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European Psychiatry xxx (2010) xxxxxx

Original article

Subjective awareness of tardive dyskinesia and insight in schizophrenia


R. Emsley *, D.J.H. Niehaus, P.P. Oosthuizen, L. Koen, B. Chiliza, D. Fincham
Department of Psychiatry, Faculty of Health Sciences, University of Stellenbosch, PO Box 19063, Tygerberg 7505, Cape Town, South Africa

A R T I C L E I N F O

A B S T R A C T

Article history: Received 13 August 2009 Received in revised form 14 December 2009 Accepted 29 December 2009

Keywords: Insight Schizophrenia Tardive dyskinesia Psychopathology

Background: Lack of awareness of tardive dyskinesia (TD) and poor insight into mental illness are common in schizophrenia, raising the possibility that these phenomena are manifestations of a common underlying dysfunction. Methods: We investigated relationships between low awareness of TD and poor insight into mental illness in 130 patients with schizophrenia and TD. We also examined selected demographic and clinical correlates of these two phenomena. Results: Sixty-six (51%) patients had no or low awareness of TD and 94 (72%) had at least mild impairment of insight into their mental illness. Low awareness of TD was not signicantly correlated with greater impairment of insight into mental illness. Regression analyses indicated that the Positive and Negative Syndrome Scale (PANSS) disorganised factor (b = 0.72, t = 11.88, p < 0.01) accounted for 52% of the variance in insight into mental illness (adjusted R2 = 0.55) (F[2, 127] = 81.00, p < 0.01) and the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale score (b = 0.47, t = 6.80, p < 0.01), PANSS disorganised factor (b = 0.26, t = 3.73, p < 0.01), and ESRS parkinsonism subscale score (b = 0.31, t = 4.55, p < 0.01) together accounted for 37% of the variance in awareness of TD (adjusted R2 = 0.37) (F[3, 126] = 26.87, p < 0.01). Conclusion: The two phenomena appear to be dissociated, and may be domain-specic. 2010 Elsevier Masson SAS. All rights reserved.

1. Introduction Tardive dyskinesia (TD) is a frequent complication of conventional antipsychotic treatment [15], and its incidence is higher with second-generation antipsychotics than previously reported [8]. Therefore, TD remains a signicant clinical problem. It is associated with social and vocational impairment and contributes to the further stigmatisation of patients receiving antipsychotics [24]. A striking feature of TD is that a large percentage of patients display an apparent lack of concern or even unawareness of the movement disorder, with reported rates ranging between 44 and 95% [1,25]. While the origins of this lack of awareness of TD are not known, it has been associated with cognitive impairment [20], the decit syndrome [3,20] and greater severity of extrapyramidal symptoms [5]. The phenomenon has been likened to anosognosia, a neurological decit characterised by unawareness of an impairment, and associated with damage to specic brain areas [25]. Poor insight into their mental illness is another common and often striking symptom in schizophrenia, with an estimated 50 to

* Corresponding author. Tel.: +27 21 9389227; fax: +27 21 9389738. E-mail address: rae@sun.ac.za (R. Emsley). 0924-9338/$ see front matter 2010 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.eurpsy.2009.12.006

80% of such individuals not being convinced that they have a disorder [10]. While previously considered a psychological defense mechanism, lack of insight into mental illness has more recently been proposed as a neurologically based condition related to damage to specic brain areas [25], and also likened to anosognosia [19]. It is therefore reasonable to hypothesise that the lack of awareness of TD and lack of insight into mental illness are manifestations of a common underlying dysfunction. Indeed, this possibility has been proposed by Arango et al. [3] who explored the relationship between awareness of TD and insight into mental illness in 43 patients with schizophrenia and TD. However, they found only a modest correlation between awareness of TD and insight into mental illness, suggesting that the two phenomena are not closely related. However, the authors pointed out that their sample was underpowered and that further studies with larger groups of patients are needed. In the present study, we investigated whether poor awareness of TD is related to poor insight into mental illness in a relatively large sample of patients with schizophrenia and TD. We also examined relationships between selected demographic and clinical factors and these two phenomena. We hypothesised that poor awareness of TD would be related to poor insight into mental illness, and that the two phenomena would have similar demographic and clinical correlates.

Please cite this article in press as: Emsley R, et al. Subjective awareness of tardive dyskinesia and insight in schizophrenia. European Psychiatry (2010), doi:10.1016/j.eurpsy.2009.12.006

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2 R. Emsley et al. / European Psychiatry xxx (2010) xxxxxx

2. Methods 2.1. Participants This was a post hoc analysis of baseline data obtained from the participants in two TD treatment studies [12,14]. In- and outpatients from Stikland and Tygerberg Academic Hospitals, as well as surrounding community clinics in the Greater Cape Town area were screened for the presence of TD. To be included participants had to be between 18 and 60 years of age, meet both Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition (DSM-IV) [2] criteria and Schoolers and Kanes criteria [29] for TD, have a Clinical Global Impression (CGI) severity of TD score of !3, a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, and to have received a xed dose of antipsychotic medication for at least the past 6 weeks. Exclusion criteria comprised an unstable psychiatric disorder, signicant neurological disorder other than TD, other signicant medical illness, substance abuse, pregnancy, breastfeeding and current use of clozapine. The initial clinical trials were approved by the Institutional Review Board of the University of Stellenbosch, and informed, written consent was obtained from all participants. Approval to conduct the post hoc analysis was also obtained from the Institutional Review Board. 2.2. Assessments All participants underwent the following assessments: Demographic information, psychiatric history and examination and medical history and examination. The duration of TD was assessed on the basis of information provided by participants and their family members and from the clinical les. Motor symptoms were assessed by means of the Extrapyramidal Symptom Rating Scale (ESRS) [6]. The level of awareness of, or concern for TD was calculated by the sum of two items on the ESRS scale that rate the patients subjective evaluation of the intensity of dyskinesia of extremities (item 1.10) and tongue, jaw, lips or face (item 1.11), each on a four-point scale (0 = absent; 1 = mild; 2 = moderate; 3 = severe) [6]. The ESRS dyskinesia score comprises the sum of seven items on the ESRS scale. Severity of TD was assessed by the total ESRS dyskinesia score and the CGI-TD scale. Other ESRS subscale scores include those for parkinsonism, dystonia and an item for akathisia [6]. Schizophrenia psychopathology was assessed by means of the Positive and Negative Syndrome Scale (PANSS) [16]. For assessing insight into mental illness we used a single item on the PANSS scale (item G12). This item rates lack of judgement and insight into the mental illness on a seven-point scale (one absent, seven extreme). While a more comprehensive insight scale would have been preferable, this single item has been used to assess insight previously [18,27] and has shown a strong correlation with other insight scales [28]. To explore correlations with schizophrenia psychopathology we examined the following PANSS scores: PANSS total (comprising the total score of all 32 items), and ve previously described factor-analysis derived symptom domains (positive, negative, disorganised, excited and depression/anxiety factors) [13]. The PANSS insight item (G12) was removed from the items to which it may have contributed, i.e. PANSS total score and PANSS positive score before analyses were conducted). Global severity of psychosis was assessed by the PANSS total score and the CGI severity of psychosis (CGI-PSY) scale. 2.3. Analyses A Pearsons product-moment correlation coefcient matrix was computed to identify variables that were correlated with insight into mental illness and awareness of TD.

Two forced entry multiple linear regression analyses were then conducted. The rst assessed the amount of variance that variables signicantly correlated with insight into mental illness could account for and the second assessed the amount of variance that variables signicantly correlated with awareness of TD could explain. 3. Results The sample comprised 130 subjects (84 men and 46 women) aged 45 11 years, with a mean duration of psychosis of 17 11 years and duration of TD of 6 6 years. The mean PANSS total score for the sample was 57 13; ESRS dyskinesia subscale score was 12 5; CGI-PSY score was 2.2 1.4; and CGI-TD was 4 1. Sixty-six (51%) patients were assessed as having no or low subjective awareness of TD (Score of <2 on the sum of items 1.10 and 1.11). Ninety-four (72%) subjects were judged to have at least mild impairment of insight into their mental illness (score of !3 on PANSS item G12). Variables that were correlated with insight into mental illness were PANSS total score (r = 0.53, p < 0.01), PANSS negative factor (r = 0.32, p < 0.01) and PANSS disorganised factor (r = 0.72, p < 0.01). Variables correlated with awareness of TD were age (r = 0.21, p < 0.05), ESRS dyskinesia score (r = 0.47, p < 0.01), PANSS disorganised factor (r = 0.24, p < 0.01), and ESRS parkinsonism score (r = 0.32, p < 0.01). Independent samples t-tests showed that there was no signicant gender effect on either insight into mental illness or awareness of TD. Insight into mental illness and awareness of TD were not signicantly correlated in the bivariate analysis (r = 0.16, p > 0.05) and consequently were not included as predictors in the regression analyses. Two forced entry multiple linear regression analyses were then conducted. The rst assessed the amount of variance that the PANSS total score and the PANSS negative and disorganised factor scores could account for in insight into mental illness. The second analysis assessed the amount of variance that age, ESRS dyskinsia subscale score, ESRS parkinsonism subscale score and PANSS disorganised factor score could explain in awareness of TD. As depicted in Table 1, PANSS total score and PANSS negative factor score were no longer associated with insight into mental illness when linearly combined with the other predictors. As such, the regression was performed again, this time with PANSS total score and PANSS negative factor score removed from the analysis. Similarly, age was no longer associated with awareness of TD when linearly combined with the other predictors. The regression was performed again with age removed from the analysis. Results indicated that the PANSS disorganised factor (b = 0.72, t = 11.88, p < 0.01) accounted for 52% of the variance in insight into mental illness (adjusted R2 = 0.55) (F[2, 127] = 81.00, p < 0.01). The squared multiple correlation coefcient yielded an extremely large effect size (2 = 1.12) [7]. The ESRS dyskinesia subscale score (b = 0.47, t = 6.80, p < 0.01), PANSS disorganised factor (b = 0.26, t = 3.73, p < 0.01), and ESRS parkinsonism subscale score (b = 0.31, t = 4.55, p < 0.01) together accounted for 37% of the variance in awareness of TD (adjusted R2 = 0.37) (F[3, 126] = 26.87, p < 0.01). The squared multiple correlation coefcient yielded a very large effect size (2 = 0.63) [7]. Regarding the assumptions of parametric regression analysis, Kolmogorov-Smirnovs tests of normality revealed that the distributions of standardised residuals were normally distributed for each analysis. Durbin-Watsons statistics revealed that the standardised residuals were also independent in each analysis. Cooks distance statistics indicated that no data points exerted undue inuence over the regression models. Examination of the standardised residuals/standardised predicted values plots showed that the assumptions of homoscedasticity and linearity

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R. Emsley et al. / European Psychiatry xxx (2010) xxxxxx Table 1 Results of forced entry multiple regression analyses for variables predicting insight into mental illness and awareness of tardive dyskinesia. Variables Insight into mental illness Regression 1 PANSS total Negative factor Positive factor Disorganised factor Regression 2 Positive factor Disorganised factor Awareness of tardive dyskinesia Regression 1 Age Dyskinesia score Disorganised factor Parkinsonism score Regression 2 Dyskinesia score Disorganised factor Parkinsonism score R2 0.57 Adj. R2 0.55 F 41.71 0.01 0.03 0.07 0.22 0.56 0.55 81.00 0.05 0.22 0.01 0.02 0.20 0.66 3.21 10.62 0.01 0.02 0.02 0.03 0.11 0.17 0.25 0.66 0.63 1.41 2.49 7.49 B SE 3

p 0.00** 0.52 0.15 0.01* 0.00** 0.00** 0.00** 0.00**

2 1.32

1.27

0.39

0.37

20.35 0.00 0.12 0.10 0.05 0.00 0.02 0.03 0.01 0.01 0.02 0.01 0.06 0.46 0.25 0.30 0.47 0.26 0.31 0.93 6.49 3.65 4.40 6.80 3.73 4.55

0.39

0.37

26.87 0.13 0.11 0.05

0.00** 0.35 0.00** 0.00** 0.00** 0.00** 0.00** 0.00** 0.00**

0.63

0.63

*: p < 0.05; **: p < 0.01; R2: variance explained; Adj. R2: adjusted R2; B: unstandardised beta coefcient; SE: standard error for B; b: standardised beta coefcient; 2: Cohens effect size measure for R2 (2 effect sizes of 0.02, 0.15, and 0.35 are considered to be small, medium, and large respectively, [7]); PANSS: Positive and Negative Syndrome Scale.

were met for each analysis. Finally, Variance Ination Factor (VIF) and tolerance statistics showed that there was no signicant multicollinearity in any of the analyses. 4. Discussion This study highlights the very high rates of poor awareness of TD, as well as impaired insight into mental illness in stable patients with schizophrenia. The rate of poor awareness of TD (52%) is consistent with previous reports [1,3,5,20,23], as is the rate of poor insight into their mental illness (72%) [3,11]. Our results suggest that lack of awareness of TD and impaired insight into mental illness are not manifestations of a common underlying pathophysiology, insofar as they were not signicantly correlated. However, regression analyses indicated that the PANSS disorganised factor contributed substantially to both phenomena. This was particularly the case for insight into mental illness where it accounted for the major proportion of the variability, whereas with awareness of TD additional factors (severity of TD and presence of parkinsonism) also played a signicant role. Our results are similar to those of Arango et al. [3] who found only a modestly signicant association between insight into mental illness and lack of awareness of TD. These authors proposed that the two phenomena are dissociated, and domain specic. However, whereas in their sample poor awareness of TD was associated with decit symptoms, in our study the strongest association was with disorganised symptoms. Pia andTamietto [27] reviewed current thinking regarding the pathogenesis of impaired insight in schizophrenia and suggest two main possibilities. First, impaired insight may be a neurological decit reecting underlying frontal lobe damage. They cite reports of an association with impairments in cognitive executive functions and neuro-imaging abnormalities (for references see [27]) in support of this hypothesis. Similarly, Shad et al. [30] reviewed studies investigating insight and neurocognitive performance and structural imaging data in schizophrenia and concluded that ndings are consistent with a relationship between impaired insight and anosognosia. They propose an insight-anosognosia model involving specic cognitive dysfunctions, primarily mediated by frontal cortex (dorsolateral prefrontal cortex and orbitofrontal cortex) and to a lesser extent the parietal cortex. The second possibility is that impaired insight is a symptom of the illness as a whole, or perhaps linked to specic symptom

domains. Whereas an earlier study [21] concluded that very little of impaired insight was related to the acute psychopathology, two more recent studies in rst-episode schizophrenia samples found poor insight to be associated with higher scores on PANSS total, positive, negative and general psychopathology scales [22,26]. Lack of insight has also been modestly associated with positive symptoms and with negative symptoms [4,12,17], thoughtbroadcasting, delusions of grandeur and sexual delusions [11]. More evidence linking poor insight to positive symptoms comes from the published PANSS factor analyses of the symptom structure of schizophrenia. In a review of such studies it was found that the PANSS lack of insight item (G12) loaded with the positive factor [13]. Finally, Cuesta et al. [9] found that higher negative and disorganisation symptom scores at baseline were associated with less improvement in insight over time, and concluded that insight and psychopathology are probably semiindependent domains. Other factors that could be linked to lack of awareness of TD insofar an association has previously been reported include the decit syndrome [3], a diagnosis of schizophrenia (as opposed to bipolar disorder), poorer cognitive function [20], higher levels of extrapyramidal symptoms [5] and greater severity of TD [27]. The most likely explanation of the inconsistent ndings across studies is that multiple factors play a role in impairing both insight into mental illness and awareness of TD. Also, small samples and different assessment instruments are likely to have contributed. Limitations of our study include its retrospective nature and the fact that specic instruments to assess levels of insight and lack of awareness of TD were not employed. However, strengths include the large sample of patients with TD and the use of validated instruments for assessing movement disorders and psychopathology. 5. Conclusions Our ndings support and extend those of previous studies suggesting that lack of awareness of TD and impaired insight into mental illness are not closely related, and that both phenomena are, at least partially, related to the disorganised symptom domain. Future studies should, in addition to investigating the cognitive and neurobiological underpinnings of poor awareness of TD, assess awareness levels in movement disorders not associated with psychosis, such as senile dyskinesia.

Please cite this article in press as: Emsley R, et al. Subjective awareness of tardive dyskinesia and insight in schizophrenia. European Psychiatry (2010), doi:10.1016/j.eurpsy.2009.12.006

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Please cite this article in press as: Emsley R, et al. Subjective awareness of tardive dyskinesia and insight in schizophrenia. European Psychiatry (2010), doi:10.1016/j.eurpsy.2009.12.006