Utilization of Mental Health Services and Risk of 12-month Problematic Alcohol Use

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1 Utilization of Mental Health Services and Risk of 12-month Problematic Alcohol Use Gaëlle Encrenaz, MPH; Viviane Kovess-Masfety, MD, PhD, DrSc David Sapinho, MS; Christine Chan Chee, MD; Antoine Messiah, MD, PhD, DrSc Objective: To examine whether mental health service utilization modifies the association between lifetime anxiety or depressive disorders (ADD) and risk of 12-month problematic alcohol use. Methods: Randomly selected members (n=6518) of a mutual health-insurance company were evaluated for lifetime ADD (DSM-IV), mental health service utilization for ADD, and risk of 12-month problematic alcohol use (DSM-IV and CAGE). Results: Risk of 12-month problematic alcohol use was reduced when mental health services had been used for several ADD (OR=3.3 vs 5.8), but not for one ADD. Conclusions: These results show the importance of taking mental health service use into account as a potential effect-modifier of psychiatric comorbidity. Key words: alcohol-related disorders; anxiety disorders; comorbidity; depressive disorders; mental health services. Am J Health Behav. 2007;31(4): Gaëlle Encrenaz, doctoral student; Antoine Messiah, Research Scientist, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique d Epidémiologie et de Développement (ISPED), Institut Fédératif de Recherche en Santé Publique (IFR INSERM 99), Victor Segalen Bordeaux 2 University, France. Viviane Kovess-Masféty, Professor; David Sapinho, Biostatistician; Christine Chan Chee, Research Scientist; MGEN Public Health foundation, Paris V University, France. Address correspondence to Ms Encrenaz, INSERM U593, Institut de Santé Publique d Epidémiologie et de Développement, Université Bordeaux 2, case 11, 146 rue Léo Saignat, Bordeaux Cedex, France. Gaelle.Encrenaz@isped.u-bordeaux2.fr Co-occurrence of alcohol abuse or dependence with other psychiatric disorders, in particular with anxiety or depressive disorders (ADD), has been demonstrated in several populationbased surveys. 1-8 Subjects with a nonsubstance-related psychiatric disorder are more likely to have an alcohol use disorder, and conversely, patients with an alcohol use disorder often suffer from other psychiatric disorders, such as anxiety and depression. In the European Study of the Epidemiology of Mental Disorders (ESEMeD), 22.8 % of subjects with any 12- month ADD had a comorbid 12-month alcohol abuse or dependence. 9 This comorbidity with ADD has also been described among heavy alcohol drinkers who did not meet alcohol abuse or dependence diagnoses. 10 Several different theories have been proposed to explain this comorbidity. Some have considered alcohol use disorders to be secondary psychiatric disorders. Accordingly, some etiological theories posited that people would drink alcohol or use psychoactive substances in order to relieve psychological symptoms. This is the case for the selfmedication hypothesis 11,12 and more generally for the alleviation of dysphoria model. 13 In the same way, alcohol drinking has been described as a way of coping with psychological symptoms. 14 ADD can also be considered as risk factors for alcohol and other psychoactive substance 392

2 Encrenaz et al abuse and dependence, a relationship that has been verified in several studies Finally, it has been found that comorbid ADD predict poor outcome of alcohol dependence treatment, such as higher relapse rates ,22,23 Utilization of mental health services for ADD could thus decrease vulnerability to alcohol use and alcohol use disorders. Subjects using mental health services are more likely to be relieved of their symptoms, leading to a lower need to use alcohol. In turn, mental health service utilization could prevent alcohol use disorders or lower the risk of problematic alcohol use and therefore modify comorbidity patterns. The role of mental health service use in the prevention of alcohol misuse has not yet been studied, and studies on comorbidity did not take mental health services utilization into account as a potential effect-modifier of comorbidity patterns. Most studies concerned with mental health services have underscored the underutilization of these services Recently, Harris and Edlund 29 studied the association between past 30-day use of alcohol and past 12-month use of and unmet need for mental health care. Heavy alcohol use was not associated with increased unmet need for mental health, but was higher among individuals with no mental health care use. However, alcohol use was studied over the 30 past days only, and subjects who met criteria for alcohol abuse or dependence were excluded. More severe cases who were more likely to use psychoactive substances in order to relieve their psychological symptoms have thus been excluded which might have prevented the emergence of an effect of mental health service use on psychiatric comorbidity. In a previous study among first-year college students, 30 it has been shown that subjects with several non-substance-related psychiatric disorders who did not use health care had significantly higher likelihood of having a lifetime comorbid substance use disorder than were those with no lifetime non-substance-related psychiatric disorders, as expected; but in contrast, those who used health care did not differ significantly from those with no non-substancerelated psychiatric disorders. However, this study was conducted among a small sample, and the dates of disorders were not taken into account. The objective of the present study was to examine how utilization of mental health services modified the association between lifetime ADD and risk of 12- month problematic alcohol use. METHODS Sample We used the data from a cross-sectional study whose aim was to assess the prevalences of psychiatric disorders in a sample of members of a French mutual health-insurance company, the MGEN (Mutuelle Générale de l Education Nationale). MGEN serves national education professionals (teachers or not) and their children and spouses, that is, a population of 2,993,328, from which 10,000 subjects aged between 20 and 60 years old were randomly selected. Between June 1999 and March 2000, a self-administered questionnaire was mailed to each of them, followed by 3 reminders for those who did not answer. The final response rate was 65.2 % (n=6518). Among them, 56 % were women (n=3621), the mean age was equal to 43.9 (SD=10.7), and 64 % were teachers. The study protocol was approved by the French regulation authority for questionnaire-based noninvasive medical research (CNIL approval number ). Data Collection and Measurements The 50-page, self-administered questionnaire collected data about socio-demographic characteristics, subject work, health status, mental health, and health care utilization. The mental health section consisted of Axis I mental disorders of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition 31 measurement with a French version of the Composite International Diagnostic Interview Simplified (CIDIS), 32 which is an abridged version of the CIDI. 33,34 Diagnoses assessed were major depressive episode, dysthymia, panic attack, panic disorder, agoraphobia, social anxiety, specific phobia, obsessive compulsive disorder, alcohol dependence and abuse, anorexia, bulimia, and somatoform disorders. In this study, we have dealt with ADD (major depressive episode, dysthymia, panic attack, panic disorders, agoraphobia, social anxiety, specific phobia, and obsessive compulsive disorder) and alcohol use disorders (abuse and dependence). Am J Health Behav. 2007;31(4):

3 Mental Health Services Risk of problematic alcohol use was also evaluated using the CAGE questionnaire, 35,36 which is a screening tool for alcohol problems. It consists of 4 questions: (a) Have you ever felt you should Cut down on your drinking? (b) Have people Annoyed you about your drinking? (c) Have you ever felt bad or Guilty about your drinking? (d) Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (Eyeopener)? This questionnaire is used to identify individuals who have alcohol-related problems/consequences or who are at risk for such difficulties. A positive response on 2 or more items qualifies as positive for risk of problematic alcohol use. Mental health service utilization included lifetime and past-12-month consultation(s) with a medical doctor or a health professional and psychotherapy sessions, motivated by the following problems: sleep disturbances, smoking, depression, phobias, anxiety, obsessing thoughts, eating disorders, alcohol problems, and somatic pain. For each type of mental health service use, a question was asked in order to know which problem(s) were addressed specifically. Mental health service use included also hospitalizations and specific treatments for these disorders, as well as emergency room visits for a suicide attempt. In this study, we focused on lifetime mental health service use for ADD-related symptoms as described below. Finally, one question gave information about social support: Have you got a close friend or member of your family with whom you can easily talk about your problems?. Variables Dependent variable. The dependent variable was a risk of past-12-month problematic alcohol use, regardless of the date of the first episode. We considered that a subject had a risk of 12-month problematic alcohol use if he or she had a DSM-IV diagnose of alcohol abuse or dependence during the previous 12 months or/and if the individual had a risk of problematic alcohol use according to the CAGE score (above 2) during the previous 12 months. Main covariate. The main explanatory variable combined the lifetime number of ADD and ADD-related mental health service utilization. A subject was considered as having used mental health services for ADD if she or he had already consulted a medical doctor or another health professional or had had psychotherapy, for any of the following ADDrelated symptoms: sleep disturbances, depression, phobias and irrational fears, anxiety, obsessing thoughts, and eating disorders. The subject was also considered as having used mental health services if he or she had already been hospitalized for one of these problems or had already been admitted to an emergency room for a suicide attempt. We limited the study of mental health service use to use for ADD-related symptoms in order to increase the likelihood that subjects had used mental health services for their ADD. We did not take into account health care use for smoking and somatic pains. Even if comorbidity between ADD and heavy smoking or somatic disorders is very frequent, subjects consulting for smoking and somatic pains may not receive care for their mental health problems. In the current study, subjects who used health care for smoking, somatic pains, or alcohol-related problems only were considered as not having used mental health services, because their utilization of these services was unlikely to be related to their ADD. For each subject, we calculated the lifetime number of ADD among available lifetime ADD diagnoses, allowing us to define 2 levels of severity. Thus, the main explanatory variable had 5 levels as follows: 1 = no ADD; 2 = 1 ADD and no mental health service use; 3 = 1 ADD and mental health service use; 4 = at least 2 ADD and no mental health service use; 5 = at least 2 ADD and mental health service use. Measurements time frame. We studied the association between the risk of 12-month problematic alcohol use and lifetime ADD and mental health service use, as a way of taking into account the chronology between these events. Statistical Analysis We first studied the association between the risk of 12-month problematic alcohol use and ADD, regardless of men- 394

4 Encrenaz et al Table 1 Lifetime Prevalences of Non-substance-related Psychiatric Disorders in the Total Sample (n=6518) Lifetime Prevalence Disorder n % Major depressive episode Panic attack Panic disorder Agoraphobia Social phobia Specific phobia Obsessive compulsive disorder Anorexia Bulimia Somatoform disorder tal health service use. Then, we examined the effect of mental health service use on this association using the aforementioned explanatory variable. The risk of 12-month problematic alcohol use was modelled using logistic regression, each level of this variable being studied as a dummy variable with 1 (no ADD) as the reference level. In each group defined by the lifetime number of ADD (one or several), regression coefficients of mental health service use were compared. We constructed 2 logistic regression models: one among subjects with one lifetime ADD and a second one among subjects with several lifetime ADD. We then tested the coefficient associated to mental health service use in each model. In each logistic regression model, conclusions were drawn according to the Wald chi-square test with one degree of freedom. 42 Other covariates were gender, age, educational level, and social support. Analyses were adjusted for gender because several studies have shown that women were less likely than men to have a problematic alcohol use. 43 Moreover, women are more often affected by other mental disorders 44 and use health care services more often. 45 It has also been shown that women with psychiatric comorbidity did not have the same health care use patterns as men. 46 Age was taken into account because older subjects are more likely to have lifetime problematic alcohol use and ADD. Moreover, it has been shown that young subjects were less likely to use mental health services than were older ones. 8,26 We have also taken into account educational level (any college vs none). Many studies have shown this variable to be linked to mental disorder and mental health service use. 45 Finally, we also studied social support, ie, if subjects had someone they could talk to about their preoccupations, including friends, family, or colleagues. Social support is known to be a protective factor for mental disorders. 47 We considered that subjects had poor social support if they did not know anyone they could talk to about their problems. Covariates were selected following a stepwise descending procedure, and an association was considered as significant when the p-value was below Models were tested with the Hosmer-Lemeshow goodness-of-fit test. 42 These statistical analyses were performed using SASÒ software (The Statistic Analysis System, version 8.2. SAS Institute, Inc, Cary, NC, USA). RESULTS Description Lifetime prevalences of non-substancerelated psychiatric disorders are described in Table 1. Major depressive episode was the most frequent disorder (31.6 %). In the total sample, 51 subjects (0.8 %) had a lifetime history of alcohol dependence; 37, (0.6%) a lifetime history of alcohol abuse; and 496 (7.9%), a CAGE score above 2, resulting in 509 subjects (8.5%) with a risk of lifetime problematic alcohol use. For 338 subjects (66.4% of subjects with a risk of lifetime problem- Am J Health Behav. 2007;31(4):

5 Mental Health Services Table 2 Associations Between Lifetime Prevalences of Anxiety or Depressive Disorders and Risk of 12-month Problematic Alcohol Use Disorder OR a b CI 95% Major depressive episode 1.8 [1.4 ; 2.2] Panic attack 1.7 [1.3 ; 2.2] Panic disorder 1.8 [0.9 ; 3.6] Agoraphobia 1.5 [1.1 ; 2.1] Social phobia 2.3 [1.5 ; 3.6] Specific phobia 3.2 [2.2 ; 4.7] Obsessive compulsive disorder 2.1 [0.9 ; 5.0] Number of disorders (ref.) [1.4 ; 2.4] 2 or more 2.5 [1.8 ; 3.3] Note. a OR: Odd Ratio : 95 % Odds Ratio confidence interval CI b 95% atic alcohol use and 5.4% of the total sample), this risk of problematic alcohol use was present within the previous 12 months. Among them, 7 had a CAGE score above 2 with missing data for DSM-IV diagnoses of alcohol abuse or dependence; 267 had a CAGE score above 2 with no DSM-IV diagnose of alcohol abuse or dependence; 55 had a CAGE score above 2 with a DSM-IV diagnose of alcohol abuse or dependence; and 9 had a CAGE score under 2 and a DSM-IV diagnose of alcohol abuse or dependence. Association Between ADD and Risk of 12-month Problematic Alcohol Use Associations between lifetime ADD and risk of 12-month problematic alcohol use are given in Table 2. The strongest associations were observed with phobia and, in particular, with specific phobia. The likelihood of 12-month problematic alcohol use increased with the number of ADD. Table 3 Risk of 12-Month Problematic Alcohol Use by Number of Lifetime Depressive or Anxiety Disorders and Mental Health Service Use Risk of 12-month problematic alcohol use N n % No depressive or anxiety disorder One depressive or anxiety disorder No mental health service use Mental health service use At least 2 depressive or anxiety disorders No mental health service use Mental health service use

6 Encrenaz et al Table 4 Logistic Regression of the Risk of 12-Month Problematic Alcohol Use by Mental-Health Service Use Status Adjusted OR a b CI 95% Main independant variable No depressive or anxiety disorder 1.0 (ref) One depressive or anxiety disorder No mental health service use 1.7 [1.2 ; 2.5] Mental health service use 2.7 [1.9 ; 3.7] At least 2 depressive or anxiety disorders No mental health service use 5.5 [3.5 ; 8.7] Mental health service use 3.2 [2.2 ; 4.5] Other covariates Gender (women vs men) Men 1.0 (ref) Women 0.2 [0.2 ; 0.3] Age [18 ; 34] 1.0 (ref) [35 ; 49] 1.9 [1.3 ; 2.7] 50 and more 2.2 [1.5 ; 3.2] CI 95% Note. a Ô b R : Odds Ratio estimate : 95 % Odds Ratio confidence interval Among individuals with a lifetime ADD (n=2543), 1531 (60.2%) had already used mental health services for ADD-related symptoms. Among subjects with a risk of 12-month problematic alcohol use and a lifetime ADD, 24 (14.4%) had used health care for their alcohol problem. Among those with a risk of 12-month problematic alcohol use but no lifetime ADD, 10 (6.8%) had already used health care for their alcohol problem. Association Between ADD and Risk of 12-month Problematic Alcohol Use According to Mental Health Service Use Risk of 12-month problematic alcohol use by number of ADD and ADD-related mental health service use is given in Table 3. Risk of 12-month problematic alcohol use was high among subjects with at least one ADD compared to those with no ADD. The highest prevalence was observed among subjects with at least 2 lifetime ADD who never used mental health services. Among subjects with one lifetime ADD, risk of 12-month problematic alcohol use was slightly higher among those who used mental health services. The logistic regression model (Table 4) showed that subjects with at least one ADD were more likely to have a risk of 12- month problematic alcohol use regardless of mental health service use. Among subjects with one lifetime ADD, those who used mental health services had a significantly greater likelihood of 12- month problematic alcohol use (OR = 2.7 vs 1.7). This difference was statistically significant (P-value=0.03). In contrast, among subjects with at least 2 ADD, those who had used mental health services were less likely to have a risk of 12- month problematic alcohol use than were those who had not (OR = 3.2 vs 5.6), and this difference was also statistically significant (P-value=0.04). The model also showed that women were significantly less likely to have a risk of 12-month problematic alcohol use than men were, and the same was true for subjects aged 34 or lower compared with their elders. Finally, the risk of 12- month problematic alcohol use likelihood was associated with neither educational level nor social support. None of these Am J Health Behav. 2007;31(4):

7 Mental Health Services factors were confounding factors: the inclusion of these covariates did not modify the other regression coefficient estimates. The Hosmer-Lemeshow goodness-offit tests indicated no lack of fit for this model (P=0.62). DISCUSSION The objective of the present study was to examine how mental health service use modified the association between lifetime ADD and risk of 12-month problematic alcohol use. We have shown that mental health service use was associated with a decreased risk of 12-month problematic alcohol use among subjects with at least 2 ADD. In contrast, among subjects with one ADD, those who used mental health services were more likely to have a risk of 12-month problematic alcohol use than were those who did not. The data derived from a cross-sectional study designed to assess psychiatric disorder prevalence among members of a mutual health-insurance company. This company covers national public-education professionals and their spouse and children. This population is not representative of the French population, with overrepresentation of women, teachers (half of subjects), and people with high educational level. These factors are known to be linked to ADD, to problematic alcohol use, and to utilization of mental health services. 9,43-46 Several studies have shown that women are less likely than men to have a problematic alcohol use and that women are more often affected by other mental disorders and use more often health care services. High socioeconomic position was linked to lower mental disorder prevalence and greater utilization of mental health services. In order for the overrepresentation to lead to a bias, it would have to affect differentially the 5 groups defined by mental health service utilization and the number of ADD, which is not necessarily the case. Thus, associations we studied were not necessarily biased by the lack of representativeness of our sample. Moreover, statistical analyses were adjusted for gender and educational level in order to minimize possible bias. Axis I DSM-IV mental disorders were assessed using a self-administered version of the CIDIS, which has been shown to reproduce with a high level of accuracy the diagnosis of the long version of the CIDI, except for generalized anxiety that was not assessed our study. 32 Risk of problematic alcohol use was studied using DSM-IV diagnoses and the CAGE questionnaire. Alcohol consumption might be more negatively perceived among public-education professionals, given their large exposure to the public and their position as role models, leading to higher rates of denial. Risk of problematic alcohol use rates might then be underestimated in the total sample. For our study, we used a self-administered questionnaire; thus some persons may not have told the truth, especially for questions dealing with stigmatizing or socially sensitive disturbances, such as alcoholrelated problems and use of mental health services for these problems. However, we used a combination of 2 instruments to assess the risk of alcohol-related problems, in order to better identify subjects with such a risk. Indeed, it has been shown that CAGE was useful to identify alcohol-related problems in women and younger people that are more often misclassified using DSM-IV criteria of alcohol abuse or dependence than in men and older people. 48 Moreover, some authors have suggested that denial rates were higher among subjects with depression. 49 We could thus have underestimated risk of problematic alcohol use differences between subjects with no ADD and those with ADD. In contrast, feeling guilty is a shared criterion of DSM-IV major depressive episode 31,50 and of the CAGE. This would result in an overestimation of risk of problematic alcohol use among subjects with ADD. Mental health services use and disorder severity have been shown to be correlated. 25,28 This could explain our results within the group of subjects with one lifetime ADD: subjects who had used mental health services had higher rates of 12-month problematic alcohol use than did those who did not, possibly because of a greater severity of their ADD. In addition, our analysis implicitly supposed that one ADD, as diagnosed with the CIDIS, implied mental health care need, which is not necessarily the case. 6 We did not take the severity of problematic alcohol use into account. Mental health service use for ADD may have prevented the most severe form of alcohol consumption only, such as dependence. 398

8 Encrenaz et al Indeed, the self-medication hypothesis was initially proposed to explain the link between non-substance-related psychiatric disorders and substance dependence. 11,12 We attempted to restrict our analyses to alcohol dependence, but convergence criteria were not met because of the low number of cases. This study focused on alcohol consumption and did not explore other psychoactive substance use. For some subjects, ADD can have led to non-alcoholic substance use, possibly leading to substance-related problems without risk of problematic alcohol use. However, in the population under scope in this study, non-alcoholic substance consumptions may be very rare, because the prevalence of alcohol dependence was yet low in comparison with the French general population. 51 We did not distinguish the different health professionals (general practitioner, psychiatrist, or psychologist) in our study. In France, people can consult a psychiatrist or a psychologist without consulting a general practitioner first. General practitioners either treat subjects with psychiatric disorders or refer them to a psychiatrist. We did not take into account mental health service use for alcohol-related problems. Including it in the logistic regression model could lead to overadjustment. Indeed, risk of problematic alcohol-use and health care use for an alcohol-related problem are strongly correlated. If we took the latter into account in the model, the corresponding coefficient would be positive because of reverse causation: subjects would have used health care because of their alcohol-related problems. It would prevent us from highlighting a protective effect of health care use for an alcohol-related problem. Moreover, someone with a comorbid condition who consulted a physician for ADD-related symptoms was likely to receive subsequent treatment of his or her alcohol use disorder. Thus, the decreased risk of 12-month problematic alcohol use after mental health service use for ADD-related symptoms can be due to treatment of alcoholrelated problems. An important limitation of our study is its cross-sectional design, which prevented us from drawing causal inferences. The questionnaire sought information about dates of ADD and problematic alcohol use episodes, but answers were missing too frequently to be used. Nevertheless, the chronology between ADD and risk of problematic alcohol use could be taken into account, by analyzing the association of lifetime ADD with a risk of problematic alcohol use that would be present over the past 12 months. However, reverse causation can still explain some of our results. It has been shown that psychiatric comorbidity increased mental health service use. 28 Some subjects might have used mental health services after the onset of problematic alcohol use; that is, once psychological symptoms had become more severe. This might have occurred especially among subjects with one ADD and could thus further explain why in this group subjects who used mental health services were at higher risk of 12-month problematic alcohol use than were those who did not. Among subjects with several lifetime ADD, in contrast, mental health service use can have been motivated by the accumulation of ADD before the onset of problematic alcohol use, resulting in actual prevention. Our results can also be explained by the multiple pathways of association between depression and substance use. 52,53 Thus, if the primary disorder is problematic alcohol use, treatment of depressive or anxiety condition may not reduce alcohol problems. Likewise, if the comorbidity between disorders is explained by common or shared risk factors, then the treatment of either condition will not necessarily have any effect on the other. However, our results among subjects with several lifetime ADD are concordant with our hypotheses and with the findings of Harris and colleagues, 29 according to which heavy alcohol use is higher among individuals who do not use mental health care for problems with emotions, nerves, or mental health. These results suggest that mental health service use is associated with a lower risk of 12-month problematic alcohol use among subjects with severe ADD, but causal inferences cannot be drawn. Hence, further investigation is needed towards establishment of causal associations. These results also show the importance of taking mental health service use into account as a potential effectmodifier in studies addressing psychiatric comorbidity. Such studies could have important clinical implications as they Am J Health Behav. 2007;31(4):

9 Mental Health Services would add arguments to support mental health care access and promotion. Acknowledgments This study was supported by the Mutuelle Générale de l Education Nationale (MGEN), and G. Encrenaz was a research fellow of the French ministry of education, research and technology. Moreover, this study was supported in part by the Conseil Régional d'aquitaine, grant number A. This work has been presented at the 6th scientific meeting of the American Academy of Health Behavior in Carmel, Calif, in March 2006 and at the 13 th European symposium, section epidemiology and social psychiatry of the Association of European Psychiatrists, in Bordeaux, France, in June The authors also want to thank Erica Gollub for her help with the manuscript. REFERENCES 1.Bromet EJ, Gluzman SF, Paniotto VI, et al. Epidemiology of psychiatric and alcohol disorders in Ukraine Findings from the Ukraine World Mental Health survey. Soc Psychiatry Psychiatr Epidemiol. 2005;40(9): Currie SR, Patten SB, Williams JV, et al. Comorbidity of major depression with substance use disorders. Can J Psychiatry. 2005;50(10): Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004;61(8): Grant BF, Stinson FS, Dawson DA, et al. Cooccurrence of 12-month alcohol and drug use disorders and personality disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004;61(4): Jacobi F, Wittchen HU, Holting C, et al. Prevalence, co-morbidity and correlates of mental disorders in the general population: results from the German Health Interview and Examination Survey (GHS). Psychol Med. 2004;34(4): Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6): Pirkola SP, Isometsa E, Suvisaari J, et al. DSM-IV mood-, anxiety- and alcohol use disorders and their comorbidity in the Finnish general population results from the Health 2000 Study. Soc Psychiatry Psychiatr Epidemiol. 2005;40(1): Wang J, El-Guebaly N. Sociodemographic factors associated with comorbid major depressive episodes and alcohol dependence in the general population. Can J Psychiatry. 2004;49(1): Alonso J, Angermeyer MC, Bernert S, et al. 12- Month comorbidity patterns and associated factors in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl. 2004(420): Bott K, Meyer C, Rumpf HJ, et al. Psychiatric disorders among at-risk consumers of alcohol in the general population. J Stud Alcohol. 2005;66(2): Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry. 1985;142(11): Khantzian EJ. The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harv Rev Psychiatry. 1997;4(5): Mueser KT, Drake RE, Wallach MA. Dual diagnosis: a review of etiological theories. Addict Behav. 1998;23(6): Crutchfield RD, Gove WR. Determinants of drug use: a test of the coping hypothesis. Soc Sci Med. 1984;18(6): Abraham HD, Fava M. Order of onset of substance abuse and depression in a sample of depressed outpatients. Compr Psychiatry. 1999;40(1): Cox BJ, Norton GR, Swinson RP, Endler NS. Substance abuse and panic-related anxiety: a critical review. Behav Res Ther. 1990;28(5): Weiss RD, Kolodziej M, Griffin ML et al. Substance use and perceived symptom improvement among patients with bipolar disorder and substance dependence. J Affect Disord. 2004;79(1-3): Donovan JE. Adolescent alcohol initiation: a review of psychosocial risk factors. J Adolesc Health. 2004;35(6):529 e Schade A, Marquenie LA, Van Balkom AJ, et al. Do comorbid anxiety disorders in alcoholdependent patients need specific treatment to prevent relapse? Alcohol Alcohol. 2003;38(3): Greenfield SF, Weiss RD, Muenz LR, et al. The effect of depression on return to drinking: a prospective study. Arch Gen Psychiatry. 1998;55(3): Burns L, Teesson M, O Neill K. The impact of comorbid anxiety and depression on alcohol treatment outcomes. Addiction. 2005;100(6): Lynskey MT. The comorbidity of alcohol dependence and affective disorders: treatment implications. Drug Alcohol Depend. 1998;52(3): Curran GM, Flynn HA, Kirchner J, Booth BM. Depression after alcohol treatment as a risk 400

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