The relationship between insight and theory of mind in schizophrenia

Schizophrenia Research 152 (2014) 217–222

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The relationship between insight and theory of mind in schizophrenia George Konstantakopoulos a,b,⁎, Dimitris Ploumpidis a, Panagiotis Oulis a, Panayiotis Patrikelis a,c, Stavrina Nikitopoulou a, George N. Papadimitriou a, Anthony S. David b a b c

First Department of Psychiatry, University of Athens, Eginition Hospital, Athens, Greece Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, King's College, London, UK Hellenic Center for Neurosurgical Research “Prof. Petros Kokkalis”, Department of Neurosurgery, University of Athens, “Evangelismos” Hospital, Athens, Greece

a r t i c l e

i n f o

Article history: Received 1 August 2013 Received in revised form 2 November 2013 Accepted 12 November 2013 Available online 8 December 2013 Keywords: Schizophrenia Theory of Mind Insight Neurocognition Social cognition Metacognition Treatment compliance

a b s t r a c t Introduction: It has been proposed that theory of mind (ToM) deficits underlying difficulties in taking the perspective of others may substantially contribute to insight impairment in schizophrenia. The present study aimed to explore the effect of ToM deficits on insight impairment independently of co-existent neurocognitive deficits and symptom severity in chronic schizophrenia. Methods: Fifty-eight chronic patients with schizophrenia and 56 matched healthy participants were assessed with the Schedule for the Assessment of Insight (SAI–E) along with a series of ToM tasks and a comprehensive battery of neuropsychological measures. Symptoms were measured with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Results: ToM impairment explained a substantial proportion of variance in overall insight and its three major components: awareness of illness, relabelling of symptoms and treatment compliance. Moreover, the effect of ToM deficits on insight remained significant even after controlling for all neurocognitive factors and symptom ratings. Regression analysis showed that symptoms and cognitive deficits also contribute to impaired insight in schizophrenia. General intellectual ability was negatively associated with both overall insight and relabelling of symptoms. Executive functions were negatively associated with relabelling. Conclusion: Our findings confirm that ToM deficits negatively affect insight independently of neurocognitive deficits and symptom severity in chronic schizophrenia. The effect of ToM deficits on insight should be further examined in the broader context of the failures in metacognition and their relationships with insight impairment in schizophrenia. © 2013 Elsevier B.V. All rights reserved.

1. Introduction Lack of insight is a core feature of schizophrenia that impacts negatively on medication adherence (Kemp and David, 1997; Dassa et al., 2010), treatment outcome (David et al., 1995; David, 2004), and social functioning (Lincoln et al., 2007; Erickson et al., 2011). According to current understanding, insight in psychosis is a continuous and multidimensional phenomenon involving the ability to recognize that one has a mental illness, the capacity to relabel unusual mental events as pathological, and compliance with treatment (David, 1990). While mechanisms underlying insight impairment are still unknown, it has been found to be associated with severity of symptoms (Mintz et al., 2003) and cognitive deficits, especially lower IQ and executive dysfunction (Morgan and David, 2004; Aleman et al., 2006). On the other hand, the positive associations of insight with depression (Mintz et al., 2003), suicidality (Crumlish et al., 2005) and internalized stigma (Lysaker ⁎ Corresponding author at: Eginition Hospital, Vas. Sofias av. 72-74, 11528 Athens, Greece. Tel.: +30 210764011; fax: +30 2107662829. E-mail addresses: [email protected], [email protected] (G. Konstantakopoulos). 0920-9964/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.schres.2013.11.022

et al., 2007) suggest that denial of illness as a defensive style or coping strategy might contribute to poor insight (Moore et al., 1999; Donohoe et al., 2004; Cooke et al., 2007). Insight entails the correct attitude toward morbid change in oneself and relies on the capacity to reflect upon self from the perspective of the other (i.e., “to see ourselves as others see us”) (David, 1999). This capacity, in turn, is clearly linked to the ability to understand mental states (e.g., beliefs, knowledge, and intentions) of others, that is, Theory of Mind (ToM) or mentalizing (Premack and Woodruff, 1978). Thus, it has been recently proposed that ToM deficits underlying difficulties in taking the perspective of others may substantially contribute to insight impairment in schizophrenia (Carruthers, 2009; Langdon and Ward, 2009; Wiffen and David, 2009). A growing body of evidence suggests that patients with schizophrenia show ToM impairment (Harrington et al., 2005; Sprong et al., 2007; Bora et al., 2009) which is relatively independent from overall cognitive dysfunction (Abdel-Hamid et al., 2009; Bozikas et al., 2011). Until now, research on the relationship between ToM and insight in schizophrenia has revealed mixed results, with some studies finding a positive association (Langdon et al., 2006; Bora et al., 2007; Langdon and Ward, 2009; Lysaker et al., 2011; Wiffen et al., 2013), and others finding no

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association (Drake and Lewis, 2003; Stewart et al., 2010) or no straightforward relationship (Pousa et al., 2008a; Pijnenborg et al., 2013). Many factors could account for these contradictory results, such as the sample size, the use of control group, the tasks used for the assessment of ToM (Harrington et al., 2005), and uncontrolled differences in cognitive factors that can affect both ToM performance (Shur et al., 2008; Couture et al., 2011) and insight. Symptomatology might be another confounding factor of the relationship between ToM and insight, since specific symptoms might be related to poorer ToM performance (Pousa et al., 2008b; Kern et al., 2009) and poorer or better insight (Mintz et al., 2003). Finally, the differences between the samples of previous studies in diagnosis and phase of illness might be a major reason for the contradictory findings, since multiple clinical and cognitive factors might affect differentially insight into psychosis across phases of the illness (Tranulis et al., 2008; Quee et al., 2011). Against the above background, we sought to explore the relationship between ToM and insight – overall and its major components – in schizophrenia focusing on chronic patients and including several clinical and cognitive factors in our investigation. We conceptualized ToM as a broad set of modular reasoning skills, one of which might support self-awareness or insight. We therefore hypothesized that there would be a significant effect of ToM deficits on insight impairment independently of co-existent neurocognitive deficits and symptom severity. 2. Methods 2.1. Participants Fifty-eight patients (34 male and 24 female) were recruited from the outpatient services of the Byron–Kessariani Community Mental Health Centre based on the following criteria: (a) diagnosis of schizophrenia according to the DSM-IV-TR criteria (American Psychiatric Association, 2000) by an experienced clinical psychiatrist, (b) duration of illness of at least 3 years, and (c) clinical stability during the past 6 months. Fifty-six healthy participants (30 male and 26 female) were recruited from the local community. The two groups were matched for gender, age and educational level. Inclusion criteria for the control subjects were no personal history of psychiatric disorder or family history of psychosis. Exclusion criteria for all participants included: mental retardation, personal or family history of any neurological disorder, history of head injury, alcohol or substance abuse in the preceding 6 months. All the patients were taking an antipsychotic medication at the time of assessment: 48 (82.8%) were on atypical and 18 (31.0%) on typical antipsychotics. In addition, 15 (25.9%) were on an anticholinergic agent, 16 (27.9%) on an antidepressant (twelve on SSRI and four on SNRI) and 12 (20.7%) on a benzodiazepine. 2.2. Assessments 2.2.1. Clinical assessments Diagnosis of schizophrenia in patients and the absence of mental disorders in the control group were confirmed using the Structural Clinical Interview for DSM-IV Axis I Disorders (First et al., 1997). Additional information for patients was obtained from their medical records and treating physicians. Antipsychotic medication dosage was converted into chlorpromazine equivalents (Woods, 2003; Bazire, 2005). Symptoms of schizophrenia were rated using the positive and negative subscales of the Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987). Depressive symptoms were separately assessed with the Calgary Depression Scale for Schizophrenia (CDSS) (Addington et al., 1992). Handedness was assessed by the Annett Handedness Questionnaire (Annett, 1970). The Schedule for the Assessment of Insight – Expanded version (SAI–E) (Kemp and David, 1997) was used to assess patient's insight into illness. This is an 11-item semi-structured interview providing a general measure of insight along with three subscales for the major

dimensions of insight: (a) awareness of illness, (b) relabelling of symptoms, and (c) treatment adherence. The Greek version of the scale has proven validity and reliability in patients with schizophrenia (Konstantakopoulos et al., 2013). 2.2.2. Cognitive evaluation A comprehensive neuropsychological battery was administered to all participants. The Vocabulary subscale of the Wechsler Adult Intelligence Scale (WAIS) (Wechsler, 1955) was used to estimate general intelligence (Groth-Marant, 1999). The cognitive domains that were assessed included: • attention and processing speed, which were assessed with the first part of the Stroop word and color naming test (Stroop-word) (Stroop, 1935) and the Trail Making Test part A (Trails A) (Reitan and Wolfson, 1985), • working memory, which was examined with the Digit Span backward test from WAIS, • visuospatial abilities, which were assessed with the Block Design subscale from WAIS and the copy trial of the Rey–Osterrieth Complex Figure Test (RCFT) (Rey, 1941; Osterreith, 1944), • verbal memory, which was examined with the Babcock story recall test (Babcock, 1930), • visual memory, which was assessed with the immediate and the delayed recall trials of the RCFT, and • executive functions, which were assessed with the interference score of the Stroop test (Stroop-interference), the Phonemic and Semantic fluency from the Verbal Fluency Test (VFT) (Benton and Hamsher, 1978), the number of categories completed and number of perseverative errors in the Wisconsin Card Sorting Test 64-version (WCST) (Kongs et al., 2000), and the Trail Making Test part B (Trails B). 2.2.3. ToM assessment ToM was assessed with a series of verbal tasks that estimate different aspects of the mentalizing capacity (Harrington et al., 2005) and have been found to discriminate between schizophrenia and non-schizophrenia samples in previous studies [e.g. (Corcoran et al., 1995; Frith and Corcoran, 1996; Shur et al., 2008; de Achaval et al., 2010)]. • The False belief task (Frith and Corcoran, 1996) consists of two stories that require appreciation of a character's false belief regarding the situation to predict his/her action. The number of correct predictions was estimated. • The Hinting task (Corcoran et al., 1995) consists of short passages in which one of the characters is dropping an obvious hint to another. The subject was then asked what the character really meant when he/she said this. For each correct response two points were given. If the subjects failed to give the correct response, an even more obvious hint was added to the story and one point was given for each correct response. Four of the original 10 passages were used in the present study, as in the study by Janssen et al. (2003). • The Faux Pas Recognition Test (Faux Pas) (Stone et al., 1998) consists of 20 stories, half of which contain a social Faux Pas (one of the characters says something that it would be better not to say). The number of correct detections of Faux Pas plus the number of correct rejections (i.e., detection of non-Faux Pas stories) was estimated. 2.2.4. Procedures All participants had been informed about the research procedures and given written informed consent as approved by the local Ethics Committee. All clinical assessments were performed by the same physician rater (D.P.) with the exception of SAI–E which was independently administered by another clinician (G.K.). The neuropsychological battery was administered to each participant within one week after the clinical assessment.

Table 1 Sample demographic and clinical characteristics.

Age (years) Education (years) Duration of illness (years) Antipsychotic daily dosage (mg)b PANSS Positive Negative CDSS SAI–E Awareness of illness Relabelling of symptoms Compliance with treatment Total score

Patients (n = 58)

Controls (n = 56)

Mean

95% CI

Mean

95% CI

42.3 11.2 17.2 404.8

2.2 0.7 2.2 60.1

42.6 11.5

2.4 0.7

17.8 20.1 5.0

1.4 1.5 0.9

8.5 6.4 3.1 18.0

1.0 1.0 0.3 2.0

t/z a

p

−0.22 −0.76

0.828 0.449

value was 0.00625. Spearman's correlations coefficients rho were computed in order to assess strength of associations between insight, ToM composite score and other variables. Multiple linear regression analysis was used to explore the independent contribution of ToM to insight and its dimensions. Statistical analyses were performed using IBM SPSS Statistics version 20. 3. Results

(Abbreviations: PANSS — Positive and Negative Syndrome Scale; CDSS — Calgary Depression Scale for Schizophrenia; SAI–E — Schedule for the Assessment of Insight — Expanded). a t-test (age) or Mann–Whitney test (education). b Chlorpromazine equivalents.

2.3. Statistical analyses The normality of distribution was examined by the means of Kolmogorov–Smirnov tests. Comparisons between patient and control groups were made using the Pearson's chi-square, the independent samples t-test or Mann–Whitney test as appropriate. Patients' scores on different neuropsychological tests were converted to z-scores using control means and standard deviations and then averaged within domains to yield a domain composite score. The alpha level was set at 0.05. However, since 8 cognitive domain scores were used, we performed a Bonferroni correction for multiple comparisons and the adjusted alpha

Demographic and clinical characteristics of the sample are presented in Table 1. There were no significant differences between patients and controls in gender (χ2 = 0.13, p = 0.718), age, years of education, or handedness (χ2 = 0.05, p = 0.823). All variables were normally distributed except for the scores on attention and processing speed, working memory, visuospatial ability, and theory of mind. As shown in Table 2 patients performed worse than healthy participants in all neuropsychological tests. Moreover, the differences in all cognitive domains and ToM remained significant even after the Bonferroni correction. Table 3 displays correlations of ToM and insight with demographic, clinical, and cognitive variables in the patient group. Significant correlations were found between ToM and SAI–E total and subscale scores. Especially the correlations between ToM and relabelling of symptoms as well as overall insight were strong according to Cohen's standards (Cohen, 1988). ToM score was significantly correlated with the positive subscale of the PANSS and performance on verbal and visual memory tasks. Overall insight was positively related to depressive symptoms, general intelligence, verbal memory, and executive functions, and inversely to negative symptoms. The effect of cognitive functions and ToM on overall insight was explored by multiple linear regression analysis with SAI–E total score as dependent variable. Independent variables were entered hierarchically into regression analysis with the ToM performance on the first step, and all cognitive domain scores on the second step. In this

Table 2 Cognitive performance of patients with schizophrenia in comparison to healthy controls. Cognitive variable

Controls (n Raw score Mean

General intelligence WAIS — Vocabulary Attention & processing speed Stroop — Word Trails A Working memory WAIS — Digit span backward Visuospatial ability WAIS — Block design RCFT — Copy Verbal memory Babcock — Immediate recall Babcock — Delayed recall Visual memory RCFT — Immediate recall RCFT — Delayed recall Executive functions Stroop — Interference VFT — Phonemic VFT — Semantic WCST — Categories WCST — Perseverative errors Trails B Theory of mind False belief task Hinting task Faux Pas

t/za

Patients (n = 58)

= 56)

Raw score 95% CI

Mean

p

Z score 95% CI

11.1

0.4

10.3

0.4

99.0 40.3

3.8 4.4

86.2 56.5

6.0 9.3

4.8

0.4

3.8

0.3

9.9 31.7

0.4 0.8

9.0 26.9

0.8 2.4

12.2 11.4

0.7 0.7

10.3 8.1

0.6 0.7

12.7 12.0

1.2 1.1

9.3 7.8

1.6 1.3

−0.2 36.9 55.2 3.0 9.7 90.9

2.3 3.2 2.8 0.4 1.2 12.5

−1.4 27.3 45.3 2.4 16.3 158.6

2.0 2.1 2.1 0.4 4.1 16.4

1.7 6.6 61.7

0.2 0.2 3.2

1.6 5.3 55.9

0.1 0.5 3.6

Mean

95% CI

−0.56

0.29

2.84

0.005

−0.93 −0.88 −0.97 −0.66

0.45 0.41 0.56 0.19

4.10

b0.001

3.43

0.001

−1.16 −0.64 −1.66 −1.01 −0.75 −1.27 −0.97 −0.78 −1.00 −0.83 −0.14 −0.80 −0.92 −0.41 −1.46 −1.42 −0.63 −0.05 −1.46 −0.51

0.60 0.56 0.84 0.23 0.23 0.29 0.34 0.37 0.32 0.23 0.23 0.17 0.20 0.25 0.92 0.34 0.27 0.23 0.49 0.29

2.75

0.006

5.85

b0.001

4.41

b0.001

5.76

b0.001

3.73

b0.001

(Abbreviations: WAIS — Wechsler Adult Intelligence Scale; RCFT — Rey Complex Figure Test; VFT — Verbal Fluency Task; WCST — Wisconsin Card Sorting Test). a t-test (general intelligence, verbal memory, visual memory, executive functions) or Mann–Whitney test (attention and processing speed, working memory, visuospatial ability, theory of mind).

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Table 3 Bivariate correlations between insight dimensions, theory of mind and other variables in patients with schizophrenia. SAI–E

Age Education Duration of illness Antipsychotic daily dosage PANSS Positive Negative CDSS General intelligence Attention & processing speed Working memory Visuospatial ability Verbal memory Visual memory Executive functions Theory of mind

Awareness Relabelling of of illness symptoms

Treatment Total compliance score

−0.16 0.15 −0.14

−0.08 0.10 −0.22

0.09 0.30⁎ −0.19

0.16

−0.13

0.10

0.07

−0.10 0.16 −0.20

Theory of mind

−0.01 −0.00 0.07 0.23

−0.04 −0.36⁎⁎ 0.46⁎⁎⁎ 0.33⁎

−0.29⁎ −0.42⁎⁎ 0.24 0.44⁎⁎

−0.03 −0.38⁎⁎ 0.01 0.39⁎⁎

−0.18 −0.43⁎⁎ 0.31⁎ 0.46⁎⁎⁎

−0.30⁎ −0.19 −0.13 0.16

0.04

0.07

0.16

0.07

0.20

0.15

0.16

0.12

0.17

0.01

0.14

0.15

0.17

0.19

0.19

0.26⁎ 0.09 0.34⁎

0.29⁎ 0.16 0.21

0.30⁎ 0.01 0.34⁎⁎

0.34⁎⁎ 0.16 0.30⁎

0.41⁎⁎ 0.31⁎ 0.18

0.45⁎⁎⁎

0.55⁎⁎⁎

0.34⁎

0.54⁎⁎⁎ –

(Abbreviations: PANSS — Positive and Negative Syndrome Scale; CDSS — Calgary Depression Scale for Schizophrenia; SAI–E — Schedule for the Assessment of Insight – Expanded). ⁎ p b 0.05. ⁎⁎ p b 0.01. ⁎⁎⁎ p b 0.001.

model, which explained 28% of the SAI–E total score variance, only the variance accounted for by ToM and general intelligence were significant (Table 4). To examine the effect of ToM and neurocognition on the insight components, a hierarchical regression analysis was performed for the each SAI–E subscale with the same sets of predictors. All of the regression models were significant and ToM score was a significant predictor in each of the models. Apart from the effect of ToM, only the effects of general intelligence and executive function on symptom relabelling were found significant (see Table 4). In addition, regression models were created with SAI–E total and subscale scores as dependent variables and the cognitive domains except ToM as predictors. All these models were non-significant (adjusted R2: 0.07 for overall insight, 0.13

Table 4 The effect of theory of mind and neurocognition on insight. Dependent variable

Model summarya

Contribution of each variable at last stepb

Adjusted R2

F

Overall insight

0.23 0.26

15.16 b0.001 3.10 0.008

Awareness of illness Relabelling of symptoms

0.21 0.21 0.21 0.32

13.91 2.51 13.39 3.83

Treatment compliance

0.18 0.19

13.50 2.29

Model p

0.001 0.026 0.001 0.002

0.001 0.139

Predictors

β

ToM General intelligence ToM

0.67 b0.001 0.47 0.018

ToM General intelligence Executive functions ToM

Predictor p

0.67 b0.001 0.64 b0.001 0.59 0.003 0.53

0.014

0.45

0.001

β = standardized regression coefficient. a Predictors entered: ToM in the first step and cognitive functions in the second step. b Only significant contributions are displayed.

Table 5 Mentalizing and symptoms as predictors of insight. Dependent variable

Adjusted F R2

Overall insight

0.50

Awareness of illness

0.51

Relabelling of symptoms

0.45

Treatment compliance

0.28

Model p

Predictorsa

14.46 b0.001 ToM Negative symptoms Depressive symptoms 14.73 b0.001 ToM Depressive symptoms 11.76 b0.001 ToM Positive symptoms Negative symptoms Depressive symptoms 6.08 b0.001 ToM Negative symptoms

β

Predictor p

0.50 b0.001 −0.30 0.004 0.46 b0.001 0.49 b0.001 0.57 b0.001 0.43 b0.001 −0.23 0.037 −0.33

0.003

0.37

0.001

0.43 −0.34

0.001 0.006

β = standardized regression coefficient. a Only significant contributions are displayed. Predictors: ToM and symptoms.

for awareness of illness, 0.02 for symptom relabelling, and 0.07 for treatment compliance). To examine the relationship between ToM and insight controlling for the effect of symptoms a multiple regression analysis was performed with SAI–E total score as dependent variable and ToM score, PANSS subscale scores, and CDSS score as predictors. In this model, which explained 50% of the SAI–E total score variance, the effects of ToM, negative and depressive symptoms were significant (Table 5). The same set of predictors was entered into a multiple regression equation for each of the three dimensions of insight (SAI–E subscales). The variance accounted for by ToM was significant in all these models. Moreover, depressive symptoms had a significant effect on illness awareness and symptom relabelling, negative symptoms on symptom relabelling and treatment compliance, and positive symptoms on relabelling of symptoms (see Table 5). 4. Discussion The findings of the present study supported our hypothesis that ToM deficits negatively affect insight independently of neurocognitive deficits and symptom severity in schizophrenia. ToM impairment explained a substantial proportion of variance in overall insight (23%) and its three major components: awareness of illness (21%), relabelling of symptoms (21%) and treatment compliance (18%). Moreover, the effect of ToM deficits on insight remained significant even after controlling for all neurocognitive factors and symptoms ratings. Noteworthy, this is the first study that examined the relationships between ToM, neurocognition and insight in schizophrenia using a comprehensive battery of neuropsychological measures. Our results are in line with a previous study that used regression analysis and found slightly higher contributions of ToM deficits in overall insight and misattribution of symptoms (Bora et al., 2007). Moreover, the associations between ToM deficits and insight components in our study were slightly stronger than these found by Langdon and Ward (2009). The current study overcomes some methodological limitations of the aforementioned studies, such as moderate sample size (Langdon and Ward, 2009) and lack of control group for the evaluation of patient's cognitive and ToM impairment (Bora et al., 2007). Another strength is that insight was assessed independently of psychopathology, hence minimizing contamination and bias. Other studies found weaker bivariate correlations than the present study, but this may be due to the differences in the study samples or in the ToM tasks used. More precisely, our sample consisted of exclusively chronic, clinically stable outpatients whereas first

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episode and post-acute patients were included in the studies by Wiffen et al. (2013) and Lysaker et al. (2011), respectively. We used a ToM battery composed exclusively of verbal tasks, whereas a non-verbal falsebelief task was used by Langdon et al. (2006). Two studies failed to find significant correlations between insight and ToM in patients with acute schizophrenia (Drake and Lewis, 2003) and a mixed sample of patients with schizophrenia and other psychotic disorders (Stewart et al., 2010). Interestingly, patients' performance in visual ToM tasks used in previous studies, namely the Visual joke test (Drake and Lewis, 2003) and the Eyes test (Bora et al., 2007), was not correlated significantly with the level of insight. It has been suggested that these inconsistencies may reflect differences between the various tasks labeled ‘ToM’, which might not tap equally a unitary underlying mechanism (Langdon and Ward, 2009). In favor of verbal tasks is that language and verbal interaction may play a crucial role in the development of ToM (Happe, 1995; Peterson and Siegal, 1998; Yirmiya et al., 1998). Regression analysis showed that other factors, clinical and cognitive, independent of ToM deficits contribute to impaired insight in schizophrenia. Positive symptoms were associated exclusively with lower symptom relabelling, while the negative symptoms were negatively associated with overall insight, symptom relabelling and treatment compliance. A positive effect of depressive symptoms on overall insight, illness awareness, and symptom relabelling was also found. These findings are consistent with previous studies on the relationships between symptoms and insight in schizophrenia (Mintz et al., 2003). With regard to the effect of neurocognition, general intellectual ability was associated with overall insight and relabelling of symptoms while executive functions were specifically associated with relabelling in agreement with the findings of a previous meta-analysis (Aleman et al., 2006). The relabelling of symptoms was more strongly connected to cognitive functions than the other components of insight as previous studies also suggested (Morgan and David, 2004). Contrary to the assumption that the association between executive function and insight may be in fact reflecting the relationship between ToM and insight (Bora et al., 2007), in our analysis both ToM disruption and executive dysfunction significantly contributed to poor symptom relabelling. Besides, the overall impact of neurocognition on insight was weak in regression models not including ToM among the predictors. Our findings provide further evidence for the notion that we need to imagine ourselves ‘as others see us’ in order to be aware of our mental disorder. This conceptualization of insight into illness predicts a specific link between impaired ability to understand the minds of other people, i.e. ToM, and poor insight. In line with this, a recent study found that ToM was correlated with illness attribution to self and others measured by the judgements of 2nd and 3rd person vignettes, respectively, in patients with first episode psychosis (Wiffen et al., 2013). However, it is yet unclear whether ToM or self-reflection is the primary ability: we are able to understand others and then apply this understanding to ourselves or we are able to reflect on ourselves and then apply this reflection to others (Carruthers, 2009). Moreover, it has been suggested that although self-reflective processing may make use of similar cognitive mechanisms as ToM processing, these processes can be affected autonomously (Wiffen and David, 2009). Recent neuroimaging studies showed a relationship between insight and the activation of brain regions related to self-reflection (Bedford et al., 2012; van der Meer et al., 2012), which also partially overlap with the ToM related brain network (Carrington and Bailey, 2009). Thus, the effect of ToM deficits on insight should be further examined in the broader context of patient's failures in metacognition, i.e. the general ability to think about thinking, and their relationships with insight impairment in schizophrenia (Lysaker et al., 2011; David et al., 2012). Among the limitations of our study, we should acknowledge that its sample consisted exclusively of chronic patients limiting the generalizability of our findings. We used exclusively verbal ToM tests, whereas mentalizing also involves implicit social cognitive processes (Abell et al., 2000; Blakemore, 2008). Moreover, we used a composite ToM

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performance score, whereas some authors have suggested that different aspects of mentalizing processing, such as cognitive and affective mental representations, must be separately examined (Shamay-Tsoory et al., 2007; Shur et al., 2008; Abu-Akel and Shamay-Tsoory, 2013) and a recent study found that affective but not cognitive ToM predicted the level of insight in patients with schizophrenia (Pijnenborg et al., 2013). Finally, ToM is only one out of several social cognitive domains relevant to schizophrenia (Green and Leitman, 2008) and further investigation of possible associations between insight and social cognitive deficits in patients with schizophrenia is warranted. In conclusion, the present study highlighted that the cognitive capacity to take the perspective of the other is necessary though not sufficient to gain insight into mental illness. Future research focusing on the interactions between ToM and other cognitive or metacognitive processes underlying insight might offer evidence crucial in developing new therapeutic interventions to improve illness awareness and treatment adherence in patients with schizophrenia. Role of funding source The authors would like to state that there was no funding for this study. Contributors G. Konstantakopoulos designed the study, wrote the protocol, collected the data, statistically analyzed the data, and wrote the first draft of the manuscript. D. Ploumpidis was involved in writing the protocol and collecting the data. P. Patrikelis and S. Nikitopoulou carried out the neuropsychological assessments of the patients. P. Oulis, G. N. Papadimitriou, and A. S. David were involved in working out the study design. All authors contributed to and have approved the final manuscript. Conflict of interest All the authors declare that they have no conflict of interest with respect to this study or its publication. Acknowledgements We thank the clinicians and the nursing staff at the Byron–Kessariani Community Mental Health Centre for their assistance with participant recruitment, as well as the participants themselves.

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