia (CHR) patients, compared to 67 comparable healthy subjects (CTL). All subjects were assessed using the CANTAB ‘attentional set-shifting (IDED)’ and ‘spatial working memory (SWM)’ tasks.

Both FE and CHR made significantly greater errors on the SWM task (p  0.001). Compared with CTL, CHR was more likely to fail at intra-dimensional (p < 0.05) and extra-dimensional (p < 0.01) shifting and reversal stages of IDED; CHR required significantly greater trials to reach criterion, which was not explained by deficits in SWM (p < 0.001). FE did not differ from CTL on IDED level reached. However, FE required significantly more trials (p = 0.001); this was no longer significant after controlling for SWM deficits (p > 0.05).

Given that the capacity to be flexible and shift attentional set is intact only at the early stages of illness, ‘neurodegenerative’ processes may explain the more severe deficits in chronic schizophrenia. In contrast, deficits in SWM identified at all stages of schizophrenia may reflect incomplete maturation prior to illness onset (‘neurodevelopmental arrest’). Longitudinal studies assessing these cognitive functions from illness onset or in prepsychotic individuals are required.

Introduction

One of the most consistent findings in schizophrenia has been the presence of set-shifting deficits (Fleming et al., 1995). In set-shifting paradigms, such as the Wisconsin Card Sorting Test (WSCT), subjects are required to shift attention between different stimulus dimensions on the basis of reinforcing feedback. In numerous studies of the WCST, patients with schizophrenia achieve fewer sorting categories than control subjects and display significantly more perseverative errors (Kolb and Whishaw, 1983, Weinberger et al., 1986, Goldberg et al., 1987, Morice, 1990). Attentional set-shifting tasks like the WCST require the contribution and co-ordination of numerous complex cognitive processes (e.g. working memory, problem solving, reasoning, inhibition). This is suggestive of the involvement of a number of frontal regions, which are collectively responsible for successful task performance. As a result, it is often difficult to determine which of these cognitive skills contribute to the deficit observed in patients. Although poor performance in patients with schizophrenia has commonly been attributed to a failure to inhibit inappropriate responses (Monchi et al., 2001) and to perseverative responding (Goldberg et al., 1987, Elliott and Sahakian, 1995), failure could be due to a number of other underlying, inter-dependent cognitive skills that are not often assessed in these investigations, such as working memory. Successful performance on the WCST is thought to depend on intact working memory and, given that individuals with schizophrenia show consistent deficits in working memory early in the disorder, failure in set-shifting ability may be a result of a working memory deficit rather than due to a failure of inhibitory control or perseverative responding (Reitan and Wolfson, 1994, Barcelo et al., 2002, Barcelo, 2003, Li et al., 2004).

Importantly, one of the most consistent deficits identified in schizophrenia is in spatial working memory ability (Pantelis et al., 1997; Saperstein et al., 2006, Haenschel et al., 2007, Barch and Smith 2008, Driesen et al., 2008, Lee et al., 2008, Premkumar, 2008). While poor performance in set-shifting tasks may be secondary to a deficit in working memory, few studies have examined the contribution of working memory abnormalities to performance on such tasks.

Recent neuropsychological studies suggest that, while abnormalities in spatial working memory are observed at all illness stages, including prepsychotic ‘at risk’ individuals (Park and Holzman, 1992, Park et al., 1995, Pantelis et al., 1997, Hutton et al., 1998, Brewer et al., 2001, Wood et al., 2002, Badcock et al., 2005, Bartok et al., 2005, Mathes et al., 2005), deficits in attentional set-shifting ability are apparent in established schizophrenia (Elliott et al., 1995, Pantelis et al., 1999, Wood et al., 2002), but not at the earliest stages of illness (Elliott and Sahakian, 1995, Hutton et al., 1998). However, more recently Murray et al. (2008) investigated a first-episode cohort and reported deficits in simple reinforcement learning and reversal learning on an attentional set-shifting task (CANTAB).

A number of studies have investigated attentional set-shifting in first-episode and chronic schizophrenia cohorts using a task derived from the CANTAB computerised battery (Elliott et al., 1998, Hutton et al., 1998, Pantelis et al., 1999). This task is broadly modelled on the WCST, which has been suggested to involve two types of set-shift (Downes et al., 1989, Owen et al., 1991). The task comprises intra-dimensional shifts (id), which involve the transfer of a rule within the same stimulus dimension (e.g. choosing circles instead of squares), and extra-dimensional shifts (ed), which require a transfer of attention across different stimulus dimensions (e.g. choosing on the basis of colour rather than the previous category of shape). In essence, ED shifting is considered the core component of the WCST, and is the basis for the achievement of novel sorting categories. ID shifting, which requires a generalisation of learning or the ability to ‘learn set’, is a more basic element of the WCST and is related to the subject's awareness of the conceptual category within which they are responding. The available cross-sectional studies using the CANTAB IDED task at different stages of schizophrenia suggest that deficits increase with greater illness chronicity (Elliott and Sahakian, 1995, Hutton et al., 1998, Pantelis et al., 1999, Joyce et al., 2002). However, these studies have not directly compared patients at different illness stages and have not accounted for the deficits in working memory ability.

The current study therefore aimed to examine set-shifting ability in patients with established schizophrenia and patients with first-episode psychosis to: (i) directly compare performance of these groups in order to investigate the impact of illness duration; and (ii) assess the relationship between working memory and set-shifting ability.

Section snippets

Patients with first-episode psychosis

First-episode (FE; n = 48) patients with schizophrenia or schizophreniform disorder were recruited from the Orygen Youth Health - Clinical Program, Melbourne, Australia. Study inclusion criteria were: (1) age of onset between 15 and 29 years; and (2) currently psychotic as reflected by the presence of at least 1 symptom (either delusions, hallucinations, disorder of thinking and/or speech other than simple acceleration or retardation, and disorganised, bizarre, or markedly inappropriate

Spatial working memory task

Both FE and CHR made significantly more total between-search errors than CTL on the SWM task [FE: z = 3.38, p = 0.001; CHR: z = 3.82, p < 0.001; covarying for age (z = 3.33, p = 0.001) and premorbid IQ (z =  1.65, p = 0.1)]. The two patient groups did not differ in their performance on the task [z =  0.37, p = 0.708].

Attrition rates

Binomial logistic regression was conducted using the ENTER technique at each of the nine levels of the IDED task (sd, sr, c_d, cd, cdr, ids, idr, eds, edr) to determine the independent associations of

Discussion

In this study we assessed attentional set-shifting and spatial working memory abilities in patients at the beginning of a schizophrenic illness, compared with established schizophrenia patients and comparable healthy control subjects. Patients both early and late in the illness were significantly impaired on a task assessing spatial working memory ability compared with healthy subjects. These findings are consistent with previous findings of SWM deficits in patients with first-episode psychosis

Role of funding source

Funding sources had no involvement in the design, execution, analysis, interpretation, writing up, or decision to submit.

Contributors

Pantelis, Brewer, Proffitt, Velakoulis, McGorry designed the study. Pantelis, Velakoulis, McGorry were Chief Investigators on grants from NHMRC. Proffitt, Mahony, Brewer, Buchanan, Velakoulis were involved in subject recruitment and data collection. Pantelis, Mahony, Wood, Testa were involved in data analysis and first draft of manuscript. All authors contributed to writing and revision of the paper.

Conflict of interest

None.

Acknowledgements

This work has been supported by the Colonial Foundation, Ian Potter Foundation, a National Health and Medical Research Council (NHMRC) Program Grant (ID: 350241) and NHMRC Project Grants (grant IDs: 145627, 981112, 970598, 970391). Dr Wood is supported by an NHMRC Career Development Award (ID:359223) and a NARSAD Young Investigator Award. A/Prof Brewer is the recipient of an NHMRC Career Development Award (ID: 454792).

References (66)

  • LenczT. et al.

    Generalized and specific neurocognitive deficits in prodromal schizophrenia

    Biol. Psychiatry

    (2006)
  • LiZ.H. et al.

    Behavioral and functional MRI study of attention shift in human verbal working memory

    Neuroimage

    (2004)
  • OwenA.M. et al.

    Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man

    Neuropsychologia

    (1991)
  • PantelisC. et al.

    Neuropsychological and olfactory dysfunction in schizophrenia: relationship of frontal syndromes to syndromes of schizophrenia

    Schizophr. Res.

    (1995)
  • PantelisC. et al.

    Comparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage

    Schizophr. Res.

    (1999)
  • PantelisC. et al.

    Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison

    Lancet

    (2003)
  • PremkumarP.

    Neuropsychological function–brain structure relationships and stage of illness: an investigation into chronic and first-episode schizophrenia

    Psychiatry Res. Neuroimaging

    (2008)
  • SunD. et al.

    Progressive brain structural changes mapped as psychosis develops in ‘at risk’ individuals

    Schizophr. Res.

    (2009)
  • TysonP.J. et al.

    Stability of set-shifting and planning abilities in patients with schizophrenia

    Psychiatry Res.

    (2004)
  • Van HarenN. et al.

    Progressive brain volume loss in schizophrenia over the course of the illness: evidence of maturational abnormalities in early adulthood

    Biol. Psychiatry

    (2008)
  • WibleC.G. et al.

    Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

    Psychiatry Res.

    (2001)
  • BarceloF. et al.

    Think differently: a brain orienting response to task novelty

    Neuroreport

    (2002)
  • BrewerW.J. et al.

    Stability of olfactory identification deficits in neuroleptic-naive patients with first-episode psychosis

    Am. J. Psychiatry

    (2001)
  • De LucaC. et al.

    Normative data from the CANTAB. I: development of executive function over the lifespan

    J. Clin. Exp. Neuropsychol.

    (2003)
  • ElliottR. et al.

    The neuropsychology of schizophrenia: relations with clinical and neurobiological dimensions

    Psychol. Med.

    (1995)
  • ElliottR. et al.

    Neuropsychological evidence for frontostriatal dysfunction in schizophrenia

    Psychol. Med.

    (1995)
  • ElliottR. et al.

    Specific neuropsychological deficits in schizophrenic patients with preserved intellectual function

    Cogn. Neuropsychiatry

    (1998)
  • GardnerW. et al.

    Regression analyses of counts and rates: Poisson, overdispersed Poisson, and negative binomial models

    Psychol. Bull.

    (1995)
  • GoldbergT.E. et al.

    Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test

    Arch. Gen. Psychiatry

    (1987)
  • HaenschelC. et al.

    Contribution of impaired early-stage visual processing to working memory dysfunction in adolescents with schizophrenia: a study with event-related potentials and functional magnetic resonance imaging

    Arch. Gen. Psychiatry

    (2007)
  • HuttonS.B. et al.

    Executive function in first-episode schizophrenia

    Psychol. Med.

    (1998)
  • JoyceE. et al.

    Executive dysfunction in first-episode schizophrenia and relationship to duration of untreated psychosis: the West London Study

    Br. J. Psychiatr. Suppl.

    (2002)
  • KayS.R. et al.

    The positive and negative syndrome scale (PANSS) for schizophrenia

    Schizophr. Bull.

    (1987)
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