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Substance abuse and related diagnoses in early psychosis
Comprehensive Psychiatry 46 (2005) 447 – 452 www.elsevier.com/locate/comppsych
Substance abuse and related diagnoses in early psychosis Jyrki A. Korkeilaa,T, Tanja Svirskisb, Markus Heinimaab, Terja Ristkarib, Jukka Huttunenb, Tuula Ilonenb, Tom McGlashanc, Raimo K.R. Salokangasa,d a
Department of Psychiatry, Turku City Hospital and Turku University Central Hospital, University of Turku, 20700 Turku, Finland b Department of Psychiatry, University of Turku, 20700 Turku, Finland c Department of Psychiatry, University of Yale, New Haven, CT, USA d Department of Psychiatry, Psychiatric Clinic, Turku University Central Hospital, 20540 Turku, Finland
Abstract Substance abuse seems to be common among those with early signs of evolving psychosis. This article seeks to determine the prevalence of substance abuse and substance use disorders (SUDs) and the association of abuse and SUD with vulnerability psychosis among a sample of first-degree relatives of schizophrenic patients (n = 70), help-seekers (n = 29), and control subjects (n = 34). The Structured Interview for Prodromal Symptoms (SIPS) 1.0 was used to define the vulnerability status and the Structured Clinical Interview for DSM-IV Axis I to diagnose the subjects. Data on various other measures, including premorbid adjustment, personality disorder symptoms, psychological distress, and abuse of substances, were collected. Those who were identified as vulnerable to psychosis reported significantly more lifetime alcohol abuse and had more commonly an SUD than controls. Substance use disorder, as well as alcohol and drug abuse, correlated significantly with personality disorder symptoms and current positive SIPS score and both types of abuse also with disorganization SIPS score. The odds ratio for having an SUD among those vulnerable to psychosis was 6.33 (95% confidence interval, 1.77-22.73). Early psychosis and substance abuse frequently occur together. D 2005 Elsevier Inc. All rights reserved.
1. Introduction Of 4 patients with schizophrenia, 3 presented with prodromal symptoms before the onset of psychosis [1]. The theoretical basis for prodromal states rests on the vulnerability-stress model of schizophrenia [2] that views vulnerability and the psychotic episode in a trait-like relation, whereas psychotic symptoms are considered to be provoked by stressful life events. Respectively, prodromal symptoms can be considered a sign of increased vulnerability to psychosis. Substance abuse and schizophrenia both originate in adolescence and young adulthood. Young subjects with schizophrenia have been found to have a 3 times higher prevalence of alcohol and substance abuse disorders than the corresponding age group in the US general population. In addition, 47% of subjects with schizophrenia had substance abuse, past or present, compared with 13.5% of the general population [3]. On the other hand, a recent study T Corresponding author. Tel.: +358 40 5514249; fax: +358 269 2528. E-mail address: [email protected] (J.A. Korkeila). 0010-440X/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.comppsych.2005.03.008
also found a high rate of coexisting psychiatric, especially mood and disruptive behavior, disorders among adolescents with a substance use disorder (SUD) [4]. The studies done since 1990 have found a 40% to 60% range of prevalence rates of abuse in schizophrenia with male sex and young age as primary correlates [5]. However, in their comprehensive review, Phillips and Johnson [6] have stated that there is considerable country-to-country variation in the prevalence and patterns of abuse among patients with schizophrenia and that these findings do not take into account confounding sociodemographic factors. There are studies showing that substance abuse may be common also in early psychosis [5,7,8] and that the abuse may even be more common preceding psychosis than immediately after the onset of psychosis [7,8]. There are several studies addressing the question of temporal relations between substance abuse and onset of psychosis. Some studies have reported an increased risk of schizophrenia in adulthood after the use of cannabis in adolescence [9,10]. Other studies have also reported that abuse has preceded the onset of first contact because of psychotic symptoms [3,5]. However, there are also studies
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that have found that abuse does not precede the onset of psychotic symptoms [5]. In a large cohort (Age, Beginning, Course study) of first-episode schizophrenic patients, Hambrecht and H7fner [11] found a diversity of temporal associations between onset of psychosis and abuse. A later analysis of the same sample revealed that about half of patients with alcohol abuse and less than two thirds of patients with drug abuse began the use before the first sign of the illness [12]. Thus, unidirectional causality seems unlikely in the light of the Age, Beginning, Course study. This article seeks to determine the prevalence and clinical correlates of substance abuse and SUD among subjects with and without vulnerability to psychosis in a sample of first-degree relatives, help-seekers, and controls. 2. Sample and methods Subjects were collected from the city of Turku and the Southwest Finland Health Care District with a total population of 430 000. The subjects represented various settings. The sampling procedure has been described elsewhere [13]. The subjects of the present study are grouped here into 3 groups according to the study setting and their help-seeking behavior: (1) first-degree relatives, (2) help-seekers, and (3) control subjects. Initially, the first-degree relatives were the target group for finding subjects vulnerable to psychosis because of an increased genetic risk for psychosis. First-degree relative group (n = 70). At the beginning, 138 (age, 14- 40 years) first-degree relatives of patients with schizophrenia and of patients with other nonaffective psychosis, and first-degree relatives of adolescent patients with severe mental illness (with psychotic or psychotic-like symptoms) were screened by a screening instrument, the PROD screen [14], developed by the project. Of these firstdegree relatives, 54 consecutive, screen-positive subjects were investigated. In addition, 20 voluntary first-degree relatives (age, 14 -40 years) of psychiatric patients from local organization of relatives of psychiatric patients were screened, and 16 screen-positive subjects were investigated. Help-seekers (n = 35). Patients (age, 18-40 years; n = 60) making their first-ever contact during the year 1999 with the Turku Community Mental Health Centre were screened using the PROD screen, 30 of whom were screened positive and thus included in the study. In addition, adolescents (n = 15; age, 14-22 years) consecutively contacting the adolescent psychiatric unit were screened using the PROD screen, and 5 screen-positive subjects were included. Controls (n = 34). Finally, randomly selected subjects (age, 14-40 years) from the local population register were contacted and recruited for more detailed investigation. All study subjects gave their written informed consent concerning the study. In the case of minors, their guardians also gave their informed consent. The ethical committee of Turku University and Turku University Central Hospital approved the study protocol.
Symptoms of vulnerability to psychosis were assessed using the Structured Interview for Prodromal Symptoms (SIPS) 1.0 developed by Miller et al [15]. The SIPS provides information on current and lifetime brief intermittent psychotic states, current and lifetime deterioration of functioning, and current and lifetime attenuated psychotic symptoms. The SIPS is a semistructured interview consisting of 5 items on positive symptoms, 6 items on negative symptoms, 4 items on disorganization symptoms, and 4 items on general symptoms, where each item is scored from 0 to 6 (0 = asymptomatic, 6 = severe, psychotic). The SIPS also includes a schizotypal personality disorder checklist, family history of mental illness, and global assessment of functioning ability (GAF-M) and it rules out current or past psychosis. Preliminary reliability and validity studies show that it is a useful tool for differentiating prodromal from nonprodromal subjects (interrater j = 0.81, psychotic conversion rate 54% at 12 months) [16]. Subjects were included in the vulnerability to psychosis group if (1) their lifetime prodromal symptoms reached 3 to 5 points in any of the positive symptom items (attenuated psychotic symptom state), (2) they had experienced brief intermittent psychotic states, or (3) they had a first-degree relative with a psychotic illness or schizotypal personality and recent functional deterioration defined as a loss of 30 GAF points or more for at least 1 month in the past year (genetic risk and deterioration). Lifetime psychiatric diagnoses were assessed using the Structured Clinical Interview for DSM-IV Axis I (SCID-I). Two experienced psychiatrists (MH and JK), an experienced PhD-level psychologist (TI), and a PhD student, trainee in psychiatry (TS), conducted the assessments. Interviewers participated in a 4-day SCID-I training session before the recruitment started. The clinical interview also assessed premorbid adjustment (Premorbid Adjustment Scale [PAS]) [17], quality of life (QOL) (Quality of Life Scale) [18], and schizophrenia symptoms (Positive and Negative Symptoms of Schizophrenia) [19]. Self-report scales were used to rate symptoms of psychological distress (Symptom Checklist 90 [SCL-90]) [20] and personality disorders (Personality Diagnostic Questionnaire 4+ [PDQ-4+]) [21]. Furthermore, information on alcohol use was elicited concerning (1) the past year and (2) lifetime use, with 4 alternatives being given: (1) not significant, (2) reasonable, (3) sometimes excessive, and (4) continuously excessive. Use of illicit drugs was covered by asking the subjects whether they had (1) never used drugs, (2) had tried drugs before the previous year, (3) had used drugs during the previous year, or (4) used drugs continuously. 2.1. Grouping of subjects Subjects were divided into 3 groups according to the lifetime scores on the positive symptom items in SIPS: (1) no symptoms (score 0-1), (2) minor psychiatric symptoms (score 2), and (3) subjects vulnerable to
J.A. Korkeila et al. / Comprehensive Psychiatry 46 (2005) 447– 452
psychosis (score 3-5). A score of 6 on the SIPS signified that the symptom was at the psychotic level of intensity. There were altogether 6 subjects who scored 6 on the SIPS and they all belonged to the help-seeker group. These subjects with psychosis were not included in the analyses of this study, thus, reducing the number of subjects in the helpseeker group to 29. In addition, the SCID was used to identify the presence of any diagnosis of substance abuse or dependence. The subjects were grouped into (1) a past or present SUD and (2) no SUD. 2.2. Statistical analysis The SPSS (SPSS, Inc, Chicago, Ill) for Windows 11.5 was used for statistical analyses. Cross-tables and v 2 test were used to study differences between those with any substance abuse diagnosis and those without a substance abuse diagnosis, in terms of sex, age group, and marital status. The 1-way analysis of variance test was used to test the significance of the difference of the mean GAF between those with a substance-related diagnosis and those without an SUD. Associations between having an SUD and childhood, adulthood and general sum scores on the PAS, symptoms on the SCL and PDQ, level of functioning, SIPS sum scores, and QOL were determined using Spearman bivariate correlation coefficient. Associations between having lifetime alcohol abuse and premorbid adjustment, symptoms on the SCL and PDQ, level of functioning, SIPS sum scores, and QOL were determined using Pearson bivariate correlation coefficient. Stepwise logistic regression (SLR) analysis was used to study the odds of having any SUD. Substance use disorder was used as the dependent variable, and status of vulnerability to psychosis, sex, marital status, study setting, age group, employment status, length of education, and level of functioning as independent variables. Lifetime alcohol and lifetime drug abuse were used as dependent variables in SLR analyses to study the associations between abuse and sex, age, marital status, study setting, status of vulnerability to psychosis, SIPS score, and personality disorder symptoms. 3. Results The sample comprised 90 (68%) women and 43 (32%) men, altogether 133 subjects. More than two thirds of the subjects were between 20 and 40 years of age (mean, 33 years; range, 14-63 years). According to their marital status, 55 (41%) were married, 49 (37%) unmarried, 15 (11%) lived in cohabitation, and 14 (11%) were divorced. Most (65%) of the subjects were employed, a fifth was unemployed, and 1 subject was on disability pension because of illness (sum is not 100% because of missing data). More than half (58%) of the subjects had received more than 12 years of education, 41% between 8 and 12 years, and 1 subject less than 8 years. Most (70 [53%]) of the subjects were first-degree relatives, 29 (22%) were help-seekers, and 34 (26%) were
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controls. According to lifetime SIPS, 39 (29%) of the subjects were vulnerable to psychosis, 17 (13%) had minor symptoms, and no SIPS symptoms were found in 77 (58%). In the group of first-degree relatives, 29% were vulnerable to psychosis, among the help-seekers 55%, and among the controls 9% ( P b .001). Five (15%) subjects among the controls had a mood disorder, but 85% received no diagnosis. In the help-seeker group, 20 (69%) subjects had a mood disorder, 8 (28%) subjects had an anxiety disorder, and 1 case another disorder. Among the firstdegree relatives, 22 (31%) subjects had a mood disorder, 9 (13%) had an anxiety disorder, and 3 had another disorder. A detailed description of the distribution of diagnoses other than SUD in our sample has been presented elsewhere [22]. About a tenth of the subjects had current and a fifth of the subjects a lifetime alcohol or drug abuse, with almost a tenth having both lifetime drug and alcohol abuse and nearly a third of the men either lifetime alcohol or drug abuse. Most of the subjects reported neither abuse of alcohol (79%) nor drugs (79%). Of the sample, 13% (n = 17) received a lifetime SUD diagnosis. There were also significantly more drug abusers among help-seekers (51%) than in the other study settings (at its highest among the controls, 15%) ( P b .001). The prevalence of SUD was nonsignificantly higher (18.2%) among the first-degree relatives of schizophrenic patients compared with the controls (5.9%) ( P = .1). The differences in the prevalence figures for lifetime abuse of drugs and alcohol were likewise statistically nonsignificant between the first-degree relatives and controls. Substance use disorder was significantly more common among the subjects vulnerable to psychosis (23%) compared with those who were not vulnerable to psychosis (7%) ( P = .033). Alcohol lifetime abuse was likewise significantly more common among the
Table 1 Correlations between lifetime abuse and SUD and PAS, symptom scores, and current level of functioning Variables PAS sum childhood PAS sum adulthood PAS sum general Level of functioning Total QOL score GAF Symptom scores Total SCL-111 score Total PDQ score SIPS score Current positive Past positive Negative Disorganization General score a b
SUD
Alcohol
Drug
0.032 0.08 0.232a
0.031 0.008 0.072
0.088 0.033 0.084
0.226a 0.192b
0.135 0.131
0.123 0.030
0.179b 0.239a
0.335a 0.392a
0.126 0.307a
0.206b 0.187b 0.091 0.080 0.062
0.198b 0.118 0.149 0.209b 0.202b
0.308a 0.245a 0.078 0.269a 0.142
Correlation is significant at the .01 level (2-tailed). Correlation is significant at the .05 level (2-tailed).
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Table 2 Odds ratios for an SUD, lifetime alcohol abuse, and lifetime drug abuse in the sample Variable SUD Sex Female Male Symptom status No symptoms Minor symptoms Vulnerable to psychosis Alcohol Symptom status PDQ total score Drug Sex Female Male Age Symptom status PDQ
P
OR
95% CI
1 5.14
1.63-16.24
1 3.40 6.33
0.68-17.00 1.77-22.67
b .001
1.053
1.025-1.082
.005 .002
1 5.473 0.884
1.687-17.751 0.817-0.956
b .001
1.063
1.029-1.099
.005 .017 .136 .005
OR indicates odds ratio; CI, confidence interval.
subjects vulnerable to psychosis (28%) than the controls (8%) ( P = .026), whereas there were no significant differences between the groups concerning drug abuse. There was a significant difference in the level of functioning between those with an SUD (GAF, 66.5; range, 33.0-95.0; SD = 18.3) and those without any SUD (GAF, 77.2; range, 20.0-100.0; SD = 17.1) ( P = .018). The prevalence of lifetime alcohol abuse was significantly more common among men than women. In addition, drug abusers were more commonly young and single than those without drug abuse. Substance use disorder was significantly more prevalent among men (23%) than women (8%) ( P = .015). In addition, only 29% of those with an SUD were married or living with someone compared with 47% of those without the diagnosis ( P b .05). Substance use disorder was significantly associated with total PAS and current level of functioning (QOL, GAF), as well as SCL, PDQ, and positive SIPS scores (Table 1). Lifetime alcohol abuse correlated significantly with SCL and PDQ, as well as with positive, disorganization, and general SIPS scores, whereas lifetime drug abuse correlated significantly with PDQ scores and positive and disorganization SIPS scores. In SLR analyses, abuse of alcohol was significantly associated with personality disorder symptoms; drug abuse with male sex, young age, and personality disorder symptoms; and SUD with male sex and vulnerability to psychosis (Table 2). 4. Discussion In this study, abuse of substances was common among those who had at least some psychiatric symptoms. Substance use disorder and lifetime alcohol abuse were more common among subjects vulnerable to psychosis compared
with those who were not, as was expected. Having an SUD was highly significantly associated with vulnerability to psychosis and being male. This is in keeping with the review and findings of Cantor-Graae et al [5]. Gerra and Zaimovic [7] have also emphasized that abuse of substances may be at a higher level before the onset of psychosis than afterward. In our study, patients with an SUD had more symptoms on several measures than subjects without the diagnosis. Their functional status was poorer. Thus, according to our findings, an SUD is associated with more severe psychiatric symptoms influencing everyday activities. Our finding that SUD and lifetime alcohol abuse are common among those with lifetime vulnerability to psychosis is in agreement with the hypothesis that substance abuse could precipitate or be an independent risk factor for the onset of psychosis [5]. However, caution should be applied when interpreting the temporal relationships based on our study as it is cross-sectional in design. This is clearly a weakness of our study design. Further follow-up of our sample is in progress and the significance of the findings of this report may be investigated at a later stage. We used a self-report method to estimate the extent of abuse in this sample. The wordings of the questions designed to measure abuse in our study rely on the subjects’ own perception of the excessiveness of substance use. The validity of such a method may be questioned, but selfreporting has been found to be reliable and valid in nonpsychotic subjects when, for example, honest selfreporting is encouraged [23]. The self-report method is likely to underestimate the use of alcohol and substances, but a selective bias regarding underreporting is unlikely [24]. In our sample, we used SCID as a measure of SUD and there were no SUDs among those who did not report abuse, which lends support to the reliability of the abuse data. Nevertheless, we did not have an objective index of substance abuse in our study protocol, and this is a weakness of our design. In a previous study, we found an increase in depression among those who were identified as vulnerable to psychosis [22]. It is quite possible that such people are prone to self-medicating apathy, anhedonia, insomnia, and lowered mood by using substances. However, the vulnerability and self-medication hypotheses of substance abuse need not be mutually exclusive in early psychosis. Abuse may be initiated as an effort to regulate anxiety and seek pleasurable experiences, but the effect turns out to be short-lived, and the attempt to seek relief may in itself be counterproductive. Our hypothesis of an association between a genetic link to schizophrenia and substance abuse was not supported, but, on the other hand, the hypothesis of increasing prevalence of SUD according to status of vulnerability to psychosis was supported. Moreover, having an SUD or either drug or alcohol abuse was significantly associated with current positive SIPS symptoms and symptoms of personality disorder. In addition, both types of abuse, but
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especially drug abuse, were associated with disorganization symptoms. However, according to the multivariate analyses, PDQ was the only symptom measure showing an independent association with abuse. The subjects with prodromal symptoms have more substance abuse than others in this study. Whether those identified as vulnerable to psychosis are truly at risk for psychosis, and whether our findings are pertinent to the issue of substance abuse and psychosis, is dependent on the ability of the SIPS to predict psychosis. The SIPS has been shown to be a promising tool for identifying persons at risk for psychosis [15,16]. This sample had a preponderance of women, although it is unlikely that those at risk for psychosis would be primarily women. Moreover, substance abuse is more common among men, and this may be a reason why the difference in SUD prevalence figures between first-degree relatives of schizophrenic patients and controls did not reach statistical significance. In this sample, alcohol was the most common substance abused. Until the late 1990s, the prevalence of illicit drug abuse remained relatively low in Finland. The level of use has, however, increased markedly during the last 5 years. In 2000, 1% of Finnish men and 0.4% of women had smoked cannabis during the previous month. In 2002, the corresponding figures were 2.8% and 1.3%. According to local estimates, in 2001, 1000 to 1500 persons were regularly injecting drugs, amphetamine, or opiates in Turku and its surroundings [25]. Our sample was collected at the end of the 1990s. The prevalence figures for drug use in this sample may thus be an underestimate of the situation early in the new millennium. The most commonly abused illicit drugs among our subjects were cannabis and amphetamine. However, we were unable to provide prevalence figures for the exact use of certain drugs in our analyses. 4.1. Conclusion This study supports the notion of an increase in substance abuse already among those who are vulnerable to psychosis. It is likely that for a substantial proportion of those who eventually become psychotic, substance abuse starts at an early phase of the disorder. Notwithstanding, a straightforward explanation for the development of the dual diagnoses is unlikely. Among the subjects vulnerable to psychosis, young men especially may be at risk for substance abuse, a fact that may complicate the identification of an evolving psychosis and, ultimately, impair the adequacy of the treatment.
Acknowledgments This study was supported financially by the JanssenCilag Company. The authors thank the city of Turku, the University of Turku Foundation, and the Turku University Central Hospital.
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Substance abuse and related diagnoses in early psychosis Jyrki A. Korkeilaa,T, Tanja Svirskisb, Markus Heinimaab, Terja Ristkarib, Jukka Huttunenb, Tuula Ilonenb, Tom McGlashanc, Raimo K.R. Salokangasa,d a
Department of Psychiatry, Turku City Hospital and Turku University Central Hospital, University of Turku, 20700 Turku, Finland b Department of Psychiatry, University of Turku, 20700 Turku, Finland c Department of Psychiatry, University of Yale, New Haven, CT, USA d Department of Psychiatry, Psychiatric Clinic, Turku University Central Hospital, 20540 Turku, Finland
Abstract Substance abuse seems to be common among those with early signs of evolving psychosis. This article seeks to determine the prevalence of substance abuse and substance use disorders (SUDs) and the association of abuse and SUD with vulnerability psychosis among a sample of first-degree relatives of schizophrenic patients (n = 70), help-seekers (n = 29), and control subjects (n = 34). The Structured Interview for Prodromal Symptoms (SIPS) 1.0 was used to define the vulnerability status and the Structured Clinical Interview for DSM-IV Axis I to diagnose the subjects. Data on various other measures, including premorbid adjustment, personality disorder symptoms, psychological distress, and abuse of substances, were collected. Those who were identified as vulnerable to psychosis reported significantly more lifetime alcohol abuse and had more commonly an SUD than controls. Substance use disorder, as well as alcohol and drug abuse, correlated significantly with personality disorder symptoms and current positive SIPS score and both types of abuse also with disorganization SIPS score. The odds ratio for having an SUD among those vulnerable to psychosis was 6.33 (95% confidence interval, 1.77-22.73). Early psychosis and substance abuse frequently occur together. D 2005 Elsevier Inc. All rights reserved.
1. Introduction Of 4 patients with schizophrenia, 3 presented with prodromal symptoms before the onset of psychosis [1]. The theoretical basis for prodromal states rests on the vulnerability-stress model of schizophrenia [2] that views vulnerability and the psychotic episode in a trait-like relation, whereas psychotic symptoms are considered to be provoked by stressful life events. Respectively, prodromal symptoms can be considered a sign of increased vulnerability to psychosis. Substance abuse and schizophrenia both originate in adolescence and young adulthood. Young subjects with schizophrenia have been found to have a 3 times higher prevalence of alcohol and substance abuse disorders than the corresponding age group in the US general population. In addition, 47% of subjects with schizophrenia had substance abuse, past or present, compared with 13.5% of the general population [3]. On the other hand, a recent study T Corresponding author. Tel.: +358 40 5514249; fax: +358 269 2528. E-mail address: [email protected] (J.A. Korkeila). 0010-440X/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.comppsych.2005.03.008
also found a high rate of coexisting psychiatric, especially mood and disruptive behavior, disorders among adolescents with a substance use disorder (SUD) [4]. The studies done since 1990 have found a 40% to 60% range of prevalence rates of abuse in schizophrenia with male sex and young age as primary correlates [5]. However, in their comprehensive review, Phillips and Johnson [6] have stated that there is considerable country-to-country variation in the prevalence and patterns of abuse among patients with schizophrenia and that these findings do not take into account confounding sociodemographic factors. There are studies showing that substance abuse may be common also in early psychosis [5,7,8] and that the abuse may even be more common preceding psychosis than immediately after the onset of psychosis [7,8]. There are several studies addressing the question of temporal relations between substance abuse and onset of psychosis. Some studies have reported an increased risk of schizophrenia in adulthood after the use of cannabis in adolescence [9,10]. Other studies have also reported that abuse has preceded the onset of first contact because of psychotic symptoms [3,5]. However, there are also studies
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that have found that abuse does not precede the onset of psychotic symptoms [5]. In a large cohort (Age, Beginning, Course study) of first-episode schizophrenic patients, Hambrecht and H7fner [11] found a diversity of temporal associations between onset of psychosis and abuse. A later analysis of the same sample revealed that about half of patients with alcohol abuse and less than two thirds of patients with drug abuse began the use before the first sign of the illness [12]. Thus, unidirectional causality seems unlikely in the light of the Age, Beginning, Course study. This article seeks to determine the prevalence and clinical correlates of substance abuse and SUD among subjects with and without vulnerability to psychosis in a sample of first-degree relatives, help-seekers, and controls. 2. Sample and methods Subjects were collected from the city of Turku and the Southwest Finland Health Care District with a total population of 430 000. The subjects represented various settings. The sampling procedure has been described elsewhere [13]. The subjects of the present study are grouped here into 3 groups according to the study setting and their help-seeking behavior: (1) first-degree relatives, (2) help-seekers, and (3) control subjects. Initially, the first-degree relatives were the target group for finding subjects vulnerable to psychosis because of an increased genetic risk for psychosis. First-degree relative group (n = 70). At the beginning, 138 (age, 14- 40 years) first-degree relatives of patients with schizophrenia and of patients with other nonaffective psychosis, and first-degree relatives of adolescent patients with severe mental illness (with psychotic or psychotic-like symptoms) were screened by a screening instrument, the PROD screen [14], developed by the project. Of these firstdegree relatives, 54 consecutive, screen-positive subjects were investigated. In addition, 20 voluntary first-degree relatives (age, 14 -40 years) of psychiatric patients from local organization of relatives of psychiatric patients were screened, and 16 screen-positive subjects were investigated. Help-seekers (n = 35). Patients (age, 18-40 years; n = 60) making their first-ever contact during the year 1999 with the Turku Community Mental Health Centre were screened using the PROD screen, 30 of whom were screened positive and thus included in the study. In addition, adolescents (n = 15; age, 14-22 years) consecutively contacting the adolescent psychiatric unit were screened using the PROD screen, and 5 screen-positive subjects were included. Controls (n = 34). Finally, randomly selected subjects (age, 14-40 years) from the local population register were contacted and recruited for more detailed investigation. All study subjects gave their written informed consent concerning the study. In the case of minors, their guardians also gave their informed consent. The ethical committee of Turku University and Turku University Central Hospital approved the study protocol.
Symptoms of vulnerability to psychosis were assessed using the Structured Interview for Prodromal Symptoms (SIPS) 1.0 developed by Miller et al [15]. The SIPS provides information on current and lifetime brief intermittent psychotic states, current and lifetime deterioration of functioning, and current and lifetime attenuated psychotic symptoms. The SIPS is a semistructured interview consisting of 5 items on positive symptoms, 6 items on negative symptoms, 4 items on disorganization symptoms, and 4 items on general symptoms, where each item is scored from 0 to 6 (0 = asymptomatic, 6 = severe, psychotic). The SIPS also includes a schizotypal personality disorder checklist, family history of mental illness, and global assessment of functioning ability (GAF-M) and it rules out current or past psychosis. Preliminary reliability and validity studies show that it is a useful tool for differentiating prodromal from nonprodromal subjects (interrater j = 0.81, psychotic conversion rate 54% at 12 months) [16]. Subjects were included in the vulnerability to psychosis group if (1) their lifetime prodromal symptoms reached 3 to 5 points in any of the positive symptom items (attenuated psychotic symptom state), (2) they had experienced brief intermittent psychotic states, or (3) they had a first-degree relative with a psychotic illness or schizotypal personality and recent functional deterioration defined as a loss of 30 GAF points or more for at least 1 month in the past year (genetic risk and deterioration). Lifetime psychiatric diagnoses were assessed using the Structured Clinical Interview for DSM-IV Axis I (SCID-I). Two experienced psychiatrists (MH and JK), an experienced PhD-level psychologist (TI), and a PhD student, trainee in psychiatry (TS), conducted the assessments. Interviewers participated in a 4-day SCID-I training session before the recruitment started. The clinical interview also assessed premorbid adjustment (Premorbid Adjustment Scale [PAS]) [17], quality of life (QOL) (Quality of Life Scale) [18], and schizophrenia symptoms (Positive and Negative Symptoms of Schizophrenia) [19]. Self-report scales were used to rate symptoms of psychological distress (Symptom Checklist 90 [SCL-90]) [20] and personality disorders (Personality Diagnostic Questionnaire 4+ [PDQ-4+]) [21]. Furthermore, information on alcohol use was elicited concerning (1) the past year and (2) lifetime use, with 4 alternatives being given: (1) not significant, (2) reasonable, (3) sometimes excessive, and (4) continuously excessive. Use of illicit drugs was covered by asking the subjects whether they had (1) never used drugs, (2) had tried drugs before the previous year, (3) had used drugs during the previous year, or (4) used drugs continuously. 2.1. Grouping of subjects Subjects were divided into 3 groups according to the lifetime scores on the positive symptom items in SIPS: (1) no symptoms (score 0-1), (2) minor psychiatric symptoms (score 2), and (3) subjects vulnerable to
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psychosis (score 3-5). A score of 6 on the SIPS signified that the symptom was at the psychotic level of intensity. There were altogether 6 subjects who scored 6 on the SIPS and they all belonged to the help-seeker group. These subjects with psychosis were not included in the analyses of this study, thus, reducing the number of subjects in the helpseeker group to 29. In addition, the SCID was used to identify the presence of any diagnosis of substance abuse or dependence. The subjects were grouped into (1) a past or present SUD and (2) no SUD. 2.2. Statistical analysis The SPSS (SPSS, Inc, Chicago, Ill) for Windows 11.5 was used for statistical analyses. Cross-tables and v 2 test were used to study differences between those with any substance abuse diagnosis and those without a substance abuse diagnosis, in terms of sex, age group, and marital status. The 1-way analysis of variance test was used to test the significance of the difference of the mean GAF between those with a substance-related diagnosis and those without an SUD. Associations between having an SUD and childhood, adulthood and general sum scores on the PAS, symptoms on the SCL and PDQ, level of functioning, SIPS sum scores, and QOL were determined using Spearman bivariate correlation coefficient. Associations between having lifetime alcohol abuse and premorbid adjustment, symptoms on the SCL and PDQ, level of functioning, SIPS sum scores, and QOL were determined using Pearson bivariate correlation coefficient. Stepwise logistic regression (SLR) analysis was used to study the odds of having any SUD. Substance use disorder was used as the dependent variable, and status of vulnerability to psychosis, sex, marital status, study setting, age group, employment status, length of education, and level of functioning as independent variables. Lifetime alcohol and lifetime drug abuse were used as dependent variables in SLR analyses to study the associations between abuse and sex, age, marital status, study setting, status of vulnerability to psychosis, SIPS score, and personality disorder symptoms. 3. Results The sample comprised 90 (68%) women and 43 (32%) men, altogether 133 subjects. More than two thirds of the subjects were between 20 and 40 years of age (mean, 33 years; range, 14-63 years). According to their marital status, 55 (41%) were married, 49 (37%) unmarried, 15 (11%) lived in cohabitation, and 14 (11%) were divorced. Most (65%) of the subjects were employed, a fifth was unemployed, and 1 subject was on disability pension because of illness (sum is not 100% because of missing data). More than half (58%) of the subjects had received more than 12 years of education, 41% between 8 and 12 years, and 1 subject less than 8 years. Most (70 [53%]) of the subjects were first-degree relatives, 29 (22%) were help-seekers, and 34 (26%) were
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controls. According to lifetime SIPS, 39 (29%) of the subjects were vulnerable to psychosis, 17 (13%) had minor symptoms, and no SIPS symptoms were found in 77 (58%). In the group of first-degree relatives, 29% were vulnerable to psychosis, among the help-seekers 55%, and among the controls 9% ( P b .001). Five (15%) subjects among the controls had a mood disorder, but 85% received no diagnosis. In the help-seeker group, 20 (69%) subjects had a mood disorder, 8 (28%) subjects had an anxiety disorder, and 1 case another disorder. Among the firstdegree relatives, 22 (31%) subjects had a mood disorder, 9 (13%) had an anxiety disorder, and 3 had another disorder. A detailed description of the distribution of diagnoses other than SUD in our sample has been presented elsewhere [22]. About a tenth of the subjects had current and a fifth of the subjects a lifetime alcohol or drug abuse, with almost a tenth having both lifetime drug and alcohol abuse and nearly a third of the men either lifetime alcohol or drug abuse. Most of the subjects reported neither abuse of alcohol (79%) nor drugs (79%). Of the sample, 13% (n = 17) received a lifetime SUD diagnosis. There were also significantly more drug abusers among help-seekers (51%) than in the other study settings (at its highest among the controls, 15%) ( P b .001). The prevalence of SUD was nonsignificantly higher (18.2%) among the first-degree relatives of schizophrenic patients compared with the controls (5.9%) ( P = .1). The differences in the prevalence figures for lifetime abuse of drugs and alcohol were likewise statistically nonsignificant between the first-degree relatives and controls. Substance use disorder was significantly more common among the subjects vulnerable to psychosis (23%) compared with those who were not vulnerable to psychosis (7%) ( P = .033). Alcohol lifetime abuse was likewise significantly more common among the
Table 1 Correlations between lifetime abuse and SUD and PAS, symptom scores, and current level of functioning Variables PAS sum childhood PAS sum adulthood PAS sum general Level of functioning Total QOL score GAF Symptom scores Total SCL-111 score Total PDQ score SIPS score Current positive Past positive Negative Disorganization General score a b
SUD
Alcohol
Drug
0.032 0.08 0.232a
0.031 0.008 0.072
0.088 0.033 0.084
0.226a 0.192b
0.135 0.131
0.123 0.030
0.179b 0.239a
0.335a 0.392a
0.126 0.307a
0.206b 0.187b 0.091 0.080 0.062
0.198b 0.118 0.149 0.209b 0.202b
0.308a 0.245a 0.078 0.269a 0.142
Correlation is significant at the .01 level (2-tailed). Correlation is significant at the .05 level (2-tailed).
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Table 2 Odds ratios for an SUD, lifetime alcohol abuse, and lifetime drug abuse in the sample Variable SUD Sex Female Male Symptom status No symptoms Minor symptoms Vulnerable to psychosis Alcohol Symptom status PDQ total score Drug Sex Female Male Age Symptom status PDQ
P
OR
95% CI
1 5.14
1.63-16.24
1 3.40 6.33
0.68-17.00 1.77-22.67
b .001
1.053
1.025-1.082
.005 .002
1 5.473 0.884
1.687-17.751 0.817-0.956
b .001
1.063
1.029-1.099
.005 .017 .136 .005
OR indicates odds ratio; CI, confidence interval.
subjects vulnerable to psychosis (28%) than the controls (8%) ( P = .026), whereas there were no significant differences between the groups concerning drug abuse. There was a significant difference in the level of functioning between those with an SUD (GAF, 66.5; range, 33.0-95.0; SD = 18.3) and those without any SUD (GAF, 77.2; range, 20.0-100.0; SD = 17.1) ( P = .018). The prevalence of lifetime alcohol abuse was significantly more common among men than women. In addition, drug abusers were more commonly young and single than those without drug abuse. Substance use disorder was significantly more prevalent among men (23%) than women (8%) ( P = .015). In addition, only 29% of those with an SUD were married or living with someone compared with 47% of those without the diagnosis ( P b .05). Substance use disorder was significantly associated with total PAS and current level of functioning (QOL, GAF), as well as SCL, PDQ, and positive SIPS scores (Table 1). Lifetime alcohol abuse correlated significantly with SCL and PDQ, as well as with positive, disorganization, and general SIPS scores, whereas lifetime drug abuse correlated significantly with PDQ scores and positive and disorganization SIPS scores. In SLR analyses, abuse of alcohol was significantly associated with personality disorder symptoms; drug abuse with male sex, young age, and personality disorder symptoms; and SUD with male sex and vulnerability to psychosis (Table 2). 4. Discussion In this study, abuse of substances was common among those who had at least some psychiatric symptoms. Substance use disorder and lifetime alcohol abuse were more common among subjects vulnerable to psychosis compared
with those who were not, as was expected. Having an SUD was highly significantly associated with vulnerability to psychosis and being male. This is in keeping with the review and findings of Cantor-Graae et al [5]. Gerra and Zaimovic [7] have also emphasized that abuse of substances may be at a higher level before the onset of psychosis than afterward. In our study, patients with an SUD had more symptoms on several measures than subjects without the diagnosis. Their functional status was poorer. Thus, according to our findings, an SUD is associated with more severe psychiatric symptoms influencing everyday activities. Our finding that SUD and lifetime alcohol abuse are common among those with lifetime vulnerability to psychosis is in agreement with the hypothesis that substance abuse could precipitate or be an independent risk factor for the onset of psychosis [5]. However, caution should be applied when interpreting the temporal relationships based on our study as it is cross-sectional in design. This is clearly a weakness of our study design. Further follow-up of our sample is in progress and the significance of the findings of this report may be investigated at a later stage. We used a self-report method to estimate the extent of abuse in this sample. The wordings of the questions designed to measure abuse in our study rely on the subjects’ own perception of the excessiveness of substance use. The validity of such a method may be questioned, but selfreporting has been found to be reliable and valid in nonpsychotic subjects when, for example, honest selfreporting is encouraged [23]. The self-report method is likely to underestimate the use of alcohol and substances, but a selective bias regarding underreporting is unlikely [24]. In our sample, we used SCID as a measure of SUD and there were no SUDs among those who did not report abuse, which lends support to the reliability of the abuse data. Nevertheless, we did not have an objective index of substance abuse in our study protocol, and this is a weakness of our design. In a previous study, we found an increase in depression among those who were identified as vulnerable to psychosis [22]. It is quite possible that such people are prone to self-medicating apathy, anhedonia, insomnia, and lowered mood by using substances. However, the vulnerability and self-medication hypotheses of substance abuse need not be mutually exclusive in early psychosis. Abuse may be initiated as an effort to regulate anxiety and seek pleasurable experiences, but the effect turns out to be short-lived, and the attempt to seek relief may in itself be counterproductive. Our hypothesis of an association between a genetic link to schizophrenia and substance abuse was not supported, but, on the other hand, the hypothesis of increasing prevalence of SUD according to status of vulnerability to psychosis was supported. Moreover, having an SUD or either drug or alcohol abuse was significantly associated with current positive SIPS symptoms and symptoms of personality disorder. In addition, both types of abuse, but
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especially drug abuse, were associated with disorganization symptoms. However, according to the multivariate analyses, PDQ was the only symptom measure showing an independent association with abuse. The subjects with prodromal symptoms have more substance abuse than others in this study. Whether those identified as vulnerable to psychosis are truly at risk for psychosis, and whether our findings are pertinent to the issue of substance abuse and psychosis, is dependent on the ability of the SIPS to predict psychosis. The SIPS has been shown to be a promising tool for identifying persons at risk for psychosis [15,16]. This sample had a preponderance of women, although it is unlikely that those at risk for psychosis would be primarily women. Moreover, substance abuse is more common among men, and this may be a reason why the difference in SUD prevalence figures between first-degree relatives of schizophrenic patients and controls did not reach statistical significance. In this sample, alcohol was the most common substance abused. Until the late 1990s, the prevalence of illicit drug abuse remained relatively low in Finland. The level of use has, however, increased markedly during the last 5 years. In 2000, 1% of Finnish men and 0.4% of women had smoked cannabis during the previous month. In 2002, the corresponding figures were 2.8% and 1.3%. According to local estimates, in 2001, 1000 to 1500 persons were regularly injecting drugs, amphetamine, or opiates in Turku and its surroundings [25]. Our sample was collected at the end of the 1990s. The prevalence figures for drug use in this sample may thus be an underestimate of the situation early in the new millennium. The most commonly abused illicit drugs among our subjects were cannabis and amphetamine. However, we were unable to provide prevalence figures for the exact use of certain drugs in our analyses. 4.1. Conclusion This study supports the notion of an increase in substance abuse already among those who are vulnerable to psychosis. It is likely that for a substantial proportion of those who eventually become psychotic, substance abuse starts at an early phase of the disorder. Notwithstanding, a straightforward explanation for the development of the dual diagnoses is unlikely. Among the subjects vulnerable to psychosis, young men especially may be at risk for substance abuse, a fact that may complicate the identification of an evolving psychosis and, ultimately, impair the adequacy of the treatment.
Acknowledgments This study was supported financially by the JanssenCilag Company. The authors thank the city of Turku, the University of Turku Foundation, and the Turku University Central Hospital.
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