Factors Affecting Smoking in Schizophrenia Stavroula Beratis, Aggeliki Katrivanou, and Philippos Gourzis There is an increased frequency of smoking among patients with schizophrenia. However, it is unknown whether the smoking behavior of the patients is similar in all schizophrenia subtypes, as well as which is the relationship between smoking initiation and disease onset. Four hundred six patients with DSM-IV schizophrenia were interviewed to determine the smoking status in relationship to gender and schizophrenic subtype, and to other factors that could affect or be affected by smoking. The frequency of smoking among patients (58%) was significantly greater than in subjects from the general population (42%) (P ⴝ .000005). Male patients smoked significantly more frequently (70%) than the corresponding control subjects (50%) (P ⴝ .000006), whereas the difference failed to reach significance between female patients (41%) and control subjects (32%). Among male patients, the number of smokers was significantly greater than in the controls in the paranoid (77%), undifferentiated (72%), and residual (78%) subtypes,
whereas there was no significant difference in the disorganized (44%) and catatonic (22%) subtypes. The findings show that the frequency of smoking in schizophrenia patients increases with increasing positive symptoms and decreases with increasing negative symptoms. Male and female smoking patients consumed approximately 10 cigarettes per day more than the corresponding control subjects (P < .000001). In 86% of the patients, smoking initiation occurred before the disease onset. Among patients who smoked, smoking initiation and disease onset occurred at age 18.7 ⴞ 4.4 and 24.1 ⴞ 6.1 years, respectively (P < .000001). It appears that smoking in schizophrenia is influenced by gender and subtype. However, the nature of this association remains uncertain because in the vast majority of the patients smoking initiation occurs earlier than the disease onset. Copyright © 2001 by W.B. Saunders Company
global functioning, and the prevalence of positive or negative symptoms.
STRONG ASSOCIATION has been known to exist between schizophrenia and smoking. Hughes et al.1 reported an 88% prevalence of smoking among outpatients with schizophrenic disorders as compared to a 70% prevalence for outpatients with manic disorders and a smoking rate of 52% among the total population of psychiatric outpatients; in local and national populationbased samples, the rate was 30% to 33%. Similarly, a high prevalence of smoking has been reported among schizophrenic inpatients. O’Farrell et al.2 reported that 88% of schizophrenic inpatients smoked, and Masterson and O’Shea3 found that 92% of the men and 82% of the women were smokers. In a study conducted by de Leon et al.,4 the overall prevalence of smoking among schizophrenic patients in a state hospital was 85%—93% for men and 70% for women patients. Although there is clear evidence that cigarette smoking is strongly associated with schizophrenia, the nature of the association remains uncertain. The purpose of this presentation is to investigate further the reported association between schizophrenia and smoking by examining the smoking status in the five subtypes of the disorder—paranoid, undifferentiated, disorganized, catatonic, and residual5—as well as the relationship of smoking to the age of smoking initiation, age at onset of the disease, number of cigarettes smoked per day,
Subjects A total of 406 schizophrenia patients were included in the study. Their mean age was 36.0 ⫾ 11.6 (SD) years, with a range from 16 to 75 years. One hundred thirty-three were inpatients, whereas the remaining 273, who were ascertained through the medical records, were outpatients at the time of the smoking status interview. The sample of the 406 cases represents the total number of patients admitted to the Psychiatry Wards during the study period, with the exception of 42 patients who were discharged and could not be contacted at the time of the smoking status interview. Of the 406 schizophrenic patients included in the study, 245 were men and 161 women. One hundred thirty-eight were admitted for the first time, 80 had two admissions, and the remaining 188 had three or more admissions. In 116 patients, the disease onset had occurred in a period of 3 years or less from the time of their evaluation. The age at onset of schizophrenia could be ascertained in 241 of the male and 160 of the female patients. The onset of the disease was determined from the time when the first prodromal symptoms required for a DSM-IV diagnosis of a schizophrenic disorder were observed.6
From the Department of Psychiatry, University of Patras Medical School, Patras, Greece. Address reprint requests to Stavroula Beratis, M.D., Department of Psychiatry, University of Patras School of Medicine, 265 00 Rion, Patras, Greece. Copyright © 2001 by W.B. Saunders Company 0010-440X/01/4205-0008$35.00/0 doi:10.1053/comp.2001.26273
Comprehensive Psychiatry, Vol. 42, No. 5 (September/October), 2001: pp 393-402
The age of smoking initiation was ascertained in 168 and 64 male and female patients, respectively. All patients had one or more hospital admissions in the inpatient service of the Department of Psychiatry of the University of Patras Medical School, Patras, Greece within the 91⁄2-year period from January 1990 through July 1999. The Department’s wards are the only inpatient service in Southwestern Greece, an area with a population of approximately 1 million, accepting cases with a 3-month maximum time of hospitalization.
Procedure All patients were interviewed by one of the authors (A.K. or P.G.) about age of disease onset, smoking status, age of smoking initiation, number of cigarettes smoked per day, marital status, occupation, educational level, and place of residence (urban or rural). Also, the antipsychotic medication obtained by the patients was recorded. Individuals who had smoked 100 or more cigarettes and were still smoking or had discontinued smoking for a time period of less than 1 month were considered to be actual smokers. Former smokers who had discontinued smoking for more than 6 months were combined with the nonsmokers for the comparisons. Those who had quit smoking for a period of 1 to 6 months were excluded from the study. One man and one woman fell into this category. At the time of evaluation, the patients’ overall highest past year level of functioning was determined using the Global Assessment of Functioning (GAF) scale.5 The original diagnosis (chart diagnosis) was made by staff psychiatrists during the patients’ hospitalization after assessment of their history, clinical symptomatology, and overall behavior. For the schizophrenia subtype diagnosis, the charts of the patients were reviewed independently by the three authors, who were blind to the staff diagnosis. The reviewers were unaware of this information because it was excluded from the case charts before assessment, as reported.6 In this study the diagnosis of the three reviewers was used. In all cases there was agreement in the diagnosis of the subtypes by at least two of the reviewers. Among the 406 cases studied there was discordance of one reviewer in 49 patients. In 190 cases, the diagnosis was made originally by the DSM-III-R7 and, subsequently, by reviewing the patients’ charts, according to DSM-IV criteria.5 The remaining 216 patients were diagnosed from the beginning according to DSM-IV criteria.5 One hundred of the patients were examined for the presence of positive and negative symptoms by two of the authors (A.K. and P.G.). Sixty-four of these patients were male and 36 female. Scoring was made according to the Positive and Negative Syndrome Scale of Kay et al.8 Four hundred six individuals, matched with the patients for age, sex, and place of residence (rural or urban), and mostly matched for occupation and educational level, were used as control subjects. These were parents, relatives, or family friends of children admitted to the Pediatric Wards of the University Hospital for acute diseases of short duration. The control subjects were asked the same questions about their smoking status as the patients of the study. The mean age of the control subjects was 36.0 ⫾ 11.4 years, with a range from 16 to 75 years. Table 1 lists demographic characteristics and the smoking status of both the patients and the control subjects.
BERATIS, KATRIVANOU, AND GOURZIS
Table 1. Demographic Characteristics and Smoking Status of 406 Schizophrenic Patients and 406 Control Subjects From the General Population Characteristic
Age (yr)* Male (n) Marital status Married Unmarried Divorced Widowed Residence† Urban Rural Education Uneducated Elementary school High school Technical school University Occupation Blue collar White collar Student Housekeeping Pension Unemployed Smoking (%) Male Female Cigarettes/d* Male Female Onset of smoking (yr)*
36.0 ⫾ 11.6 245
36.0 ⫾ 11.6 245
80 289 32 5
205 175 17 9
9 147 175 37 58
9 152 178 25 42
127 69 29 68 11 102 58 70 41 31.5 ⫾ 15.3 33.5 ⫾ 15.1 26.3 ⫾ 14.7 18.7 ⫾ 4.7
127 175 14 53 10 27 42 50 32 19.7 ⫾ 10.2 21.3 ⫾ 10.9 15.5 ⫾ 7.6 18.1 ⫾ 2.4
* Mean ⫾ SD. † Suburban are classified with urban.
Reliability The interrater reliability among the three reviewers for the diagnosis of schizophrenia versus nonschizophrenia was estimated by reviewing 60 randomly selected case charts. There was complete agreement in all cases ( ⫽ 1.0, z ⫽ 6.213, P ⬍ .00001). The unweighted kappa for interrater agreement among the three reviewers for the schizophrenia subtype diagnosis of the 406 patients was 0.886 (z ⫽ 32.961, P ⬍ .00001). Reliability of the positive and negative symptoms for two raters was estimated by the Pearson correlation as suggested by the author.9 Among the 100 patients evaluated, the mean ⫾ SD positive symptom score of the two examiners was 33.0 ⫾ 7.3 and 32.9 ⫾ 7.5 (n ⫽ 100, r ⫽ .997, P ⬍ .000001). For the negative symptoms it was 29.1 ⫾ 8.4 and 28.5 ⫾ 8.1 (n ⫽ 100, r ⫽ .878, P ⬍ .000001). To test reliability of the disease age at onset, the smoking or nonsmoking status of the subjects studied, the age of smoking initiation, and the number of cigarettes smoked per day, 100 patients were evaluated by two of the authors (A.K. and P.G.). In reference to the onset of the disease, there was agreement between the two interviewers in 99 cases. The mean age of
SMOKING IN SCHIZOPHRENIA
onset recorded by the reviewers was 22.26 ⫾ 6.12 years and 22.24 ⫾ 6.11 years, respectively (n ⫽ 100, r ⫽ .99, P ⬍ .000001). For the reliability of the smoking or nonsmoking status of the patients, there was 100% agreement between the interviewers (57 smoking patients, ⫽ 1.0). Regarding the 57 smoking patients, there was agreement between the two interviewers for (1) the number of cigarettes smoked per day in 54 of the cases (mean number of cigarettes, 30.44 ⫾ 12.83 and 30.88 ⫾ 12.86 respectively; n ⫽ 57, r ⫽ .988, P ⬍ .000001), and (2) the age of smoking initiation in 55 of the cases (mean age of starting smoking, 17.94 ⫾ 2.65 years and 17.97 ⫾ 2.58 years, respectively; n ⫽ 57, r ⫽ .998, P ⬍ .000001). To test reliability of the evaluation of the GAF scale score, 100 patients were evaluated by two of the authors (A.K. and P.G.). The mean ⫾ SD GAF score of the two examiners was 35.4 ⫾ 10.3 and 35.4 ⫾ 10.2 (n ⫽ 100, r ⫽ .974, P ⬍ .000001).
Statistical Analysis For the analysis of the data the Pearson chi-square test for one and two groups, the Fisher exact test, and the paired and unpaired t test were used, as appropriate. Multiple values were compared with one-way analysis of variance (ANOVA), with Tukey’s post hoc tests. To test reliability of the evaluators, the unweighted kappa statistic and the Pearson correlation were used as appropriate. Data were analyzed with the Fasted program for the Macintosh computer, Version 2 (Sistat, Evanston, IL). Values are expressed as the mean ⫾ SD. The level of significance was set at .05.
Subtypes Of the 406 (245 males) patients with schizophrenia investigated, 177 (105 males) were diagnosed as being of the paranoid subtype, 95 (50 males) of the undifferentiated, 54 (27males) of the disorganized, 69 (54 males) of the residual, and 11 (9 males) of the catatonic subtype. Prevalence of Smoking Patients versus controls. Among the 406 patients of the schizophrenic group, 237 (58%) were found to be smokers, whereas in the same number of control subjects, 172 (42%) were smokers (2 ⫽ 20.81, df ⫽ 1, P ⫽ .000005). Among the 245 men of the schizophrenic group, 171 (70%) were smokers, whereas among the male control subjects, 122 (50%) were smokers (2 ⫽ 20.38, df ⫽ 1, P ⫽ .000006). On the other hand, among the 161 female schizophrenic patients and an equal number of female control subjects, 66 (41%) and 51 (32%) were smokers, respectively (2 ⫽ 3.02, df ⫽ 1, P ⫽ .082). The number of male smokers in the control group was 2.4-fold greater than that of the female smokers (2 ⫽ 13.04, df ⫽ 1, P ⫽ .0003), whereas in the group of schizophrenic patients it
was 2.6-fold greater (2 ⫽ 33.17, df ⫽ 1, P ⬍ .000001). Among the schizophrenic patients with the paranoid subtype, 116 (66%) were smokers, whereas in the corresponding control group 85 (48%) were smokers (2 ⫽ 11.06, df ⫽ 1, P ⫽ .0008). In the undifferentiated subtype and the corresponding control subjects, 56 (59%) and 34 (36%) were smokers, respectively (2 ⫽ 10.22, df ⫽ 1, P ⫽ .001). In the residual subtype and the control subjects, the numbers of smokers were 45 (66%) and 27 (39%), respectively (2 ⫽ 9.41, df ⫽ 1, P ⫽ .002). However, in the group of patients with the disorganized subtype, there were 18 (33%) smokers, whereas in the corresponding control subjects there were 23 smokers (43%) (2 ⫽ 0.98, df ⫽ 1, P ⫽ .321). Similarly, of the 11 patients with the catatonic subtype, two (18%) were smokers and nine (82%) nonsmokers, whereas in the control group four (36%) were smokers and seven (64%) nonsmokers (Fisher exact test P ⫽ .635). Within patients. When the patients with the disorganized subtype were compared to the patients with the other subtypes it was shown that the number of smokers among the patients with this subtype was significantly smaller than in the paranoid (2 ⫽ 17.62, df ⫽ 1, P ⫽ .00003), undifferentiated (2 ⫽ 9.04, df ⫽ 1, P ⫽ .003), and residual (2 ⫽ 12.33, df ⫽ 1, P ⫽ .0004). No significant difference in the number of smokers was observed between the disorganized and the catatonic subtypes (2 ⫽ 0.99, df ⫽ 1, P ⫽ .321). Intensity of Smoking Patients versus controls. The mean number of cigarettes smoked per day by the combined population of male and female patients with schizophrenia who were smokers was 31.5 ⫾ 15.3, whereas in the control subjects it was 21.6 ⫾ 11.3. The difference is highly significant (t ⫽ 5.98, df ⫽ 407, P ⬍ .000001). Also, the mean number of cigarettes smoked per day by all male schizophrenic patients who were smokers was 33.5 ⫾ 15.0, whereas in the control subjects it was 23.1 ⫾ 11.5 (t ⫽ 5.71, df ⫽ 291, P ⫽ .000001). In the female patients the mean number of cigarettes smoked per day was 26.3 ⫾ 14.7 and in the control subjects it was 15.5 ⫾ 7.6 (t ⫽ 3.07, df ⫽ 115, P ⫽ .0028). Comparison of the number of cigarettes smoked per day by the male patients with the paranoid, undifferentiated, residual, and disorganized subtypes, with the num-
BERATIS, KATRIVANOU, AND GOURZIS
Table 2. Number of Cigarettes Smoked per Day by 171 Male Smoking Schizophrenic Patients According to the Subtype and 119 Control Subjects Who Were Smokers
Paranoid Undifferentiated Disorganized Residual Catatonic
Schizophrenics (mean ⫾ SD)
32.5 ⫾ 15.3 34.5 ⫾ 14.0 30.8 ⫾ 13.2 33.9 ⫾ 15.1 62.5
Controls (mean ⫾ SD)
22.6 ⫾ 11.7 21.6 ⫾ 9.7 20.8 ⫾ 8.7 19.9 ⫾ 10.4 26.3 ⫾ 17.0
1.4 1.6 1.5 1.7 —
4.31 3.99 2.04 4.51 —
⬍.000 ⬍.000 .059 ⬍.000 —
Abbreviations: P, patients; C, controls.
ber of cigarettes consumed by the control subjects showed that in each subtype the patients smoked a significantly greater number of cigarettes per day than the corresponding control subjects (Table 2). Also, female patients with the paranoid, undifferentiated, and disorganized subtypes smoked a significantly greater number of cigarettes per day than the control subjects. No sufficient number of female patients with the residual and the catatonic subtypes were available for analysis (Table 3). Within patients. By comparing the number of cigarettes smoked per day by the male and female subjects it was found that the total group of the male patients who were smokers consumed a significantly greater number of cigarettes per day than the female patients who smoked (t ⫽ 3.44, df ⫽ 235, P ⫽ .001). Also, the control male smokers consumed more cigarettes per day than the control female smokers (t ⫽ 3.97, df ⫽ 171, P ⫽ .0001). One-way ANOVA of the number of cigarettes smoked per day did not show any significant difference among the subtypes in either the male or female patients. Smoking Cessation Patients versus controls. Of the 294 schizophrenia patients who ever smoked, 11 (4%) had quit smoking at the time of examination for a period greater than 6 months, whereas of the 200 control subjects who ever smoked, 28 (14%) had
discontinued smoking (2 ⫽ 17.226, df ⫽ 1, P ⫽ .00003). Within patients. All patients who had discontinued smoking had the paranoid or the undifferentiated subtype. Thus, of the 183 patients with these subtypes who ever smoked, 11 (6%) had quit smoking, whereas of the 65 smoking patients with the disorganized, the residual and the catatonic subtype, none had discontinued smoking (2 ⫽ 4.088, df ⫽ 1, P ⫽ .043). Disease Onset and Smoking Initiation In the total sample of both male and female patients studied, the mean onset of the disease in those who were smokers was 24.1 ⫾ 6.1 years, and in those who were nonsmokers it was 23.4 ⫾ 8.7 years (t ⫽ 0.97, df ⫽ 404, P ⫽ .335). However, in the male patients it was 23.8 ⫾ 5.7 years and 22.2 ⫾ 6.5 years (t ⫽ 1.93, df ⫽ 243, P ⫽ .055), whereas in the female patients it was 25.1 ⫾ 6.7 years and 25.9 ⫾ 9.4 years (t ⫽ 0.60, df ⫽ 159, P ⫽ .550), respectively. The mean age at onset in the smoking and nonsmoking 54 male and female patients with the disorganized subtype was 17.7 ⫾ 3.0 years, whereas in the remaining 346 patients (in six cases no sufficient data were available) it was 25.0 ⫾ 6.8 years (t ⫽ 7.782, df ⫽ 398, P ⬍ .000001). The mean age at which smoking started in the male and female schizophrenic patients was
Table 3. Number of Cigarettes Smoked per Day by 66 Female Smoking Schizophrenic Patients According to the Subtype and 51 Control Subjects Who Were Smokers
Paranoid Undifferentiated Disorganized Residual
Schizophrenics (mean ⫾ SD)
24.8 ⫾ 15.1 28.2 ⫾ 16.7 26.5 ⫾ 9.7 30.0 ⫾ 10.0
Controls (mean ⫾ SD)
16.1 ⫾ 7.7 16.1 ⫾ 5.6 15.6 ⫾ 6.0 10.0
1.5 1.7 1.7 —
2.89 3.04 2.83 —
.006 .006 .017 —
SMOKING IN SCHIZOPHRENIA
18.7 ⫾ 4.4 years, whereas in the control subjects who smoked it was 18.1 ⫾ 2.4 years (t ⫽ 1.50, df ⫽ 407, P ⫽ .135). The male patients initiated smoking at 17.9 ⫾ 3.9 years and the male control subjects at 17.6 ⫾ 1.9 years, whereas the female patients and the female control subjects at 20.5 ⫾ 4.9 and 19.4 ⫾ 2.8 years, respectively. The difference of the male and female patients from the corresponding control subjects is not significant. Also, ANOVA of the age of smoking initiation did not show a significant difference among the subtypes. Of the 229 both male and female schizophrenia patients who smoked, and sufficient data for analysis were available, in 197 (86%) smoking initiation occurred before the onset of the disease, in 15 (7%) within the year of the disease onset, and in the remaining 17 (7%) after the onset of the disease. The difference between those who started smoking before the disease onset and the combined population of those who initiated smoking with the onset or after the onset of the disease is significant (2 ⫽ 67.61, df ⫽ 1, P ⬍ .000001). Similarly, in each of the three subtypes, paranoid, undifferentiated, and residual, smoking started significantly more frequently before the disease onset. The lowest ratio between the number of patients with smoking initiation before the disease onset over the number of patients with smoking initiation in the same year or after the year of the disease onset was observed in the disorganized subtype, in which the difference between the two groups of patients was not significant (Table 4). In the whole sample of the male and female
schizophrenic patients who smoked, the initiation of smoking occurred at the age of 18.7 ⫾ 4.4 years, whereas the disease onset occurred at the age of 24.1 ⫾ 6.1 years (t ⫽ 11.278, df ⫽ 472, P ⬍ .000001). In the male patients smoking initiation and disease onset occurred at 17.9 ⫾ 3.9 and 23.8 ⫾ 5.7 years, respectively (t ⫽ 10.87, df ⫽ 340, P ⬍ .000001), and in the female patients at 20.5 ⫾ 4.9 and 25.1 ⫾ 6.6 years, respectively (t ⫽ 4.461, df ⫽ 130, P ⫽ .000018). Also, in each of the four most frequent subtypes, the initiation of smoking occurred at a significantly earlier age than the onset of the disease (Table 5). Positive and Negative Symptoms and Smoking Of the 100 schizophrenia patients studied for positive and negative symptoms, 50 had the paranoid, 20 undifferentiated, 26 disorganized, and four catatonic subtype. The number of smokers in each of the subtypes was 32 (64%), 11 (55%), nine (35%), and one (25%), respectively. The mean score of the positive symptoms in the patients with the paranoid subtype was 38.5 ⫾ 3.8, whereas of the negative symptoms it was 22.0 ⫾ 2.1. The score of the positive symptoms is significantly greater than that of the negative ones (t ⫽ 27.156, df ⫽ 48, P ⬍ .000001). In the undifferentiated subtype, the mean scores of the positive and negative symptoms was 30.0 ⫾ 6.9 and 28.9 ⫾ 4.5, respectively (t ⫽ 0.600, df ⫽ 18, P ⫽ .552). In the disorganized subtype, the mean scores were 24.9 ⫾ 3.9 and 39.8 ⫾ 3.3, respectively (t ⫽ -14.750, df ⫽ 24, P ⬍ .000001). In the catatonic subtype, the values were 29.8 ⫾ 5.3 and 36.0 ⫾ 1.4, respectively (t ⫽ 2.273, df ⫽ 2, P ⫽ .063).
Table 4. Smoking Initiation in Relationship to the Age at Onset in 165* Male and 64† Female Schizophrenic Patients Who Smoked Smoking Initiation
BDO n (%)
ADO ⫹ SDO n (%)
Paranoid Undifferentiated Disorganized Residual Catatonic
102 (90) 46 (87) 12 (67) 35 (81) 2
11 (10) 7 (13) 6 (33) 8 (19) 0
9.3 6.6 2.0 4.4 —
44.13 8.98 — 8.79 —
⬍.000 .003 .500§ .003 —
Abbreviations: BDO, before disease onset; ADO, after disease onset; SDO, disease onset and smoking initiation in the same year. * In six additional cases there was insufficient relevant information. † In two additional cases there was insufficient relevant information. ‡ Ratio of number of patients with smoking initiation before disease onset over number of patients with smoking initiation after or in the same year with disease onset. § Fisher exact test.
BERATIS, KATRIVANOU, AND GOURZIS Table 5. Mean ⴞ SD Age of Smoking Initiation and Disease Onset (years) in 237 Male and Female Schizophrenic Patients Who Smoked Significance
Paranoid Undifferentiated Disorganized Residual Catatonic
19.0 ⫾ 4.5 18.7 ⫾ 3.9 16.9 ⫾ 2.7 18.5 ⫾ 5.0 17.5
25.8 ⫾ 6.6 23.0 ⫾ 4.1 18.7 ⫾ 2.6 23.3 ⫾ 5.3 27.5
9.01 5.54 2.10 4.28 —
⬍.000 ⬍.000 .043 ⬍.000 —
One-way ANOVA of the positive scores obtained in the four subtypes showed that there was a significant difference among them (F ⫽ 53.627, P ⬍ .000001). Tukey’s post hoc tests showed that the positive scores in the paranoid patients were significantly greater than in the undifferentiated (P ⫽ .0001), the disorganized (P ⫽ .0001), and the catatonic subtypes (P ⫽ .0018). Also, in the undifferentiated subtype the positive scores were significantly greater than in the disorganized (P ⫽ .002). Likewise, one-way ANOVA of the negative scores showed a significant difference among the subtypes (F ⫽ 207.240, P ⬍ .000001). Post hoc tests showed that the negative scores in the patients with the paranoid subtype were significantly lower than in the patients with the undifferentiated, disorganized, and catatonic subtypes (P ⬍ .0001). In addition, in the undifferentiated subtype they were lower than in the disorganized (P ⫽ .0001) and catatonic subtypes (P ⫽ .0003). The mean score of the positive symptoms in the schizophrenia patients who smoked was 35.0 ⫾ 7.1, whereas in the nonsmokers it was 30.5 ⫾ 7.1 (t ⫽ 3.153, df ⫽ 98, P ⫽ .002). Conversely, the mean score of the negative symptoms in the smoking patients was 26.6 ⫾ 7.4 and in the nonsmoking 30.7 ⫾ 8.5 (t ⫽ -2.604, df ⫽ 98, P ⫽ .01). Smoking, Subtype, and GAF Score To identify any differences among the subtypes in reference to the GAF scale score and the smoking status of the patients, we performed one-way ANOVA with Tuckey’s post hoc tests. There was a significant difference in the GAF score among the subtypes in both the smoking and the nonsmoking patients. The mean GAF scores in the male and female smoking patients with the paranoid, undifferentiated, disorganized, and residual subtypes were 41.7 ⫾ 11.1, 36.8 ⫾ 12.0, 27.3 ⫾ 7.3, and 30.4 ⫾ 7.0, respectively (F ⫽ 17.5, P ⬍ .000001).
Post hoc tests showed a significant difference between the paranoid and undifferentiated subtypes (P ⫽ .036), paranoid and disorganized (P ⫽ .000009), paranoid and residual (P ⫽ .000008), undifferentiated and disorganized (P ⫽ .008), and undifferentiated and residual (P ⫽ .016). The mean GAF scores in the male and female nonsmoking patients with the paranoid, undifferentiated, disorganized, and residual subtypes were 41.0 ⫾ 12.6, 40.0 ⫾ 10.0, 30.3 ⫾ 10.7, and 29.2 ⫾ 8.8, respectively (F ⫽ 11.4, P ⫽ .000001). Significant differences were observed between paranoid and disorganized (P ⫽ .00004), paranoid and residual (P ⫽ .0001), undifferentiated and disorganized (P ⫽ .001), and undifferentiated and residual (P ⫽ .0014). The mean GAF score in the whole group of the smoking male and female schizophrenic patients was 37.1 ⫾ 11.6 and in the nonsmoking 36.3 ⫾ 12.3 (t ⫽ 0.668, P ⫽ .505). In the male smoking and nonsmoking patients the mean GAF scores were 35.8 ⫾ 10.7 and 35.9 ⫾ 12.0, respectively. Comparison of the GAF scores between smoking and nonsmoking male patients in each subtype showed greater scores in the nonsmoking than in the smoking patients with the undifferentiated (41.6 ⫾ 11.5 and 34.6 ⫾ 9.2, respectively; t ⫽ 2.334, P ⫽ .024) and the disorganized subtype (31.9 ⫾ 9.4 and 24.1 ⫾ 6.4, respectively; t ⫽ 2.083, P ⫽ .05). In the female smoking and nonsmoking patients the mean GAF scores were 40.4 ⫾ 13.1 and 36.5 ⫾ 12.7, respectively (t ⫽ 1.813, P ⫽ .072), with no significant differences between smoking and nonsmoking patients in any of the subtypes. Effect of Typical and Atypical Antipsychotics on Smoking Of the 406 patients studied, 365 were treated with typical antipsychotic medications and 44 with
SMOKING IN SCHIZOPHRENIA
atypical. Of the 365 patients treated with typical antipsychotics, 217 (59%) were smokers, whereas of the 44 patients treated with atypical medications 20 (45%) were smokers (2 ⫽ 5.163, P ⫽ .023). None of the patients treated with atypical antipsychotics discontinued smoking during therapy. The mean number of cigarettes smoked per day by the patients treated with typical antipsychotic medications was 31.9 ⫾ 15.1 and with atypical 27.9 ⫾ 14.4 (t ⫽ 1.179, P ⫽ .25). Patients With a Disease Onset of 3 Years or less Of the 116 patients in this group, 77 were males and 39 females. Sixty-one (45 males) had the paranoid, 32 (17 males) undifferentiated, 20 (12 males) disorganized, and three (3 males) catatonic subtype. Prevalence of smoking. Of the 116 patients, 72 (62%) were smokers and 44 (38%) nonsmokers (2 ⫽ 11.66, df ⫽ 1, P ⫽ .00064). Of the 77 male patients, 52 (68%) were smoking, whereas among the male control subjects 34 (44%) were smoking (2 ⫽ 8.53, df ⫽ 1, P ⫽ .0035). Of the 39 female patients and the same number of female control subjects 20 (50%) and 12 (31%) were smokers, respectively (2 ⫽ 2.77, df ⫽ 1, P ⫽ .096). In the male and female patients with the paranoid subtype, 47 (77%) were smokers and in the corresponding control subjects 27 (44%) were smokers (2 ⫽ 13.74, df ⫽ 1, P ⫽ .0002). In the whole group of male and female patients with the undifferentiated subtype and the control subjects 19 (59%) and 13 (41%) were smokers, respectively (2 ⫽ 2.25, df ⫽ 1, P ⫽ .13). In both the male and female patients with the disorganized subtype as well as the corresponding control subjects there were six (30%) smokers in each group. All three male catatonic patients were nonsmokers. A significantly smaller number of patients with the disorganized subtype were smokers than among the patients with the paranoid subtype (2 ⫽ 14.74, df ⫽ 1, P ⫽ .0001) and the undifferentiated subtype (2 ⫽ 4.25, df ⫽ 1, P ⫽ .039). Intensity of smoking. The mean number of cigarettes smoked per day by the group of male and female patients and the control subjects who were smokers was 28.9 ⫾ 14.4 and 19.7 ⫾ 9.5, respectively (t ⫽ 4.14, df ⫽ 114, P ⫽ .00007). The male patients smoked 32.1 ⫾ 14.9 cigarettes per day and the corresponding control subjects 20.7 ⫾ 8.8 cigarettes per day (t ⫽ 4.46, df ⫽ 84, P ⫽ .00002).
The female patients and control subjects smoked 22.3 ⫾ 11.4 and 15.4 ⫾ 5.4, respectively (t ⫽ 2.29, df ⫽ 30, P ⫽ .029). The male patients who were smokers smoked a significantly greater number of cigarettes than the female patients (t ⫽ 2.99, df ⫽ 70, P ⫽ .004). Disease onset and smoking initiation. Of the 72 male and female smoking patients in 67 (93%) smoking started before the disease onset and in five (7%) after or within the year of the disease onset (2 ⫽ 32.77, df ⫽ 1, P ⬍ .000001). In the total group of male and female patients the mean age of smoking initiation was 18.5 ⫾ 3.9 years, whereas the mean age of the disease onset was 25.0 ⫾ 5.3 years (t ⫽ 8.34, df ⫽ 142, P ⬍ .000001). In the male patients smoking initiation and disease onset occurred at 17.9 ⫾ 3.4 years and 24.3 ⫾ 4.9 years, respectively (t ⫽ 7.55, df ⫽ 102, P ⬍ .000001), whereas in the female patients at 19.9 ⫾ 4.6 years and 26.8 ⫾ 5.9 years, respectively (t ⫽ 4.15, df ⫽ 38, P ⫽ .0002). DISCUSSION
The findings of this study are in agreement with reports in the literature that smoking is more frequent among schizophrenic patients than in the general population.1,4,10 However, the prevalence of smoking among the patients we studied was only 58%, as compared to rates of 85% to 92% reported earlier.1,2,4 This difference may have a cultural basis, but it is possible that another factor or factors may have been exerting a negative effect on the smoking rate among the patients in our study group. The finding of a lower cigarette consumption, though nonsignificant, among the smoking schizophrenic patients, when treated with atypical than with conventional antipsychotics, is in agreement with earlier reports indicating a reduced cigarette consumption after administration of clozapine.11,12 However, the observed lower frequency of smoking among the patients treated with atypical antipsychotics cannot be attributed to the medications, because none of these patients quit smoking during treatment. In addition, our data show that, although the male schizophrenics smoked significantly more frequently than the control subjects, the female patients tended to smoke more frequently than the control subjects, but the difference failed to reach statistical significance. This gender difference in the frequency of smoking among the schizophrenic patients cannot be easily explained. It may be partly explained by a better pre- and post-morbid
functioning of the female schizophrenics that could protect them from the need to smoke. However, once a schizophrenic patient has become a smoker, both male and female subjects consume per day approximately 10 to 12 cigarettes more than the corresponding smoking control subjects among the general population. Thus, not only the prevalence of smoking is greater among the schizophrenia patients,1-4 but also patients who smoke consume a greater number of cigarettes per day than control subjects without psychiatric disorders. The observation that the schizophrenic patients with the paranoid, the undifferentiated and the residual subtype smoked significantly more frequently than the control subjects, whereas the patients with the disorganized and the catatonic subtypes tended to smoke with a lower frequency than the control subjects indicates that the increased prevalence of smoking is not a uniform phenomenon in schizophrenia, but it depends on the subtype of the illness or certain characteristics of the subtypes that may effect smoking. Thus, the overall greater frequency of smoking among the schizophrenia patients results from the fact that the vast majority of patients are of the paranoid, the undifferentiated, and the residual subtypes,13 which are associated with a greater frequency of smoking. It appears that in patients with two of the schizophrenia subtypes, namely, the paranoid and undifferentiated subtypes, in which positive symptoms predominate and affect is relatively preserved, the tendency to smoke is higher. Thus, the finding that nicotine reduces anxiety and improves mood14 could lead to the hypothesis that, at least for patients who started smoking after the disease onset, when affect is preserved, nicotine can enhance mood improvement, whereas nicotine is ineffective when affect is severely disturbed. Moreover, the finding that dysphoria is particularly associated with positive symptoms of schizophrenia15 provides an additional explanation of the observed greater frequency of smoking among the schizophrenic subtypes with prominent positive symptoms. The observed increased frequency of smoking among patients with the residual subtype, in spite of the affective flattening,5 is most probably due to the fact that such patients manifest originally another subtype, eventually progressing into the residual subtype. The hypothesis of a positive association between
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positive symptoms and smoking may be applied only to those cases in which smoking started after the disease onset or even during the prodromal phase of the disease. This hypothesis, however, seems unlikely for the cases in which smoking initiation occurred before the prodromal phase of the disease, except if these patients experienced, even before the overt onset of the prodromal phase, inapparent symptoms which led them to smoking. The early age at onset of the disorganized subtype,6 which was verified in this study as well, inevitably results to a short prepsychotic vulnerable period for initiating smoking in these patients. This is because although the patients with the disorganized subtype showed the same mean age of smoking initiation with the whole group of the schizophrenia patients (18.7 ⫾ 2.6 and 18.7 ⫾ 4.4 years, respectively), the age at onset of the disease in this subtype occurred 7.3 years earlier than in the schizophrenia patients with the four other subtypes. Thus, the short prepsychotic vulnerable period for initiating smoking in conjunction with the finding that most of the schizophrenic patients started smoking before the disease onset could explain, to a major degree, the low frequency of smoking observed in this type of the disease. This hypothesis is further corroborated by the observation that there was a similar percentage of patients with the paranoid (15%), the undifferentiated (14%) and the disorganized (14%) subtype who initiated smoking after the onset of the disease. The higher prevalence of smoking among patients suffering from schizophrenia than in control subjects observed in this study was not due to the duration of the illness because (1) in the vast majority of patients the onset of illness occurred after the day of smoking initiation, and (2) the smoking rate among patients was not related to the time that had elapsed from the onset of the disease. Similarly, other investigators1,4 could not attribute the high rate of smoking among their schizophrenic patients to institutionalization or to boredom. Moreover, the difference in the prevalence of smoking cannot be attributed to other confounding factors, such as age, sex, educational level, and place of residence, urban or rural, because the control subjects were matched with the patients for these parameters. The patients were modestly matched with the controls for occupation, whereas they were unmatched for marital status. However,
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these parameters could not affect the smoking status of the patients to a significant degree because in the vast majority of cases the smoking habit was established at an earlier age. The fact that smoking initiation preceded the onset of the disease by 5 and 4.6 years in the male and the female patients, respectively, indicates that the psychotic phase of the disease per se is not the major factor leading to the increased frequency of smoking. The high frequency of smoking among the schizophrenia patients could be explained by hypothesizing the pre-existence of a personality prone to smoking among these patients. Also, the finding of Adler et al.16 that nicotine significantly improves cognitive functioning in schizophrenia patients and relatives could explain the increased frequency of smoking, if the cognitive impairment, which responds to nicotine, is present during the prepsychotic phase of the illness. However, both possibilities cannot be supported by our findings because in either of these cases the patients’ age of smoking initiation would be expected to be earlier than in the control subjects. The observation that patients with an onset of the disease within 3 years from the day of the study had similar characteristics with the total group of patients indicates that the findings of the study were not influenced by any subtype change, which might have occurred due to lack of stability of the subtypes.17,18 The finding that patients with the paranoid and the undifferentiated subtypes quit smoking more frequently than patients with the disorganized, the residual and the catatonic subtypes suggests that schizophrenia patients with sufficient overall functioning are more capable of mastering the nicotine dependency. On a similar vein, the data show that it is more difficult for schizophrenia patients to discontinue smoking when compared to normal subjects. Thus, once a patient started smoking he had a possibility of only 4% to quit smoking, whereas among the control subjects it was 14%, at least up to the age patients and controls were studied. Analysis of the GAF scores found in the patients showed that there were differences among the subtypes. The greatest GAF scores were found in both the smoking and the nonsmoking patients with the para-
noid subtype, followed by the undifferentiated, the residual and the disorganized. This is in accordance with the Levels of Functioning Scale Scores reported by Kendler et al.19 in 97 schizophrenia patients. The greater GAF scores observed in the nonsmoking than in the smoking male patients with the undifferentiated and the disorganized subtype is worth mentioning, because if it is real and it has not occurred by chance, it suggests that smoking may contribute to the impairment of functioning in these patients. The absence of a significant difference in the GAF scores between smoking and nonsmoking male patients with the paranoid subtype may be due to the fact that these patients had the smallest reduction in functioning suggesting that patients with the paranoid subtype are more resistant to the additive effect of other contributing factors, such as the tobacco smoke, for lowering functioning. Conversely, the absence of a difference in the GAF scores between smoking and nonsmoking male patients with the residual subtype may mean that the observed profound reduction of functioning in this subtype results from the effect of other factors, which may obscure a milder similar effect of the tobacco smoke on the functioning of these patients. The number of the female patients with the undifferentiated and the disorganized subtypes included in the study was small to discern any existing differences in functioning between smoking and nonsmoking female schizophrenics, possibly similar to those observed in the male patients. In conclusion, the observed greater frequency of smoking among the schizophrenic patients results from the highly significant increase of smoking in the paranoid, the undifferentiated and the residual subtypes. On the other hand the frequencies of smoking in the disorganized and the catatonic subtypes do not differ significantly from those of the control subjects; actually they show a tendency to be lower. Also, the overall increased frequency of smoking in schizophrenia patients does not appear to be provoked by the psychotic phase of the disease because in the vast majority of the patients smoking started significantly earlier than the disease onset.
REFERENCES 1. Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren BA. Prevalence of smoking among psychiatric outpatients. Am J Psychiatry 1986;143:993-997.
2. O’Farrell TJ, Connors GJ, Upper D. Addictive behaviors among hospitalized psychiatric patients. Addict Behav 1983;8: 329-333.
3. Masterson E. O’Shea B. Smoking and malignancy in schizophrenia. Br J Psychiatry 1984;145:429-432. 4. de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM. Schizophrenia and smoking: an epidemiological survey in a state hospital. Am J Psychiatry 1995;152:453-455. 5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Ed. 4. Washington, DC: American Psychiatric Association, 1994. 6. Beratis S, Gabriel J, Hoidas S. Age-at-onset in subtypes of schizophrenic disorders. Schizophr Bull 1994;20:287-296. 7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Ed. 3. Rev. Washington, DC: American Psychiatric Association, 1987. 8. Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261-276. 9. Kay SR. Positive and Negative Syndromes in Schizophrenia. Assessment and Research. New York, NY: Brunner/Mazel, 1991. 10. Glassman AH. Cigarette smoking: implication for psychiatric illness. Am J Psychiatry 1993;150:546-553. 11. George TP, Sernyak MJ, Ziedonis DM, Woods SW. Effects of clozapine on smoking in chronic schizophrenic outpatients. J Clin Psychiatry 1995;56:344-346. 12. McEnvoy JP, Freudenreich O, Wilson WH. Smoking and
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therapeutic response to clozapine in patients with schizophrenia. Biol Psychiatry 1999;46:125-129. 13. Beratis S, Gabriel J. Hoidas S. Gender differences in the frequency of schizophrenic subtypes in unselected hospitalized patients. Schizophr Res 1997;23:239-244. 14. Niaura R, Golstein MG, Ward KD, Abrams DB. Reasons for smoking and severity of residual nicotine withdrawal symptoms when using nicotine chewing gum. Br J Addict 1989;84: 681-687. 15. Lysaker PH, Bell MD, Bioty SM, Zito WS. The frequency of associations between positive and negative symptoms and dysphoria in schizophrenia. Compr Psychiatry 1995; 36:113-117. 16. Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, et al. Schizophrenia, sensory gating and nicotine receptors. Schizophr Bull 1998; 24:189-202. 17. Kendler KS, Gruenberg AM, Tsuang MT. Subtype stability in schizophrenia. Am J Psychiatry 1985;142:827-832. 18. Deister A, Marneros A. Long-term stability of subtypes in schizophrenic disorders: a comparison of four diagnostic systems. Eur Arch Psychiatry Clin Neurosci 1993;242: 184-190. 19. Kendler KS, McGuire M, Gruenberg AM, Walsh D. Outcome and family study of the subtypes of schizophrenia in the West of Ireland. Am J Psychiatry 1994;151:849-856.