Psychiatry Research 220 (2014) 834–839

Contents lists available at ScienceDirect

Psychiatry Research journal homepage: www.elsevier.com/locate/psychres

Clinical and cognitive predictors of vocational outcome in first-episode schizophrenia: A prospective 3 year follow-up study Wing Chung Chang a,n, Jennifer Yee Man Tang a, Christy Lai Ming Hui a, Sherry Kit Wa Chan a, Edwin Ho Ming Lee a, Eric Yu Hai Chen a,b a b

Department of Psychiatry, the University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong State Key Laboratory of Brain and Cognitive Sciences, the University of Hong Kong, Hong Kong

art ic l e i nf o

a b s t r a c t

Article history: Received 2 April 2014 Received in revised form 13 August 2014 Accepted 19 September 2014 Available online 30 September 2014

Schizophrenia is associated with pronounced vocational impairment. Previous research has mostly focused on chronic patients and few studies were conducted to investigate predictors of work outcome in first-episode populations. The impact of cognitive dysfunction on employment outcome in early psychosis was under‐studied. In this study, we prospectively followed up 93 patients aged 18–55 years presented with first-episode schizophrenia-spectrum disorder for 3 years with an aim to identify early clinical and cognitive predictors of vocational outcome. Pre-morbid adjustment, baseline symptomatology and cognitive functions, and employment outcome were assessed. Result indicated that approximately half of the patients (53.8%) were engaged in full-time work at intake and at 3 years. Pre-morbid adjustment, baseline occupational status and Wisconsin Card Sorting Test (WCST) performance were found to predict vocational outcome. Analysis on a subgroup of patients who were unemployed at intake showed that subjects who remained unemployed over 3 years had poorer WCST performance and more severe positive symptoms at baseline than those having job attainment during follow-up. Our results thus confirmed predictive value of pre-morbid functioning and baseline occupational status on vocational outcome. In addition, our findings suggested that executive function might be a critical cognitive determinant of employment outcome in the early course of schizophrenia. & 2014 Elsevier Ireland Ltd. All rights reserved.

Keywords: Employment Vocational outcome Executive function Cognitive impairment First-episode schizophrenia

1. Introduction Schizophrenia is a severe mental illness that constitutes one of the highest disease burdens globally (Whiteford et al., 2013). The disorder causes profound disruptions in individuals' functioning including independent living skills, social relationship, scholastic and occupational domains. In particular, substantial evidence indicated that a significant proportion of schizophrenia patients exhibited persistent vocational impairment. Literature consistently reported low employment rate in patients with schizophrenia and approximately half of the first-episode psychosis patients were already unemployed at initial presentation (Marwaha and Johnson, 2004; Killackey et al., 2006). It is recognized that unemployment was associated with worse symptomatic outcome, poorer quality of life, lower self-esteem, social exclusion and increased indirect costs of the illness (Bond et al., 2001; Knapp et al., 2004; Turner et al., 2009; Drake et al., 2013). Alternatively,

n

Corresponding author. Tel.: þ 852 22554486; fax: þ 852 28551345. E-mail address: [email protected] (W.C. Chang).

http://dx.doi.org/10.1016/j.psychres.2014.09.012 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.

studies revealed that both patients and psychiatrists regarded job attainment as a key element signifying functional recovery (Tsang and Chen, 2007; Lam et al., 2011). Previous research indicated that pre-morbid adjustment, work history, cognitive dysfunction, and socio-contextual factors such as discrimination and welfare policy predicted occupational status in schizophrenia (Marwaha and Johnson, 2004; Bond and Drake, 2008; Tsang et al., 2010; Giugiario et al., 2012). Nonetheless, the majority of these studies focused mainly on patients with chronic illness. Relatively few studies were conducted to examine the determinants of vocational outcome in the early stage of illness and most had follow-up duration of less than 2 years (Rinaldi et al., 2010). In addition, although cognitive impairment is a core feature of schizophrenia (Elvevag and Goldberg, 2000; Kahn and Keefe, 2013) and is associated with functional disability (Green et al., 2000), its impact on occupational functioning in early psychosis was the focus of only a limited number of investigations and the findings thus far were inconsistent (Rinaldi et al., 2010; Tandberg et al., 2011). Some studies showed that global cognitive deficit (Holtausen et al., 2007; Nuechterlein et al., 2011) or impairment in specific cognitive domains such as executive

W.C. Chang et al. / Psychiatry Research 220 (2014) 834–839

835

function (Jaeger and Douglas, 1992; Dickerson et al., 2008), attention (Milev et al., 2005; Tandberg et al., 2011), or verbal memory (Dickerson et al., 2007) predicted work outcome, while others failed to find such a relationship (Johnstone et al., 1990; Verdoux et al., 2002). Given that the onset of schizophrenia most frequently occurs in late adolescence or early adulthood which are critical life stages for individuals' occupational development, identification of factors predictive of work functioning and provision of effective vocational interventions in the early course of illness may thus minimize social disability and improve long-term employment outcome. In this article, we report a prospective 3 year follow-up study in a cohort of Chinese patients presenting with first-episode schizophrenia-spectrum disorder with an aim to examine the employment rate and to identify pre-treatment and early clinical and cognitive predictors of vocational outcome.

subscales were more related to disorganization dimension. Montgomery–Asberg Depression Scale (MADS) (Montgomery and Asberg, 1979) was used to assess depression. Vocational outcome was measured as the number of months in fulltime employment, which was defined as full-time paid work or full-time study (Tandberg et al., 2012), over 3 year study period. A brief battery of cognitive assessments was administered to all subjects, comprising logical memory test (Wechsler Memory Scale Revised, WMS-R-HK) (Hong Kong Psychological Society, 1989a), visual reproduction test (WMS-R-HK), forward digit span (Wechsler Adult Intelligence Scale, WAIS-R-HK) (Hong Kong Psychological Society, 1989b), category verbal fluency and Modified Wisconsin Card Sorting Test (MWCST) (Nelson, 1976). General verbal intelligence was estimated at baseline using information subscale from the WAIS-R-HK (Chen et al., 2005). Psychopathological evaluation was conducted for each subject at intake and after clinical stabilization of the first psychotic episode (mean¼ 42.6 days after initial assessment). To maximize cooperation and to reduce state effects of acute psychosis, cognitive assessment undertaken when patients were clinically stabilized was regarded as baseline cognitive measure. A group of healthy controls, matched with age, sex and educational level, were recruited via advertisements and were evaluated with the same battery of cognitive assessments as patients at baseline for comparison of cognitive performance.

2. Methods

2.3. Statistical analysis

2.1. Subjects and setting

Patients were categorized into two groups based on the median split of the length of full-time employment over 3 years. Patients with good outcome achieved full-time employment of more than 8 months, while those with poor outcome were employed for 8 months or less. In this study, we focused on identifying pretreatment as well as early clinical (at baseline and clinical stabilization) and cognitive (at clinical stabilization) predictors of vocational outcome. Group differences with regard to pre-morbid adjustment, socio-demographics, baseline clinical and cognitive measures, and treatment characteristics were analyzed using chisquare test and independent t-test as appropriate. Those pre-morbid and baseline variables that were found to be statistically significant in bivariate analyses were then entered into a backward stepwise binary logistic regression model (Wald statistics) to determine which factors independently predicted employment outcome. In an attempt to explore early clinical and cognitive determinants of fulltime employment acquisition during follow-up in a subgroup of patients who were unemployed at intake, we conducted comparative analyses between subjects who remained unemployed over 3 years since initial presentation (unemployed group) and those who had ever attained full-time work within the study period (employed group) in pre-treatment and baseline variables, followed by binary logistic regression analysis. Duration of untreated psychosis was log-transformed due to its skewed distribution. Standardized z scores for cognitive functions were computed for analyses based on performance of healthy controls, with a mean score of 0 and standard deviation of 1. The level of statistical significance for all analyses was set at p o0.05.

One hundred and thirty-eight consecutive patients aged 18 to 55 years with first-episode schizophrenia, schizophreniform disorder or schizoaffective disorder were recruited from both outpatient and inpatient psychiatric units covering a defined catchment area in Hong Kong. Patients with known neurological disorder, learning disability or current substance abuse were excluded from the study. Of the initial cohort, 93 subjects completed the 3 year follow-up, 40 defaulted, four committed suicide and one died of medical disease. There were no significant differences between completers and non-completers in socio-demographics, duration of untreated psychosis, baseline symptom ratings and cognitive functions. Patients in this study were initially treated with low-dose first-generation antipsychotic medications. The current study was part of a prospective 3 year follow-up study in first-episode schizophrenia-spectrum disorder and findings regarding persistent negative symptoms, the impact of duration of untreated psychosis on illness outcome, and clinical and cognitive predictors of symptomatic remission have been reported elsewhere (Chang et al., 2011, 2013a, 2013c). The study was approved by local institutional review board and conducted in accordance with the Declaration of Helsinki. All of the subjects gave written informed consent before participation.

2.2. Assessments Diagnostic assignment was based on longitudinal approach taking into consideration that diagnostic change may take place over time (Chang et al., 2009a, 2009b). The3 year diagnosis of each subject was determined according to DSM-IV criteria (American Psychiatric Association, 1994) using all available information encompassing the whole follow-up period including the Chinese-bilingual Structured Clinical Interview for DSM-IV (CB-SCID-I/P) (So et al., 2003) administered at baseline and at 3 years, informant histories and medical records. Previous validation study showed that CB-SCID-I/P yielded reliable DSM-IV diagnoses in Chinese patients with psychotic disorders (So et al., 2003). Pre-morbid functioning was measured with the Pre-morbid Adjustment Scale (PAS) (Cannon-Spoor et al., 1982). We only included childhood ( r11 years) and early adolescence (12–15 years) periods for assessment to avoid any possible confounding with early symptoms because the onset of prodrome and psychosis usually occur in late adolescence and early adulthood (Cassidy et al., 2010; Chang et al., 2013b). The PAS total score was calculated by summing the scores on all items encompassing both childhood and early adolescence periods and dividing by the total possible score (score range 0–1, higher score indicates lower functioning). Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS) (Hafner et al., 1992) was used to confirm the first-episode status and to assess duration of untreated psychosis which was defined as the time interval between the onset of positive psychotic symptoms and treatment initiation. Positive symptoms were assessed using Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987) with intra-class correlation coefficient (ICC) being 0.83 for positive symptoms subscale. High Royds Evaluation of Negativity Scale (HEN) (Mortimer et al., 1989) was employed to measure negative symptoms. It comprises six subscales and 18 items which are rated along an anchored five-point severity scale (range 0–4, higher score indicates more severe negative symptoms). Validation of HEN for use in Chinese schizophrenia patients has previously been reported (Chen et al., 1996). ICCs for the subscales ranged from 0.74 (Thought) to 0.85 (Speech). In this study, we only included four of the six subscales, i.e., Affect, Behavior, Speech and Functioning subscales for analysis (Chang et al., 2011) as the remaining two, namely Thought and Appearance

3. Results 3.1. Characteristics and employment status of the sample The 93 subjects were predominantly single (74.2%) and 45.2% were male. The mean age of the sample at intake was 31.2 years (S. D.¼9.6) and the average educational level was 10.54 years (S. D.¼2.9). The median duration of untreated psychosis of the sample was 180 days (mean¼ 473.7, S.D.¼ 786.4). Diagnoses for the cohort were schizophrenia (n ¼75), schizophreniform disorder (n ¼13) and schizoaffective disorder (n ¼5). Full-time employment rate at intake as well as at the end of 3 year follow-up was 53.8% (n ¼50). Of the 43 subjects who were not working at intake, 53.3% (n ¼23) remained unemployed over 3 years. The median length of full-time employment of the sample over 3 year follow-up was 8 months (mean ¼13.6, S.D. ¼14.6, range 0–36). The control sample comprised 114 subjects with 41.2% being male. The mean age and educational level of the control group were 33.4 years (S.D. ¼10.0) and 11.1 years (S.D. ¼2.2), respectively. There were no significant differences between patients and healthy controls in age, sex and educational level (see Table S1). Patients performed significantly worse than controls in all cognitive tests with a range from 0.4 (forward digit span) to 1.0 (logical memory, delayed recall) standard deviations below those of controls with the exception of visual reproduction test which

836

W.C. Chang et al. / Psychiatry Research 220 (2014) 834–839

yielded no significant differences between the two groups (Chang et al., 2013a, 2013c). 3.2. Predictors of vocational outcome Patients with good vocational outcome had significantly better pre-morbid adjustment, superior performance in MWCST (fewer perseverative errors) and visual reproduction test at clinical stabilization, and were more likely to be employed at intake than those with poor vocational outcome (Table 1). No significant differences between the two groups in symptom ratings and treatment characteristics were observed. Binary logistic regression analysis revealed that pre-morbid adjustment, baseline employment status and MWCST performance independently predicted vocational outcome (χ² ¼25.49, p o0.001, Nagelkerke R2 ¼0.346) (Table 2). Our results on a subgroup of patients who were unemployed at intake showed that subjects in “employed group” had significantly better MWCST performance at clinical stabilization and fewer baseline positive symptoms than those in “unemployed group” (Table 3). There were no significant between-group differences in pre-morbid adjustment, socio-demographics, treatment characteristics, and other baseline clinical and cognitive measures. Logistic regression analysis revealed that MWCST performance and positive symptom severity remained in the final equation (χ² ¼9.50, p o0.01, Nagelkerke R2 ¼ 0.270), though both failed to reach statistical significance (MWCST: p¼ 0.06; positive symptom severity: p ¼0.07).

4. Discussion Our findings that only half of the cohort had full-time work at intake and at 3 years were consistent with the literature (Marwaha and Johnson, 2004; Killackey et al., 2006) and thus highlighted the significance of unemployment problems in the first-episode. In line with previous research on both first-episode (Rinaldi et al., 2010) and chronic schizophrenia (Tsang et al., 2010), we found that pre-morbid adjustment and baseline occupational status strongly predicted employment outcome. A lack of significant association between baseline symptom profile and vocational outcome as revealed by our study concurred with many (Rinaldi et al., 2010) but not all past reports on early psychosis which demonstrated that depressive (Dickerson et al., 2008) and positive symptoms (Tandberg et al., 2011) at intake predicted work status at follow-up. Of particular note, our findings of lack of significant relationship between baseline negative symptoms and 3 year vocational outcome was at odds with most studies on chronic samples which indicated negative symptoms as independent determinant of employment outcome (Tsang et al., 2010). Nonetheless, it might be possible that as the nature and severity of symptoms often fluctuates considerably in the initial phase of psychotic illness (McGorry, 1994; Chang et al., 2011), the predictive value of baseline symptomatology on vocational functioning may thus be compromised in first-episode populations. Contrary to the findings of several previous early psychosis studies which demonstrated that vocational impairment was associated with global cognitive dysfunction (Holtausen et al., 2007; Nuechterlein et al., 2011) or deficits in discrete cognitive domains of attention or memory (Milev et al., 2005; Dickerson et al., 2007; Tandberg et al., 2011), we found that poor MWCST performance at baseline predicted worse employment outcome over 3 year follow-up and was thus consistent with some other prior reports which showed that executive function was a cognitive determinant of vocational functioning (Jaeger and Douglas, 1992; Dickerson et al., 2008). Further, our results suggested that

better MWCST performance was associated with an increased likelihood of job acquisition during follow-up in a subgroup of patients who were unemployed at intake. Our findings thus echoed a recent review focusing on chronic schizophrenia which indicated that executive function was an important predictor of occupational outcome (Tsang et al., 2010). It should, however, be noted that the contribution of executive function to vocational outcome as revealed by the current study was modest. In addition, there are only limited data regarding the prospective relationship between cognitive functions and vocational outcome in patients with first-episode schizophrenia (Rinaldi et al., 2010; Tandberg et al., 2011) and the findings were less consistent than those reported in chronic samples (Rinaldi et al., 2010). In fact, some previous studies failed to demonstrate any significant associations between cognitive functions and employment outcome in early psychosis patients (Johnstone et al., 1990; Tandberg et al., 2012). It is thus posited that the relationship between cognitive impairment and vocational functioning may be stronger for chronic patients than those in the early course of illness (Tandberg et al., 2012). It is suggested that critical involvement of executive function in planning, problem-solving, cognitive flexibility and social skills may contribute to its predictive capacity on work attainment and job tenure (Lysaker et al., 1995; McGurk and Meltzer, 2000; Lysaker et al., 2005). Alternatively, recent data revealed that beneficial effects of cognitive remediation including executive function enhancement in chronic schizophrenia may be generalized for early psychosis patients (Wykes et al., 2007; Eack et al., 2009). As it is plausible that cognitive dysfunction may be more amenable to intervention applied in the early illness phase, more research should be conducted to evaluate the efficacy of cognitive remediation (Barlati et al., 2012) in first-episode patients on cognitive improvement which may in turn increase the likelihood of functional enhancement. Several methodological limitations warrant consideration in interpreting the study results. First, we did not have data on receipt of disability allowance which was shown to be a disincentive to employment (Rosenheck et al., 2006). Second, our study did not include measures for social cognition and functional capacity which were found to be associated with occupational outcome and might mediate the relationship between cognition and vocational functioning in schizophrenia (Bowie et al., 2008; Schmidt et al., 2011). Third, the length of sustained employment during follow-up was not evaluated, and thus precluded us from investigating factors that differentiate a subset of patients who could maintain their work from those who could not within the study period. Fourth, our sample comprised slightly more females than males, which was contrary to many (Marshall et al., 2005), but not all first-episode studies (Oosthuizen et al., 2005; Ucok et al., 2004) showing male preponderance, and thus may limit generalizability of our results. One possible reason was that we recruited patients aged from 18 to 55 years with a relatively older mean age of entry (31.2 years), therefore it may be more likely for female schizophrenia patients to be included in our study as the literature showed that females had an older age of illness onset than males and a second (though smaller) peak age of onset in 40s (Hafner et al., 1993; Castle et al., 1998). Fifth, the relatively older mean age of our cohort (our study adopted a wider age range as an inclusion criterion than the majority of first-episode studies) may also render our findings less comparable to the literature of firstepisode research as there may be significant variations in illness impacts on clinical, cognitive and functional outcomes between patients with a more typical age at onset (i.e., late adolescence or early adulthood) and those whose psychosis manifests in later years. Sixth, the number of subjects included in this study was modest, particularly in subgroup analysis restricting to those who were unemployed at initial presentation. Replication by further

W.C. Chang et al. / Psychiatry Research 220 (2014) 834–839

837

Table 1 Premorbid adjustment, demographics, baseline clinical variables, and treatment characteristics of patients with good and poor vocational outcomes. Variables of interest

Socio-demographics Age at entry, mean (S.D.) Male sex, n (%) Years of education, mean (S.D.) Employed at intake, n (%)

Subjects with good vocational outcome (n¼ 46)

32.1 22 10.6 32

(9.8) (47.8) (4.0) (69.6)

Subjects with poor vocational outcome (n¼ 47)

30.4 20 10.5 18

Statistics (χ²/t, d. P f.) value

(9.4) (42.6) (2.3) (38.3)

0.9, 91 0.3, 1 0.9, 91 9.1, 1

0.374 0.609 0.928 0.002

Premorbid adjustment PAS total score, mean (S.D.)

0.3 (0.1)

0.4 (0.1)

 2.9, 85

0.005

Baseline clinical characteristics Log DUPa, mean (S.D.)

4.6 (1.8)

5.3 (1.6)

 1.8, 82

0.080

Symptom severity at intake PANSS Positive symptom score, mean (S.D.) HEN total score, mean (S.D.) MADRS total score, mean (S.D.)

19.1 (5.7) 14.1 (11.1) 8.8 (9.1)

20.4 (5.1) 13.1 (11.8) 10.5 (14.0)

 1.1, 91 0.4, 91  0.7, 91

0.262 0.680 0.482

Symptom severity at clinical stabilization PANSS Positive symptom score, mean (S.D.) HEN total score, mean (S.D.) MADRS total score, mean (S.D.)

9.3 (2.7) 11.2 (9.2) 3.2 (5.3)

9.2 (2.8) 11.1 (10.3) 3.4 (5.4)

0.2, 91 0.1, 91  0.1, 91

0.873 0.948 0.897

1.5, 90 1.6, 89 2.6, 89 1.8, 90 1.2, 90 2.7, 90

0.131 0.115 0.012 0.077 0.243 0.009

Cognitive functioningb at clinical stabilization WAIS-R-HK Information subscale, mean (S.D.) Logical memory, mean (S.D.) Visual reproduction, mean (S.D.) Forward digit span, mean (S.D.) Category verbal fluency, mean (S.D.) MWCST perseverative errorc, mean (S.D.) Treatment characteristics CPZ equivalence at intake, mean (S.D.) CPZ equivalence at clinical stabilization, mean (S. D.) CPZ equivalence at 12 months, mean (S.D.) CPZ equivalence at 24 months, mean (S.D.) CPZ equivalence at 36 months, mean (S.D.) Taking SGA at 12 monthsd, n (%) Taking SGA at 24 months, n (%) Taking SGA at 36 months, n (%)

 0.4  0.7 0.1  0.2  0.4  0.1

 0.7  1.0  0.4  0.6  0.6  1.4

(1.3) (0.8) (0.8) (0.8) (0.7) (1.4)

(1.0) (0.9) (1.0) (1.3) (0.9) (2.9)

109.5 (156.5) 358.5 (355.2)

226.3 (583.3) 340.5 (373.2)

 1.3, 91 0.2, 91

0.193 0.812

242.9 261.7 215.1 3 6 8

325.4 273.1 250.7 5 9 10

 1.2, 91  0.1, 91  0.6, 91 0.5, 1 0.6, 1 0.2, 1

0.252 0.882 0.569 0.714 0.450 0.635

(221.4) (315.2) (320.3) (6.5) (13.0) (17.4)

(428.2) (410.4) (279.4) (10.6) (19.1) (21.3)

Abbreviation: CPZ¼ Chlorpromazine, DUP ¼Duration of untreated psychosis, HEN ¼ High Royds Evaluation of Negativity Scale, MADRS ¼ Montgomery-Asberg Depression Rating Scale, MWCST¼Modified Wisconsin Card Sorting Test, PANSS ¼ Positive and Negative Syndrome Scale, PAS ¼ Premorbid Adjustment Scale, SGA ¼ Second-generation antipsychotic, WAIS-R-HK ¼Wechsler Adult Intelligence Scale Revised Cantonese version, Hong Kong a

DUP was log-transformed due to its skewed distribution. Standardized z-scores were computed for cognitive tests. c MWCST perseverative error z-score was multiplied by  1 so that higher score indicated better performance (i.e., less errors). d Fisher's exact test was applied. b

Table 2 Binary logistic regression analysis for predictors of good vocational outcome. Variables in the equation

B

S.E.

PAS total score  4.577 2.162 Employment status at intake 1.275 0.520 MWCST perseverative errors at clinical stabilization 0.283 0.139 Constant 1.138 0.879 Final model: Nagelkerke R2 ¼ 0.346, χ² ¼25.49, p o 0.001 Hosmer and Lemeshow test supported the goodness of fit of the model (χ² ¼7.41, d.f. ¼ 8, p ¼0.387)

Wald

d.f.

Sig.

Exp (B)

4.484 6.017 4.148 1.677

1 1 1 1

0.034 0.014 0.042 0.195

0.010 3.577 1.327 3.120

Visual reproduction test score at clinical stabilization, which entered stepwise logistic regression model, was excluded as predictors of good vocational outcome after analysis. Abbreviations: MWCST¼ Modified Wisconsin Card Sorting Test, PAS ¼ Premorbid Adjustment Scale.

studies with large sample size is warranted to confirm our findings that executive function is an independent cognitive predictor of employment outcome in the early course of schizophrenia. In conclusion, our results indicated that pre-morbid adjustment, baseline occupational status and executive function predicted employment outcome in the initial 3 years of treatment for patients presenting with first-episode schizophrenia. Poor vocational outcome may therefore represent a marker of a more severe

illness. Our findings also highlighted the importance and clinical utility of routinely assessing patients' pre-morbid functioning at intake, which currently may not be systematically evaluated in all psychiatric services. Owing to limited data on the relationship between cognitive impairment and occupational status in the early stage of schizophrenia, more prospective research should be conducted to clarify whether deficits in executive function specifically predict longitudinal vocational outcome.

838

W.C. Chang et al. / Psychiatry Research 220 (2014) 834–839

Table 3 Premorbid adjustment, demographics, baseline clinical variables, and treatment characteristics of a subgroup of patients who were unemployed at intake. Variables of interest Socio-demographics Age at entry, mean (S.D.) Male sex, n (%) Years of education, mean (S.D.)

Employed groupa (n¼ 20)

29.4 (7.4) 10 (50.0) 9.7 (2.3)

Unemployed groupb (n¼ 23)

30.9 (9.5) 11 (47.8) 10.2 (1.7)

Statistics (χ²/t, d.f.)

P value

0.6, 41 0.02, 1 0.8, 41

0.553 0.887 0.403

Premorbid adjustment PAS total score, mean (S.D.)

0.4 (0.1)

0.4 (0.1)

 1.0, 38

0.342

Baseline clinical characteristics Log DUPc, mean (S.D.)

4.6 (1.5)

5.6 (1.7)

 1.9, 34

0.068

 2.1, 41 0.3, 41 1.1, 41

0.040 0.767 0.294

1.4, 41 0.6, 41 1.1, 41

0.173 0.524 0.268

Symptom severity at intake PANSS Positive symptom score, mean (S.D.) HEN total score, mean (S.D.) MADRS total score, mean (S.D.)

17.0 (4.6) 13.9 (11.3) 12.4 (7.8)

20.2 (5.1) 12.9 (10.4) 8.7 (13.7)

Symptom severity at clinical stabilization PANSS Positive symptom score, mean (S.D.) HEN total score, mean (S.D.) MADRS total score, mean (S.D.)

10.1 (2.7) 11.4 (11.4) 3.7 (5.2)

8.9 (2.8) 9.3 (9.5) 2.1 (3.6)

Cognitive functioningd at clinical stabilization WAIS-R-HK Information subscale, mean (S.D.) Logical memory, mean (S.D.) Visual reproduction, mean (S.D.) Forward digit span, mean (S.D.) Category verbal fluency, mean (S.D.) MWCST perseverative errore, mean (S.D.) Treatment characteristics CPZ equivalence at intake, mean (S.D.) CPZ equivalence at clinical stabilization, mean (S.D.) CPZ equivalence at 12 months, mean (S.D.) CPZ equivalence at 24 months, mean (S.D.) CPZ equivalence at 36 months, mean (S.D.) Taking SGA at 12 monthsf, n (%) Taking SGA at 24 monthsf, n (%) Taking SGA at 36 monthsf, n (%)

 0.9  0.9 0.9  0.2  0.3  0.2 170.1 256.6 241.0 278.4 300.3 1 4 4

(1.0) (0.8) (0.7) (1.1) (0.8) (1.0)

 0.7  1.0  0.4  0.4  0.8  1.8

(0.8) (1.0) (1.1) (1.0) (0.8) (3.0)

 0.6, 40 0.4, 39 1.9, 39 0.7, 40 1.7, 40 2.3, 40

0.552 0.701 0.075 0.493 0.094 0.030

(181.4) (214.6) (197.1) (401.7) (440.0) (5.0) (20.0) (20.0)

205.7 313.8 359.0 236.7 332.5 3 5 6

(251.1) (277.3) (214.6) (287.6) (343.3) (13.0) (21.7) (26.2)

 0.7, 41  0.8, 41  1.3, 41 0.4, 41  0.3, 41 0.8, 1 0.02, 1 0.2, 1

0.523 0.459 0.210 0.695 0.790 0.610 0.889 0.728

Abbreviation: CPZ¼ Chlorpromazine, DUP ¼Duration of untreated psychosis, HEN ¼ High Royds Evaluation of Negativity Scale, MADRS ¼ Montgomery-Asberg Depression Rating Scale, MWCST¼Modified Wisconsin Card Sorting Test, PANSS ¼ Positive and Negative Syndrome Scale, PAS ¼ Premorbid Adjustment Scale, SGA ¼ Second-generation antipsychotic, WAIS-R-HK¼ Wechsler Adult Intelligence Scale Revised Cantonese version, Hong Kong a

Employed group was defined as a group of patients who were unemployed at intake and had ever attained full-time work within 3 year follow-up. Unemployed group was defined as a group of patients who were unemployed at intake and remained unemployed within 3 year follow-up. c DUP was log-transformed due to its skewed distribution. d Standardized z-scores were computed for cognitive tests. e MWCST perseverative error z-score was multiplied by  1 so that higher score indicated better performance (i.e., less errors). f Fisher's exact test was applied. b

Conflict of interests

Appendix A. Supporting information

Author E.Y.H.C. has participated in the paid advisory board for Otsuka, has received educational grant support from Janssen-Cilag, and research funding from Astra-Zeneca, Janssen-Cilag, Eli Lilly, Sanofi-Aventis and Otsuka. Author E.H.M.L has participated in the paid advisory board for Eli Lilly and Astra-Zeneca. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.psychres.2014.09.012.

Acknowledgments The study was funded by grant 21500.10202404 from Research Grants Council of Hong Kong. We thank all the coordinating clinicians and staff from the psychiatric units, as well as the medical records department at the Queen Mary Hospital for their kind assistance.

References American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th edition American Psychiatric Association, Washington DC. Barlati, S., De Peri, L., Deste, G., Fusar-Poli, P., Vita, A., 2012. Cognitive remediation in the early course of schizophrenia: a critical review. Current Pharmaceutical Design 18, 534–541. Bond, G.R., Resnick, S.G., Drake, R.E., Xie, H., McHugo, G.J., Bebout, R.R., 2001. Does competitive employment improve non-vocational outcomes for people with severe mental illness? Journal of Consulting and Clinical Psychology 69, 489–501. Bond, G.R., Drake, R.E., 2008. Predictors of competitive employment among patients with schizophrenia. Current Opinions in Psychiatry 21, 362–369. Bowie, C.R., Leung, W.W., Reichenberg, A., McClure, M.M., Patterson, T.L., Heaton, R. K., Harvey, P.D., 2008. Predicting schizophrenia patients' real-world behavior with specific neuropsychological and functional capacity measures. Biological Psychiatry 63, 505–511. Cannon-Spoor, H.E., Potkin, S.G., Wyatt, R.J., 1982. Measurement of premorbid adjustment in chronic schizophrenia. Schizophrenia Bulletin 8, 470–484.

W.C. Chang et al. / Psychiatry Research 220 (2014) 834–839

Cassidy, C.M., Norman, R., Manchanda, R., Schmitz, N., Malla, A., 2010. Testing definitions of symptom remission in first-episode psychosis for prediction of functional outcome at 2 years. Schizophrenia Bulletin 36, 1001–1008. Castle, D., Sham, P., Murray, R., 1998. Differences in distribution of ages of onset in males and females with schizophrenia. Schizophrenia Research 33, 179–183. Chang, W.C., Chan, S.S.M., Chung, D.W.S., 2009a. Diagnostic stability of functional psychosis: a systematic review. Hong Kong Journal of Psychiatry 19, 30–41. Chang, W.C., Pang, S.L.K., Chung, D.W.S., Chan, S.S.M., 2009b. Five-year stability of ICD-10 diagnoses among Chinese patients presented with first-episode psychosis in Hong Kong. Schizophrenia Research 115, 351–357. Chang, W.C., Hui, C.L.M., Tang, J.Y.M., Wong, G.H., Lam, M.M., Chan, S.K., Chen, E.Y., 2011. Persistent negative symptoms in first-episode schizophrenia: a prospective three-year follow-up study. Schizophrenia Research 133, 22–28. Chang, W.C., Hui, C.L.M., Tang, J.Y.M., Wong, G.H.Y., Chan, S.K.W., Lee, E.H.M., Chen, E.Y.H., 2013a. Impacts of duration of untreated psychosis on cognition and negative symptoms in first-episode schizophrenia: a 3-year prospective followup study. Psychological Medicine 43, 1883–1893. Chang, W.C., Tang, J.Y.M., Hui, C.L.M., Wong, G.H.Y., Chan, S.K.W., Lee, E.H.M., Chen, E.Y.H., 2013b. The relationship of early premorbid adjustment with negative symptoms and cognitive functions in first-episode schizophrenia: a prospective three-year follow-up study. Psychiatry Research 209, 353–360. Chang, W.C., Hui, C.L.M., Wong, G.H.Y., Chan, S.K.W., Lee, E.H.M., Chen, E.Y.H., 2013c. Symptomatic remission and cognitive impairment in first-episode schizophrenia: a prospective 3-year follow-up study. Journal of Clinical Psychiatry 74, e1046–e1053. Chen, E.Y.H., Lam, L.C.W., Chen, R.Y.L., Nguyen, D.G.H., 1996. Negative symptoms, neurological signs and neuropsychological impairments in 204 Hong Kong Chinese patients with schizophrenia. British Journal of Psychiatry 168, 227–233. Chen, E.Y.H., Hui, C.L.M., Dunn, E.L.W., Miao, M.Y.K., Yeung, W.S., Wong, C.K., Chan, W.F., Tang, W.N., 2005. A prospective 3-year longitudinal study of cognitive predictors of relapse in first-episode schizophrenic patients. Schizophrenia Research 77, 99–104. Dickerson, F.B., Stallings, C., Origoni, A., Boronow, J.J., Sullens, A., Yolken, R., 2007. The association between cognitive functioning and occupational status in persons with recent onset of psychosis. Journal of Nervous and Mental Disease 195, 566–571. Dickerson, F.B., Stallings, C., Origoni, A., Boronow, J.J., Sullens, A., Yolken, R., 2008. Predictors of occupational status six months after hospitalization in persons with recent onset of psychosis. Psychiatry Research 160, 278–284. Drake, R.E., Xie, H, Bond, G.R., McHugo, G.J., Caton, C.L.M., 2013. Early psychosis and employment. Schizophrenia Research 146, 111–117. Eack, S.M., Greenward, D.P., Hogarty, S.S., Cooley, S.J., DiBarry, A.L., Montrose, D.M., Keshavan, M.S., 2009. Cognitive enhancement therapy for early-course schizophrenia: effects of a two-year randomized controlled trial. Psychiatric Services 60, 1468–1476. Elvevag, B., Goldberg, T.E., 2000. Cognitive impairment in schizophrenia is a core of the disorder. Critical Reviews in Neurobiology 14, 1–21. Green, M.F., Kern, R.S., Braff, D.L., Mintz, J., 2000. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”? Schizophrenia Bulletin 26, 119–136. Giugiario, M., Crivelli, B., Mingrone, C., Montemagni, C., Scalese, M., Sigaudo, M., Rocca, G., Rocca, P., 2012. Cognitive function and competitive employment in schizophrenia: relative contribution of insight and psychopathology. Social Psychiatry and Psychiatric Epidemiology 47, 553–561. Hafner, H., Riecher-Rossler, A., Hambrecht, M., Maurer, K., Meissner, S., Schmidtke, A., Fätkenheuer, B., Löffler, W., van der Heiden, W., 1992. IRAOS: an instrument for the assessment of onset and early course of schizophrenia. Schizophrenia Research 6, 209–223. Hafner, H., Riecher-Rossler, A., an der Heiden, W., Maurer, K., Fatkenheuer, B., Loffler, W., 1993. Generating and testing a causal explanation of the gender difference in age at first onset of schizophrenia. Psychological Medicine 23, 925–940. Holtausen, E.A.E., Wiersma, D., Cahn, W., Kahn, R.S., Dingemans, P.M., Schene, A.H., van den Bosch, RJ., 2007. Predictive value of cognition for different domains of outcome in recent-onset schizophrenia. Schizophrenia Research 149, 71–80. The Wechsler Memory Scale-Revised (Cantonese version). Hong Kong Psychological Society, Hong Kong. The Wechsler Adult Intelligence Scale-Revised (Cantonese version). Hong Kong Psychological Society, Hong Kong. Jaeger, J., Douglas, E., 1992. Neuropsychiatric rehabilitation for persistent mental illness. Psychiatric Quarterly 63, 71–101. Johnstone, E.C., Macmillan, J.F., Frith, C.D., Benn, D.K., Crow, T.J., 1990. Further investigation of the predictors of outcome following first schizophrenic episodes. British Journal of Psychiatry 157, 182–189. Kahn, R.S., Keefe, R.S.E., 2013. Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry 70, 1107–1112. Kay, S.R., Opler, L.A., Fiszbein, A., 1987. Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276. Killackey, E.J., Jackson, H.J., Gleeson, J., Hickie, I.B., McGorry, P.D., 2006. Exciting career opportunity beckons! Early intervention and vocational rehabilitation in first-episode psychosis: emerging cautious optimism. Australian and New Zealand Journal of Psychiatry 40, 951–962. Knapp, M., Mangalore, R., Simon, J., 2004. The global costs of schizophrenia. Schizophrenia Bulletin 30, 279–293.

839

Lam, M.M.L., Pearson, V., Ng, R.M.K., Chiu, C.P.Y., Law, C.W., Chen, E.Y.H., 2011. What does recovery from psychosis mean? Perceptions of young first-episode patients. International Journal of Social Psychiatry 57, 580–587. Lysaker, P.H., Bell, M.D., Zito, W.S., Bioty, S.M., 1995. Social skill impairments at work: deficits and predictors of improvement in schizophrenia. Journal of Nervous and Mental Disease 183, 688–692. Lysaker, P.H., Bryson, G.J., Davis, L.W., Bell, M.D., 2005. Relationship of impaired processing speed and flexibility of abstract thought to improvements in work performance over time in schizophrenia. Schizophrenia Research 75, 211–218. Marshall, M., Lewis, S., Lockwood, A., Drake, R., Jones, P., Croudace, T., 2005. Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Archives of General Psychiatry 62, 975–983. Marwaha, S., Johnson, S., 2004. Schizophrenia and employment: a review. Social Psychiatry and Psychiatric Epidemiology 39, 337–349. McGorry, P.D., 1994. The influence of illness duration on syndrome clarity and stability in functional psychosis: does the diagnosis emerge and stabilize with time? Australian and New Zealand Journal of Psychiatry 28, 607–619. McGurk, S.R., Meltzer, K.T., 2000. The role of cognition in vocational functioning in schizophrenia. Schizophrenia Research 45, 175–184. Milev, P., Ho, B.C., Arndt, S., Andreasen, N.C., 2005. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. American Journal of Psychiatry 162, 495–506. Montgomery, S.A., Asberg, M.A., 1979. A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382–389. Mortimer, A.M., McKenna, P.J., Lund, C.E., Mannuzza, S., 1989. Rating of negative symptoms using the High Royds Evaluation of Negativity (HEN) Scale. British Journal of Psychiatry 155 (Suppl. 7), S89–S91. Nelson, H.E., 1976. A modified card sorting test sensitive to frontal lobe defects. Cortex 12, 313–324. Nuechterlein, K.H., Subotnik, K.L., Green, M.F., Ventura, J., Asarnow, R.F., Gitlin, M.J., Yee, C.M., Gretchen-Doorly, D., Mintz, J., 2011. Neurocognitive predictors of work outcome in recent-onset schizophrenia. Schizophrenia Bulletin 37 (Suppl. 2), S33–S40. Oosthuizen, P., Emsley, R.A., Keyter, N., Niehaus, D.J.H., Koen, L., 2005. Duration of untreated psychosis and outcome in first-episode psychosis: perspective from a developing country. Acta Psychiatrica Scandinavica 111, 214–219. Rinaldi, M., Killackey, E., Smith, J., Shepherd, G., Singh, S.P., Craig, T., 2010. First episode psychosis and employment: a review. International Review of Psychiatry 22, 148–162. Rosenheck, R., Leslie, D., Keefe, R., McEvoy, J., Swartz, M., Perkins, D., Stroup, S., Hsiao, J.K., Lieberman, J., 2006. Barriers to employment for people with schizophrenia. American Journal of Psychiatry 163, 411–417. Schmidt, S.J., Mueller, D.R., Roder, W., 2011. Social cognition as a mediator variable between neurocognition and functional outcome in schizophrenia: empirical review and new results by structural equation modeling. Schizophrenia Bulletin 37 (Suppl. 2), S41–S54. So, E., Kam, I., Leung, C.M., Chung, D., Liu, Z., Fong, S., 2003. The Chinese-bilingual SCID-I/P project: stage 1: reliability for mood disorders and schizophrenia. Hong Kong Journal of Psychiatry 13, 7–18. Tandberg, M., Ueland, T., Sundet, K., Haahr, U., Joa, I., Johannessen, J.O., Larsen, T.K., Opjordsmoen, S., Rund, B.R., Røssberg, J.I., Simonsen, E., Vaglum, P., Melle, I., Friis, S., McGlashan, T., 2011. Neurocognition and occupational functioning in patients with first-episode psychosis: a 2-year follow-up study. Psychiatry Research 188, 334–342. Tandberg, M., Ueland, T., Andreassen, O.A., Sundet, K., Melle, I., 2012. Factors associated with occupational and academic status in patients with first-episode psychosis with a particular focus on neurocognition. Social Psychiatry and Psychiatric Epidemiology 47, 1763–1773. Tsang, H.W., Chen, E.Y., 2007. Perceptions on remission and recovery in schizophrenia. Psychopathology 40, 469. Tsang, H.W.H., Leung, A.Y., Chung, R.C.K., Bell, M., Cheung, W.M., 2010. Review on vocational predictors: a systematic review of predictors of vocational outcomes among individuals with schizophrenia: an update since 1998. Australian and New Zealand Journal of Psychiatry 44, 495–504. Turner, N., Browne, S., Clarke, M., Gervin, M., Larkin, C., Waddington, J.L., O'Callaghan, E., 2009. Employment status amongst those with psychosis at first presentation. Social Psychiatry and Psychiatric Epidemiology 44, 863–869. Ucok, A., Polat, A., Genc, A., Cakir, S., T, N., 2004. Duration of untreated psychosis may predict acute treatment response in first-episode schizophrenia. Journal of Psychiatric Research 38, 163–168. Verdoux, H., Liraud, F., Assens, F., Abalan, F., van Os, J., 2002. Social and clinical consequences of cognitive deficits in early psychosis: a two-year follow-up study of first-admitted patients. Schizophrenia Research 56, 149–159. Whiteford, H.A., Degenhardt, L., Rehm, J., Baxter, A.J., Ferrari, A.J., Erskine, H.E., Charlson, F.J., Norman, R.E., Flaxman, A.D., Johns, N., Burstein, R., Murray, C.J., Vos, T., 2013. Global burden of disease attributable to mental and substance use disorders: findings from the global burden of disease 2010. Lancet 382, 1575–1586. Wykes, T., Newton, E., Landau, S., Rice, C., Thompson, N., Frangou, S., 2007. Cognitive remediation therapy (CRT) for young early onset patients with schizophrenia: an exploratory randomized controlled trial. Schizophrenia Research 94, 221–230.