- Email: [email protected]
Temperament in schizophrenia: a study of the tridimensional personality questionnaire (TPQ)
Eur Psychiatry 2002; 17: 379-83 © 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved S0924933802007009/FLA
ORIGINAL ARTICLE
Temperament in schizophrenia: a study of the tridimensional personality questionnaire (TPQ) Andrei Szöke1,2, Franck Schürhoff1,2, Nathalie Ferhadian1, Frank Bellivier1,2, Frédéric Rouillon1,2, Marion Leboyer1,2* 1
Service de psychiatrie adulte, Hôpital Henri Mondor et Albert Chenevier, 40, rue de Mesly, AP-HP, 94000 Créteil, France; 2 Inserm U 513, Laboratoire Neurobiologie et Psychiatrie, Faculté de Médecine Henri Mondor, 94000 Créteil, France (Received 12 February 2002; accepted 16 September 2002)
Summary – Purpose: The aim of this study was to assess dimensions of temperament as defined by Cloninger’s neurobiological model using the tridimensional personality questionnaire (TPQ) in a sample of consecutively recruited schizophrenic patients. Subjects and methods: We used the French version of the TPQ to compare 45 stable, euthymic schizophrenic patients with 126 controls with no personal or familial history of psychiatric disorder. After comparison of TPQ scores between groups, we also performed a multivariate analysis to avoid the confounding effects of age, gender, and alcohol and substance use disorder comorbidity. Results: Harm avoidance (HA) was higher in schizophrenic patients than in controls. Discussion and conclusion: This replicates and extends the results of previous studies suggesting that schizophrenic patients have high HA and that HA might be a marker for underlying genetic vulnerability to schizophrenia. © 2002 Éditions scientifiques et médicales Elsevier SAS Temperament / Schizophrenia / Tridimensional personality questionnaire
INTRODUCTION The aim of this study was to assess dimensions of temperament as defined by Cloninger’s neurobiological model using the tridimensional personality questionnaire (TPQ) [3,4] in a sample of consecutively recruited schizophrenic patients. This model provides a useful framework for exploring relationships between classical categorical disorders and underlying neurochemical and heritable factors. Cloninger’s unified biosocial model of personality was developed to investigate four independent heritable dimensions of temperament: novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (P) [5], each
*Corresponding author. E-mail address: [email protected] (M. Leboyer).
of which are proposed to be affected by specific neurotransmitters. Temperament is viewed as the automatic associative responses to basic emotional stimuli that determine habits and skills, and is highly heritable. Harm avoidance is described as a heritable bias in the inhibition or cessation behaviors such as pessimistic worry in anticipation of future problems, passive avoidant behaviors such as fear of uncertainty and shyness with strangers, and rapid fatigability. Novelty seeking encompasses the activation or initiation of exploratory activity, impulsive decision-making, quick loss of temper and avoidance of frustration. Reward dependence is a dimension of intense and continuous response to reward signals and is manifest as sentimen-
380
A. Szöke et al.
tality, social attachment and dependence on approval of others. Persistence, which reflects perseverance despite frustration, was initially considered a RD component but individualized later and considered a fourth dimension of temperament. The TPQ has been widely used in clinical studies. Although numerous studies have explored the TPQ dimensions in patients with depression [2,7,12], bipolar disorder [13,15,21], alcoholism [6] and bulimia nervosa [20], very few studies have explored these dimensions in patients with schizophrenia. Van Ammers et al. [19] showed that schizophrenic patients have high HA and low RD compared to normative data. However, this study, which focused on substance abuse and temperamental dimensions in schizophrenics, was performed in a small sample of male patients (n = 28), most of whom had drug abuse and/or dependence comorbidity. Furthermore, no control population was used. A second study, performed on 94 relatives of schizophrenic patients, showed that relatives with schizophrenia (n = 11) or with schizophrenia spectrum disorders (n = 7) had higher HA scores than controls [18]. The results of these two studies suggest that schizophrenic patients have a particular temperament profile, although both studies were performed on small, non-systematically recruited samples, and neither study assessed the patients’ mood. As Cloninger suggested that temperament is directly linked to genetic determinants of behavior and as previous studies have shown that the affective state influences the assessment of temperament, both the inclusion criteria of controls and the state of the patients may affect the TPQ scores. Therefore, it seems important to include schizophrenic patients after controlling for their euthymia, and to include only controls that do not carry vulnerability factors for schizophrenia and schizophrenia spectrum disorders. We used the TPQ to compare stable, euthymic schizophrenic patients with controls with no personal or family history of psychiatric disorders to determine whether schizophrenic patients have a temperament profile characterized by high HA and low RD. SUBJECTS AND METHODS Schizophrenic patients (26 men and 19 women) were consecutively recruited before being discharged from two university-affiliated hospitals (Pitié-Salpétrière and Albert Chenevier, Paris). All of the patients were diagnosed as being schizophrenic according to the DSM IV
criteria, as assessed with the French version of the semi-structured diagnostic interview for genetic studies (DIGS) [12]. All of the subjects gave informed consent before inclusion. Patients included were in a euthymic state as assessed with MADRS (Montgomery and Asberg depressive rating scale [11]) (score < 15) and MAS (Bech and Rafaelsen Mania rating scale [1]) (score < 6). They were also considered to be in a stable state, as their symptoms had not worsened and their medication had not been changed in the two weeks before recruitment. These patients belonged to a larger cohort, recruited for genetic studies (n = 105). Eight of the 105 patients were excluded because they were not euthymic or in a stable state and 31 were excluded because they had residual symptoms (mainly negative) that made them unable to complete the TPQ correctly. Of the 66 remaining subjects, 49 (74.2%) agreed to answer the TPQ and 45 filled it in correctly (i.e. no more then three incorrect or omitted answers). Controls (n = 126) were randomly selected from blood donors at the blood transfusion center at the Pitié-Salpétrière hospital in Paris. They were all interviewed with the DIGS to ensure that they had no personal or familial history of psychiatric disorders. After diagnostic assessment, the patients and controls were asked to answer the 100 questions in the French version of TPQ [10] so that the four temperament dimensions could be assessed. Statistical analysis The mean TPQ scores of the two groups were compared by two tailed t-tests. Given the number of variable tested, only P-values of 0.01 or less (instead of 0.05) were considered to be significant (Bonferoni correction for four comparisons). We also used the general linear model (GLM) procedure to ensure that any differences between the two groups were not the consequence of confounding factors (age, sex, addictive comorbidity). When significant differences in TPQ scores were found we conducted the same statistical analysis to compare the subscales described by Cloninger, to identify characteristics that differed between the two populations more accurately. All statistical analyses were performed using the analyst application of the SAS V 8.2 software [14]. Eur Psychiatry 2002; 17: 379–83
381
Temperament in schizophrenia Table I. Mean temperament scores in schizophrenic patients (N = 45) and in controls (N = 126)
NS HA RD P RD + P
Patients
Controls
t-test (P-value)
Group effect after correction for confounding factors (P-value)
15.9 ± 4.9 22.0 ± 6.4 11.3 ± 4.0 4.5 ± 1.9 15.8 ± 5.1
14.5 ± 5.3 10.8 ± 5.4 11.2 ± 3.8 4.4 ± 2.0 15.6 ± 4.6
0.12 < 0.0001 0.85 0.86 0.82
0.99 < 0.0001 0.63 0.52 0.86
NS: novelty seeking; HA: harm avoidance; RD: reward dependence; P: persistence.
RESULTS We compared 45 schizophrenic patients (26 men and 19 women) with 126 controls (82 men and 44 women). The age at interview of the schizophrenic patients was of 32.2 ± 9.7 years, whereas the age at interview of the control sample was 43.6 ± 8.7 years. Fourteen of the schizophrenic patients (31.1%) had comorbidity for alcoholic or psychoactive substance abuse. Temperament dimension scores are shown in table I. The only significant difference between the two groups was that schizophrenic patients had higher HA scores than the controls (P < 0.0001). The schizophrenic patients still had significantly higher HA scores after correcting for possible confounding factors such as gender, age at interview and comorbid substance abuse. All of the subscale scores of
HA were also higher in schizophrenic patients: HA1 (Anticipatory worry), HA2 (Fear of uncertainty), HA3 (Shyness with strangers), HA4 (Fatigability) (table II). Concerning the confounding factors the only significant difference in our sample was observed for gender on RD and RD + P dimensions (P = 0.008, higher scores in female subjects). A tendency to statistical difference (not reaching significance) was observed on NS dimension for gender (P = 0.05, higher scores in females) and age (P = 0.09, NS scores declining with age) and on HA2 and HA3 subscales for gender (P = 0.06 and 0.07, respectively, higher scores in females). As the inclusion criteria for the control sample (i.e. absence of personal or familial history of psychiatric disorders) differed from those normally used, we also compared our results with normative data collected in
Table II. Mean harm avoidance (HA) subscales scores in schizophrenic patients (n = 45) and controls (n = 126)
HA1 (anticipatory worry) HA2 (fear of uncertainty) HA3 (shyness with strangers) HA4 (fatigability)
Patients
Controls
t-test (P-value)
Group effect after correction for confounding factors (P-value)
6.4 ± 2.3 5.2 ± 1.8 4.1 ± 1.5 6.3 ± 2.6
3.1 ± 2.1 3.4 ± 2.0 2.4 ± 1.6 1.9 ± 1.9
< 0.0001 < 0.0001 < 0.0001 < 0.0001
< 0.0001 < 0.0001 < 0.0001 < 0.0001
Table III. TPQ scores in three control populations
N NS HA RD P RD + P –: Not reported. Eur Psychiatry 2002; 17: 379–83
Controls in our study
US normative data (Cloninger et al., 1991)
Controls from the Belgian sample (Le Bon et al., 1997)
126 14.5 ± 5.3 10.8 ± 5.4 11.2 ± 3.8 4.4 ± 2.0 15.6 ± 4.6
1019 13.0 ± 5.0 12.0 ± 5.9 13.4 ± 3.4 5.5 ± 1.9 –
104 16.5 ± 6.5 12.3 ± 6.0 – 4.7 ± 2.0 16.7 ± 4.4
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A. Szöke et al.
the US [4] and in a French-speaking Belgian population [8] (table III). The mean scores were comparable in the three populations of controls. A similar impact of gender on RD and of age on NS was reported in two studies [4,8]. Cloninger et al [4], but not Le Bon et al [8] found also a statistically significant difference in NS for gender. By contrast both studies reported an impact of gender on HA which we do not find here (P = 0.13). DISCUSSION We showed that stable euthymic schizophrenic patients have higher HA scores than controls with no personal or familial history of psychiatric disorders. This result is not due to confounding factors such as age at interview, gender or substance abuse. This is consistent with previous studies [18,19]. The HA scores for male patients (21 ± 6.6) were similar to those obtained by Van Ammers et al. [19] with both self-rated TPQ (17.6 ± 7) and when the TPQ was completed by case managers who had been in close contact with the patients for several years (25.7 ± 7.4). As the TPQ has not been standardized for schizophrenic patients who might have cognitive difficulties that may hamper the assessment of the TPQ score, it is interesting that similar results were obtained with different assessments (direct and indirect). High HA may be characteristic of euthymic schizophrenic patients and may be a marker for underlying genetic vulnerability. Strakowski et al. [16] found that psychotic depressed patients had elevated HA scores. However, the high HA score observed in our study is not due to the depressive state, as our patients were all euthymic. Our study also demonstrates that high HA score is not due to substance abuse, as substance abuse did not affect the HA score. Unlike Van Ammers et al. [19], we found that RD scores were not lower in schizophrenic patients than in controls. In our sample as in other studies [4,8] RD scores are influenced by gender, with lower scores in male subjects. As Van Ammers et al. [19] only included male patients and compared their scores with normative data from a mixed (i.e. male and female) population, the difference in RD scores can be partly explained by this bias. Another potentially confounding factor was the use of scores derived from case manager ratings. As shown in their study, self-rating scores are much more similar to scores in the general US population. We used mixed populations for both schizophrenics and controls and did not find differences in RD. Thus,
our results suggest that low RD is not a temperamental characteristic of schizophrenic subjects. All of our patients were receiving neuroleptic treatment, which might influence the assessment of an underlying temperamental trait. The fact we could not correct our data for the potentially confounding role of treatment is one limitation of our study. The genetic basis of high HA in schizophrenia remains to be demonstrated. To explore further the hypothesis that high HA score is a marker trait for vulnerability to schizophrenia, at risk subjects who have not yet received treatment should be studied, for example subjects with prodromal symptoms or unaffected first-degree relatives. Stompe et al. [18] studied TPQ dimensions in 40 unaffected relatives of schizophrenics and found that they had lower HA values than controls. The meaning of this result is unclear and needs to be replicated. It should also be stressed that patients with other psychiatric disorders, such as euthymic unipolar [21] and euthymic bipolar patients [13,17], also have elevated HA scores. Thus, high HA might be a common vulnerability factor. CONCLUSION This study replicates, in a larger sample of euthymic patients, previous findings that schizophrenia is associated with higher HA. This temperamental profile may represent an endophenotype [9], i.e. a trait marker of genetic vulnerability. Further studies, in subjects at genetic risk are necessary to test this hypothesis. ACKNOWLEDGEMENTS This research was supported by grants from the Assistance Publique-Hôpitaux de Paris (PHRC AOM 98152) and Fondation pour la Recherche Médicale (grant attributed to A.S.). REFERENCES 1 Bech P, Bolwig TG, Kramp P, Rafaelsen OJ. The Bech–Rafaelsen Mania scale and the Hamilton depression scale. Acta Psych Scand 1979;59:420–30. 2 Chien AJ, Dunner DL. The tridimensional personality questionnaire in depression: state versus trait issues. J Psychiatr Res 1996;30:21–7. 3 Cloninger CR. A systematic method for clinical description and classification of personality variants. Arch Gen Psychiatr 1987;44:573–88. 4 Cloninger CR, Przybeck TE, Svrakic DM. The tridimensional Eur Psychiatry 2002; 17: 379–83
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5 6 7 8 9 10
11 12
13
personality questionnaire: US normative data. Psychol Rep 1991;69:1047–57. Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatr 1993;50:975–90. Cloninger CR. Neurogenetic adaptive mechanisms in alcoholism. Science 1987;236:410–6. Joyce PR, Mulder RT, Cloninger CR. Temperament predicts clomipramine and desipramine response in major depression. J Affective Disord 1994;30:35–46. Le Bon O, Staner L, Tecco J, Pull C, Pelc I. Questionnaire de personnalité tridimensionnel (TQP): validation chez une population contrôle francophone. Encéphale 1997;24:40–5. Leboyer M, Bellivier F, Nosten-Bertrand M, Jouvent R, Pauls D, Mallet J. Psychiatric genetics: search for phenotype. Trends Neurosci 1998;21:102–5. Lépine JP, Pélissolo A, Téodorescu R, Téhérani M. Evaluation des propriétés psychométriques de la version française du questionnaire tridimensionnel de la personnalité (TPQ). Encéphale 1994;20:747–53. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatr 1979;134:382–9. Nurnberger Jr JI, Blehar MC, Kaufmann CA, York-Cooler C, Simpson SG, Harkavy-Friedman J, et al. Diagnostic interview of genetic studies; rationale, unique features and training. Arch Gen Psychiatr 1996;51:249–59. Osher Y, Cloninger CR, Belmaker RH. TPQ in euthymic Manic-Depressive patients. J Psychiatr Res 1996;5:353–7.
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14 SAS Institute Inc.. The analyst application, 1st ed. Cary NC: SAS Institute Inc.; 1999. 15 Strakowski SM, Stoll AL, Tohen M, Faedda GL, Goodwin DC. The tridimensional questionnaire as a predictor of six-month outcome in first episode mania. Psychiatr Res 1993; 48:1–8. 16 Strakowski SM, Faedda GL, Tohen M, Goodwin DC, Stoll AL. Possible affective-state dependence of the tridimensional personality questionnaire in first-episode psychosis. Psychiatr Res 1992;41:215–26. 17 Strakowski SM, Dunayevich E, Keck PE, McElroy SL. Affective state dependence of the tridimensional personality questionnaire. Psychiatr Res 1995;57:209–14. 18 Stompe T, Willinger U, Fischer G, Meszaros K, Berger P, Strobl R, et al. The unified biosocial model of personality in schizophrenia families and controls. Psychopathology 1998; 31:45–51. 19 Van Ammers EC, Sellman JD, Mulder RT. Temperament and substance abuse in schizophrenia: is there a relationship? J Nerv Ment Dis 1997;185:283–5. 20 Waller DA, Gullion CM, Petty F. Tridimensional personality questionnaire and serotonin in bulimia nervosa. Psychiatr Res 1993;49:9–15. 21 Young LT, Bagby RM, Cooke RG, Parker JDA, Levitt AJ, Joffe RT. A comparison of tridimensional personality questionnaire dimension in bipolar disorder and unipolar depression. Psychiatr Res 1995;58:139–43.
ORIGINAL ARTICLE
Temperament in schizophrenia: a study of the tridimensional personality questionnaire (TPQ) Andrei Szöke1,2, Franck Schürhoff1,2, Nathalie Ferhadian1, Frank Bellivier1,2, Frédéric Rouillon1,2, Marion Leboyer1,2* 1
Service de psychiatrie adulte, Hôpital Henri Mondor et Albert Chenevier, 40, rue de Mesly, AP-HP, 94000 Créteil, France; 2 Inserm U 513, Laboratoire Neurobiologie et Psychiatrie, Faculté de Médecine Henri Mondor, 94000 Créteil, France (Received 12 February 2002; accepted 16 September 2002)
Summary – Purpose: The aim of this study was to assess dimensions of temperament as defined by Cloninger’s neurobiological model using the tridimensional personality questionnaire (TPQ) in a sample of consecutively recruited schizophrenic patients. Subjects and methods: We used the French version of the TPQ to compare 45 stable, euthymic schizophrenic patients with 126 controls with no personal or familial history of psychiatric disorder. After comparison of TPQ scores between groups, we also performed a multivariate analysis to avoid the confounding effects of age, gender, and alcohol and substance use disorder comorbidity. Results: Harm avoidance (HA) was higher in schizophrenic patients than in controls. Discussion and conclusion: This replicates and extends the results of previous studies suggesting that schizophrenic patients have high HA and that HA might be a marker for underlying genetic vulnerability to schizophrenia. © 2002 Éditions scientifiques et médicales Elsevier SAS Temperament / Schizophrenia / Tridimensional personality questionnaire
INTRODUCTION The aim of this study was to assess dimensions of temperament as defined by Cloninger’s neurobiological model using the tridimensional personality questionnaire (TPQ) [3,4] in a sample of consecutively recruited schizophrenic patients. This model provides a useful framework for exploring relationships between classical categorical disorders and underlying neurochemical and heritable factors. Cloninger’s unified biosocial model of personality was developed to investigate four independent heritable dimensions of temperament: novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (P) [5], each
*Corresponding author. E-mail address: [email protected] (M. Leboyer).
of which are proposed to be affected by specific neurotransmitters. Temperament is viewed as the automatic associative responses to basic emotional stimuli that determine habits and skills, and is highly heritable. Harm avoidance is described as a heritable bias in the inhibition or cessation behaviors such as pessimistic worry in anticipation of future problems, passive avoidant behaviors such as fear of uncertainty and shyness with strangers, and rapid fatigability. Novelty seeking encompasses the activation or initiation of exploratory activity, impulsive decision-making, quick loss of temper and avoidance of frustration. Reward dependence is a dimension of intense and continuous response to reward signals and is manifest as sentimen-
380
A. Szöke et al.
tality, social attachment and dependence on approval of others. Persistence, which reflects perseverance despite frustration, was initially considered a RD component but individualized later and considered a fourth dimension of temperament. The TPQ has been widely used in clinical studies. Although numerous studies have explored the TPQ dimensions in patients with depression [2,7,12], bipolar disorder [13,15,21], alcoholism [6] and bulimia nervosa [20], very few studies have explored these dimensions in patients with schizophrenia. Van Ammers et al. [19] showed that schizophrenic patients have high HA and low RD compared to normative data. However, this study, which focused on substance abuse and temperamental dimensions in schizophrenics, was performed in a small sample of male patients (n = 28), most of whom had drug abuse and/or dependence comorbidity. Furthermore, no control population was used. A second study, performed on 94 relatives of schizophrenic patients, showed that relatives with schizophrenia (n = 11) or with schizophrenia spectrum disorders (n = 7) had higher HA scores than controls [18]. The results of these two studies suggest that schizophrenic patients have a particular temperament profile, although both studies were performed on small, non-systematically recruited samples, and neither study assessed the patients’ mood. As Cloninger suggested that temperament is directly linked to genetic determinants of behavior and as previous studies have shown that the affective state influences the assessment of temperament, both the inclusion criteria of controls and the state of the patients may affect the TPQ scores. Therefore, it seems important to include schizophrenic patients after controlling for their euthymia, and to include only controls that do not carry vulnerability factors for schizophrenia and schizophrenia spectrum disorders. We used the TPQ to compare stable, euthymic schizophrenic patients with controls with no personal or family history of psychiatric disorders to determine whether schizophrenic patients have a temperament profile characterized by high HA and low RD. SUBJECTS AND METHODS Schizophrenic patients (26 men and 19 women) were consecutively recruited before being discharged from two university-affiliated hospitals (Pitié-Salpétrière and Albert Chenevier, Paris). All of the patients were diagnosed as being schizophrenic according to the DSM IV
criteria, as assessed with the French version of the semi-structured diagnostic interview for genetic studies (DIGS) [12]. All of the subjects gave informed consent before inclusion. Patients included were in a euthymic state as assessed with MADRS (Montgomery and Asberg depressive rating scale [11]) (score < 15) and MAS (Bech and Rafaelsen Mania rating scale [1]) (score < 6). They were also considered to be in a stable state, as their symptoms had not worsened and their medication had not been changed in the two weeks before recruitment. These patients belonged to a larger cohort, recruited for genetic studies (n = 105). Eight of the 105 patients were excluded because they were not euthymic or in a stable state and 31 were excluded because they had residual symptoms (mainly negative) that made them unable to complete the TPQ correctly. Of the 66 remaining subjects, 49 (74.2%) agreed to answer the TPQ and 45 filled it in correctly (i.e. no more then three incorrect or omitted answers). Controls (n = 126) were randomly selected from blood donors at the blood transfusion center at the Pitié-Salpétrière hospital in Paris. They were all interviewed with the DIGS to ensure that they had no personal or familial history of psychiatric disorders. After diagnostic assessment, the patients and controls were asked to answer the 100 questions in the French version of TPQ [10] so that the four temperament dimensions could be assessed. Statistical analysis The mean TPQ scores of the two groups were compared by two tailed t-tests. Given the number of variable tested, only P-values of 0.01 or less (instead of 0.05) were considered to be significant (Bonferoni correction for four comparisons). We also used the general linear model (GLM) procedure to ensure that any differences between the two groups were not the consequence of confounding factors (age, sex, addictive comorbidity). When significant differences in TPQ scores were found we conducted the same statistical analysis to compare the subscales described by Cloninger, to identify characteristics that differed between the two populations more accurately. All statistical analyses were performed using the analyst application of the SAS V 8.2 software [14]. Eur Psychiatry 2002; 17: 379–83
381
Temperament in schizophrenia Table I. Mean temperament scores in schizophrenic patients (N = 45) and in controls (N = 126)
NS HA RD P RD + P
Patients
Controls
t-test (P-value)
Group effect after correction for confounding factors (P-value)
15.9 ± 4.9 22.0 ± 6.4 11.3 ± 4.0 4.5 ± 1.9 15.8 ± 5.1
14.5 ± 5.3 10.8 ± 5.4 11.2 ± 3.8 4.4 ± 2.0 15.6 ± 4.6
0.12 < 0.0001 0.85 0.86 0.82
0.99 < 0.0001 0.63 0.52 0.86
NS: novelty seeking; HA: harm avoidance; RD: reward dependence; P: persistence.
RESULTS We compared 45 schizophrenic patients (26 men and 19 women) with 126 controls (82 men and 44 women). The age at interview of the schizophrenic patients was of 32.2 ± 9.7 years, whereas the age at interview of the control sample was 43.6 ± 8.7 years. Fourteen of the schizophrenic patients (31.1%) had comorbidity for alcoholic or psychoactive substance abuse. Temperament dimension scores are shown in table I. The only significant difference between the two groups was that schizophrenic patients had higher HA scores than the controls (P < 0.0001). The schizophrenic patients still had significantly higher HA scores after correcting for possible confounding factors such as gender, age at interview and comorbid substance abuse. All of the subscale scores of
HA were also higher in schizophrenic patients: HA1 (Anticipatory worry), HA2 (Fear of uncertainty), HA3 (Shyness with strangers), HA4 (Fatigability) (table II). Concerning the confounding factors the only significant difference in our sample was observed for gender on RD and RD + P dimensions (P = 0.008, higher scores in female subjects). A tendency to statistical difference (not reaching significance) was observed on NS dimension for gender (P = 0.05, higher scores in females) and age (P = 0.09, NS scores declining with age) and on HA2 and HA3 subscales for gender (P = 0.06 and 0.07, respectively, higher scores in females). As the inclusion criteria for the control sample (i.e. absence of personal or familial history of psychiatric disorders) differed from those normally used, we also compared our results with normative data collected in
Table II. Mean harm avoidance (HA) subscales scores in schizophrenic patients (n = 45) and controls (n = 126)
HA1 (anticipatory worry) HA2 (fear of uncertainty) HA3 (shyness with strangers) HA4 (fatigability)
Patients
Controls
t-test (P-value)
Group effect after correction for confounding factors (P-value)
6.4 ± 2.3 5.2 ± 1.8 4.1 ± 1.5 6.3 ± 2.6
3.1 ± 2.1 3.4 ± 2.0 2.4 ± 1.6 1.9 ± 1.9
< 0.0001 < 0.0001 < 0.0001 < 0.0001
< 0.0001 < 0.0001 < 0.0001 < 0.0001
Table III. TPQ scores in three control populations
N NS HA RD P RD + P –: Not reported. Eur Psychiatry 2002; 17: 379–83
Controls in our study
US normative data (Cloninger et al., 1991)
Controls from the Belgian sample (Le Bon et al., 1997)
126 14.5 ± 5.3 10.8 ± 5.4 11.2 ± 3.8 4.4 ± 2.0 15.6 ± 4.6
1019 13.0 ± 5.0 12.0 ± 5.9 13.4 ± 3.4 5.5 ± 1.9 –
104 16.5 ± 6.5 12.3 ± 6.0 – 4.7 ± 2.0 16.7 ± 4.4
382
A. Szöke et al.
the US [4] and in a French-speaking Belgian population [8] (table III). The mean scores were comparable in the three populations of controls. A similar impact of gender on RD and of age on NS was reported in two studies [4,8]. Cloninger et al [4], but not Le Bon et al [8] found also a statistically significant difference in NS for gender. By contrast both studies reported an impact of gender on HA which we do not find here (P = 0.13). DISCUSSION We showed that stable euthymic schizophrenic patients have higher HA scores than controls with no personal or familial history of psychiatric disorders. This result is not due to confounding factors such as age at interview, gender or substance abuse. This is consistent with previous studies [18,19]. The HA scores for male patients (21 ± 6.6) were similar to those obtained by Van Ammers et al. [19] with both self-rated TPQ (17.6 ± 7) and when the TPQ was completed by case managers who had been in close contact with the patients for several years (25.7 ± 7.4). As the TPQ has not been standardized for schizophrenic patients who might have cognitive difficulties that may hamper the assessment of the TPQ score, it is interesting that similar results were obtained with different assessments (direct and indirect). High HA may be characteristic of euthymic schizophrenic patients and may be a marker for underlying genetic vulnerability. Strakowski et al. [16] found that psychotic depressed patients had elevated HA scores. However, the high HA score observed in our study is not due to the depressive state, as our patients were all euthymic. Our study also demonstrates that high HA score is not due to substance abuse, as substance abuse did not affect the HA score. Unlike Van Ammers et al. [19], we found that RD scores were not lower in schizophrenic patients than in controls. In our sample as in other studies [4,8] RD scores are influenced by gender, with lower scores in male subjects. As Van Ammers et al. [19] only included male patients and compared their scores with normative data from a mixed (i.e. male and female) population, the difference in RD scores can be partly explained by this bias. Another potentially confounding factor was the use of scores derived from case manager ratings. As shown in their study, self-rating scores are much more similar to scores in the general US population. We used mixed populations for both schizophrenics and controls and did not find differences in RD. Thus,
our results suggest that low RD is not a temperamental characteristic of schizophrenic subjects. All of our patients were receiving neuroleptic treatment, which might influence the assessment of an underlying temperamental trait. The fact we could not correct our data for the potentially confounding role of treatment is one limitation of our study. The genetic basis of high HA in schizophrenia remains to be demonstrated. To explore further the hypothesis that high HA score is a marker trait for vulnerability to schizophrenia, at risk subjects who have not yet received treatment should be studied, for example subjects with prodromal symptoms or unaffected first-degree relatives. Stompe et al. [18] studied TPQ dimensions in 40 unaffected relatives of schizophrenics and found that they had lower HA values than controls. The meaning of this result is unclear and needs to be replicated. It should also be stressed that patients with other psychiatric disorders, such as euthymic unipolar [21] and euthymic bipolar patients [13,17], also have elevated HA scores. Thus, high HA might be a common vulnerability factor. CONCLUSION This study replicates, in a larger sample of euthymic patients, previous findings that schizophrenia is associated with higher HA. This temperamental profile may represent an endophenotype [9], i.e. a trait marker of genetic vulnerability. Further studies, in subjects at genetic risk are necessary to test this hypothesis. ACKNOWLEDGEMENTS This research was supported by grants from the Assistance Publique-Hôpitaux de Paris (PHRC AOM 98152) and Fondation pour la Recherche Médicale (grant attributed to A.S.). REFERENCES 1 Bech P, Bolwig TG, Kramp P, Rafaelsen OJ. The Bech–Rafaelsen Mania scale and the Hamilton depression scale. Acta Psych Scand 1979;59:420–30. 2 Chien AJ, Dunner DL. The tridimensional personality questionnaire in depression: state versus trait issues. J Psychiatr Res 1996;30:21–7. 3 Cloninger CR. A systematic method for clinical description and classification of personality variants. Arch Gen Psychiatr 1987;44:573–88. 4 Cloninger CR, Przybeck TE, Svrakic DM. The tridimensional Eur Psychiatry 2002; 17: 379–83
Temperament in schizophrenia
5 6 7 8 9 10
11 12
13
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