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Competence to give informed consent in acute psychosis is associated with symptoms rather than diagnosis
Schizophrenia Research 77 (2005) 211 – 214 www.elsevier.com/locate/schres
Competence to give informed consent in acute psychosis is associated with symptoms rather than diagnosis V. Howea, K. Foistera, K. Jenkinsa,b, L. Skenec, D. Copolova,d, N. Keksa,d,e,T a
Mental Health Research Institute, Locked Bag 11, Parkville, Victoria, 3052, Australia b Alfred Hospital, P.O. Box 315 Prahran, Victoria, 3181, Australia c Melbourne Law School, Level 9, The University of Melbourne, Victoria 3010, Australia d Department Psychological Medicine, Monash Medical Centre, Level 3 P Block, 246 Clayton Road, Clayton, Victoria, 3168, Australia e Box Hill Hospital, Department Psychiatry, 131 Thames St, Box Hill, Victoria, 3128, Australia Received 3 June 2004; received in revised form 1 March 2005; accepted 4 March 2005 Available online 27 April 2005
Abstract To investigate the association between competence to give informed consent to treatment, specific symptomology and diagnostic category, 110 inpatients diagnosed with DSM-IV acute schizophrenia (n = 64), schizoaffective disorder (n = 25) and bipolar affective disorder (n = 21) were interviewed using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) and the Positive and Negative Syndrome Scale (PANSS). Results indicated no significant difference in competence between the three disorders. Elevated positive, cognitive and excitement PANSS factor scores had lower MacCAT-T scores. Further analyses indicated symptoms that impair cognition; particularly, conceptual disorganisation and poor attention were most consistently related to poor performance on competence tests. D 2005 Elsevier B.V. All rights reserved. Keywords: Competence; Psychosis; MacArthur Competence Assessment Tool for Treatment
1. Introduction
T Corresponding author. Mental Health Research Institute, Locked bag 11, Parkville, Victoria, 3052, Australia. Tel.: +61 3 9895 4965; fax: +61 3 9895 4993. E-mail addresses: [email protected] (V. Howe), [email protected] (K. Foister), [email protected] (K. Jenkins), [email protected] (L. Skene), [email protected] (D. Copolov), [email protected] (N. Keks). 0920-9964/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2005.03.005
The legal requirement of informed consent is the foundation of ethical research and clinical practice. It ensures patients have all necessary information and agree to a procedure prior to undergoing any intervention. The notion that a patient must possess competence to give consent has important legal and clinical ramifications. Appelbaum and Grisso (1988) specify that consent may not be legally binding unless the patient has sufficient competence in four
212
V. Howe et al. / Schizophrenia Research 77 (2005) 211–214
key areas: understanding information, appreciating the relevance of that information to their situation, reasoning between benefits and risks of all possible treatments and, finally, expressing a choice. Mental disorders are heterogeneous. Clinical experience supported by new research suggests that while some patients have impaired decision-making abilities, many are competent to provide consent in a wide variety of circumstances and continually exercise this competence in their daily lives (Dunn et al., 2001). Clearly a patient’s right to autonomy and self-
Table 1 Areas of competency assessed and items included in the MacCAT-T Area of competency Understanding (1) Disordera Course
Appreciation (1) Disorder
Question content Diagnosis, 3 symptoms experienced If untreated, symptoms continue and may worsen
2. Method Acknowledgement of disorder
Understanding (2) Current treatmenta Treatment effect Benefits of treatment Risks of treatment
Type, administration, dose Therapeutic effect in 2 weeks Reduce symptoms and anxiety Sedation, extrapyramidal side effects
Appreciation (2) Current treatment
Could this treatment be useful? Why?
Understanding (3) Alternative treatment Treatment effect Benefits of alternative Risk of alternative
Medication X, given orally, once daily Therapeutic effect in 2 weeks Most effective treatment, reduces anxiety Sweating, 1/20 chance of a convulsion
Reasoning (1) Choice of treatment Current treatment Alternative treatment
Choice Treatment
Reasoning (2) Choice a
determination must be balanced with the assurance that patients with impaired competence are protected from decisions that may be harmful. Accurate identification of relevant variables is therefore paramount. The MacArthur Competency Assessment Tool-Treatment (MacCAT-T) (Grisso and Appelbaum, 1998), a semi-structured interview, was used in this investigation. Details of the areas assessed and the items included are provided in Table 1. Among the various disorders, schizophrenia has been particularly associated with impaired competence (Grisso and Appelbaum, 1995). Such diagnostic associations have serious implications for patients and deserve careful evaluation. This investigation aims to test whether diagnostic categories of acute psychosis differ with respect to competence or whether specific symptoms, irrespective of diagnosis, are more likely to affect competence.
Which is your preferred treatment? Why? Given the risks and benefits, how may bpreferred treatmentN affect you? Given the risks and benefits, how may balternative treatmentN affect you?
Which of these treatments do you think is best?
Logical consistency of choice (examiner rated)
Questions tailored specifically to the patient.
Participants (n = 110) from two major Australian public treatment facilities were interviewed. All participants met DSM-IV criteria for schizophrenia (n = 64), schizoaffective disorder (n = 25) or bipolar affective disorder (n = 21, manic episode = 16, mixed episode = 5) determined by the treating psychiatrist. Subsequently these diagnoses were confirmed by case review, using a modified protocol of the Structured Clinical Interview for DSM-IV, Research Version (SCID). All participants were educated at or above junior high school level. There were 54 males and 56 females with a mean age of 37.2 F 12.3 years. All were inpatients in early stage treatment for acute psychosis. The data reported here were extracted from a broader ongoing study examining issues of competence approved by both hospital ethics committees and for which all subjects gave written informed consent. The MacCAT-T (Grisso and Appelbaum, 1998) was used to evaluate the four areas considered central for the legal, ethical and clinical determination of competence noted above. bExpressing a choiceQ was excluded from the analysis as only patients able to express a choice participated. The MacCAT-T was modified to standardise the interview protocol, providing the same general infor-
V. Howe et al. / Schizophrenia Research 77 (2005) 211–214
213
mation regarding illness, current treatment and standard treatment alternatives (refer to Table 1). Scoring was performed in accordance with published criteria (Grisso and Appelbaum, 1998) by a single trained rater. To document the extent and severity of
symptoms, a PANSS was completed for each participant by 3 treating psychiatrists who were trained in PANSS rating and blind to MacCAT-T results. A high standard of inter-rater agreement was obtained during the PANSS training sessions (kappa exceeding 0.8).
Table 2 Pearson correlation coefficients between MacCAT-T and PANSS scores
3. Results
PANSS score
MacCAT-T score Understanding Appreciation Reasoning
Total score (sum P1–G16) Factor scores Positive (sum P1,P3,P5,P6,G9) Negative (sum N1,N2,N3,N4,N6,G7) Cognitive (sum N5,N7,P2,G10,G11) Excitement (sum P4,P7,G4,G8,G14) Depression (sum G2,G3,G6) Individual items Positive: P1 delusions P3 hallucinatory behaviour P5 grandiosity P6 suspiciousness/ persecution G9 unusual thought content Cognitive: N5 difficulty in abstract thinking N7 stereotyped thinking P2 conceptual disorganisation G10 disorientation G11 poor attention Excitement: P4 excitement P7 hostility G4 tension G8 uncooperativeness G14 poor impulse control a b
0.364a
0.218b
0.217b
0.364a
0.055
0.150
0.127
0.156
0.061
0.191b
0.325a
0.378a
0.328a
0.128
0.122
0.009
0.119
0.113
0.312a 0.135
0.051 0.164
0.147 0.010
0.276a 0.291a
0.179 0.051
0.149 0.089
0.352a
0.104
0.193b
0.107
0.224b
0.337a
0.088
0.163
0.124
0.200b
0.221b
0.361a
0.030 0.247a
0.184 0.307a
0.135 0.285a
0.238b 0.342a 0.198b 0.276a 0.172
0.083 0.158 0.003 0.374a 0.079
0.122 0.088 0.011 0.197b 0.046
Correlation is significant at the 0.01 level (2-tailed). Correlation is significant at the 0.05 level (2-tailed).
To determine if competence performance differed dependent on diagnostic category, multivariate analysis of variance (MANOVA) was performed between diagnostic group and the three MacCAT-T scores (understanding, appreciation and reasoning). No significant difference in MacCAT-T performance was evident between the diagnostic categories: schizophrenia, schizoaffective disorder and bipolar mood disorder (manic/mixed phase). In contrast to the negative finding with diagnostic categories, the total PANSS score was correlated with all three measures of competency (refer to Table 2). The impact of symptomology on competence scores was further examined using ratings obtained on PANSS factor scores. The factor structure used, derived by Lykouras et al. (2000), is detailed in Table 2. Correlational analyses performed between each factor score and the three MacCAT-T measures indicated that patients with more severe cognitive dysfunction performed consistently worse on each of the MacCAT-T measures in comparison to those without cognitive dysfunction. There were relationships with positive symptoms and the excitement factor although this was true for the bunderstandingQ section of the MacCAT-T only. There were no significant effects for the negative or depression factors (Table 2). Correlations between the individual PANSS items forming the positive, cognitive and excitement factors and MacCAT-T scores are also presented in Table 2. The most consistent findings were with conceptual disorganisation and poor attention. Other positive symptoms were also correlated but to a limited extent.
4. Discussion The results indicate that psychiatric diagnostic categories in acute psychosis did not differ in performance on a test of competence. An inverse relationship was evident between competence and specific positive symptom factor scores, particularly those related to cognition. At the symptom level, conceptual disorganisation and poor attention were
214
V. Howe et al. / Schizophrenia Research 77 (2005) 211–214
associated with competence. In contrast, hallucinations and items relating to negative symptoms did not have a significant relationship. Phase of illness has major implications for competence in psychoses. Cognitive dysfunction is a key predictor of competence in acute patients. In contrast to chronic illness, where cognitive deficits have also been implicated (Carpenter et al., 2000), impaired competency in acute illness appears to be particularly associated with the symptom of thought disorder. This finding reinforces the notion that competency is best understood as a neurocognitive concept and should be assessed accordingly. This investigation had several limitations. The MacCAT-T interview was initially designed for qualitative not quantitative interpretation (Grisso and Appelbaum, 1998). Some scales are not as psychometrically robust as others, which may have introduced error. The dunderstandingT scale however appears the most consistent in this and other research (Grisso et al., 1997) possibly due to its larger range of scoring in comparison to the appreciation and reasoning scales. Finally, all patients in this investigation had severe illness in acute phase. This sample is therefore not representative of non-acute illness. While diagnostic categories failed to predict competence, the identification of specific symptoms might assist the clinician to identify those patients for whom competency may be an issue. In acute psychosis, the presence of cognitively related symptoms, such as thought disorder rather than diagnosis, may better identify the subgroup of patients who require particular support with consent procedures. Although these findings are not surprising, these
observations contribute significantly to the empirical evidence on competence impairment in different phases of psychoses.
Acknowledgements This research was supported by a grant from the National Health and Medical Research Council of Australia, Grant number 149885.
References Appelbaum, P.S., Grisso, T., 1988. Assessing patients’ capacities to consent to treatment. N. Engl. J. Med. 319, 1635 – 1638. Carpenter, W.T., Gold, J.M., Lahti, A.C., Queern, C.A., Conley, R.R., Bartko, J.J., Kovnick, J., Appelbaum, P.S., 2000. Decisional capacity for informed consent in schizophrenia research. Arch. Gen. Psychiatry 57, 533 – 538. Dunn, L.B., Lindamer, L.A., Palmer, B.W., Schneiderman, L.J., Jeste, D.V., 2001. Enhancing comprehension of consent for research in older patients with psychosis: a randomised study of a novel consent procedure. Am. J. Psychiatry 158, 1911 – 1913. Grisso, T., Appelbaum, P.S., 1995. Abilities of patients to consent to psychiatric and medical treatments. Law Hum. Behav. 19, 149 – 174. Grisso, T., Appelbaum, P.S., 1998. Assessing Competence to Consent to Treatment: a Guide for Physicians and Other Health Professionals. Oxford University Press, New York. Grisso, T., Appelbaum, P.S., Hill-Fotouhi, C., 1997. The MacCATT: a clinical tool to assess patients’ capacities to make treatment decisions. Psychiatr. Serv. 48, 1415 – 1419. Lykouras, L., Oulis, P., Psarros, K., Daskalopoulou, E., Botsis, A., Christodoulou, G.N., Stefanis, C., 2000. Five-factor model of schizophrenic psychopathology: how valid is it? Eur. Arch. Psychiatry Clin. Neurosci. 250, 93 – 100.
Competence to give informed consent in acute psychosis is associated with symptoms rather than diagnosis V. Howea, K. Foistera, K. Jenkinsa,b, L. Skenec, D. Copolova,d, N. Keksa,d,e,T a
Mental Health Research Institute, Locked Bag 11, Parkville, Victoria, 3052, Australia b Alfred Hospital, P.O. Box 315 Prahran, Victoria, 3181, Australia c Melbourne Law School, Level 9, The University of Melbourne, Victoria 3010, Australia d Department Psychological Medicine, Monash Medical Centre, Level 3 P Block, 246 Clayton Road, Clayton, Victoria, 3168, Australia e Box Hill Hospital, Department Psychiatry, 131 Thames St, Box Hill, Victoria, 3128, Australia Received 3 June 2004; received in revised form 1 March 2005; accepted 4 March 2005 Available online 27 April 2005
Abstract To investigate the association between competence to give informed consent to treatment, specific symptomology and diagnostic category, 110 inpatients diagnosed with DSM-IV acute schizophrenia (n = 64), schizoaffective disorder (n = 25) and bipolar affective disorder (n = 21) were interviewed using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) and the Positive and Negative Syndrome Scale (PANSS). Results indicated no significant difference in competence between the three disorders. Elevated positive, cognitive and excitement PANSS factor scores had lower MacCAT-T scores. Further analyses indicated symptoms that impair cognition; particularly, conceptual disorganisation and poor attention were most consistently related to poor performance on competence tests. D 2005 Elsevier B.V. All rights reserved. Keywords: Competence; Psychosis; MacArthur Competence Assessment Tool for Treatment
1. Introduction
T Corresponding author. Mental Health Research Institute, Locked bag 11, Parkville, Victoria, 3052, Australia. Tel.: +61 3 9895 4965; fax: +61 3 9895 4993. E-mail addresses: [email protected] (V. Howe), [email protected] (K. Foister), [email protected] (K. Jenkins), [email protected] (L. Skene), [email protected] (D. Copolov), [email protected] (N. Keks). 0920-9964/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2005.03.005
The legal requirement of informed consent is the foundation of ethical research and clinical practice. It ensures patients have all necessary information and agree to a procedure prior to undergoing any intervention. The notion that a patient must possess competence to give consent has important legal and clinical ramifications. Appelbaum and Grisso (1988) specify that consent may not be legally binding unless the patient has sufficient competence in four
212
V. Howe et al. / Schizophrenia Research 77 (2005) 211–214
key areas: understanding information, appreciating the relevance of that information to their situation, reasoning between benefits and risks of all possible treatments and, finally, expressing a choice. Mental disorders are heterogeneous. Clinical experience supported by new research suggests that while some patients have impaired decision-making abilities, many are competent to provide consent in a wide variety of circumstances and continually exercise this competence in their daily lives (Dunn et al., 2001). Clearly a patient’s right to autonomy and self-
Table 1 Areas of competency assessed and items included in the MacCAT-T Area of competency Understanding (1) Disordera Course
Appreciation (1) Disorder
Question content Diagnosis, 3 symptoms experienced If untreated, symptoms continue and may worsen
2. Method Acknowledgement of disorder
Understanding (2) Current treatmenta Treatment effect Benefits of treatment Risks of treatment
Type, administration, dose Therapeutic effect in 2 weeks Reduce symptoms and anxiety Sedation, extrapyramidal side effects
Appreciation (2) Current treatment
Could this treatment be useful? Why?
Understanding (3) Alternative treatment Treatment effect Benefits of alternative Risk of alternative
Medication X, given orally, once daily Therapeutic effect in 2 weeks Most effective treatment, reduces anxiety Sweating, 1/20 chance of a convulsion
Reasoning (1) Choice of treatment Current treatment Alternative treatment
Choice Treatment
Reasoning (2) Choice a
determination must be balanced with the assurance that patients with impaired competence are protected from decisions that may be harmful. Accurate identification of relevant variables is therefore paramount. The MacArthur Competency Assessment Tool-Treatment (MacCAT-T) (Grisso and Appelbaum, 1998), a semi-structured interview, was used in this investigation. Details of the areas assessed and the items included are provided in Table 1. Among the various disorders, schizophrenia has been particularly associated with impaired competence (Grisso and Appelbaum, 1995). Such diagnostic associations have serious implications for patients and deserve careful evaluation. This investigation aims to test whether diagnostic categories of acute psychosis differ with respect to competence or whether specific symptoms, irrespective of diagnosis, are more likely to affect competence.
Which is your preferred treatment? Why? Given the risks and benefits, how may bpreferred treatmentN affect you? Given the risks and benefits, how may balternative treatmentN affect you?
Which of these treatments do you think is best?
Logical consistency of choice (examiner rated)
Questions tailored specifically to the patient.
Participants (n = 110) from two major Australian public treatment facilities were interviewed. All participants met DSM-IV criteria for schizophrenia (n = 64), schizoaffective disorder (n = 25) or bipolar affective disorder (n = 21, manic episode = 16, mixed episode = 5) determined by the treating psychiatrist. Subsequently these diagnoses were confirmed by case review, using a modified protocol of the Structured Clinical Interview for DSM-IV, Research Version (SCID). All participants were educated at or above junior high school level. There were 54 males and 56 females with a mean age of 37.2 F 12.3 years. All were inpatients in early stage treatment for acute psychosis. The data reported here were extracted from a broader ongoing study examining issues of competence approved by both hospital ethics committees and for which all subjects gave written informed consent. The MacCAT-T (Grisso and Appelbaum, 1998) was used to evaluate the four areas considered central for the legal, ethical and clinical determination of competence noted above. bExpressing a choiceQ was excluded from the analysis as only patients able to express a choice participated. The MacCAT-T was modified to standardise the interview protocol, providing the same general infor-
V. Howe et al. / Schizophrenia Research 77 (2005) 211–214
213
mation regarding illness, current treatment and standard treatment alternatives (refer to Table 1). Scoring was performed in accordance with published criteria (Grisso and Appelbaum, 1998) by a single trained rater. To document the extent and severity of
symptoms, a PANSS was completed for each participant by 3 treating psychiatrists who were trained in PANSS rating and blind to MacCAT-T results. A high standard of inter-rater agreement was obtained during the PANSS training sessions (kappa exceeding 0.8).
Table 2 Pearson correlation coefficients between MacCAT-T and PANSS scores
3. Results
PANSS score
MacCAT-T score Understanding Appreciation Reasoning
Total score (sum P1–G16) Factor scores Positive (sum P1,P3,P5,P6,G9) Negative (sum N1,N2,N3,N4,N6,G7) Cognitive (sum N5,N7,P2,G10,G11) Excitement (sum P4,P7,G4,G8,G14) Depression (sum G2,G3,G6) Individual items Positive: P1 delusions P3 hallucinatory behaviour P5 grandiosity P6 suspiciousness/ persecution G9 unusual thought content Cognitive: N5 difficulty in abstract thinking N7 stereotyped thinking P2 conceptual disorganisation G10 disorientation G11 poor attention Excitement: P4 excitement P7 hostility G4 tension G8 uncooperativeness G14 poor impulse control a b
0.364a
0.218b
0.217b
0.364a
0.055
0.150
0.127
0.156
0.061
0.191b
0.325a
0.378a
0.328a
0.128
0.122
0.009
0.119
0.113
0.312a 0.135
0.051 0.164
0.147 0.010
0.276a 0.291a
0.179 0.051
0.149 0.089
0.352a
0.104
0.193b
0.107
0.224b
0.337a
0.088
0.163
0.124
0.200b
0.221b
0.361a
0.030 0.247a
0.184 0.307a
0.135 0.285a
0.238b 0.342a 0.198b 0.276a 0.172
0.083 0.158 0.003 0.374a 0.079
0.122 0.088 0.011 0.197b 0.046
Correlation is significant at the 0.01 level (2-tailed). Correlation is significant at the 0.05 level (2-tailed).
To determine if competence performance differed dependent on diagnostic category, multivariate analysis of variance (MANOVA) was performed between diagnostic group and the three MacCAT-T scores (understanding, appreciation and reasoning). No significant difference in MacCAT-T performance was evident between the diagnostic categories: schizophrenia, schizoaffective disorder and bipolar mood disorder (manic/mixed phase). In contrast to the negative finding with diagnostic categories, the total PANSS score was correlated with all three measures of competency (refer to Table 2). The impact of symptomology on competence scores was further examined using ratings obtained on PANSS factor scores. The factor structure used, derived by Lykouras et al. (2000), is detailed in Table 2. Correlational analyses performed between each factor score and the three MacCAT-T measures indicated that patients with more severe cognitive dysfunction performed consistently worse on each of the MacCAT-T measures in comparison to those without cognitive dysfunction. There were relationships with positive symptoms and the excitement factor although this was true for the bunderstandingQ section of the MacCAT-T only. There were no significant effects for the negative or depression factors (Table 2). Correlations between the individual PANSS items forming the positive, cognitive and excitement factors and MacCAT-T scores are also presented in Table 2. The most consistent findings were with conceptual disorganisation and poor attention. Other positive symptoms were also correlated but to a limited extent.
4. Discussion The results indicate that psychiatric diagnostic categories in acute psychosis did not differ in performance on a test of competence. An inverse relationship was evident between competence and specific positive symptom factor scores, particularly those related to cognition. At the symptom level, conceptual disorganisation and poor attention were
214
V. Howe et al. / Schizophrenia Research 77 (2005) 211–214
associated with competence. In contrast, hallucinations and items relating to negative symptoms did not have a significant relationship. Phase of illness has major implications for competence in psychoses. Cognitive dysfunction is a key predictor of competence in acute patients. In contrast to chronic illness, where cognitive deficits have also been implicated (Carpenter et al., 2000), impaired competency in acute illness appears to be particularly associated with the symptom of thought disorder. This finding reinforces the notion that competency is best understood as a neurocognitive concept and should be assessed accordingly. This investigation had several limitations. The MacCAT-T interview was initially designed for qualitative not quantitative interpretation (Grisso and Appelbaum, 1998). Some scales are not as psychometrically robust as others, which may have introduced error. The dunderstandingT scale however appears the most consistent in this and other research (Grisso et al., 1997) possibly due to its larger range of scoring in comparison to the appreciation and reasoning scales. Finally, all patients in this investigation had severe illness in acute phase. This sample is therefore not representative of non-acute illness. While diagnostic categories failed to predict competence, the identification of specific symptoms might assist the clinician to identify those patients for whom competency may be an issue. In acute psychosis, the presence of cognitively related symptoms, such as thought disorder rather than diagnosis, may better identify the subgroup of patients who require particular support with consent procedures. Although these findings are not surprising, these
observations contribute significantly to the empirical evidence on competence impairment in different phases of psychoses.
Acknowledgements This research was supported by a grant from the National Health and Medical Research Council of Australia, Grant number 149885.
References Appelbaum, P.S., Grisso, T., 1988. Assessing patients’ capacities to consent to treatment. N. Engl. J. Med. 319, 1635 – 1638. Carpenter, W.T., Gold, J.M., Lahti, A.C., Queern, C.A., Conley, R.R., Bartko, J.J., Kovnick, J., Appelbaum, P.S., 2000. Decisional capacity for informed consent in schizophrenia research. Arch. Gen. Psychiatry 57, 533 – 538. Dunn, L.B., Lindamer, L.A., Palmer, B.W., Schneiderman, L.J., Jeste, D.V., 2001. Enhancing comprehension of consent for research in older patients with psychosis: a randomised study of a novel consent procedure. Am. J. Psychiatry 158, 1911 – 1913. Grisso, T., Appelbaum, P.S., 1995. Abilities of patients to consent to psychiatric and medical treatments. Law Hum. Behav. 19, 149 – 174. Grisso, T., Appelbaum, P.S., 1998. Assessing Competence to Consent to Treatment: a Guide for Physicians and Other Health Professionals. Oxford University Press, New York. Grisso, T., Appelbaum, P.S., Hill-Fotouhi, C., 1997. The MacCATT: a clinical tool to assess patients’ capacities to make treatment decisions. Psychiatr. Serv. 48, 1415 – 1419. Lykouras, L., Oulis, P., Psarros, K., Daskalopoulou, E., Botsis, A., Christodoulou, G.N., Stefanis, C., 2000. Five-factor model of schizophrenic psychopathology: how valid is it? Eur. Arch. Psychiatry Clin. Neurosci. 250, 93 – 100.