Attentional set-shifting ability in first-episode and established schizophrenia: Relationship to working memory
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)
- et al.
Spatial working memory and planning ability: contrasts between schizophrenia and bipolar I disorder
Cortex
(2005) The Madrid card sorting test (MCST): a task switching paradigm to study executive attention with event-related potentials
Brain Res. Brain Res. Protoc.
(2003)- et al.
The Cognitive Neuroscience of Working Memory: relevance to CNTRICS and schizophrenia
Biol. Psychiatry
(2008) - et al.
Cognitive functions in prepsychotic patients
Prog. Neuro-psychopharmacol. Biol. Psychiatry
(2005) - et al.
Reductions in frontal, temporal and parietal volume associated with the onset of psychosis
Schizophr. Res.
(2008) - et al.
Impaired extra-dimensional shift performance in medicated and unmedicated Parkinson's disease: evidence for a specific attentional dysfunction
Neuropsychologia
(1989) - et al.
Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence
Biol. Psychiatry
(2008) - et al.
Verbal working memory dysfunction in schizophrenia: use of a Brown–Peterson paradigm
Psychiatry Res.
(1995) - et al.
Grey matter changes over time in high risk subjects developing schizophrenia
Neuroimage
(2005) - et al.
Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis
Biol. Psychiatry
(2006)