Predictors of early stable symptomatic remission after an exacerbation of schizophrenia: The significance of symptoms, neuropsychological performance and cognitive biases

Psychiatry Research 210 (2013) 729–734

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Predictors of early stable symptomatic remission after an exacerbation of schizophrenia: The significance of symptoms, neuropsychological performance and cognitive biases Christina Andreou a,n, Daniela Roesch-Ely b, Ruth Veckenstedt a, Francesca Bohn a, Julia Aghotor b, Ulf Köther a, Ute Pfueller b, Steffen Moritz a a b

Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of General Adult Psychiatry, University of Heidelberg, Heidelberg, Germany

art ic l e i nf o

a b s t r a c t

Article history: Received 22 October 2012 Received in revised form 11 August 2013 Accepted 12 August 2013

Neuropsychological deficits and severity of initial psychopathology have been repeatedly associated with poor symptomatic outcomes in schizophrenia. The role of higher-order cognitive biases on symptomatic outcomes of the disorder has not yet been investigated. The present study aimed to assess the contribution of cognitive biases, psychopathology and neuropsychological deficits on the probability of achieving early symptomatic remission after a psychotic episode in patients with schizophrenia. Participants were 79 patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder undergoing an acute psychotic episode, and 25 healthy controls. According to psychopathology assessments, patients were split into those who had achieved remission after an average follow-up interval of 7 months, and those who had not (NR). Patients who achieved remission exhibited higher premorbid IQ and better performance on the TMT-B, as well as lower baseline positive, disorganized and distress symptoms than NR patients. TMT-B performance and positive symptoms at baseline were the best predictors of remission. Cognitive biases and negative symptoms were not associated with later remission. The findings highlight the significance of initial symptom severity for at least short-term symptomatic outcomes and, thus, the importance of adequate symptomatic treatment and prevention of psychotic outbreaks in patients. & 2013 Elsevier Ireland Ltd. All rights reserved.

Keywords: Schizophrenia Remission Outcome Cognitive biases Neuropsychology

1. Introduction Despite advances in antipsychotic drug treatment, schizophrenia remains a chronic disorder compromising multiple aspects of everyday functioning and quality of life (Hofer et al., 2006). However, expectations of improved outcomes have been heightened in recent years (Emsley et al., 2011), due in part to the fact that symptomatic remission has been shown to be an achievable goal for approximately 50% of patients in average (Emsley et al., 2011; Lambert et al., 2010b). Remission of symptoms has been shown to constitute a necessary, albeit not sufficient (Lambert et al., 2010b), condition for functional outcome (van Os et al., 2006) and quality of life (Emsley et al., 2007) in patients with schizophrenia. Thus, research into early markers of symptomatic remission is important to predict the course of illness.

n Correspondence to: Universitätsklinikum Hamburg-Eppendorf, Klinik für Psychiatrie und Psychotherapie, Martinistraße 52, D-20246 Hamburg, Germany. Tel.: þ 49 40471 059460; fax: þ 40 7410 52999. E-mail addresses: [email protected], [email protected] (C. Andreou).

0165-1781/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psychres.2013.08.019

It is widely known that patients with schizophrenia exhibit impairments in several cognitive domains, such as attention, executive function, as well as verbal and non-verbal memory (Nieuwenstein et al., 2001) and social cognition, for example as facial emotion recognition and theory of mind (e.g. Green et al., 2008). Neuropsychological deficits have been repeatedly shown to be associated with various measures of clinical outcome, such as positive (Verdoux et al., 2002) and negative symptomatology (Novick et al., 2007), as well as re-hospitalization rates (Verdoux et al., 2002) and overall time in psychosis (Holthausen et al., 2007), after a first episode of psychosis. Moreover, cross-sectional studies have revealed marked differences in neuropsychological performance according to whether or not patients meet criteria for remission (Hofer et al., 2011). Beyond elementary neuropsychological deficits, in recent years there has been increased interest in cognitive biases in schizophrenia research, that is, specific types of higher-grade cognitive distortions relating to the integration and interpretation of perceived stimuli, or thinking styles. Patients with schizophrenia have been shown to exhibit a jumping-to-conclusions bias (i.e., a tendency to make strong judgments on the basis of poor evidence; Garety et al., 1991),

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overconfidence in errors (i.e. increased confidence for false judgments; Moritz et al., 2004), and a bias against disconfirmatory evidence (i.e., strong tendency to stick to previously held opinions in the face of substantial counter-evidence; Woodward et al., 2006). These biases have been implicated in some clinical dimensions of schizophrenia, particularly in the formation and/or maintenance of delusions (Garety and Freeman, 1999). Although cognitive biases do show some improvement upon remission on symptoms (Lincoln et al., 2010; Peters and Garety, 2006; Woodward et al., 2009), they are also present in remitted patients (Menon et al., 2008; Peters and Garety, 2006), as well as in individuals at high-risk (Broome et al., 2007; Zawadzki et al., 2012) or with subclinical delusional propensity (Buchy et al., 2007; Moritz et al., 2012). Thus, they are not only associated with state symptomatology, but also constitute a putative trait factor predisposing to the emergence of delusions (So et al., 2010) and/or moderating treatment response (Menon et al., 2008). This might be of relevance for the symptomatic outcome of schizophrenia, since clinical features such as baseline psychopathology (Lambert et al., 2010b) and early treatment response (Emsley, 2009) have been consistently shown to predict outcome in patients with schizophrenia. An important methodological consideration in longitudinal studies of outcome is the timing of baseline and follow-up assessments. Previous studies have, for the most part, included recent-onset or never-treated patients (Addington and Addington, 2008b; Caton et al., 2006; Emsley et al., 2006, 2007; Gasquet et al., 2005; Holthausen et al., 2007; Lambert et al., 2008; Novick et al., 2007; Wolwer et al., 2008), and/or have assessed symptomatic outcome in the long term, that is, two to three years after study inclusion (Addington and Addington, 2008b; Emsley et al., 2006, 2007; Gasquet et al., 2008; Lambert et al., 2008, 2006; Novick et al., 2007, 2009). Such studies are certainly of utmost importance for gaining insights into the course of schizophrenia and developing appropriate interventions, as well as for predicting the longterm care needs of patients. However, it would also be interesting to investigate the predictors of symptomatic remission in the immediate aftermath of a psychotic episode occurring at any time during the course of the illness. Such an approach would also carry a significant advantage for everyday clinical practice, such as forensic issues and decisions regarding intensity of treatment. To the best of our knowledge, no such study exists so far. Thus, the present study aimed to investigate the factors influencing the probability of achieving early stable symptomatic remission after an index psychotic episode in patients with schizophrenia. For this purpose, remission was defined according to the widely accepted criteria defined by the Remission in Schizophrenia Working Group (RSWG; Andreasen et al., 2005), and predictors were sought among measures of psychopathology, neuropsychological performance, as well as cognitive biases.

according to the principles laid out in the current version of the Declaration of Helsinki, and was approved by the local ethics committees. Diagnosis was confirmed by means of the Mini International Neuropsychiatric Interview MINI, (MINI; Sheehan et al., 1998). Inclusion criteria for all participants were age between 18 and 65 years, and the ability to provide written informed consent. Exclusion criteria were current substance dependence, severe brain damage, and IQ less than 70. Moreover, patients scoring high on hostility and uncooperativeness (Z5 and Z6 in the respective PANSS items) were excluded from participation. For the present analysis, patients with diagnoses of psychotic disorders other than schizophrenia or schizoaffective disorder, and patients or controls with a history of alcohol or drug dependence in the six months prior to participation in the study were excluded from the original cohort, leading to a final sample of 79 patients and 25 healthy controls. At the time of inclusion in the study, all but six patients (7.6%) were receiving treatment with antipsychotics; the vast majority of patients were treated with atypical antipsychotics or clozapine (n¼ 61, 77.2%), six patients were receiving typical antipsychotics (7.6%), and six patients were treated with both typical and atypical antipsychotics (7.6%). Approximately half of patients (n ¼36, 45.6%) were receiving adjunctive medication (benzodiazepines, n¼ 8; antidepressants, n ¼22; antiepileptics, n¼ 10, lithium, n¼ 2).

2.2. Assessments Sociodemographic data were collected for all subjects, as well as duration of illness and previous hospitalizations for patients (Table 1). Baseline assessments included: (a) psychopathology (only for patients), assessed with the PANSS (Kay et al., 1987). The five PANSS factors (positive, negative, disorganization, excitement, and distress) described by van der Gaag et al. (2006) were used in the analyses; (b) an estimate of premorbid IQ (Mehrfachwortschatztest, MWT-B; Lehrl, 1991); (c) measures of attention (Trail Making Test A and B, Reitan and Wolfson, 1985; d2 letter cancellation test, Brickenkamp, 1994); (d) verbal memory (Rivermead Behavioural Memory Test, RBMT; Wilson et al., 1985); (e) emotion recognition, consisting in the Reading-the-Mind-in-the-Eyes Test (RMET; Baron-Cohen et al., 2001); and (f) two measures of cognitive biases: the jumping-to-conclusions (JTC) bias was assessed with a computerized variant (Moritz et al., 2006) of the beads task (Huq et al., 1988), in which subjects are additionally asked to provide probability estimates as to the origin of each drawn bead. The main variable of interest was the presence or absence of JTC bias, defined as reaching a decision based on two beads or less; moreover, the decision threshold (i.e. the lowest probability estimate, at which the subject reached a decision concerning to the origin of a bead) was used as an additional, putatively more sensitive measure of JTC bias (Moritz et al., 2006). As a second measure or cognitive bias, subjects were asked to provide confidence ratings for their RMET responses, which were used to assess overconfidence in errors; the variable of interest consisted in the sum of highly confident incorrect responses (cf. Koether et al., 2012). For patients, a follow-up assessment of psychopathology was carried out four weeks (mean: 5 7 1.6 weeks) after entering the study (T1), and a second assessment at least six months (T2) after the first one (mean: 6.8 71 month). Based on these two assessments, patients were split into those having reached remission status according to criteria defined by the Remission in Schizophrenia Working Group (Andreasen et al., 2005), and those who did not meet remission criteria. RSWG criteria require a score of three or less for a period of at least 6 months on all of the following PANSS items: P1 (Delusions), P2 (Conceptual Disorganization), P3 (Hallucinations), N1 (Blunted Affect), N4 (Social Withdrawal), N6 (Lack of Spontaneity), G5 (Mannerisms/Posturing) and G9 (Unusual Thought Content). In the present study, the six-month duration criterion was taken into account for the definition of remission. Thus, patients meeting remission criteria would have achieved and maintained remission quite early in the course of treatment.

2.3. Statistical analysis 2. Methods 2.1. Participants Participants were patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder undergoing an acute psychotic exacerbation, and healthy controls. Patients were selected from a cohort of 165 in- and outpatients participating in a larger study that compared the effects of two different 4-week intervention programs (a metacognitive skill training program (MCT; Moritz et al., 2005)), and a cognitive remediation program (CogPack®; Marker, 2003) as adjunctive treatments in patients with psychotic disorders in a randomized, double-blind fashion. Recruitment of patients was carried out from December 2006 to August 2009 at two German University hospitals (Hamburg and Heidelberg). Since this was a non-pharmacological intervention trial with an extensive psychological test battery requiring sufficient task comprehension and sustained attention, study enrolment occurred when patients were deemed sufficiently stable for participation according to their attending psychiatrist. Healthy controls were recruited from the community through word of mouth. The study was conducted

Data on remission status at T2 were available for 69 patients. Variables not meeting normality assumptions (the five PANSS factors, TMT-A and TMT-B score) were normalized using logarithmic transformations. Departure from normality was also noted for confidence ratings on the RMET, but these were used in their raw form, as transformations did not improve their distribution. A multivariate analysis of covariance (MANCOVA) was used to compare the profile of cognitive performance among the groups, using group membership (patients remitted at T2 vs. patients not remitted at T2 vs. healthy controls) as the between-groups factor, and cognitive biases, neuropsychological and social cognitive performance as the within-group factors. Further, a second MANCOVA was conducted, in which patients who had achieved remission and those who had not were compared across severity of psychopathology, number of previous hospitalizations, length of illness, and first-episode status (i.e. patients with duration of illness of r 2 years and r 1 hospitalization including the present one). Variables, for which there were significant differences between the two patient groups in the above MANCOVAs, were subsequently entered as predictors in a stepwise logistic regression model (likelihood ratio method) with remission status at T2 as the dependent variable.

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Table 1 Baseline characteristics of patients with schizophrenia and healthy controls. Healthy controls (N ¼25) Mean/N Gender (f/m) Age (years) Education (years) Education father (years) Education mother (years) Premorbid IQ (MWTB) TMT A (sec) TMT B (sec) D2 score RBMT immediate score RBMT delayed score JTC (present/absent) JTC decision threshold RMET score Overconfidence in errors Length of illness (years) Previous hospitalizations Recent-onseta Antipsychotic medication doseb PANSS total score PANSS positive factor PANSS negative factor PANSS disorganization factor PANSS excitement factor PANSS distress factor

14/11 33.32 11.72 10.82 9.92 113.40 22.42 52.58 182.00 12.02 10.48 11/14 85.73 25.64 0.48

Patients (N ¼ 79) S.D.

11.63 1.72 1.76 1.55 9.76 7.26 13.84 38.94 2.75 3.12 9.24 3.72 0.77

Mean/N 33/46 36.70 11.72 10.95 10.17 104.67 32.25 72.85 142.23 8.87 7.22 43/36 74.99 20.53 1.39 8.27 2.89 25.3% 74.84 52.56 13.60 14.24 15.23 12.38 16.59

t/χ2

p

S.D.

11.39 1.52 2.51 2.07 13.51 11.56 32.08 37.19 3.28 3.59 24.98 4.64 3.16 8.64 3.96

2.99 5.05 4.44 4.52 4.33 4.08 3.12 5.01 2.35

n.s. n.s. n.s. n.s. n.s. 0.004 o 0.001 o 0.001 o 0.001 o 0.001 o 0.001 n.s. 0.002 o 0.001 0.02

63.76 15.10 7.18 6.01 5.59 4.22 6.12

Notes: MWTB: Mehrfachwortschatz test (reported values correspond to standardized IQ scores); TMT A, TMTB: Trail Making Test, Parts A and B; D2: d2 letter cancelation test; RBMT: Rivermead behavioural Memory Test; JTC: Jumping-to-conclusions bias; RMET: Reading-the-Mind-in-the-Eyes Test. a b

Recent-onset was defined as a length of illness of two years or less and no more than one psychiatric admission including the present one. Cumulative dose in percent of the highest daily dosage according to the German Red List Manual (Rote-Listes-Service-GmbH 2011).

3. Results Of the 69 patients for whom data at follow-up were available, 45% had achieved symptomatic remission for at least 6 months (n ¼31), a rate comparable to that reported by previous studies (see Lambert et al. (2010a) for a comprehensive recent review). The two patient groups and healthy controls did not differ significantly in age and gender, but there were significant differences in premorbid IQ (Table 1). Post-hoc comparisons with Bonferroni correction indicated that patients who had not achieved remission had significantly lower premorbid IQ (101.35 712.0) than those who had achieved remission (109.19 714.1, p ¼0.04) and healthy controls (113.40 79.76, p ¼0.001), who did not significantly differ from each other. Therefore, premorbid IQ was entered as a covariate in the analyses. The first MANCOVA (two patient subgroups, controls) yielded a significant main effect of group (F¼ 2.78, d.f. ¼16, p o0.001). The effect of IQ as a covariate was significant (F¼4.37, d.f. ¼8, p o0.001). Univariate ANOVAs revealed significant differences across the groups in all domains tested except JTC bias and overconfidence in errors. For the tests, in which differences were noted, post hoc comparisons indicated that the two patient groups displayed significant deficits compared to healthy controls; the only exception to this pattern was performance on the TMT-B, in which non-remitted patients scored significantly lower than controls, whereas remitted patients did not significantly differ either from non-remitted patients or healthy controls (Table 2). In the second MANCOVA, there was a significant main effect of group (remitted vs. non-remitted patients: F¼2.79, d.f. ¼8, p ¼0.01). The effect of IQ as covariate was not significant. Univariate ANOVAs revealed significant differences between the two groups for PANSS positive [F(1,64) ¼18.48 p o0.001], disorganization [F(1,64) ¼5.68, p ¼0.04] and distress factors [F(1,64) ¼ 11.38,

p¼ 0.001]; in all three cases, patients who had not achieved remission exhibited higher scores compared to those who had (Table 2). PANSS positive score and TMT-B performance emerged as the only significant predictors of remission (Table 3) in the logistic regression analysis. The correct classification rate was 75.8% overall (73.3% for patients who had achieved remission, 77.8% for patients who had not). 3.1. Additional analyses Because decision threshold differentiated patients from controls more successfully than the presence or absence of JTC bias in the present sample (see Table 1), the first three-group MANCOVA was repeated with use of the former variable as a measure of JTC bias. Results remained unchanged, with the univariate ANOVA for decision threshold failing to reach significance levels (p ¼0.177). Moreover, since performance on the TMT-B is a rather unspecific measure of general cognitive capacity (see below for a more detailed discussion), the first MANCOVA analysis was repeated after substituting TMT-A and TMT-B scores with their difference score as a more specific measure of cognitive flexibility in the dependent variable list. Results for all other variables remained essentially unchanged, but there was no significant difference among the three groups for the TMT-difference score (p¼ 0.248).

4. Discussion In the present study, patients who achieved criteria for complete remission after an acute exacerbation of schizophrenia or schizoaffective psychosis exhibited significantly lower premorbid IQ and TMTB performance, and lower initial positive, disorganization and distress

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Table 2 Comparisons of patients who did (R) and did not (NR) achieve remission, and healthy controls (HC) Patients

Previous admissions Length of illness (years) first episode (% yes) PANSS positive PANSS negative PANSS disorganized PANSS excitement PANSS distress TMT A (sec) TMT B (sec) D2 Test RBMT immediate RBMTdelayed RMET Overconfidence in errors JTC bias (draws to decision) a

Healthy controls (HC)

No remission (NR)

Remission (R)

Mean/%

Mean/%

3.39 9.0 37% 15.68 15.19 16.08 12.49 17.87 33.46 79.84 136.32 8.72 6.89 20.68 0.92 2.61

S.D. 5.14 9.32

2.61 7.40 34.7% 10.27 12.71 13.00 11.19 13.90 32.65 64.57 144.97 9.31 7.77 21.10 1.74 2.77

7.11 5.82 5.42 3.65 4.83 11.87 32.47 36.36 3.22 3.43 4.64 2.55 1.64

S.D.

Mean / %

22.42 52.58 182.00 12.02 10.48 25.64 0.48 2.96

p

1.55 1.13 0.02 18.48 2.54 5.68 2.17 11.38 8.03 4.03 8.47 5.87 4.68 6.98 1.94 1.82

0.22a 0.29a 0.90a o 0.001a 0.12a 0.02a 0.15a 0.001a 0.001a 0.02a o 0.001a 0.004a 0.01a 0.002a 0.15a 0.17a

Post-hoc

S.D.

2.88 8.44 4.32 5.51 3.11 3.51 5.06 10.13 21.77 29.28 3.23 3.59 4.91 3.22 2.27

F

7.26 13.84 38.94 2.75 3.12 3.72 0.77 2.01

NR4 R NR4 R NR4 R NR¼ R4HC NR4 HC NR¼ Ro HC NR¼ Ro HC NR¼ Ro HC NR¼ Ro HC

Covariate: premorbid IQ.

Table 3 Results of logistic regression (Dependent variable: remission status T2). B

S.E. Wald p

Exp(B) 95% C.I. for EXP(B)

Constant 18.72 5.38 12.12 0.000 PANSS positive factor T0  7.45 2.07 12.92 0.000 0.001 TMT-B score T0  6.02 2.25 7.15 0.007

Lower

Upper

0.000

0.034

Note: R2 ¼ 0.28 (Hosmer and Lemershow), 0.32 (Cox and Snell), 0.43 (Nagelkerke). Model χ2(2)¼ 25.83, p o0.001.

symptoms, than patients who failed to achieve remission. Logistic regression identified TMT-B performance and PANSS positive score as significant predictors of remission status at follow-up. Negative symptomatology, cognitive biases and emotion recognition did not significantly differ between patients who achieved remission and those who did not. To the best of our knowledge, this is the first study to investigate cognitive biases as a predictor of remission after a psychotic episode. The absence of a significant effect might be explained by the fact that cognitive biases appear to be associated with a specific dimension of clinical psychopathology, namely the presence of delusions (Garety and Freeman, 1999), rather than with overall symptomatology. Our findings are also consistent with those of a previous study (Menon et al., 2008), in which a measure of jumping to conclusions similar to the one used in the present study did not predict changes in positive symptoms after four weeks of antipsychotic treatment (although scores on an emotionally salient version of the task did appear to act as a moderator of treatment response). Another interesting explanation for this negative finding is provided by another recent study (Lincoln et al., 2010), which found that differences in jumping-toconclusions between remitted and non-remitted patients disappeared when controlling for negative symptoms and intelligence. Thus, differences in premorbid intelligence between the two patient groups may have masked any effects of cognitive biases on the possibility to achieve remission in the present study. On the other hand, it would be interesting to assess the effects of treatment-related changes in cognitive biases on outcome in future studies, as these biases appear to be amenable to specific

treatment interventions (Ross et al., 2011; Waller et al., 2011), and the latter interventions have been shown to improve positive symptoms (Moritz et al., 2011; Waller et al., 2011). Our finding that positive symptoms at episode onset significantly predicted remission at follow-up is consistent with similar findings of previous studies (Addington and Addington, 2008b; Gasquet et al., 2008; Lambert et al., 2010b; Rossi et al., 2009). On the other hand, other studies report negative symptoms as the sole predictor or remission (Novick et al., 2007, 2009), or as an additional predictor to positive symptoms (Addington and Addington, 2008b; Gasquet et al., 2005; Gasquet et al., 2008; Rossi et al., 2009), and yet others altogether fail to find such a correlation (Emsley et al., 2007; Lambert et al., 2010a, 2008, 2006). It is highly probable that these disparate results are due to methodological differences such as patient selection criteria and definition of remission. Indeed, more than half of the studies reporting negative symptoms as significant predictors of clinical outcome originate from the same larger study (SOHO) (Gasquet et al., 2005, 2008; Novick et al., 2007, 2009). An important feature that sets our study apart from previous ones is that we investigated the probability of remission in the immediate aftermath of an index psychotic episode, whereas most previous studies have studied remission in the long term (2–3 years) (Gasquet et al., 2005, 2008; Lambert et al., 2008, 2006; Novick et al., 2007, 2009) and/or exclusively in first episode or previously unmedicated patients (Addington and Addington, 2008b; Emsley et al., 2006; Lambert et al., 2008; Novick et al., 2007). Our results might then be interpreted as to suggest that symptoms related to the productive dimension of psychosis (positive, disorganized, distress) are more important for predicting the achievement of remission early on after a psychotic episode, whereas negative symptoms are more important for long-term remission. However, this is only a tentative conclusion, since patients included in the present study exhibited rather low baseline scores on the negative factor of the PANSS, and therefore, the lack of a significant effect might simply reflect the low variance of the respective variable. Apart from baseline symptomatology, the present study indicated performance on the TMT-B as a significant predictor of remission. This finding corroborates previous ones, according to which neuropsychological performance is associated with the presence of clinical remission (Hofer et al., 2011) in crosssectional studies, as well with various measures of clinical

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outcome in longitudinal studies, such as time in psychosis (Holthausen et al., 2007) and persistent negative symptoms (Stirling et al., 2003). Along a similar line, self-perceived neuropsychological dysfunction has also shown to be associated with symptomatic outcome in first-episode patients (Moritz et al., 2002). Interestingly, in a study assessing the effects of cognition and clinical symptoms after an 8-week acute treatment phase on the probability of clinical deterioration one year later, performance on the TMT-B was also the strongest predictor of the clinical course (Wolwer et al., 2008). As the authors of the latter study point out, TMT-B is a relatively unspecific test assessing a variety of neuropsychological functions such as visual scanning/attention, processing speed, and abstract conceptual processing/cognitive flexibility (Palmer and Heaton, 2000); thus, it is possible that the probability of achieving clinical remission depends on general cognitive ability rather than a specific neuropsychological function. This conclusion is supported by our failure to find significant differences between groups, when the difference score of the two parts of the TMT was used as a more specific, attention- and speed-independent, measure of cognitive flexibility. It is also consistent with our finding that the only other cognitive variable that significantly differed between the two outcome groups was premorbid IQ. In line with the above, previous studies have shown significant intercorrelations among individual cognitive variables, which tend to load on a single global cognitive factor (e.g. Keefe et al., 2006), and it has been suggested that findings of decreased domain-specific neuropsychological performance in schizophrenia might rather reflect general cognitive ability (Dickinson and Harvey, 2009). Specific mention deserves social cognitive performance (reflected in emotion recognition), which was not associated with clinical outcome. Although social cognition has been consistently linked to functional outcomes in schizophrenia (Green et al., 2008), our finding is not surprising, given that social cognitive deficits have been shown to be independent of clinical fluctuations (Addington and Addington, 2008a) or phase of the illness (Green et al., 2012). Thus, it is possible that social cognition is more important for functional rather than clinical outcomes of schizophrenia. The most important limitation of the present study is that it did not consider other factors reported to significantly affect symptomatic outcome, such as medication adherence, premorbid adjustment and functional capacity at baseline (Lambert et al., 2010b) or insight (Caton et al., 2006). Moreover, although length of illness and previous admissions did not appear to affect later remission probability, there was no data available on other measures of illness severity, such as length of previous psychotic episodes. This might explain why the two factors identified, TMT-B performance and positive symptoms at baseline, only explained about a third of the outcome variance. However, it is noteworthy that the correct classification rate based on these two factors was reasonable, suggesting that these might indeed be particularly important for the short-term clinical outcome after an episode of schizophrenia. Another shortcoming of the present analysis was that it was based on a non-pharmacologic intervention study requiring high levels of cooperation and clinical stability, and thus our patient sample exhibited rather low baseline symptom scores. Since patients were included in the study after an initial stabilization phase, the possibility should be entertained that early (positive) symptom response to treatment, rather than actual baseline symptomatology, was the actual factor associated with clinical outcome. In summary, cognitive biases did not contribute significantly to the probability of clinical remission in the immediate aftermath of a psychotic episode in the present sample of patients with schizophrenia and schizoaffective disorder. Patients who achieved remission

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differed from those who did not on positive, disorganized and distress symptoms, as well as on premorbid IQ and performance on the TMTB. Among those factors, TMT-B performance (a rather unspecific measure of cognitive capacity) and positive symptoms at baseline were the best predictors of remission. The present findings underline the significance of cognitive capacity and severity of initial symptomatology for at least short-term symptomatic outcomes in patients with schizophrenia and, thus, the importance of adequate symptomatic treatment and prevention of psychotic outbreaks in patients.

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