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Nicotine use in schizophrenia and disinhibition
Psychiatry Research 128 (2004) 229 – 234 www.elsevier.com/locate/psychres
Nicotine use in schizophrenia and disinhibition Alain Dervaux a,b,*, Franck J. Bayle´ b, Xavier Laqueille b, Marie-Chantal Bourdel b, Miche`le-He´le`ne Le Borgne a, Jean-Pierre Olie´ b, Marie-Odile Krebs b b
a Service de Psychiatrie, BP 27, Centre Hospitalier, F91401 Orsay, France INSERM E0117 and Service Hospitalo-Universitaire de Sante´ Mentale et de Therapeutique, Universite´ Paris V, Centre Hospitalier Sainte-Anne, 1, rue Cabanis, 75674 Paris 14, France
Received 26 May 2003; received in revised form 18 February 2004; accepted 28 May 2004
Abstract The role of personality in nicotine use has been little studied in patients with schizophrenia. The objectives of the present study were to compare impulsivity, sensation seeking and anhedonia in a group of schizophrenic patients with and without current cigarette smoking. One hundred patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria) were assessed with the Positive and Negative Syndrome Scale, the Fagerstro¨m Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale. Among these patients, 67% were current smokers. The mean scores for sensation seeking were higher in the group of smokers than in the group of nonsmokers. The differences were found exclusively with the ‘‘disinhibition’’ subscale. No significant difference was found for impulsivity and physical anhedonia mean scores. The scores on the Sensation Seeking Scale were especially low in nonsmokers. Cigarette smoking could influence disinhibition and possibly help to normalize inhibition in schizophrenic patients. D 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Schizophrenia; Nicotine use; Nicotine dependence; Impulsivity; Sensation seeking; Anhedonia
1. Introduction It is well established that the prevalence of cigarette smoking is significantly higher among schizophrenic patients than in the general population (Dalack et al., 1998). Nicotine is well known to improve cognitive functions in non-schizophrenic patients and could alleviate some schizophrenic symptoms or neuroleptic side effects (Dalack et al.,
* Corresponding author. Tel.: +33-1-45-65-80-64; fax: +33-145-65-83-92. E-mail address: [email protected] (A. Dervaux).
1998; Mancuso et al., 1999; Warburton and Arnall, 1994). For instance, Adler et al. (1998) have suggested that an altered expression and function of the alpha7-nicotinic cholinergic receptor may be responsible for the auditory sensory gating deficit characterized in schizophrenic patients. Freedman et al. (1997) reported suggestive evidence for a biological link between the alpha7-nicotinic receptor gene and schizophrenia. Nicotine use improves auditory deficits in schizophrenic patients (Adler et al., 1993). Nicotine administration also reduces the haloperidolinduced cognitive deficit in a working memory test (Levin et al., 1996). Chronic nicotine treatment could change dopamine metabolism in the prefrontal cortex
0165-1781/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2004.05.021
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A. Dervaux et al. / Psychiatry Research 128 (2004) 229–234
(Dalack et al., 1998). It has been hypothesized that schizophrenic patients smoke to stimulate cortical activity without altering subcortical activity (Dalack et al., 1998). In addition, while nicotine decreases the frequency of leading saccades in schizophrenic patients during a smooth pursuit task, nicotine has no similar positive effects on the frequency of large anticipatory saccades in a smooth pursuit task, suggesting that the use of nicotine may reflect a specific pharmacological effect on prefrontal inhibition (Olincy et al., 2001). Thus, inhibitory dysfunction in schizophrenia may have multiple sources; some of them may be related to the loss of cholinergic function, while other defects may involve other neurobiological pathways (Olincy et al., 2001). Recently, Zammit et al. (2003) suggested that cigarette smoking may be an independent protective factor against developing schizophrenia, consistent with animal models showing both neuroprotective effects of nicotine and a differential release of prefrontal dopamine in response to nicotine. However, not all schizophrenic patients are smokers. Therefore, other factors could lead patients to smoke. The relationship between personality or temperament and tobacco consumption has been little studied in schizophrenic patients (Herran et al., 2000). In a sample of 28 male schizophrenics, novelty seeking, a concept close to sensation seeking, was significantly related to current use of nicotine (Van Ammers et al., 1997). In non-schizophrenic subjects, impulsivity is higher in regular smokers than subjects who have never smoked as measured using personality scales or in a behavioral choice task examining the effects of reward delays (Bickel et al., 1999; Mitchell, 1999). Sensation seeking is higher in smokers than in nonsmokers as well (Zuckerman et al., 1990; Carton et al., 1994, 2000; Kassel et al., 1994). To our knowledge, no study has been conducted regarding the role of impulsivity, sensation seeking or anhedonia in tobacco use in schizophrenic patients. In a previous study, we reported that substance abuse, mainly alcohol and cannabis, was related to impulsivity and sensation seeking in schizophrenic patients (Dervaux et al., 2001). We have now examined impulsivity, sensation seeking and anhedonia in current smokers and nonsmokers in a sample of 100 schizophrenic patients.
2. Methods 2.1. Study design and population From December 1996 to December 1998, all inpatients or outpatients aged 18 or older meeting the DSM-III-R criteria for schizophrenia and schizoaffective disorder at a psychiatric department at Orsay hospital (Paris suburbs) were proposed to participate in the study (N = 105). Exclusion criteria were primary neurologic conditions, mental retardation, dementia, amnestic disorders, mental disorders due to a general medical condition and substance-induced psychotic disorders. Five patients refused to participate in the study. The socio-demographic characteristics of the subjects excluded were comparable to those of the subjects included in the study. The study finally included 100 inpatients (N = 76) or outpatients (N = 24) with diagnoses of schizophrenia (N = 91) or schizoaffective disorders (N = 9) according to DSM-III-R. The study was approved by the local ethical committee, and all subjects provided written informed consent prior to their inclusion in the study. Patients were assessed with the Positive and Negative Syndrome Scale (PANSS, Kay et al., 1987), the Fagerstro¨m Scale for tobacco consumption (Fagerstro¨m, 1978), the Barratt Impulsivity Scale 10 (a 34-item self-report, Patton et al., 1995), the Zuckerman Sensation Seeking Scale form V (a 40-item selfreport, Zuckerman, 1978), and the Chapman Physical Anhedonia Scale (a 61-item self-report, Chapman et al., 1976). History of substance abuse was assessed with the psychoactive substance use disorder section of the Composite International Diagnostic Interview (CIDI) for computerized DSM-III-R diagnoses of abuse or dependence on alcohol, cannabis, amphetamines, sedatives, opioids, cocaine, hallucinogens, phencyclidine, inhalants and others (Robins et al., 1988). A standardized questionnaire gave additional information on the age of the first psychiatric treatment, the number of psychiatric hospitalizations, and the dose of neuroleptics expressed in chlorpromazine equivalents. 2.2. Data analysis Smokers were compared with nonsmokers. The chi-square statistic was used to compare categorical
A. Dervaux et al. / Psychiatry Research 128 (2004) 229–234
variables. The quantitative variables were studied using analysis of covariance (ANCOVA) adjusted on the basis of age and gender since these variables could be confounding factors (Zuckerman et al., 1990; Scourfield et al., 1996). Abuse of other substances could not be used as a third factor of ANCOVA because the nonsmoker group was too small. To eliminate a possibly confounding effect of concommitant substance abuse, we compared smokers vs. nonsmokers after excluding patients with substance abuse or dependence. We studied the correlations between the current Fagerstro¨m scale scores and the disinhibition subscale scores on the Sensation Seeking Scale using Pearson correlation tests. All the tests were two-tailed, with alpha level set at 0.05.
3. Results Sixty-seven subjects in the study presented current nicotine use. All subjects were cigarette smokers. There were no subjects who used a nicotine transdermal patch or nicotine gum. The average number of cigarettes smoked was 22.6 per day, S.D. = 15.4. The mean score on the Fagerstro¨ m Scale was 5.9, S.D. = 2.5. Eleven subjects were former smokers. Fifty-two smokers (77.6%) were male compared with 16 (48.5%) in the group of nonsmoker patients
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(v2 = 8.62, df = 1, P = 0.003). The smokers were younger than the nonsmokers (mean = 32.9 years, S.D. = 9.3 vs. mean = 38.4 S.D. = 12.7, ANCOVA: F = 5.92, df = 1,96, P = 0.02). The smokers had a younger mean age of first psychiatric treatment (mean = 22.9 years, S.D. = 5.5 vs. mean = 27.6, S . D . = 9 . 8 , A N C O VA : F = 11 . 5 4 , d f = 1 , 9 6 , P = 0.001). There was a higher proportion of substance-abusing patients in the smoker group (58%) than in the nonsmoker group (19%). There was no significant difference between the two groups in marital status, (v2 = 1.82, df = 1, P = 0.18), level of education, (v2 = 0.14, df = 1, P = 0.70), mean number of hospitalizations (mean = 4.2, S.D. = 4.2 vs. mean = 5.7, S.D. = 8.3, ANCOVA: F = 3.00, df = 1,87, P = 0.09), or CPZequivalent dose (mean = 1129.5, S.D. = 1879.3 vs. mean = 845.1, S.D. = 1287.6, ANCOVA: F = 0.67, df = 1,93, P = 0.41). Twelve patients were receiving atypical anti-psychotic drugs, i.e. risperidone (n = 8) and olanzapine (n = 4). These patients were distributed in a comparable manner between the two groups (10.4% in the group of smokers, n = 7; 15.2% in the group of nonsmokers, n = 5). Regarding psychopathologic assessment, there was no significant difference between the two groups on PANSS scores, Barratt Impulsivity Scale scores or Physical Anhedonia Scale scores (Table 1).
Table 1 Ratings of impulsivity, sensation seeking and anhedonia for smoking or nonsmoking schizophrenic patients Measure
PANSS total score Barratt Impulsivity Scale Total score Motor subscale Cognitive subscale Non-planning subscale Zuckerman Sensation Seeking Scale Total score Disinhibition subscale Thrill and adventure subscale Experience seeking subscale Boredom susceptibility subscale Chapman Physical Anhedonia Scale a
Age and gender adjusted.
Nonsmokers (N = 33)
Smokers (N = 67)
Men (N = 16)
Men (N = 50)
Women (N = 17)
ANCOVA Women (N = 14)
Comparing smokers and nonsmokers
Mean
S.D.
Mean
S.D.
Mean
S.D.
Mean
S.D.
F (df = 1,92)
Pa
83.3
11.1
75.92
14.3
78.9
13.0
82.4
17.5
0.11
0.74
56.1 14.9 20.7 20.5
16.8 8.6 7.5 6.1
52.6 14.7 20.6 17.3
14.1 7.1 6.0 5.1
59.9 18.0 21.2 20.7
17.8 8.0 7.0 6.8
54.8 17.8 19.9 16.6
15.8 7.6 5.9 6.9
0.60 2.77 0.00 0.02
0.44 0.10 0.96 0.89
12.6 3.4 3.7 3.3 2.2 22.2
5.6 1.7 2.6 2.2 1.4 10.2
12.1 1.5 4.5 4.1 2.0 15.8
6.1 1.4 2.9 2.2 1.5 5.4
17.1 4.4 5.4 4.4 2.9 19.9
6.6 2.2 2.8 2.0 1.7 7.7
13.3 3.2 4.2 3.9 2.0 14.7
6.6 2.1 3.1 2.4 1.5 5.5
4.06 8.20 1.27 0.96 0.75 0.90
0.047 0.005 0.26 0.33 0.39 0.34
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Mean scores on the Sensation Seeking Scale were significantly higher in the group of smokers than in the group of nonsmokers. The differences were found exclusively with the ‘‘disinhibition’’ subscale (Table 1). These results remained significant when the substance-abusing patients (N = 41), mainly abusers of alcohol and cannabis, were excluded (ANCOVA: F = 6.04, df = 1,52, P = 0.02). The disinhibition scores also remained significant, after exclusion of the five items linked to drug or alcohol use (ANCOVA: F = 7.79, df = 1,92, P = 0.006). The distribution of the scores on disinhibition was normal, without high-scoring individuals. There was no correlation between the Fagerstro¨m scale scores and the disinhibition subscale scores on the Sensation Seeking Scale (Pearson correlation test r = 0.07, P = 0.61).
4. Discussion The legality of tobacco and its easy availability make it the first choice and most widely used psychoactive substance among the general population (lifetime prevalence of daily smoking: 49.5%, Breslau et al., 2001). It is even more widely used by the patients in our study (67% of the patients were current smokers and 11% former smokers). In agreement with previous studies (see Dalack et al., 1998), the frequency of smoking in schizophrenia was greater among men and inversely related to age. The absence of significant differences between smokers and nonsmokers with regard to physical anhedonia and PANSS subscale scores does not support the hypothesis of self-medication for positive or negative schizophrenic symptoms. Our results suggest that impulsivity plays a minor role in tobacco consumption in schizophrenic patients, whereas impulsivity is related to tobacco consumption in non-schizophrenic subjects (Bickel et al., 1999; Mitchell, 1999) as well as alcohol and other drug abuse or dependence in schizophrenic patients (Dervaux et al., 2001) or in a mixed group of psychotic and mood disorder patients (Liraud and Verdoux, 2000). In contrast, smoking in schizophrenia was related to sensation seeking, especially disinhibition, as in non-schizophrenic subjects (Zuckerman, 1978; Carton et al., 1994). The observed differences in disinhibition scores between the groups are unlikely to be related to
alcohol or other drug abuse or dependence rather than nicotine use since the results remained statistically significant when the subjects with substance abuse were removed from the analysis. The disinhibition subscale includes five items related to drug or alcohol use, and five items expressing a hedonistic way of life including new experiences, sexual experiences, unusual dressing, dating someone attractive, and watching erotic scenes in movies. The findings remained significant after exclusion of the items related to drug or alcohol use. As nicotine appears to reduce neurolepticinduced extrapyramidal side effects, some authors have suggested that smoking is associated with neuroleptic treatment. However, heavy smoking was found to be related to a diagnosis of schizophrenia, independently of neuroleptic treatment (De Leon et al., 1995; Breese et al., 2000). Since there were no differences between smokers and nonsmokers in doses of neuroleptic medication, treatment did not seem to have a major effect. Atypical antipsychotics, particularly clozapine, have been reported to reduce smoking in schizophrenic patients (McEvoy et al., 1999). We were unable to test the hypothesis of a differential impact of atypical antipsychotics, on smoking compared to classical neuroleptics since only a few patients (n = 12) received atypical antipsychotics in this sample (and none clozapine). It is noteworthy that medication adherence could be a confounding factor, since Liraud and Verdoux (2001) suggested that greater sensation seeking was associated with poor medication adherence in patients presenting with psychotic disorders, independent of a history of substance use. The relationship between disinhibition and cigarette smoking in schizophrenia is difficult to interpret. Disinhibition may be either a trait marker that predisposes one to smoke, as reported in the general population (Zuckerman et al., 1990; Carton et al., 1994), or a consequence of nicotine consumption. According to Zuckerman (1983), while sensation seeking may be an underlying motive for initial (or even continued) cigarette use, particularly in social situations, it may have little to do with nicotine addiction (Zuckerman et al., 1990). Moreover, the sensation seeking trait seems to be stable in the population over the years, and could be a
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genetically influenced trait (Zuckerman, 1983). However, it is possible that the higher scores on disinhibition subscale reflect neuropharmacological changes caused by nicotine. This question needs to be addressed by comparing former and current smokers, but the size of this sample did not allow such an analysis. Consistent with previous studies that have demonstrated low sensation seeking scores in schizophrenic patients (Kish, 1970; Zuckerman, 1978), the scores for the patients in our study were lower than those in a French control population, especially in nonsmokers (Carton et al., 1994), and in particular the disinhibition scores (nonsmokers: male: 4.2, female: 3.1, smokers: male: 4.8, female: 5.0). As a result, the schizophrenic patients could smoke in order to alleviate their inhibition, rather to seek hyperdisinhibition. However, the significance of this finding is uncertain and its relation to nicotine’s effects is questionable. According to Zuckerman (1983, 1990), sensation seeking correlates most highly with smoking in social situations. In smokers with schizophrenia, some authors have suggested that social disabilities could also be improved by increasing sensation seeking in addition to the positive effects of nicotine on cognitive functioning (Leonard et al., 1996; Adler et al., 1998; Rezvani and Levin, 2001). Interestingly, no relationship between the degree of dependence and disinhibition subscale scores was found. A previous study in male non-schizophrenic patients has found similar results (Carton et al., 1994). Zuckerman et al. (1990) and Kassel et al. (1994) also found that there was no significant relationship between sensation seeking and amount of tobacco smoked. 4.1. Conclusions We found that cigarette smoking was related to higher level of disinhibition (or rather a lower level of inhibition) in schizophrenia. However, it is not clear whether disinhibition is a preexisting driving force for smoking or the consequence of the pharmacological effect of nicotine on cognition and behavior. Further studies, in particular in former smokers, will be needed to fully understand the relation between nicotine smoking and schizophrenia.
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Nicotine use in schizophrenia and disinhibition Alain Dervaux a,b,*, Franck J. Bayle´ b, Xavier Laqueille b, Marie-Chantal Bourdel b, Miche`le-He´le`ne Le Borgne a, Jean-Pierre Olie´ b, Marie-Odile Krebs b b
a Service de Psychiatrie, BP 27, Centre Hospitalier, F91401 Orsay, France INSERM E0117 and Service Hospitalo-Universitaire de Sante´ Mentale et de Therapeutique, Universite´ Paris V, Centre Hospitalier Sainte-Anne, 1, rue Cabanis, 75674 Paris 14, France
Received 26 May 2003; received in revised form 18 February 2004; accepted 28 May 2004
Abstract The role of personality in nicotine use has been little studied in patients with schizophrenia. The objectives of the present study were to compare impulsivity, sensation seeking and anhedonia in a group of schizophrenic patients with and without current cigarette smoking. One hundred patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria) were assessed with the Positive and Negative Syndrome Scale, the Fagerstro¨m Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale. Among these patients, 67% were current smokers. The mean scores for sensation seeking were higher in the group of smokers than in the group of nonsmokers. The differences were found exclusively with the ‘‘disinhibition’’ subscale. No significant difference was found for impulsivity and physical anhedonia mean scores. The scores on the Sensation Seeking Scale were especially low in nonsmokers. Cigarette smoking could influence disinhibition and possibly help to normalize inhibition in schizophrenic patients. D 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Schizophrenia; Nicotine use; Nicotine dependence; Impulsivity; Sensation seeking; Anhedonia
1. Introduction It is well established that the prevalence of cigarette smoking is significantly higher among schizophrenic patients than in the general population (Dalack et al., 1998). Nicotine is well known to improve cognitive functions in non-schizophrenic patients and could alleviate some schizophrenic symptoms or neuroleptic side effects (Dalack et al.,
* Corresponding author. Tel.: +33-1-45-65-80-64; fax: +33-145-65-83-92. E-mail address: [email protected] (A. Dervaux).
1998; Mancuso et al., 1999; Warburton and Arnall, 1994). For instance, Adler et al. (1998) have suggested that an altered expression and function of the alpha7-nicotinic cholinergic receptor may be responsible for the auditory sensory gating deficit characterized in schizophrenic patients. Freedman et al. (1997) reported suggestive evidence for a biological link between the alpha7-nicotinic receptor gene and schizophrenia. Nicotine use improves auditory deficits in schizophrenic patients (Adler et al., 1993). Nicotine administration also reduces the haloperidolinduced cognitive deficit in a working memory test (Levin et al., 1996). Chronic nicotine treatment could change dopamine metabolism in the prefrontal cortex
0165-1781/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2004.05.021
230
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(Dalack et al., 1998). It has been hypothesized that schizophrenic patients smoke to stimulate cortical activity without altering subcortical activity (Dalack et al., 1998). In addition, while nicotine decreases the frequency of leading saccades in schizophrenic patients during a smooth pursuit task, nicotine has no similar positive effects on the frequency of large anticipatory saccades in a smooth pursuit task, suggesting that the use of nicotine may reflect a specific pharmacological effect on prefrontal inhibition (Olincy et al., 2001). Thus, inhibitory dysfunction in schizophrenia may have multiple sources; some of them may be related to the loss of cholinergic function, while other defects may involve other neurobiological pathways (Olincy et al., 2001). Recently, Zammit et al. (2003) suggested that cigarette smoking may be an independent protective factor against developing schizophrenia, consistent with animal models showing both neuroprotective effects of nicotine and a differential release of prefrontal dopamine in response to nicotine. However, not all schizophrenic patients are smokers. Therefore, other factors could lead patients to smoke. The relationship between personality or temperament and tobacco consumption has been little studied in schizophrenic patients (Herran et al., 2000). In a sample of 28 male schizophrenics, novelty seeking, a concept close to sensation seeking, was significantly related to current use of nicotine (Van Ammers et al., 1997). In non-schizophrenic subjects, impulsivity is higher in regular smokers than subjects who have never smoked as measured using personality scales or in a behavioral choice task examining the effects of reward delays (Bickel et al., 1999; Mitchell, 1999). Sensation seeking is higher in smokers than in nonsmokers as well (Zuckerman et al., 1990; Carton et al., 1994, 2000; Kassel et al., 1994). To our knowledge, no study has been conducted regarding the role of impulsivity, sensation seeking or anhedonia in tobacco use in schizophrenic patients. In a previous study, we reported that substance abuse, mainly alcohol and cannabis, was related to impulsivity and sensation seeking in schizophrenic patients (Dervaux et al., 2001). We have now examined impulsivity, sensation seeking and anhedonia in current smokers and nonsmokers in a sample of 100 schizophrenic patients.
2. Methods 2.1. Study design and population From December 1996 to December 1998, all inpatients or outpatients aged 18 or older meeting the DSM-III-R criteria for schizophrenia and schizoaffective disorder at a psychiatric department at Orsay hospital (Paris suburbs) were proposed to participate in the study (N = 105). Exclusion criteria were primary neurologic conditions, mental retardation, dementia, amnestic disorders, mental disorders due to a general medical condition and substance-induced psychotic disorders. Five patients refused to participate in the study. The socio-demographic characteristics of the subjects excluded were comparable to those of the subjects included in the study. The study finally included 100 inpatients (N = 76) or outpatients (N = 24) with diagnoses of schizophrenia (N = 91) or schizoaffective disorders (N = 9) according to DSM-III-R. The study was approved by the local ethical committee, and all subjects provided written informed consent prior to their inclusion in the study. Patients were assessed with the Positive and Negative Syndrome Scale (PANSS, Kay et al., 1987), the Fagerstro¨m Scale for tobacco consumption (Fagerstro¨m, 1978), the Barratt Impulsivity Scale 10 (a 34-item self-report, Patton et al., 1995), the Zuckerman Sensation Seeking Scale form V (a 40-item selfreport, Zuckerman, 1978), and the Chapman Physical Anhedonia Scale (a 61-item self-report, Chapman et al., 1976). History of substance abuse was assessed with the psychoactive substance use disorder section of the Composite International Diagnostic Interview (CIDI) for computerized DSM-III-R diagnoses of abuse or dependence on alcohol, cannabis, amphetamines, sedatives, opioids, cocaine, hallucinogens, phencyclidine, inhalants and others (Robins et al., 1988). A standardized questionnaire gave additional information on the age of the first psychiatric treatment, the number of psychiatric hospitalizations, and the dose of neuroleptics expressed in chlorpromazine equivalents. 2.2. Data analysis Smokers were compared with nonsmokers. The chi-square statistic was used to compare categorical
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variables. The quantitative variables were studied using analysis of covariance (ANCOVA) adjusted on the basis of age and gender since these variables could be confounding factors (Zuckerman et al., 1990; Scourfield et al., 1996). Abuse of other substances could not be used as a third factor of ANCOVA because the nonsmoker group was too small. To eliminate a possibly confounding effect of concommitant substance abuse, we compared smokers vs. nonsmokers after excluding patients with substance abuse or dependence. We studied the correlations between the current Fagerstro¨m scale scores and the disinhibition subscale scores on the Sensation Seeking Scale using Pearson correlation tests. All the tests were two-tailed, with alpha level set at 0.05.
3. Results Sixty-seven subjects in the study presented current nicotine use. All subjects were cigarette smokers. There were no subjects who used a nicotine transdermal patch or nicotine gum. The average number of cigarettes smoked was 22.6 per day, S.D. = 15.4. The mean score on the Fagerstro¨ m Scale was 5.9, S.D. = 2.5. Eleven subjects were former smokers. Fifty-two smokers (77.6%) were male compared with 16 (48.5%) in the group of nonsmoker patients
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(v2 = 8.62, df = 1, P = 0.003). The smokers were younger than the nonsmokers (mean = 32.9 years, S.D. = 9.3 vs. mean = 38.4 S.D. = 12.7, ANCOVA: F = 5.92, df = 1,96, P = 0.02). The smokers had a younger mean age of first psychiatric treatment (mean = 22.9 years, S.D. = 5.5 vs. mean = 27.6, S . D . = 9 . 8 , A N C O VA : F = 11 . 5 4 , d f = 1 , 9 6 , P = 0.001). There was a higher proportion of substance-abusing patients in the smoker group (58%) than in the nonsmoker group (19%). There was no significant difference between the two groups in marital status, (v2 = 1.82, df = 1, P = 0.18), level of education, (v2 = 0.14, df = 1, P = 0.70), mean number of hospitalizations (mean = 4.2, S.D. = 4.2 vs. mean = 5.7, S.D. = 8.3, ANCOVA: F = 3.00, df = 1,87, P = 0.09), or CPZequivalent dose (mean = 1129.5, S.D. = 1879.3 vs. mean = 845.1, S.D. = 1287.6, ANCOVA: F = 0.67, df = 1,93, P = 0.41). Twelve patients were receiving atypical anti-psychotic drugs, i.e. risperidone (n = 8) and olanzapine (n = 4). These patients were distributed in a comparable manner between the two groups (10.4% in the group of smokers, n = 7; 15.2% in the group of nonsmokers, n = 5). Regarding psychopathologic assessment, there was no significant difference between the two groups on PANSS scores, Barratt Impulsivity Scale scores or Physical Anhedonia Scale scores (Table 1).
Table 1 Ratings of impulsivity, sensation seeking and anhedonia for smoking or nonsmoking schizophrenic patients Measure
PANSS total score Barratt Impulsivity Scale Total score Motor subscale Cognitive subscale Non-planning subscale Zuckerman Sensation Seeking Scale Total score Disinhibition subscale Thrill and adventure subscale Experience seeking subscale Boredom susceptibility subscale Chapman Physical Anhedonia Scale a
Age and gender adjusted.
Nonsmokers (N = 33)
Smokers (N = 67)
Men (N = 16)
Men (N = 50)
Women (N = 17)
ANCOVA Women (N = 14)
Comparing smokers and nonsmokers
Mean
S.D.
Mean
S.D.
Mean
S.D.
Mean
S.D.
F (df = 1,92)
Pa
83.3
11.1
75.92
14.3
78.9
13.0
82.4
17.5
0.11
0.74
56.1 14.9 20.7 20.5
16.8 8.6 7.5 6.1
52.6 14.7 20.6 17.3
14.1 7.1 6.0 5.1
59.9 18.0 21.2 20.7
17.8 8.0 7.0 6.8
54.8 17.8 19.9 16.6
15.8 7.6 5.9 6.9
0.60 2.77 0.00 0.02
0.44 0.10 0.96 0.89
12.6 3.4 3.7 3.3 2.2 22.2
5.6 1.7 2.6 2.2 1.4 10.2
12.1 1.5 4.5 4.1 2.0 15.8
6.1 1.4 2.9 2.2 1.5 5.4
17.1 4.4 5.4 4.4 2.9 19.9
6.6 2.2 2.8 2.0 1.7 7.7
13.3 3.2 4.2 3.9 2.0 14.7
6.6 2.1 3.1 2.4 1.5 5.5
4.06 8.20 1.27 0.96 0.75 0.90
0.047 0.005 0.26 0.33 0.39 0.34
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Mean scores on the Sensation Seeking Scale were significantly higher in the group of smokers than in the group of nonsmokers. The differences were found exclusively with the ‘‘disinhibition’’ subscale (Table 1). These results remained significant when the substance-abusing patients (N = 41), mainly abusers of alcohol and cannabis, were excluded (ANCOVA: F = 6.04, df = 1,52, P = 0.02). The disinhibition scores also remained significant, after exclusion of the five items linked to drug or alcohol use (ANCOVA: F = 7.79, df = 1,92, P = 0.006). The distribution of the scores on disinhibition was normal, without high-scoring individuals. There was no correlation between the Fagerstro¨m scale scores and the disinhibition subscale scores on the Sensation Seeking Scale (Pearson correlation test r = 0.07, P = 0.61).
4. Discussion The legality of tobacco and its easy availability make it the first choice and most widely used psychoactive substance among the general population (lifetime prevalence of daily smoking: 49.5%, Breslau et al., 2001). It is even more widely used by the patients in our study (67% of the patients were current smokers and 11% former smokers). In agreement with previous studies (see Dalack et al., 1998), the frequency of smoking in schizophrenia was greater among men and inversely related to age. The absence of significant differences between smokers and nonsmokers with regard to physical anhedonia and PANSS subscale scores does not support the hypothesis of self-medication for positive or negative schizophrenic symptoms. Our results suggest that impulsivity plays a minor role in tobacco consumption in schizophrenic patients, whereas impulsivity is related to tobacco consumption in non-schizophrenic subjects (Bickel et al., 1999; Mitchell, 1999) as well as alcohol and other drug abuse or dependence in schizophrenic patients (Dervaux et al., 2001) or in a mixed group of psychotic and mood disorder patients (Liraud and Verdoux, 2000). In contrast, smoking in schizophrenia was related to sensation seeking, especially disinhibition, as in non-schizophrenic subjects (Zuckerman, 1978; Carton et al., 1994). The observed differences in disinhibition scores between the groups are unlikely to be related to
alcohol or other drug abuse or dependence rather than nicotine use since the results remained statistically significant when the subjects with substance abuse were removed from the analysis. The disinhibition subscale includes five items related to drug or alcohol use, and five items expressing a hedonistic way of life including new experiences, sexual experiences, unusual dressing, dating someone attractive, and watching erotic scenes in movies. The findings remained significant after exclusion of the items related to drug or alcohol use. As nicotine appears to reduce neurolepticinduced extrapyramidal side effects, some authors have suggested that smoking is associated with neuroleptic treatment. However, heavy smoking was found to be related to a diagnosis of schizophrenia, independently of neuroleptic treatment (De Leon et al., 1995; Breese et al., 2000). Since there were no differences between smokers and nonsmokers in doses of neuroleptic medication, treatment did not seem to have a major effect. Atypical antipsychotics, particularly clozapine, have been reported to reduce smoking in schizophrenic patients (McEvoy et al., 1999). We were unable to test the hypothesis of a differential impact of atypical antipsychotics, on smoking compared to classical neuroleptics since only a few patients (n = 12) received atypical antipsychotics in this sample (and none clozapine). It is noteworthy that medication adherence could be a confounding factor, since Liraud and Verdoux (2001) suggested that greater sensation seeking was associated with poor medication adherence in patients presenting with psychotic disorders, independent of a history of substance use. The relationship between disinhibition and cigarette smoking in schizophrenia is difficult to interpret. Disinhibition may be either a trait marker that predisposes one to smoke, as reported in the general population (Zuckerman et al., 1990; Carton et al., 1994), or a consequence of nicotine consumption. According to Zuckerman (1983), while sensation seeking may be an underlying motive for initial (or even continued) cigarette use, particularly in social situations, it may have little to do with nicotine addiction (Zuckerman et al., 1990). Moreover, the sensation seeking trait seems to be stable in the population over the years, and could be a
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genetically influenced trait (Zuckerman, 1983). However, it is possible that the higher scores on disinhibition subscale reflect neuropharmacological changes caused by nicotine. This question needs to be addressed by comparing former and current smokers, but the size of this sample did not allow such an analysis. Consistent with previous studies that have demonstrated low sensation seeking scores in schizophrenic patients (Kish, 1970; Zuckerman, 1978), the scores for the patients in our study were lower than those in a French control population, especially in nonsmokers (Carton et al., 1994), and in particular the disinhibition scores (nonsmokers: male: 4.2, female: 3.1, smokers: male: 4.8, female: 5.0). As a result, the schizophrenic patients could smoke in order to alleviate their inhibition, rather to seek hyperdisinhibition. However, the significance of this finding is uncertain and its relation to nicotine’s effects is questionable. According to Zuckerman (1983, 1990), sensation seeking correlates most highly with smoking in social situations. In smokers with schizophrenia, some authors have suggested that social disabilities could also be improved by increasing sensation seeking in addition to the positive effects of nicotine on cognitive functioning (Leonard et al., 1996; Adler et al., 1998; Rezvani and Levin, 2001). Interestingly, no relationship between the degree of dependence and disinhibition subscale scores was found. A previous study in male non-schizophrenic patients has found similar results (Carton et al., 1994). Zuckerman et al. (1990) and Kassel et al. (1994) also found that there was no significant relationship between sensation seeking and amount of tobacco smoked. 4.1. Conclusions We found that cigarette smoking was related to higher level of disinhibition (or rather a lower level of inhibition) in schizophrenia. However, it is not clear whether disinhibition is a preexisting driving force for smoking or the consequence of the pharmacological effect of nicotine on cognition and behavior. Further studies, in particular in former smokers, will be needed to fully understand the relation between nicotine smoking and schizophrenia.
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