Executive Dysfunction in First-Episode Schizophrenia and Relationship To

BRITISH JOURNAL OF PSYCHIATRY (2002), 181 (suppl. 43), s38^s38^s44 s44

Executive dysfunction in first-episode schizophrenia DSM–IV (American Psychiatric Associa- tion, 1994) criteria at regular review meet- and relationship to duration of untreated psychosis: ings held by two experienced clinicians (E.J., T.B.). A total of 95% of the subjects fulfilled the diagnostic criteria for schizo- the West London Study* phrenia and the remainder, for schizophreniform disorder. Normal volunteers EILEEN JOYCE, SAM HUTTON, STAN MUTSATSA, HEIDI GIBBINS, ((nn¼81) served as controls and were re- EMMA WEBB, SONJA PAUL, TREVOR ROBBINS and THOMAS BARNES cruited from the same catchment area by advertising in local job centres and hospi- tals. Exclusion criteria were a history of mental illness themselves or in their Background Many studies have The presence of cognitive dysfunction early first-first-degreedegree relatives, the presence of a med- demonstrated earlygeneralised cognitive in the course of schizophrenia is well docu- ical illness which might impair cognitive mented (Bilder et aletal, 1992, 2000; Hoff et aletal,, function and a history of alcohol or drug impairment in schizophrenia. 1992; Saykin et aletal, 1994; Albus et aletal, 1996;,1996; misuse. Permission to conduct the study Aims To examine executive functioninfunction in HuttonHutton et aletal, 1998; Mohamed et aletal, 1999).,1999). was obtained from Riverside, Merton, Most studies describe a general impairment Sutton and Wandsworth, Kingston and first-episode schizophrenia, characterise which differs from that of chronic patients Richmond and Ealing, Hammersmith and the nature ofthe impairment and specify only in degree (Saykin et aletal, 1994). Many Fulham Local Research Ethics Committees. anyrelationships with symptoms and first-episode studies have used large batteries Patients and controls gave written informed duration of untreated psychosis (DUP). of neuropsychological tests and have derived consent. Data from 30 patients and 30 global measures of function. Although this controls have been presented previously MethodMethod Patients ((Patients nn¼136) and normal strategy produces robust measures, infor- (Hutton(Hutton et aletal, 1998).,1998). controls (nn¼81) were assessed with the mation concerning the specific nature of cognitive impairment is lost (Hutton et aletal,, Cambridge Automated Neuropsycho- Clinical assessments 1998). We therefore examined neuro- Patients were assessed on recruitment with logical Test Battery,National Adult psychological performance in detail using the Scales for the Assessment of Positive ReadingTest IQ, and Scales for the the Cambridge Automated Neuropsycho- Symptoms (SAPS; Andreasen, 1981) and Assessmentof Positive and Negative logical Test Battery (CANTAB), which Negative Symptoms (SANS; Andreasen, allows decomposition of performance into Symptoms. 1983). Scores for positive, disorganisation more fundamental cognitive processes and negative syndromes of schizophrenia (Hutton(Hutton et aletal, 1998). In a small group of ResultsResults Memory and executive (Liddle & Barnes, 1990) were calculated first-episode patients we found a specific impairmentsin patients were independent for each patient by summing the SAPS and profile of executive impairment that differed of IQ level. Spatial working memory was SANS global sub-scale scores pertaining to from that of chronic patients (Elliott et aletal,, each factor. Duration of untreated psycho- impaired because of inadequate strategy 1995, 1998; Pantelis et aletal, 1997). We now sis (DUP) was established for each patient use.On a planning task, patients showed report our findings in a larger group of by reviewing relevant information in the patients. We also explored the effect of reduced planning times and suboptimal case notes, and questioning the patient chronicity on cognitive function by examin- problem-solving.On an attentional set- and relatives and/or carers. A modified ing the relationship between neuropsycho- questionnaire (Loebel et aletal, 1993) was shifting task, 75% of patients were able to logical performance and duration of used, relating to the onset of positive psy- perform an extra-dimensional shift untreated psychosis. chotic symptoms (Lieberman et aletal, 1993).,1993). thoughtto be a core attribute of prefrontal cortex function.Those who failed had Cognitive function significantlylonger DUP. METHOD In order to test as wide a range of patients Subjects Conclusions Prefrontal cortex as possible and to reduce state effects, Patients (Patients(nn¼136) were recruited as soon as neuropsychological assessments were under- function deteriorates atthe onset of possible after presentation to mental health taken when the patient was able to co- psychosis and continues to worsen over services. The catchment population in- operate with the requirements of the time. cluded deprived inner-city and relatively af- testing procedure, usually once they had fluent suburban areas of west London, UK. been medicated. To examine the specificity Declaration of interest None. The patients eligible for the study were aged of frontal executive impairments, IQ and Funding from The WellcomeTrust. between 16 and 50 years, were presenting to memory were also assessed. The National mental health services with a schizophreni- Adult Reading Test (NART) was used to form psychosis for the first time and had estimate IQ (Nelson & Willison, 1991). *Presented in part atthe European First Episode received no more than 12 weeks of anti- Several subjects in both groups declined to Schizophrenia Network Meeting,Whistler BC,Canada, psychotic medication. In each case the take this test because of dyslexia or other 27 April 2001. diagnosis was determined according to reading problems. IQ was obtained for

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110 patients and 73 controls. CANTAB each problem, a yoked control condition for two-group single variable measures, tests of memory and executive function provided measures of motor initiation and with degrees of freedom adjusted according were administered on an IBM-compatible execution times. As a stringent measure of to Levene’s test for equality of variance. For PC with a touch-sensitive screen (Sahakian accuracy, the proportion of problems repeated measures data, the analysis of & Owen, 1992). solved in the minimum number of moves, variance (ANOVA) was used. To explore i.e. perfect solutions, was used. Latency whether general IQ explained performance Spatial span (Owen et al, 1990) measures were: (a) initial thinking time on the more specific tests, Pearson’s corre- (planning time), derived by subtracting the lation coefficients between NART IQ and This measured the ability to remember the time taken to complete the first move of memory and executive variables were cal- order of sequences of squares presented each problem during the control phase culated and, where significant, the analyses on the screen in increasing number. This from that of the planning phase; and (b) were repeated with an analysis of covar- task was completed by 135 patients. subsequent thinking time per move, derived iance (ANCOVA) entering IQ as a covari- by subtracting the time to complete the task ate. For the attentional set-shifting task, Pattern and spatial recognition memory after the first move during the control phase the numbers of subjects and controls pas- (Sahakian et al,1988)al, 1988) from that of the planning phase, divided by sing or failing each stage were cast into In the pattern recognition test, 12 abstract the number of moves taken for each contingency tables and analysed using the visual stimuli were presented sequentially problem. A total of 135 patients completed likelihood ratio method (Kullback, 1959; on the screen. Each stimulus was then this task.thistask. Robbins, 1977). The resultant information

presented along with a novel stimulus and statistic (2statistic(2ii) is distributed as chi-squared. the subjects were asked to touch the familiar Attentional set-shifting (Owen et al, 1991) Because of multiple comparisons, aa waswas stimulus. This was repeated with 12 differ- set at 0.01.0.01.setat Subjects were required to learn a series of ent stimuli, giving a maximum possible visual discriminations in which one of two score of 24. In the spatial task, five identical stimulus dimensions (shape or line) was RESULTSRESULTS squares were presented in series, each in a relevant. Once correct responding was different location. One square was then Subjects established, they were introduced to differ- presented at each target location along with Eighty-eight per cent of patients were tested ent exemplars of the same dimensions. a square at a novel location. Subjects were within 8 weeks of recruitment (median 2.7 Subjects needed to maintain attention to asked to touch the square at the location weeks; range 0–43). Fifty-eight patients the same dimension for correct responding, they recognised from the learning phase. were prescribed the newer antipsychotic thus testing their ability to generalise the rule Four such trials using different locations drugs (42 olanzapine, 15 risperidone, 2 they had just learned (intra-dimensional were administered, giving a maximum clozapine), 64 patients were prescribed shift, IDS). At the later, extra-dimensional possible score of 20. These tasks were traditional antipsychotic drugs, including shift stage (EDS), the rule was reversed so completed by 132 patients. sulpiride (24), and 14 patients were drug- that the previously irrelevant dimension naınaıve.ve. To investigate medication effects, a now became relevant. This tested the ¨ series ofseriesof tt-tests between those receiving Spatial working memory (Owen et al, 1990) ability to inhibit the previously correct traditional and newer antipsychotic drugs Subjects were required to ‘open’ sets of response set and adopt a new response were performed on neuropsychological boxes, varying between three and eight in set by shifting attention from one dimen- variables and DUP. No differences were number, to find tokens. Errors were sion to the other. Thus, the EDS stage is evident (range of tt was 0.08–1.5). recorded when boxes in which tokens had analogous to the attentional shift involved Patients and controls were matched for been found were reopened. A common in Wisconsin Card Sorting Test perfor- age but not gender ratio (Table 1). Preli- strategy employed in the performance of mance. A total of 133 patients completed minary analyses were performed on control this task is to follow a predetermined this task.thistask. sequence, beginning with one box and data and no gender differences in neuro- returning to start each new search with psychological performance were found, in Statistical analysis thatthatboxbox after a token has been found. A line with previous work with these tests measuremeasureofof this strategy was derived by Results were analysed using SPSS 10. (Robbins(Robbins et aletal, 1994). The mean IQ of the counting the number of search sequences Latency and DUP data were log1010 trans-trans- patient group was significantly lower than starting with the same box at the six- and formed to reduce skew; tt-tests were used that of the control group. The relationship eight-box stages. All patients completed this task.thistask. Ta b l e 11Tab Age, gender and IQ for patients with first-episode schizophrenia and controls

Planning (Owen et al, 1990) Schizophrenia Controls StatisticStatistic In this modification of the Tower of ((nn¼136) ((nn¼81) London task (Shallice, 1982), subjects Age, years (mean (s.d.)) 25.74 (7.99)(7.99)25.74 26.12 (5.19)(5.19)26.12 tt(213)(213) 770.43, PP 0.670.67 moved coloured ‘balls’ in an arrangement ¼ ¼ displayed on the screen to match a goal Gender: male/female 107/29 49/3249/32Chi-squared (1)¼8.31, PP¼0.004 arrangement. Subjects were asked to attempt NART IQ (mean (s.d.))11 99.67 (10.37)104.64 (9.54) tt(181)¼773.28,3.28, PP¼0.001

the solution in the minimum number of NART,NART,National National Adult ReadingTest. moves, which could be 2, 3, 4 and 5. For 1.1.Completed Completed in 110 patients with schizophrenia and 73 controls.

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between IQ and memory and executive Ta b l e 2 Differences between patients with first-episode schizophrenia and controls on CANTAB tests.Values function was examined statistically as are group mean (s.d.) described above. SchizophreniaControls Statistic Spatial span, pattern and spatial recognition memory Spatial span 5.62 6.586.58 tt(214)(214)¼775.01 As shown in Table 2, patients were signi- (1.37) (1.30)(1.30) PP550.001 ficantly impaired on all three memory Pattern recognition memory: % correct84.44 92.8192.81 tt(205)(205)¼775.855.85 tasks. Pattern and spatial recognition (0.12)(0.12) (0.08)(0.08) PP550.001 memory correlated significantly with IQ Spatial recognition memory: % correct67.73 76.47 tt(208)(208)¼774.484.48 ((rr¼0.26 and 0.24, respectively; PP550.001).0.001). (0.14)(0.14) (0.13)(0.13) PP550.001 ANCOVAs showed that, although IQ con- Attentional set-shifting: stage reached 8.37 8.89 tt(177)(177)¼774.104.10 tributed to performance (FF1,1771,177¼7.17 and7.17and (maximum¼9)9) (1.33)(1.33) (0.45)(0.45) PP550.001 6.38, respectively; PP550.01) the group dif- Spatial working memory: strategy score34.96 29.05 tt(142)¼7.687.68 ferences remained significant (FF ¼16.1916.19 1,1771,177 (4.77) (5.86) PP550.001 and 9.65, respectively; PP550.01). Thus, specific impairments in short-term spatial CANTAB,CambridgeCANTAB, Cambridge Automated Neuropsychological TestBattery. memory capacity and long-term episodic memory were evident in the patient group. Planning IQ correlated with perfect solutions ((rr¼0.29,0.29, PP550.001). An ANCOVA Spatial working memory Figure 1 shows that patients solved fewer showed that, although IQ contributed

Figure 1(a) shows that patients made more problems perfectly at the 3-, 4- and 5-move to performance (FF1,1791,179¼6.89,6.89, PP550.01),0.01), errors than controls at the more difficult levels of difficulty (group effect: the group difference in perfect solutions

six- and eight-box stages (group effect: FF1,2131,213¼43.01,43.01, PP550.001; group66difficultydifficulty remained highly significant (FF1,1791,179¼21.66,21.66, 55 FF1,2141,214¼39.90,39.90, PP550.001; group66difficultydifficulty interaction:interaction: FF1,6391,639¼12.51,12.51, PP 0.001).0.001). PP550.001).0.001).

interaction:interaction: FF3,6423,642¼28.28,28.28, PP550.001). IQ correlated with total errors (rr¼770.36,0.36, PP550.001). An ANCOVA showed that, although IQ contributed to performance

((FF1,791,79¼19.32,19.32, PP550.001), the group difference for errors remained highly significant

((FF1,1791,179¼16.98,16.98, PP550.001).0.001). Performance of this task can be influ- enced by both short-term memory capacity and the degree to which an efficient strategy is adopted (Owen et aletal, 1990). In our previous study (Hutton et aletal, 1998), spatial span and working memory strategy score correlated with spatial working memory errors in the patient group. Therefore, in the present study, we entered these measures as covariates in separate ANCOVAs. After covarying for strategy, there was no group difference in spatial working memory error

score (group effect: FF1,2131,213¼2.05, n.s.), the effect of strategy being highly significant

((FF1,2131,213¼138.87,138.87, PP550.001). After covarying for spatial span, the group difference for spatial working memory errors remained

significant (group effect: FF1,2121,212¼20.17,20.17, PP550.001) despite a significant effect of

spatial span (FF1,2121,212¼35.82,35.82, PP550.001).0.001). Thus, there was a specific impairment in spatial working memory in the patient group. The group difference in errors was largely accounted for by the less efficient use of a search strategy in the patient group Fig. 11Fig. (a) Spatial working memory errors and (b) percentage of perfect solutions obtained on theTower of rather than differences in short-term spatial London planning task across varying levels of difficulty in patients with first-episode schizophrenia (^^)and memory capacity. normal controls (&&). Error bars represent the s.e.m.

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of errors at the intra-dimensional and extra- dimensional shift stages (IDS: patients 1.81 (s.d. 4.94), controls 0.81 (s.d. 0.92); EDS: patients 9.54 (s.d. 9.14), controls 6.13 (s.d. 6.69)). Although there was tendency for patients to make more errors than

controls overall (group effect: FF1,1741,174¼3.60,3.60, PP¼0.06) they did not make proportionately more errors at the EDS stage (group66stagestage

interaction:interaction: FF1,1741,174¼0.08, n.s.). When those passing and failing this task were compared for IQ, spatial span, pattern and spatial recognition memory, spatial working memory errors and perfect solutions on the planning task, there were no significant differences (range of tt: 0.26–0.87).

Relationships between neuropsychological function, symptoms and duration of untreated psychosis Correlations were performed in the patient group between IQ, spatial working memory errors, number of perfect solutions on the planning task, stage reached on the attentional set-shifting task, pattern and spatial

recognition memory scores, log1010 DUP andDUPand scores for positive, negative and disorganisation syndromes (Table 3). The data showed that the neuropsychological scores Fig. 22Fig. (a) Initial thinking times and (b) subsequent thinking times across varying levels of difficulty in the tended to intercorrelate except for the Tower of London planning task in patients with schizophrenia (^^) and normal controls (&&). Error bars attentional set-shifting task score, which represent the s.e.m. failed to correlate with any other task. Conversely, only performance on the atten-

tional set-shifting task correlated with log1010 Figure 2 shows that the time spent Thus, patients were impaired in planning DUP (DUP(rr¼770.23,0.23, PP¼0.01), indicating that thinking about the problem prior to the in that they solved fewer moves perfectly. the shorter the duration of untreated psy- first move increased linearly with increas- In addition, patients spent significantly less chosis the higher the stage reached. WhenWhen ing problem difficulty in the control group. time planning the solutions. Performance patients passing and failing this task weretaskwere This effect was not seen in the patients who was highly related to planning time for compared, log1010 DUP was significantly were significantly faster (group difference: the hardest problems in controls but not longer in the group that failed (47.5 (s.d. 72.54) weeks vv. 93.6 (s.d. 118.05) weeks; FF1,2141,214¼15.42,15.42, PP550.001; group66difficultydifficulty in patients.inpatients. tt(113)(113)¼772.59,2.59, PP¼0.01).0.01). interaction:interaction: FF3,6423,642¼2.95,2.95, PP¼0.03). An0.03).An ANCOVA showed that IQ did not contri- There were no significant correlations Attentional set-shifting between syndrome scores and neuro- bute to initial thinking time (FF1,1801,180¼1.87,1.87, n.s.). Patients and controls did not differ Figure 3 shows that more patients than con- psychological scores or log1010 DUP (range in the time taken for each subsequent move trols failed the test. This was significant ofof rr¼0.00–0.16).

((FF1,2141,214¼2.83, n.s.).2.83,n.s.). when measured either by stage reached Correlations were performed for each ((tt(177)(177)¼774.11,4.11, PP550.001) or by number DISCUSSION

group between log1010 initial thinking time passing and failing (2ii¼12.26,12.26, PP550.001).0.001). and proportion of perfect solutions When the number of subjects passing and This study replicates our original finding obtained for each stage of difficulty. A failing each stage was examined, this was that patients with first-episode schizo- highly significant positive relationship was significant at the extra-dimensional shift phrenia are impaired on executive tasks of

found between time taken to think about stage only (2ii¼7.65,7.65, PP¼0.006). IQ did not planning and spatial working memory but the 5-move problem and performance in correlate with stage reached (rr¼770.09,0.09, not attentional set-shifting (Hutton et aletal,, the control group (rr¼0.53,0.53, PP550.001) and0.001)and n.s.).n.s.). 1998). We also found similar impairments a weaker, non-significant relationship for As the majority of patients passed the in short- and long-term episodic memory. the same measures in the patient group test, we looked for other evidence of im- NART IQ correlated with many ((rr¼0.16,0.16, PP¼0.07).0.07). pairment in these by examining the number measures of memory and executive function,,function

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These conclusions are in agreement with previously published studies (Hoff et aletal,, 1992; Saykin et aletal, 1994; Bilder et aletal,, 2000).2000).

Nature of executive impairment at the onset of schizophrenia The analysis of an enlarged cohort of patients and controls and the inclusion of additional neuropsychological and clinical measures allows further interpretation of our results.ourresults. The pattern of reduced number of perfect solutions on the planning task and increased spatial working memory errors, because of the inadequate use of a search strategy, is also found in patients with chronic schizophrenia (Elliott et aletal, 1998;,1998; PantelisPantelis et aletal, 1999). Patients with frontal lobe resections are similarly impaired but not those with temporal lobe resections or cortical and subcortical dementia such as Alzheimer’s disease and Parkinson’s disease Fig. 33Fig. Percentage of patients passing each stage of the attentional set-shifting task in patients with (Owen(Owen et aletal, 1990, 1992, 1995, 1996cc;; schizophrenia (^^) and normal volunteers (&&).The stages are: sd, simple discrimination; sdr, simple SahgalSahgal et aletal, 1992). Functional imaging discrimination reversal; c/s and cs, compound discrimination stages; cdr, compound discrimination reversal; studies of the planning and spatial working ids,intra-dimensionalshift;idr,intra-dimensionalshiftreversal;eds,extra-dimensionalshift;edr,ids, intra-dimensional shift; idr, intra-dimensional shift reversal; eds, extra-dimensional shift; edr, memory tasks in normal volunteers have extra-dimensional shift reversal. shown that the critical area of activation is the dorsolateral prefrontal cortex (Baker questioning the specificity of our findings. Neuropsychological performance in theinthe et aletal, 1996; Owen et aletal, 1996,1996aa,, bb). Taken).Taken However, in all cases, significant differen- patient group was not related to symptoms together, our results suggest that dorsolat- ces remained between the groups when IQ or medication type. Taken together, these eral prefrontal cortex function is impaired was taken into account in the statistical data suggest that specific impairments in at the onset of schizophrenia. analysis. In the patient group, measures memory and executive function are present However, the performance of our of planning, working memory strategy at the onset of chizophrenia and that defi- patients differs from that of patients with and recognition memory intercorrelated.correlated.inter cits in the two cognitive domains coexist. chronic schizophrenia and frontal lobe resection in several important respects. In the planning task, our patients were faster Ta b l e 3 Pearson correlation coefficients (rr) for cognitive and clinical measures to initiate responses than controls but no different in the time taken to complete each subsequent move. Patients with frontal Duration ofofDuration Negative Positive Disorganisation resections and chronic schizophrenia, by 11 22 33 untreateduntreated syndrome syndromesyndrome syndromesyndrome contrast, have normal initial thinking times psychosis (log10)) but are slower in thinking about subsequent moves than controls (Owen et aletal, 1990;,1990; NART IQ 770.110.00 770.020.02 770.020.02 PantelisPantelis et aletal, 1999).,1999). Attentional set-shifting: stage reached 770.23* 770.04 770.060.05 Another difference between the perfor- Planning: perfect solutions 770.110.11 770.100.100.10 0.00 mance of our patients and that of patients Spatial working memory: errors 0.07 770.03 770.070.07 770.020.02 with frontal lobe resection and chronic Pattern recognition memory: % correct 770.030.030.14 0.09 770.01 schizophrenia is with respect to attentional Spatial recognition memory: % correct0.02 0.00 770.020.02 770.01 set-shifting task performance. Far fewer Spatial spanspanSpatial 0.130.01 770.070.07 770.140.14 first-episode patients failed this task {{ compared with groups of patients with Duration of untreated psychosis (log10)0) 0.11.11770.16 0.020.02 frontal resection (Owen et aletal, 1991) and SANS, Scales for the Assessment of Negative Symptoms; SAPS, Scale for the Assessment of Positive Symptoms; NART, chronic schizophrenia (Elliott et aletal, 1995;,1995; National Adult ReadingTest. 1.Derived from sum of global scores for SANS items affective flattening, alogia, avolition, anhedonia. PantelisPantelis et aletal, 1999). Approximately 75% 2. Derived from sum of global scores for SAPS items hallucinations and delusions. of our patients performed this task normally. 3. Derived from sum of global scores for SAPS items bizarre behaviour and positive formal thought disorder and SANS attention.attention. They completed the task and made no more **PP¼0.01; {{PP¼0.07; remaining values not significant. errors on the most stringent EDS stage than

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controls. This contrasts markedly with patients with chronic schizophrenia, who CLINICAL IMPLICATIONS are most impaired on the attentional set- shifting task out of all CANTAB executive && Specific deficits in memory and executive function are present in patients with tasks (Elliott et aletal, 1998).,1998). schizophrenia at illness onset. The minority of patients who did fail the attentional set-shifting task were speci- && The profile of impairment in executive impairment is different from that of chronic fically impaired on the EDS stage, which patients and this may be relevant for cognitive rehabilitation strategies at illness requires inhibition of a previously acquired onset. response set and a shift of attention away from one stimulus dimension to another. && Pathophysiological processes in prefrontal cortex underlying executive The ability to inhibit a pre-potent response impairment may begin to deteriorate at the onset of psychosis and continue to and execute an alternate response is con- worsen with time. sidered a core attribute of prefrontal cortex function and fundamental to performance LIMITATIONS of other so-called frontal tasks such as the && We were unable to distinguish between the effect on cognitive performance of Wisconsin Card Sorting Task. This specific illness duration and delay of antipsychotic drug treatment. pattern of impairment on the attentional set-shifting task was also found in patients && Duration of untreated psychosis was determined retrospectively. with frontal resections (Owen et aletal, 1991),1991) and performance of the EDS stage critically && IQ was estimated using the National Adult ReadingTest,whichReadingTest, which may better reflect activated dorsolateral prefrontal cortex in a premorbid IQ than current IQ. functional imaging study of normal volunteers (Rogers et aletal, 2000). In patients with chronic schizophrenia, however, failure occurred on EDS and other stages, indicating additional cognitive difficulties in this EILEEN JOYCE, FRCPsych, SAM HUTTON, DPhil, STAN MUTSATSA, MSc, HEIDI GIBBINS, BSc, EMMA WEBB, group such as discrimination learning and MSc, SONJA PAUL, BSc, Imperial College Faculty of Medicine, London; TREVOR ROBBINS, PhD,University of rule abstraction (Elliott et aletal, 1995; Pantelis Cambridge;Cambridge;THOMAS THOMAS BARNES, FRCPsych, Imperial College Faculty of Medicine, London et aletal, 1999).,1999). Correspondence: Dr Eileen Joyce, Imperial College Faculty of Medicine,Charing Cross Site, St Dunstan’s Road, London W6 8RP. e-mail: e.joyce@@ic.ac.uk Relationship between neuropsychological function and duration of untreated psychosis ill for almost twice as long (93.6 weeks). available, we are unable to distinguish be- Our findings indicate that at illness onset, One possible explanation is that prefrontal tween the effects of illness chronicity per seperse the nature of the executive impairment is function begins to deteriorate at the onset and treatment delay onthe pathophysio- different from that of chronic patients. of psychosis and thus is more evident in logical processes underlyingschizophrenia. The finding that first-episode patients initi- those who had had a longer DUP. In sup- ally respond quicker than controls and the port of this, we found that attentional set- lack of relationship between planning time shifting performance had deteriorated at REFERENCES and correct performance apparent in con- 1-year follow-up assessments in a smaller trols requires further investigation, as this group of patients (Joyce et aletal, 1999). This Albus, M., Hubman,W., Ehrenberg, C., et aletal (19 9 6) may reflect the involvement of different would also explain why many more Neuropsychological impairment in first episode and cognitive processes in the two groups. patients with chronic schizophrenia are chronic schizophrenia. European Archives of Psychiatry and Clinical Neuroscience,, 246, 249^255. 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