Typologies of alcohol use disorders among men with schizophrenic disorders

Addictive Behaviors 32 (2007) 1146 – 1163

Typologies of alcohol use disorders among men with schizophrenic disorders Åsa Eriksson a,⁎, Anders Tengström a , Sheilagh Hodgins a,b a

b

Department of Clinical Neuroscience, Section of Alcohol and Drug Dependence Research, Karolinska Institute, Box 500, S-112 81 Stockholm, Sweden Department of Forensic Mental Health Science, Institute of Psychiatry, King's College London, Box PO23, De Crespigny Park, Denmark Hill, London SE5 8AF, United Kingdom

Abstract Alcohol use disorders are common among persons with schizophrenia and are associated with a vast array of negative consequences: criminality, poor compliance with treatment, and reoccurrence of acute episodes of psychosis. In samples of non-mentally disordered individuals, typologies of alcohol use disorders have been shown to be useful in furthering understanding of etiology and of effective treatments. Such typologies, however, have not previously been examined in individuals with schizophrenia. The main objective of the study was to validate four unidimensional typologies and the multi-dimensional Type I/II – Type A/B typology in a sample of men with schizophrenic disorders and alcohol use disorders. All uni-dimensional typologies showed at least some degree of concurrent validity. The Type I/II – Type A/B typology was successfully replicated with fair concurrent validity across the domains of pre-morbid risk factors and drug use, but not for the domains of criminality, illness, or personality. The predictive validity was poor for all typologies. The results provide evidence for the heterogeneity of alcohol use disorders among men with schizophrenia. © 2006 Elsevier Ltd. All rights reserved. Keywords: Schizophrenia; Alcoholism; Dual diagnosis; Typologies

⁎ Corresponding author. Present address: Department of Forensic Psychiatry, National Board of Forensic Medicine, Box 4044, S-141 44 Huddinge, Sweden. Tel.: +46 8 607 15 17; fax: +46 8 711 71 41. E-mail address: [email protected] (Å. Eriksson). 0306-4603/$ - see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.addbeh.2006.08.003

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1. Introduction The prevalence of alcohol use disorders is higher among persons with schizophrenia than in the general population (Cantor-Graae, Nordström, & McNeil, 2001; Fowler, Carr, Carter, & Lewin, 1998; Regier et al., 1990; Van Mastrigt, Addington, & Addington, 2004). Among persons with schizophrenia, alcohol is the most common substance of abuse (Addington & Duchack, 1997; Drake & Mueser, 2002; Fowler et al., 1998; Kavanagh, McGrath, Saunders, Dore, & Clark, 2002; Margolese, Malchy, Negrete, Tempier, & Gill, 2004; Van Mastrigt et al., 2004). Among persons with schizophrenia, alcohol use disorders are associated with an increased risk of committing violent crimes (Räsänen et al., 1998) and with reduced responsiveness to treatment. Persons with schizophrenia and alcohol and/or drug disorders comply poorly with treatment and negative outcomes are common (Dixon, 1999; Kavanagh et al., 2002; Phillips & Johnson, 2001; Rosenthal, 1998). Alcohol dependence has been found to be specifically associated with the reoccurrence of acute episodes of psychosis (Gerding, Labbate, Measom, Santos, & Arana, 1999). 1.1. Typologies of alcohol use disorders among non-mentally disordered individuals It is well-established that individuals with alcohol use disorders constitute a heterogeneous population (Babor et al., 1992). This heterogeneity has led to an interest in the identification of subtypes of individuals with an alcohol use disorder in order to understand the etiology and pathophysiology of alcohol misuse (Basu, Ball, Feinn, Gelernter, & Kranzler, 2004; Penick et al., 1999), treatment response, and prevention (Babor, Webb, Burleson, & Kaminer, 2002; Mueser, Yarnold, Rosenberg, Swett, Miles, & Hill, 2000). 1.1.1. Uni-dimensional typologies The most common uni-dimensional typology is based on the distinction between alcohol abuse and alcohol dependence (American Psychiatric Association, 1994). In many clinical settings, this classification is made routinely. Another well-known uni-dimensional typology is based on the presence or absence of antisocial personality traits (Bahlmann, Preuss, & Soyka, 2002; Holdcraft, Iacono, & McGue, 1998; Zucker, Ellis, & Fitzgerald, 1994). A typology based on age of onset of alcohol use disorder has been commonly used in research (Farren & Dinan, 1996; Irwin, Schuckit, & Smith, 1990; Johnson, Cloninger, Roache, Bordnick, & Ruiz, 2000; Lykouras, Moussas, & Botsis, 2004; Watson, Hancock, Gearhart, Malovrh, Mendez, & Raden, 1997). Subtyping persons with alcohol use disorders according to their family history of alcohol use disorders represents yet another approach (Hasin, Paykin, & Endicott, 2001; Hill & Yuan, 1999; Lieb, Merikangas, Hofler, Pfister, Isensee, & Wittchen, 2002; Penick, Powell, Bingham, Liskow, Miller, & Read, 1987). 1.1.2. Multidimensional typologies The most studied multidimensional typologies are the Type I/II typology (Cloninger, Bohman, & Sigvardsson, 1981, Cloninger, Sigvardsson, & Bohman, 1996) and the Type A/B typology (Babor et al., 1992). The two typologies share many characteristics and will be referred to as the Type I/II – Type A/B typology throughout. Type I/A drinkers are characterized by fewer childhood risk factors, later onset of abuse, fewer alcohol-related consequences, and less severe psychopathology. By contrast, Type II/B drinkers display an early onset of abuse, more serious consequences of drinking, and a poorer prognosis. The two subtypes of the Type I/II – Type A/B typology differ as to personality. Both Cloninger et al.

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(1996) and Babor et al. (1992) described Type II/B drinkers as impulsive and novelty seeking. Cloninger et al., however, suggested that Type I drinkers drink to relieve anxiety, while Babor et al. viewed Type A drinkers as more conservative, more controlled, and more relaxed as compared to Type B drinkers. It has been proposed that Type I/A drinkers may be more prevalent than Type II/B drinkers (Ball, Jaffe, CouseArtus, Rounsaville, & O'Malley, 2000; Cloninger et al., 1981; Schuckit et al., 1995) although the original study by Babor et al. (1992) yielded two equally large subgroups (for an overview, see Carpenter & Hasin, 2001). 1.2. Validation of typologies Penick et al. (1999) evaluated eleven typologies and concluded that all had at least some clinical validity and that none was superior to the others. Basu et al. (2004) compared four typologies and Epstein, Labouvie, McCardy, Jensen, and Hayaki (2002) examined four others. Both groups concluded that the Type A/B typology had better validity than the other typologies. While Epstein et al. (2002) restricted their evaluation to construct validity, Penick et al. (1999) and Basu et al. (2004) used external variables to investigate concurrent validity, i.e. family risk factors, personality measures, functioning, and predictive validity, e.g., abstinence. 1.3. Aims of the study Similar to what has been observed among non-mentally disordered individuals with alcohol use disorders, individuals with schizophrenia and alcohol use disorders may constitute a heterogeneous population. In samples of non-mentally disordered individuals typologies have been shown to be useful in examining this heterogeneity. Such typologies, however, have not previously been examined in samples of individuals with schizophrenia. To explore whether typologies would be useful in research and clinical practice among individuals with schizophrenia, a first step would be to validate typologies shown to be valid in samples of non-mentally disordered individuals. The aim of this study was to validate four uni-dimensional typologies: 1) alcohol abuse/dependence; 2) presence/absence of antisocial personality disorder (ASPD); 3) early/late age of onset; 4) presence/absence of a parent with substance abuse; and the multi-dimensional Type I/II – Type A/B typology in a sample of 139 men with schizophrenic disorders and life-time diagnoses of alcohol abuse and/or dependence. The study also explored whether a typology with more than two subtypes would be valid and clinically useful in this population.

2. Method 2.1. Participants The sample consisted of 139 men with schizophrenic disorders (schizophrenia, n = 110; schizoaffective disorder, n = 29) and a lifetime diagnosis of an alcohol use disorder. The participants were recruited at discharge from forensic hospitals (n = 88) and general psychiatric hospitals (n = 51) in four sites in Canada, Finland, Germany, and Sweden. The age of the participants ranged from 20 to 70, with a mean of 39.7 years (S.D. = 11.3). Fifty percent of the participants met criteria for alcohol abuse and

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50% were diagnosed with alcohol dependence. More than half of the participants (54%) also met criteria for a drug use disorder. Forty-one of the participants (29.5%) met the criteria for antisocial personality disorder (ASPD). The mean score on the Global Assessment of Function Scale (GAF) was 49.7 (S.D. = 12.6). 2.2. Instruments 2.2.1. Structured Clinical Interview for DSM-IV (SCID; Spitzer, Williams, Gibbon, & First, 1990a; Spitzer, Williams, Gibbon, & First, 1990b) Diagnoses were made using the SCID I and II by experienced psychiatrists who were trained and examined by the authors of the instrument. Diagnoses were based on information from the participants, family members, treatment staff, and complete records of psychiatric and social care. Information on the age of onset of the alcohol use disorder was obtained from the SCID interview. Inter-rater reliabilities were measured by a second assessment on 15% of the participants and was excellent for schizophrenia spectrum diagnosis versus other diagnoses, κ = 1.0 (n = 35) and good for alcohol abuse or dependence, κ = .79 (n = 35). 2.2.2. Positive and Negative Symptom Scale (PANSS; Kay, Fiszbein, & Opler, 1987) Positive and negative symptoms of schizophrenia were assessed with PANSS, a standardized and validated instrument. The assessments were conducted by the psychiatrists who were trained to use the instrument. The positive and negative scales each include seven items rated 1 (absent) to 7 (extreme). The inter-rater reliability for the instrument was better for the positive scale as compared to the negative scale (ICC = .71; ICC = .52, respectively, n = 34). 2.2.3. Psychopathy Checklist (PCL-R; Hare, 1991) Psychopathy is a psychological and behavioral disorder characterized by deficient affective and interpersonal traits, and antisocial behavior (Cooke & Michie, 1999). Psychopathic traits were assessed with the PCL-R, an instrument based on multiple sources of information and including twenty items, each rated 0 to 2. The instrument has been shown to be valid among individuals with schizophrenia (Tengström & Hodgins, 2002). The assessments were made by the psychiatrists in collaboration with the research assistants who had done the interviews with the patients and the collaterals and who had read all the files. The psychiatrists had been trained and examined by the author of the instrument. A second measurement on 15% of the participants revealed a very good inter-rater reliability (ICC = .94, n = 35). 2.2.4. Neo Personality Inventory Revised (Neo-PI-R; Costa & McCrae, 1992) All participants completed the NEO-PI-R self-report form to assess personality traits. The instrument is based on the Five Factor model of personality. It comprises 243 items, each rated on a 5-point scale. The results are summarized into five factors, each consisting of six facet scales for more detailed analysis. From the factors, the facets of anxiety, depression, impulsiveness, and excitement-seeking were selected. NEO-PI-R has previously been used in samples of individuals with schizophrenia with consistent results (Bagby et al., 1997; Kentros et al., 1997). Generally the standard procedure of the instrument was followed. If needed, the research assistants read the questions to the participant or explained the meaning.

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2.2.5. Pre-morbid risk factors Information on mental disorders, substance abuse, and criminality among parents and siblings was collected from the participant, a family member, and from records as was information on childhood attention/hyperactivity problems and depression/anxiety. 2.2.6. Criminality Information on criminality was extracted from official criminal files. The term conviction is used to include judgments of non-responsibility due to a mental disorder. Violent offences were defined as all offences causing physical harm, threat of violence or harassment, sexual offence, arson, robbery, forcible confinement, and illegal possession of firearms or explosives. All other offences were defined as nonviolent. 2.2.7. Follow-up measures Information on alcohol and drug use and medication non-compliance was collected from participants at four interviews conducted at six month intervals during the two-year follow-up period. At each interview, the protocol developed by the MacArthur Risk Assessment Project was used to interview participants and an informant with whom they were in regular contact. At each interview session, it was asked if the patient had used alcohol and/or drugs during the last week, if the patient had been non-compliant with medication, or had committed an aggressive behavior during the six month period since the last interview session. Aggressive behaviors included minor acts, e.g., pushing someone, as well as major acts, e.g., rape and threat with a gun (for methodological details, see Steadman et al., 1998). Participants knew that all information collected for the research project remained confidential and was not communicated to the clinical team caring for the patient. 2.3. Procedure Data for the study were available from the Comparative study of the Prevention of Crime by Mentally Ill Persons, a follow-up study on forensic and general psychiatric patients, conducted in Canada, Finland, Germany, and Sweden. The project is described in detail elsewhere (Hodgins et al., in press). The participants were recruited into the project between 1998 and 2002. Every effort was made to invite all persons with a major mental disorder (schizophrenia, schizo-affective disorder, bipolar disorder, major depression, other non-toxic psychoses) about to be discharged from the forensic hospitals within the catchment area to participate in the study. The patients gave their written informed consent to participate, authorized access to medical and criminal records, and also named a family member to provide information on them. After consent was given, a structured diagnostic interview was completed. If a diagnosis of a major mental disorder was confirmed, the patient was included into the study. Persons discharged from general psychiatric hospitals were matched with the forensic sample on diagnosis, sex, and age. The procedure of inclusion into the study was the same for persons discharged from general psychiatric hospitals as for the persons discharged from forensic hospitals. Out of the 475 persons originally invited to participate, 308 agreed. Analyses revealed that the refusal rate was higher among persons discharged from general psychiatric hospitals than among persons discharged from forensic hospitals (42.2%; 29.5%, respectively), χ 2 (1, N = 475) = 8.212, p = .01. The present study included all male participants with a schizophrenia spectrum disorder and an alcohol use

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disorder (n = 139) enrolled in the project at the time the analyses were undertaken. Females were not included due to their low number (n = 8). An extensive battery of structured interviews and tests were conducted in the two weeks preceding discharge. After discharge, the participants were interviewed and re-assessed four times at six monthly intervals. Follow-up data were also based on multiple informants. At each follow-up interview, the participants provided the name of a collateral who had been in frequent contact with them during the last six months. 2.4. Classification of participants into typologies 2.4.1. Alcohol abuse/dependence The participants who had a DSM-IV diagnosis of alcohol abuse were assigned to one subtype (alcohol abuse, n = 65) while the participants with a DSM-IV diagnosis of alcohol dependence were assigned to the other subtype (alcohol dependence, n = 65). 2.4.2. Presence/absence of ASPD The participants were assigned to subtypes on the basis of a presence or absence of a diagnosis of ASPD (ASPD, n = 41, no ASPD, n = 98). The diagnosis of ASPD requires the presence of conduct disorder before age 15. 2.4.3. Early/late age of onset The participants were assigned to subtypes by age of onset of alcohol abuse or dependence (b 18 years, n = 45, ≥ 18 years, n = 65). This cut-off may seem low. In previous research on typologies, the age of 25 has been commonly used (Gilligan, Reich, & Cloninger, 1988; Johnson et al., 2000). It has been suggested, however, that adolescent-onset (before the age of 18) substance use disorders may constitute a distinct subtype as compared to adult-onset substance use disorders (Clark, Kirisci, & Tarter, 1998). 2.4.4. Presence/absence of parent with substance abuse The participants who had at least one parent with substance abuse were assigned to one subtype (presence of parent with substance abuse, n = 56), while those participants with no parents with substance abuse were assigned to the other subtype (absence of parent with substance abuse, n = 67). 2.4.5. The Type I/II – Type A/B typology To establish the multi-dimensional typology, several decisions had to be taken. The Type I/II typology was originally based on results from a Swedish adoption study (Cloninger et al., 1981). To replicate the typology, different methods of sub-typing have been used by different research groups. Generally, a classification schema is used. There are, however, inconsistencies across studies as to the measures used (Epstein et al., 2002). A drawback of the method is that some individuals may not be classified into either subtype (Anthenelli, Smith, Irwin, & Schuckit, 1994; Epstein et al., 2002). The Type A/B typology was originally established with k-means cluster analysis based on 17 variables (Babor et al., 1992). It has been replicated in later studies with the number of variables ranging between 5 and 17 and with some differences in the ways the variables were operationalized (Ball et al., 2000; Schuckit et al., 1995). The method of classification used in this study represents a compromise between the methods previously employed to classify subjects according to the Type I/II typology and the Type A/B typology.

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To avoid non-classified participants, the method of choice for this study was k-means cluster analysis. However, we did not have access to the same 17 variables as used in the original study, and consequently only those variables considered to reflect the most important characteristics of both the Type I/II typology and the Type A/B typology were entered into the analysis: severity of alcohol abuse or dependence; age of onset of alcohol abuse or dependence; number of conduct disorder symptoms (before age 15); and proportion of first degree relatives with a history of substance abuse. To establish the severity of abuse or dependence, the four questions from the SCID alcohol abuse module and seven questions from the SCID alcohol dependence module were used. All items with a score of 2 (sub-threshold) and 3 (threshold or true) were summed for a score ranging from 0 to 33. The proportion of first-degree relatives with substance abuse did not include children of the participants. It has been suggested that variables entered into a cluster analysis should have a relative statistical independence from each other (r b.4) (Basu et al., 2004). There were no significant correlations among the variables entered except between the proportion of first-degree relatives with substance abuse and the score for symptoms of abuse/dependency (r = .302, p = .000). 2.5. Measures of validity To examine the validity of the typologies, analyses were conducted to investigate whether individuals assigned to distinct subtypes differed from each other as would be expected from reports from earlier studies in the domains of pre-morbid risk factors, drug use, and personality traits, and prediction of future alcohol and drug use. Due to the characteristics of this sample, measures of psychiatric illness and criminality were expected to vary between subtypes and were thus added. The concurrent validity of each typology was examined by using information collected at the time of discharge, classified into the following domains: 1) Pre-morbid risk factors included the presence or absence of at least one family member with a mental disorder, presence or absence of at least one family member with a criminal record, presence or absence of attention problems, hyperactivity problems, or both, before the age of 18, presence or absence of depression, anxiety, or both, before the age of 18; 2) Drug use included drug abuse/dependence, defined as the presence or absence of a life-time drug use disorder according to DSM-IV, and the number of drugs used as reported in the SCID interview; 3) Criminality was indexed by age of first conviction, and the number of crimes; 4) Symptoms were defined as the scores for positive and negative symptoms of schizophrenia; 5) Personality traits were defined as scores on four of the facets of NEO-PI-R, anxiety, depression, impulsiveness, and excitement-seeking, and the PCL-R score. It was expected that participants assigned to the more severe subtypes of each of the typologies would differ from the participants assigned to the less severe subtypes in that they would show more negative characteristics in each of the domains. It was considered that alcohol dependence would constitute a more severe subtype as compared to alcohol abuse. Accordingly, presence of ASPD, early age of onset, presence of parent with substance use disorder, and Type II/B would constitute more severe subtypes as compared to the absence of ASPD, late age of onset, absence of parent with substance abuse, and Type I/A, respectively. Predictive validity was examined by measuring reports of alcohol and drug use, medication noncompliance, and aggressive behavior during the two year follow-up period. Alcohol and/or drug use during follow-up was scored positively if alcohol and/or any drug was used during the week before any of the four follow-up occasions. Medication non-compliance was scored positively if reported at least once during the follow-up period. Aggressive behavior was scored positively if reported at least once during the follow-up

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period by either the participant or the informant. It was expected that participants assigned to the more severe subtypes would be more likely to relapse into alcohol and drug use, and to show medication noncompliance and aggressive behavior as compared to participants assigned to the less severe subtypes. The construct validity of the multi-dimensional Type I/II – Type A/B typology was examined. It was expected that participants assigned to the Type I/A subtype would be characterized by a less severe alcohol use disorder, later age of onset, a lower number of conduct disorder symptoms, and lesser proportion of first degree relatives with a history of substance abuse as compared to participants assigned to the Type II/B subtype. 2.6. Missing data Due to missing data on specific variables, the number of participants varied between typologies. There were missing data on type of alcohol use disorder (missing = 9), age of onset of alcohol use disorder (missing = 29), presence/absence of parent with substance abuse (missing = 16), proportion of first degree relatives with substance abuse (missing = 16), severity of abuse/dependence (missing = 4), and number of conduct disorder symptoms (missing = 4). 2.7. Analyses Kappa statistics and intra-class correlations were calculated to assess inter-rater reliability. To test the validity of the uni-dimensional subtypes, χ2 -tests and t-tests were performed for the purpose of detecting significant differences between the subtypes on the measures of validity. Kappa statistics were used to compare all uni-dimensional typologies to assess their agreement. The Type I/II – Type A/B typology was established using k-means cluster analysis. The defining variables had previously been z-transformed due to differences in scaling. All standard values exceeding the absolute value of 3.0 were set equal to ± 3.0. To validate the Type I/II – Type A/B typology, a two-cluster solution was requested. To explore whether other numbers of subtypes would fit the data better, three-, four-, and five-cluster solutions were also requested. To test the validity of the multi-dimensional subtypes, χ2 -tests and t-tests (ANOVAs for the three-cluster solution) were used to detect significant differences between the subtypes in measures of validity. In case of a severely skewed distribution of a variable, t-tests and ANOVAs were performed on the log-transformed variable.

3. Results 3.1. The uni-dimensional typologies Table 1 shows the presence or absence of significant differences between the subtypes of the unidimensional typologies on each of the validity measures across the different domains. All significant differences between the subtypes were in the expected direction. Participants from the more severe subtype of each of the typologies showed more negative characteristics than the participants from the other subtype. As shown in Table 1, all typologies showed at least some degree of concurrent validity although each typology demonstrated fairer or poorer validity in different domains. As an example, the alcohol abuse/

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Table 1 The validity of four uni-dimensional typologies Type of alcohol Antisocial Age of onset of alcohol Parent with use disorder personality disorder use disorder substance abuse Abuse, n = 65

Absent, n = 98

Early, b 18, n = 45

Absent, n = 67

Dependence, n = 65

Present, n = 41

Late, ≥ 18, n = 65

Present, n = 56

−

−

+

− +

− −

+ −

Pre-morbid risk factors At least one family member with mental + disorder At least one family member criminal − Attention problems, hyperactivity or both + before age 18 Drug use Lifetime drug abuse/dependency Number of drugs used

− −

+ −

+ −

+ +

Criminality Age at first conviction Number of crimes

− −

+ +

+ −

+ −

Illness PANSS positive score PANSS negative score

− −

− −

− +

+ −

Personality NEO-PI-R Anxiety NEO-PI-R Depression NEO-PI-R Impulsiveness NEO-PI-R Excitement-seeking PCL-R score

+ + + − −

− − + − +

− − − − −

− − − + +

Follow-up Used alcohol Used drug Did not take medicine as prescribed Aggressive behavior

− + − −

− − − +

− − − −

− − − −

“+” means a significant difference between subtypes (p b .05). “−” means no significant difference between subtypes.

dependence typology showed fair validity in the personality domain but poor validity in the criminality domain, in which the typology based on presence/absence of ASPD was superior as compared to the other typologies. When ranked on the basis of the validity measures of this study, the typology based on presence/absence of parent with substance abuse was superior to the other typologies with significant differences between the subtypes on eight of the fourteen measures of concurrent validity. The typology based on early/late age of onset showed poor overall validity. Predictive validity was poor across all typologies.

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Table 2 The validity of the Type I/II – Type A/B typology 1

2

Type I/A

Type II/B

n = 71

n = 25

1.34 S.D. = 1.843 .10 S.D. = .1484 12.31 S.D. = 5.961 19.63 S.D. = 3.979

3.92 S.D. = 3.662 .47 S.D. = .2971 22.32 S.D. = 6.524 17.80 S.D. = 6.657

t(94) = 4.550 p = .000 t(94) = 7.998 p = .000 t(94) = 7.045 p = .000 t(94) = −1.295 p = .198

Pre-morbid risk factors At least one family member with mental disorder

39.4%

68.0%

At least one family member criminal

21.1%

44.0%

Attention problems, hyperactivity or both before age 18

50.7%

68.0%

χ2(1, N = 96) = 6.058 p = .014 χ2(1, N = 96) = 4.898 p = .027 χ2(1, N = 96) = .237 p = .135

Drug use Life-time drug abuse/dependency

52.3%

76.9%

2.48 S.D. = 2.500

4.44 S.D. = 3.477

χ2(1, N = 104) = 6.240 p = .012 t(94) = 3.030 p = .003

24.69 S.D. = 8.696 13.58 S.D. = 22.234

23.20 S.D. = 8.514 15.52 S.D. = 33.834

t(79) = −.668 p = .506 t(92) = −.757 p = .451

14.41 S.D. = 7.040 18.30 S.D. = 5.976

14.60 S.D. = 5.454 17.44 S.D. = 6.552

t(92) = .125 p = .901 t(92) = −.604 p = .547

54.23 S.D. = 10.267 57.42 S.D. = 8.734 50.69 S.D. = 8.915

56.00 S.D. = 12.352 61.55 S.D. = 11.01 54.318 S.D. = 9.949

t(73) = .641 p = .523 t(73) = 1.724 p = .089 t(73) = 1.547 p = .126

Defining variables of the typology Number of conduct disorder symptoms Proportion of first degree relatives with substance abuse Sum of SCID symptoms of abuse/dependency Age of onset of alcohol use disorder

Number of drugs used

Criminality Age at first conviction Number of crimes

Illness PANSS positive score PANSS negative score

Personality NEO-PI-R Anxiety NEO-PI-R Depression NEO-PI-R Impulsiveness

(continued on next page)

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Table 2 (continued ) 1

2

Type I/A

Type II/B

n = 71

n = 25

49.66 S.D. = 8.591 14.20 S.D. = 8.008

52.45 S.D. = 9.064 15.71 S.D. = 9.624

t(73) = 1.262 p = .211 t(94) = .772 p = .442

Follow-up Used alcohol

35.1%

33.3%

Used drug

12.3%

25.0%

Did not take medicine as prescribed

26.7%

33.3%

Aggressive behavior

19.0%

25.0%

χ2(1, N = 81) = .023 p = .880 χ2 (1, N = 81) = 2.028 p = .154 χ2(1, N = 81) = .373 p = .541 χ2(1, N = 82) = .376 p = .540

NEO-PI-R Excitement-seeking PCL-R score

3.2. The Type I/II – Type A/B typology As shown in Table 2, a typology similar to the Type I/II – Type A/B typology was established from the k-means cluster analysis. The construct validity was good with significant differences between the two subtypes on all of the defining variables except age of onset of an alcohol use disorder. The Type I/A – Type II/B ratio was 2.8:1. The concurrent validity was fair in the domains of pre-morbid risk factors and drug use. No differences were found between subtypes in the domain of personality. The predictive validity was poor, with no significant differences between the subtypes on any of the four measures assessed during the two year follow-up. Table 3 Construct validity of the three-cluster solution

Defining variables of the typology Number of conduct disorder symptoms Proportion of first degree relatives with substance abuse Sum of SCID symptoms of abuse/dependency Age of onset

1

2

3

“Less severe alcohol use disorder”

“Antisocial”

“Family history of substance abuse and severe alcohol use disorder”

n = 61

n = 13

n = 22

.92 S.D. = 1.038 .10 S.D. = .147 11.95 S.D. = 6.065 20.00 S.D. = 7.071

6.85 S.D. = 2.478 .08 S.D. = .099 16.85 S.D. = 6.998 17.15 S.D. = 3.313

2.18 S.D. = 2.822 .55 S.D. = .242 22.00 S.D. = 6.466 18.00 S.D. = 3.703

p = .000 1b3b2 p = .000 1, 2 b 3 p = .000 1, 2 b 3 p = .188

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Type I/A

Type II/B

n = 71

n = 25

n = 61

n=7

n=3

n=6

1157

n = 19

”Less severe alcohol use disorder”

”Antisocial”

”Family history of substance abuse and severe alcohol use disorder”

n = 61

n = 13

n = 22

Fig. 1. Reclassification from the Type I/II – Type A/B typology to the three-cluster solution.

The Type I/A drinkers in the present study were thus characterized by fewer childhood conduct disorder symptoms, a less severe alcohol use disorder, and fewer first-degree relatives with substance abuse, mental disorder, or a criminal conviction as compared to the Type II/B drinkers. The Type II/B drinkers were more likely to have a lifetime diagnosis of drug abuse/dependency, and to have used a larger number of drugs as compared to the Type I/A drinkers. 3.3. The three-cluster solution Additional k-means cluster analyses were performed and three-, four-, and five-cluster solutions were requested. The solution that was judged to best fit the data, was a three-cluster solution with subtypes labeled “less severe alcohol use disorder”, “antisocial”, and “family history of substance abuse and severe alcohol use disorder”. As was the case for the Type I/II – Type A/B typology, the construct validity was good (see Table 3). However, tests of concurrent and predictive validity indicated that the three-cluster solution was not superior to the Type I/II – Type A/B typology (data not shown but available from the first author on request). All of the statistically significant differences on the validity measures were between the “less severe alcohol use disorder” subtype and the other two subtypes. Post-hoc analyses revealed that Type II/B of the Type I/II – Type A/B typology was split into two subcategories when the three-cluster solution typology was established (see Fig. 1).

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4. Discussion In a sample of men with schizophrenic disorders, widely used uni-dimensional typologies of alcohol use disorders, that have been developed among non-mentally disordered individuals, showed some degree of concurrent validity, but poor predictive validity. A multi-dimensional typology, similar to the Type I/II – Type A/B typology was replicated with good construct validity, some degree of concurrent validity, but again with poor predictive validity. The correlations between the uni-dimensional typologies of alcohol abuse/dependence, presence/ absence of ASPD, early/late onset of alcohol use disorder, and presence/absence of parent with substance abuse, were generally low (.07–.28). This indicates that the same individual may be assigned to a more severe subtype of one typology and a less severe subtype of another typology. Results also indicated that the different uni-dimensional typologies demonstrated validity in different domains. Overall, the findings suggest that the choice of uni-dimensional typology, either for research or clinical practice, should be based on considerations of which domain is the focus of interest. To our knowledge, this is the first study designed to validate the Type I/II – Type A/B typology among men with schizophrenia. The good construct validity, the consistency between the Type I/A – Type II/B ratio in the present study and in previous research among non-disordered populations, and the similarity of the characteristics of each sub-type indicates that the Type I/II – Type A/B typology may be a useful construct for pursuing an understanding of alcohol use disorders among men with schizophrenia. However, despite the good construct validity of the Type I/II – Type A/B typology, its concurrent and predictive validity was not equally good. In all, none of the typologies showed more than some degree of validity. Thus, the clinical usefulness of the studied typologies among individuals with schizophrenia may be limited. The present study revealed findings that were contrary to what has been demonstrated in research on typologies of alcohol use disorders among non-mentally disordered individuals. Age of onset was of little value for classification. The typology based on early/late age of onset of alcohol use disorder showed poor validity. In the multi-dimensional Type I/II – Type A/B typology, no significant difference was found between subtypes as to age of onset. The mean age of onset of alcohol use disorder was low for the entire sample (M = 19.5 years, S.D. = 6.5). This may be due to the fact that individuals with schizophrenia have a heightened sensitivity to the effects of alcohol and drugs (Mueser, Drake, & Wallach, 1998). Another unexpected finding was the lack of difference between the Type I/A and the Type II/B subtypes as to personality. Following the original work by Cloninger et al. (1981) and Babor et al. (1992), it was expected that the former subtype would show anxious and depressive traits while the latter subtype would present impulsive, excitement-seeking, and psychopathic traits. This was, however, not the case in the present study. As an example, individuals from both subtypes showed elevated scores for anxiety and depression as compared to a normal adult sample. Since many individuals with schizophrenia display symptoms of general psychopathology (Kay et al., 1987) and abnormalities in basic dimensions of personality (Bagby et al., 1997; Camisa et al., 2005; Gurrera, Nestor, & O'Donnell, 2000; Kentros et al., 1997; Reno, 2004), the Type I/II – Type A/B typology may not be useful among individuals with schizophrenia within the personality domain. The method of choice to assess personality traits may also have limited the quality of the results since problems with cognition and attention problems among individuals with schizophrenia may interfere with their capacity to fill out self-report questionnaires (Kentros et al., 1997). An obvious reason for the limited validity of the studied typologies is that they were originally developed in samples of non-mentally disordered individuals. Individuals with schizophrenia have severe

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psychiatric difficulties that may interact with their alcohol use disorder. It may be that typologies of alcohol use disorder among individuals with schizophrenia should be based on psychiatric features as well as on characteristics from the traditional typologies. Such a typology has been presented by Mueser et al. (1998). The model consists of two subtypes, a super-sensitive subtype and an antisocial subtype. It has been suggested that each of the subtypes has a distinct etiology. According to the model, individuals of the supersensitive subtype would develop abuse/dependence due to a heightened sensitivity to the effect of substances, specific to individuals with schizophrenia. Individuals of the antisocial subtype, on the other hand, would develop abuse/dependence as a consequence of an antisocial lifestyle, similarly to nondisordered individuals with an antisocial lifestyle. In this sample of men with schizophrenia, all of the uni-dimensional typologies and the multidimensional Type I/II – Type A/B typology demonstrated poor predictive validity. One reason may be the previously discussed fact that the studied typologies did not include psychiatric features. It should also be held out, however, that participants who were assessed as presenting a high risk of relapse into alcohol and/or drug use were supervised more closely than other participants, thus reducing the risk for relapse, enhancing medication compliance, and preventing aggressive behavior. It is also reasonable to assume that a number of patients within the hospitals regarded as the most “high-risk” were never discharged and thus not included into the study. The three-cluster solution obtained in this study was similar to a typology previously identified by Johnson et al. (Johnson, van den Bree, Gupman, & Pickens 1998; Johnson, van den Bree, & Pickens 1996) who examined non-mentally disordered individuals with alcohol dependence. In their typology, the largest subtype was labeled “mild” and found to include more than 50% of two samples that were studied. This subtype is similar to the largest subtype of our three-cluster solution, “less severe alcohol use disorder”. A second subtype, labeled “severe”, was characterized by a family history of alcohol use disorders. It corresponds to a similar subtype in the present study. The third subtype was the “dyssocial”, characterized by socially deviant or conflictual behavior in association with alcohol consumption, similar to our “antisocial” subtype. While the concurrent and predictive validity of the tree-cluster solution was not superior to any of the other typologies of the present study, it does have strengths as to its clinical utilization in its differentiation between the two subtypes of Type II/B individuals. A man with schizophrenia who displays antisocial personality traits would require antipsychotic medication for schizophrenia, cognitivebehavioral interventions aimed at reducing antisocial behaviors, attitudes, and ways of thinking (Hodgins & Müller-Isberner, 2004), and treatment to reduce alcohol abuse that takes account of his antisocial personality traits. By contrast, a man with schizophrenia and a family history of substance abuse and severe alcohol use disorder may be marked by having been raised in a family with substance abuse. Such an individual might benefit from broad interventions aimed at strengthening his social network, activities, and habits (Drake & Mueser, 2001), as well as specific skills training, effective for coping with high-risk situations for alcohol use (Bellack & DiClemente, 1999). The present study is characterized by a number of strengths. Diagnoses, symptom measures, and PCLR ratings were made by experienced clinicians trained specifically to use each of the standardized and validated instruments. Data were acquired from multiple sources including the participant, family members and staff, and from medical, social service, and criminal records. The multi-site design may have reduced the risk of obtaining results, specific to the drinking habits within a certain culture. The major limitation of the study is that data were acquired retrospectively. However, information from multiple sources was used to reduce possible biases that may arise when retrieving retrospective information. Data on parents' mental disorders may be less reliable since diagnoses were not made by a clinician

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and their criminal records were not available. The rate of refusal to participate in the study was high. More than one third of the patients who were invited to participate refused. Analyses revealed that there was no difference between the individuals who refused and those who agreed to participate as to the presence of a history of substance abuse (60.6%; 68.4%, respectively), χ2 (1, N = 475) = 2.859, p = .093. The large number of comparisons increased the risk of Type I errors. The validity measures tested were, however, chosen to be similar to measures of previous research with clear hypotheses. It was thus considered that a level of significance of .05 would be sufficient. The present study aimed to explore whether typologies would be a useful construct to understand alcohol use disorders among individuals with schizophrenia. While all the studied typologies showed at least some degree of validity, it may be that their clinical usefulness for individuals with schizophrenia is limited. The study nevertheless provided evidence for the heterogeneity of alcohol use disorders among men with schizophrenia. Subtypes of alcohol use disorders may have distinct etiologies that imply different developmental trajectories and different mechanisms for initiating and maintaining alcohol misuse. Findings obtained from studies on subtypes could be used to inform treatment programs so that interventions are more specifically tailored to the needs of patients. Such a strategy is likely to increase the effectiveness of treatments designed to reduce alcohol misuse among men with schizophrenic disorders. By defining uni-dimensional and multi-dimensional typologies and validating them in other samples of individuals with schizophrenia, more refined hypotheses about etiology, development, course, treatment, and outcome of alcohol use disorders may be formulated and tested. Acknowledgements “The Comparative study of the Prevention of Crime and Violence by Mentally Ill Persons” is being conducted by S. Hodgins, Ph.D., Institute of Psychiatry, King's College London and Canada: Derek Eaves, M.D., Vancouver; Stephen Hart, Ph.D., Simon Fraser University; Christopher Webster, Ph.D., Simon Fraser University and McMaster University; Deborah Ross, Riverview Hospital, Coquitlam, British Columbia. Finland: Jari Tiihonen, M.D., Ph.D., Markku Eronen, M.D., Ph.D., Vanha Vaasa Hospital, Vaasa and Niuvanniemi Hospital, Kuopio; Aija Räsänen, Eila Repo-Tiihonen, M.D., Ph.D., Kirsi Väänä, Niuvanniemi Hospital, Kuopio; Päivi Toivonen, M.D., Aila Vokkolainen, MSc., Vanha Vaasa Hospital, Vaasa; Irma Kotilainen, M.D. National Authority for Medicolegal Affairs, Helsinki; Heikki Vartiainen, M.D., Ph.D., Helsinki Central University Hospital, Helsinki. Germany: Roland Freese, M.D., Dieter Jöckel, Dr.med., Rüdiger Müller-Isberner, Dr.med., Klinik für forensische Psychiatrie Haina, Haina (Kloster). Sweden: Robert Kronstrand, Ph.D., Rättsmedicinalverket and Linköping University, Linköping; Sten Levander, M.D., Ph.D., Eva Tuninger, M.D., Universitetssjukhuset, Lund. Grants to support the study have been awarded by the BIO-MED-II programme of the European Union; Canada: the Forensic Psychiatric Services Commission of British Columbia, the Mental Health, Law and Policy Institute, Simon Fraser University, Riverview Hospital; Finland: Niuvanniemi and Vanha Vaasa State Mental Hospitals; Germany: Deutsche Forschungsgemeinschaft, Institut für forensische Psychiatrie Haina; Sweden: Medicinska Forskningsrådet,Vårdalstiftelsen, National Board of Forensic Medicine, Forensic Science Centre, Linköping University, and Linköping University. The present study was supported by Rättsmedicinalverket, Professor Bror Gadelius' minnesfond, and Vårdalstiftelsen.

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