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Original Investigation |

A Prospective Assessment of Reports of Drinking to Self-medicate Mood Symptoms With the Incidence and Persistence of Alcohol Dependence FREE

Rosa M. Crum, MD, MHS1,2,4,6; Ramin Mojtabai, MD, PhD2,4; Samuel Lazareck, MD, MSc7; James M. Bolton, MD, FRCPC7,8; Jennifer Robinson, MA7,8; Jitender Sareen, MD7,8,9; Kerry M. Green, PhD10; Elizabeth A. Stuart, PhD2,3; Lareina La Flair, MPH2; Anika A. H. Alvanzo, MD, MS5; Carla L. Storr, ScD2,11
[+] Author Affiliations
1Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
2Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
3Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
4Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland
5Division of General Internal Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland
6Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Health Institutions, Baltimore, Maryland
7Department of Psychiatry, University of Manitoba, Winnipeg, Manitoba, Canada
8Department of Psychology, University of Manitoba, Winnipeg, Manitoba, Canada
9Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
10Department of Behavioral and Community Health, University of Maryland College Park School of Public Health, College Park
11Department of Family and Community Health, University of Maryland School of Nursing, Baltimore
JAMA Psychiatry. 2013;70(7):718-726. doi:10.1001/jamapsychiatry.2013.1098.
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Published online

Importance  Mood disorders and alcohol dependence frequently co-occur. Etiologic theories concerning the comorbidity often focus on drinking to self-medicate or cope with affective symptoms. However, there have been few, if any, prospective studies in population-based samples of alcohol self-medication of mood symptoms with the occurrence of alcohol dependence. Furthermore, it is not known whether these associations are affected by treatment or symptom severity.

Objective  To evaluate the hypothesis that alcohol self-medication of mood symptoms increases the probability of subsequent onset and the persistence or chronicity of alcohol dependence.

Design  Prospective study using face-to-face interviews—the National Epidemiologic Survey on Alcohol and Related Conditions.

Setting  Nationally representative survey of the US population.

Participants  Drinkers at risk for alcohol dependence among the 43 093 adults surveyed in 2001 and 2002 (wave 1); 34 653 of whom were reinterviewed in 2004 and 2005 (wave 2).

Main Outcomes and Measures  Association of alcohol self-medication of mood symptoms with incident and persistent DSM-IV alcohol dependence using logistic regression and the propensity score method of inverse probability of treatment weighting.

Results  The report of alcohol self-medication of mood symptoms was associated with an increased odds of incident alcohol dependence at follow-up (adjusted odds ratio [AOR], 3.10; 95% CI, 1.55-6.19; P = .002) and persistence of dependence (AOR, 3.45; 95% CI, 2.35-5.08; P < .001). The population-attributable fraction was 11.9% (95% CI, 6.7%-16.9%) for incident dependence and 30.6% (95% CI, 24.8%-36.0%) for persistent dependence. Stratified analyses were conducted by age, sex, race/ethnicity, mood symptom severity, and treatment history for mood symptoms.

Conclusions and Relevance  Drinking to alleviate mood symptoms is associated with the development of alcohol dependence and its persistence once dependence develops. These associations occur among individuals with subthreshold mood symptoms, with DSM-IV affective disorders, and for those who have received treatment. Drinking to self-medicate mood symptoms may be a potential target for prevention and early intervention efforts aimed at reducing the occurrence of alcohol dependence.

Many clinical studies13 have documented the comorbid occurrence of alcohol dependence with depression. Although there are exceptions,4 patients with these types of co-occurring disorders tend to have a worse prognosis than do those with either condition alone.3,515 Data from population-based surveys1619 also indicate high frequencies of comorbidity for mood and alcohol use disorders. In many nationally representative surveys, the prevalence of comorbid mood and alcohol disorders is relatively high. The conditions co-occur to a greater degree than would be expected by chance. For example, in analyses19,20 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), mood disorders, including major depression, dysthymia, mania, and hypomania, were found to have consistently positive associations with alcohol dependence. Among individuals with prior-year depression, 11.0% met the criteria for alcohol dependence.19 Among those with alcohol dependence in the previous year, 20.5% had concurrent depression.19 Furthermore, there is evidence in some studies17,18,21 that stronger comorbid associations are found among females. Alcohol abuse also has been found to be associated with mood conditions, although in some instances, it has a weaker comorbid association with affective disorders.17,19

Prior studies of the comorbid relationship of mood and alcohol conditions provided evidence that there is likely a bidirectional association. Some studies22,23 have found that alcohol dependence is the primary condition and is associated with increases in the risk of depression and other mood conditions; others24 have found alcohol dependence to be secondary, whereby mood disorders are associated with an increased risk for the new development of alcohol use disorders. In most instances, depression has been found to be secondary to alcohol dependence.25 It is also plausible that there is a common source for both conditions that might include genetic vulnerability or environmental factors.26 Etiologic theories to account for mood disorder as the primary condition often focus on the potential use of alcohol as a method of self-medicating or coping with affective symptoms.27 Although a frequently considered hypothesis, there is a paucity of research that has assessed this association. In particular, there are few data from prospective population-based studies, which reduce potential biases related to temporal association and sample selection. In an inpatient sample, Holahan and colleagues28 found that drinking to cope among patients with depression was associated with an increased probability for consumption of alcohol and development of alcohol problems during a 10-year follow-up period. Nevertheless, studies in clinical settings may not provide an adequate assessment of self-medication for mood symptoms with alcohol dependence. Although a high proportion of individuals with mood and alcohol disorders are seen in clinical settings, many, if not most, of those affected with these conditions fail to be identified and never receive treatment.29,30 Estimates indicate that only approximately 42.1% to 60.9% of those with an affective disorder20 receive treatment for their mood symptoms. A much lower proportion of individuals with an alcohol use disorder ever receive clinical attention, and some studies estimate that only 4.8% to 27.9% of people with alcohol abuse or dependence receive treatment.29

Swendsen and colleagues31 used experience sampling to assess self-medication of negative mood states with drinking behavior and found that nervousness, but no other affective symptom, was associated with alcohol use later in the day. Studies using experience sampling methods have the advantage that information is gathered as the participant experiences the negative mood during daily activities. Any subsequent alcohol use may be monitored throughout the day and assessed in temporal relationship to mood status. On the other hand, population-based studies may provide information on a large representative sample of the population regardless of whether they have received treatment.

Prior studies of the NESARC have examined self-medication using cross-sectional assessments of co-occurring conditions3234 and found strong associations of using alcohol and drugs to self-medicate mood disorders with comorbid psychopathologic conditions. Among participants with a mood disorder, 24.1% reported using alcohol or drugs to self-medicate their symptoms.32 In addition, self-medication of anxiety symptoms has been shown to be associated with an increased risk of drug use disorders.35 Using data from the National Comorbidity Survey, it was found that between 7.9% and 35.6% of individuals with anxiety disorders reported self-medication with alcohol or drugs.36 In the present analyses, we hypothesized that self-medication with alcohol for mood symptoms would be associated with an increased incidence of new-onset alcohol dependence over time. In addition, there has been a paucity of population-based assessments of whether drinking to self-medicate mood symptoms alters the potential for chronicity or persistence of alcohol dependence. Consequently, we also evaluated the hypothesis that self-medication of mood symptoms with alcohol would be associated with persistence of alcohol dependence. Because prior findings indicated sex differences for these comorbid relationships,31,32 we also examined whether the association of self-medication with alcohol dependence would vary by sex. We further explored these associations in race- and age-specific strata. In addition, we assessed whether these potential relationships would vary by treatment history and by diagnosis of mood disorder as compared with subthreshold mood symptoms. Our rationale for these latter assessments was to garner information as to whether self-medication drinking may be indicative of failure to receive treatment for an affective disorder or the presence of refractory mood symptoms. We also aimed to assess whether individuals who met the full criteria for a mood disorder, such as major depression, would be more likely to self-medicate compared with individuals who had subthreshold symptoms.

Sample

The sample for the present study was drawn from the NESARC waves 1 and 2. The design and sample characteristics of the NESARC have been described.19,37 Briefly, the NESARC is a survey of a nationally representative sample of the population in the United States, including residents of Hawaii and Alaska, conducted by the National Institute on Alcohol Abuse and Alcoholism. The interviews were conducted face-to-face. To ensure accurate estimates among racial and ethnic minority populations and among younger adults, the NESARC protocol included oversampling of blacks, Hispanics, and young adults, aged 18 to 24 years. The NESARC sample was weighted to adjust for the unequal probabilities of selection and to provide nationally representative estimates.

The first wave of the NESARC was conducted between 2001 and 2002 and included 43 093 participants who were aged 18 years or older. Of these, 39 959 participants were eligible for wave 2 interviews. Ineligible respondents were those who could not participate in the follow-up interview because they had died, had been deported, were mentally or physically impaired, or were on active military duty. Of the eligible wave 1 participants, 34 653 were successfully monitored and reinterviewed in the wave 2 survey between 2004 and 2005. The response rates for wave 1 and eligible wave 2 surveys were 81% and 87%, respectively.

The present study sample was restricted to individuals with mood symptoms who were asked about self-medication with alcohol, reported having used alcohol in their lifetime, and were reinterviewed at wave 2 (n = 5768). For the analyses that assessed incident alcohol dependence, individuals with current and lifetime alcohol dependence at baseline were excluded (n = 1547), leaving a study sample of 4221 (12 870 person-years of follow-up). For the analyses that assessed persistence of alcohol dependence, only individuals with current or lifetime alcohol dependence at the baseline interview were included, resulting in a study sample of 1547 (4756 person-years of follow-up).

Measures

In this study, data from NESARC wave 1 were used to assess baseline characteristics. Mental disorders were ascertained based on DSM-IV criteria using the National Institute on Alcohol Abuse and Alcoholism’s Alcohol Use Disorder and Associated Disabilities Interview Schedule–DSM-IV Version,38,39 a structured diagnostic interview designed for use by lay interviewers to derive information on lifetime and 12-month substance use and mental disorders. Mood disorders included major depression, bipolar disorder, and dysthymia. We focused on the experience of mood symptoms in the past year and distinguished between threshold and subthreshold mood syndromes. Threshold mood syndromes were cases that met the full diagnostic criteria for the specific mood disorder. The subthreshold mood syndromes were those that had some symptoms but did not meet all criteria, including the clinical significance criteria for any mood disorder. Other disorders assessed were current or lifetime alcohol abuse and dependence, drug abuse and dependence (heroin, other narcotics, cocaine, stimulants, hallucinogens, and/or marijuana), nicotine dependence, 12-month anxiety disorders (generalized anxiety, panic, and/or social anxiety), and personality disorders measured at both waves (antisocial, narcissistic, histrionic, borderline, schizoid, schizotypal, paranoid, obsessive-compulsive, dependent, and/or avoidant).

Alcohol self-medication was assessed by asking whether participants had drunk alcohol in the past year to improve their mood (asked of participants reporting depression and dysthymia symptoms) or to calm down (asked of participants reporting manic or hypomanic symptoms). Treatment history for mood symptoms was assessed by asking whether participants had ever sought treatment for depressive or manic symptoms from a counselor, therapist, doctor or other professional; had been hospitalized overnight or had gone to an emergency department because of mood symptoms; and whether a doctor had ever prescribed medication for mood symptoms.

Other variables included in these analyses were sex, age (18-29, 30-39, 40-54, and ≥55 years), race/ethnicity (non-Hispanic white, black, Hispanic, and other), educational level (<12 years, 12 years or completion of the General Equivalency Diploma test, and >12 years), family history of alcoholism, alcohol consumption patterns in the past year (every day/nearly every day vs less than every day), and amount of alcohol used on drinking days in the past year (≥5 drinks per drinking day vs <5 drinks). Family history of alcoholism was assessed by asking whether any first-degree relatives had ever been an “alcoholic or problem drinker.” Separate questions assessed participants’ biological mother, father, sisters, brothers, daughters, and sons.

Analyses

The 2 outcome variables of interest in this study were the incidence of new episodes of alcohol dependence during the follow-up period and persistence of alcohol dependence through wave 2 of the study. Participants who did not meet the criteria for alcohol dependence at baseline but who did meet the criteria during the 3-year follow-up period were defined as new-onset or incident cases of alcohol dependence. For the incidence analyses, individuals with a history of alcohol abuse were not excluded because many individuals develop alcohol abuse before dependence. In addition, a diagnosis of alcohol abuse at the time of the baseline interview was held constant in all multivariate analyses. In supplemental analyses examining incident alcohol abuse together with incident dependence as the outcome variable, among participants who did not meet criteria at wave 1, the overall association was similar to that presented for alcohol dependence alone.

We defined persistent dependence as meeting diagnostic criteria for alcohol dependence at both waves of the study. In other words, individuals with a history of 12-month or lifetime alcohol dependence at the baseline interview who also met criteria for alcohol dependence during the 3-year follow-up interval were classified as having persistent alcohol dependence.

The analyses were conducted in 3 stages. First, the sociodemographic characteristics, alcohol use patterns, psychiatric and substance use comorbidity, family history, and treatment for mood symptoms were compared across participants who did or did not develop alcohol dependence, as well as for those who did or did not have persistence of alcohol dependence. Second, these same characteristics were compared across participants by report of alcohol self-medication for mood symptoms at baseline separately for the study samples used to assess each outcome. These analyses were conducted to identify potential confounders and variables to be included in computation of propensity score weights. In the third stage of the analyses, the association of self-medication with each alcohol dependence outcome was assessed in the total sample and in strata based on sociodemographic characteristics, mood disorder diagnosis, and treatment history to examine whether the effect was more pronounced in some population subgroups than others. These analyses were conducted using bivariate and multivariate models. The multivariate logistic regression models adjusted for sociodemographic, psychopathologic, substance use, and treatment variables and whether or not the participants’ symptoms met the diagnostic thresholds for mood disorder diagnoses. However, there are limitations to the use of regression adjustment, in particular, model dependence when the groups differ on the observed characteristics.40,41 Therefore, in addition to regression adjustment, we used the propensity score method of inverse probability of treatment weighting (IPTW)42,43 to adjust for differences between self-medicating and non–self-medicating participants. In this technique, propensity scores (probability of self-medication) are computed first, using a logistic regression model. These scores reflect participants’ likelihood of self-medicating with alcohol given their sociodemographic and clinical characteristics. Next, data are weighted by their inverse probabilities of being in their observed group (self-medicating vs non–self-medicating).41

The NESARC used a complex sampling design. Analyses used commercial software (Svy routines in Stata, version 11.0; StataCorp) to take into account survey weights, clustering, and stratification of the data. The propensity score weights described in the previous paragraph were multiplied by the survey weights, and the resulting combined weights were used in analyses of the association of self-medication with alcohol dependence during follow-up. To assess the effectiveness of the IPTW in balancing the composition of the self-medicating and non–self-medicating groups, we compared the characteristics of the groups before and after applying the combined weights. Application of inverse probability of treatment weighting in these analyses was successful, since the groups in analyses for both alcohol outcomes (incidence of alcohol dependence and persistence of alcohol dependence) were similar with respect to the observed characteristics after using the weights.44 Population-attributable fraction (PAF) was computed using the Punaf program for the statistical software.45 The program implements the method for estimating PAFs as recommended by Greenland and Drescher46 for cohort and cross-sectional studies.

Among the study participants with mood symptoms, 226 new-onset cases of alcohol dependence developed during follow-up. A total of 1708 of the baseline sample (40.5%) met the criteria for a 12-month DSM-IV mood disorder, and an additional 2513 individuals (59.5%) had mood symptoms without meeting full criteria for a mood disorder diagnosis. A total of 455 cases of persistent alcohol dependence were identified by the time of the wave 2 interview. The baseline characteristics associated with incidence and persistence of alcohol dependence are presented in Table 1. In the initial bivariate analyses, individuals who developed new-onset alcohol dependence, as well as those with persistence of alcohol dependence, were more likely to report having used alcohol to self-medicate their mood symptoms. In addition, individuals with incident or persistent alcohol dependence were more likely to be men, to be among the youngest age group classification (aged 18-29 years), to report greater quantity and frequency of consumption, and to have a diagnosis of illicit drug or nicotine dependence. Furthermore, persistence of alcohol dependence tended to be more strongly associated with a mood and/or substance use disorder, family history of alcoholism, and lower educational level. Incident alcohol dependence was more strongly associated with minority race/ethnicity. Similar characteristics were associated with baseline alcohol self-medication in both study samples (eTable in Supplement).

Table Graphic Jump LocationTable 1.  Characteristics of NESARC Participants With Mood Symptoms at the Wave 1 (Baseline) Interview With Incidence and Persistence of Alcohol Dependence at the Time of the Follow-up Interview (Wave 2)

The findings for the multivariate IPTW logistic regression models are presented in Table 2. The analyses were completed for the entire study sample and separately within specific strata. For example, in the sex-stratified analyses, we ran models separately for men and women. The adjusted analyses took into account the IPTW and adjusted for sociodemographic, psychopathologic, and treatment history covariates. For the total sample, self-medication of mood symptoms with alcohol was associated with an increased odds for incident alcohol dependence during follow-up (adjusted odds ratio [AOR], 3.10; 95% CI, 1.55-6.19; P = .002), and for persistent alcohol dependence (AOR, 3.45; 95% CI, 2.35-5.08; P < .001). The proportion of incident alcohol dependence cases potentially attributable to alcohol self-medication in the population, taking into account survey weights, was approximately 12% (PAF, 11.9%, 95% CI, 6.7%-16.9%). However, 30.6% (95% CI, 24.8%-36.0%) of persistent alcohol dependence cases may be attributable to drinking to self-medicate mood symptoms.

Table Graphic Jump LocationTable 2.  Association of Self-medication Drinking With Alcohol Dependence Outcomes

In the sex-, age-, and race-stratified analyses, little evidence for differences among the subgroups was found, since there was significant overlap in CIs. Because self-medication may be less likely to occur with fewer or less severe mood symptoms, we examined the associations by whether individuals met full diagnostic criteria for mood disorders or had subthreshold symptoms. Although odds ratios in both subgroups were elevated, self-medication drinking tended to have a stronger and statistically significant association with incident dependence among individuals with subthreshold symptoms (AOR, 3.88; 95% CI, 1.63-9.26; P = .003). On the other hand, self-medication drinking was associated with persistent alcohol dependence for participants with subthreshold symptoms, as well as those who met full criteria for a mood disorder. Self-medication drinking among individuals who reported having received treatment for mood symptoms was associated with a 4-fold increased odds of incident alcohol dependence in follow-up (AOR, 3.94; 95% CI, 1.82-8.53 P = .001), whereas a weaker association of self-medication with dependence was found among those without a treatment history (AOR, 1.97; 95% CI, 0.50-7.76, P = .33). Drinking to self-medicate mood symptoms was strongly associated with persistence of alcohol dependence among those with and without a treatment history (AOR, 4.81; 95% CI, 2.91-7.94; P < .001 and AOR, 2.18; 95% CI, 1.27-3.74; P = .006, respectively), but those with a treatment history had a significantly stronger association with persistent dependence (F1,61 = 4.95; P = .03).

In supplemental analyses, we assessed the association between alcohol self-medication of mood symptoms and incident alcohol abuse, as well as incident alcohol dependence at follow-up (after exclusion of all baseline cases of alcohol abuse and alcohol dependence). In these propensity score–adjusted analyses, we found a similar overall association with drinking to self-medicate mood symptoms (AOR, 3.04; 95% CI, 1.43-6.47; P = .005); however, power was attenuated to complete the proposed stratified analyses.

Consistent with our principal hypotheses, drinking to self-medicate mood symptoms is associated with the development of alcohol dependence. Once the dependence has developed, self-medicating with alcohol is associated with an increased probability of persistent dependence. In this population-based sample, the odds for developing alcohol dependence were 3 times greater for participants who self-medicated their symptoms relative to those who reported no self-medication. The odds for persistence were also 3-fold greater for individuals who reported drinking to self-medicate their mood symptoms. In our study samples, approximately 12% of new cases of alcohol dependence and 30% of persistent cases were potentially attributable to alcohol self-medication of mood symptoms. Contrary to our initial hypotheses, the association of alcohol self-medication with incident or persistent dependence did not appreciably vary within strata by sex, age, or race/ethnicity. Furthermore, the associations were elevated among individuals who met the full criteria for a mood disorder, as well as among individuals who met some but not all required criteria for an affective condition. This subthreshold group would be less likely to receive mental health treatment because of the lower severity of their symptoms.

Although self-medication with alcohol is a commonly mentioned explanation for the comorbid occurrence of mood disorders and alcohol dependence, there are relatively few data examining whether this association may increase the probability of developing dependence. There is also little assessment of whether the self-medication is associated with persistence of dependence in population-based samples. Consistent with some prior cross-sectional and clinical studies31,4749 using different methodology and within select study samples, the present analyses provide evidence that self-medication of mood symptoms with alcohol is associated with the new onset of dependence as well as the persistence of dependence over time. This association was found to be equally strong for men and women, across race/ethnicity subgroups, and among older individuals as well as young adults. Furthermore, the findings indicate that even among individuals who have some mood symptoms but who do not meet the full criteria for a mood disorder, self-medication by drinking may put them at a similar potential risk for dependence as was found for those with more severe mood conditions, such as bipolar disorder or major depression.

Although we found that alcohol use for self-medication of mood symptoms is associated with an increased risk of subsequent alcohol dependence, there are other possible explanations for the comorbid associations between affective conditions and alcohol use disorders not explored here. In prior assessments of bidirectional comorbidity, most instances of comorbidity appear to result from mood disorders occurring subsequent to the alcohol use disorder.25 There may be several physiologic mechanisms that explain the comorbidity.36,5052 Thus, it is likely that both causal pathways may operate.53,54 Furthermore, there may be common underlying genetic as well as social or environmental factors that predispose an individual to an increased risk for both disorders.5560

Individuals who report a history of treatment for mood disorders had a stronger association of self-medication drinking with incident as well as persistent alcohol dependence in contrast to those without any treatment history. This finding may indicate that individuals with a treatment history have more severe mood symptoms or symptoms that are refractory to the treatment received. It also may indicate that receiving treatment for mood conditions does not necessarily mean that some individuals will not also self-medicate with alcohol. Simply addressing the mood symptoms does not necessarily mitigate the subsequent drinking behavior.61 Once alcohol use becomes problematic, treatment modalities would need to address the mood and substance use symptoms, as well as personal and environmental issues that may need to be considered when developing appropriate treatment plans.62,63 Some individuals may drink in response to mood symptoms, as well as to achieve relief and separation from painful or stressful emotional experiences62 or to attempt to bolster inadequate or poorly developed coping skills. All of these issues may be challenging to address and often require a multimodal treatment strategy. In addition, it may be necessary to provide further educational efforts in treatment-seeking populations concerning the risks associated with use of alcohol as a potential coping mechanism or to alleviate symptoms.

Several limitations of these analyses are noteworthy. First, the present study did not incorporate an experience sampling methodology.64 As a consequence, we did not have the ability to evaluate mood symptoms because they might occur on a daily basis or might be linked to subsequent alcohol consumption within a limited time interval. However, this type of methodology is less feasible when attempting to link behavior changes over extended periods. It also would be challenging to use this methodology to establish transition to the new onset of a substance use disorder or provide evidence for the development of a chronic dependent condition in a population-based sample. Second, although using the population-based sample reduces selection biases that would likely occur within a clinical context, the potential for misclassification bias may occur because of differential reporting of self-medication. Individuals need to be aware of their behavior to acknowledge self-medication and report its occurrence. Some individuals with mood conditions may consume alcohol without the insight that their consumption may be an attempt to alleviate negative affect. We were able to take into account differences in consumption patterns by frequency and quantity, as well as differences in diagnostic history. These characteristics in our analyses did not explain the self-medication/dependence associations. Related to this potential reporting bias is the concern that adequate validation of the single survey item to assess self-medication drinking has not been completed and poses further concerns regarding potential misclassification. However, although some individuals may underreport their self-medication drinking, those who report this behavior may be an appropriate target for prevention and early intervention efforts at reducing the occurrence of dependence. Furthermore, if many individuals in the sample had mood symptoms but underreported their self-medication drinking, this would tend to weaken the hypothesized associations in our analyses. This indicates that our findings may underestimate the self-medication/dependence associations. However, reporting biases may work the other way, in that individuals who drink heavily may want to use self-medication as a way of rationalizing their drinking, even if they do not have mood symptoms. We were not able to assess whether individuals without affective symptoms or depression also report self-medication drinking, as the questions concerning self-medication were asked only of individuals with mood and anxiety symptoms. Third, although we were able to hold constant a large number and range of confounding characteristics, the potential for residual confounding remains. Individual-level characteristics such as coping skills, neighborhood-level items such as poverty and the availability of liquor stores, and medical community–level factors such as access to mental health care or substance disorder treatment may explain some of the associations found in our present study. Although we were not able to hold constant all potentially explanatory characteristics, we were able to use propensity score methodology to assess the causal inferences of these associations. The use of this methodology reduces confounding resulting from observed characteristics and any unobserved characteristics associated with the observed ones. However, noncausal explanations for the reported associations are still possible. Fourth, although this is one of the largest prospective population-based samples available with the degree of mental health and substance use measurement necessary for this complex assessment, some analyses are still limited by small subgroup sizes, such as those by specific type of treatment history and diagnostic classification. As a consequence, the power to examine these additional subgroups was inadequate.

Notwithstanding these limitations, the present analyses highlight a potentially significant risk factor for the development and persistence of alcohol dependence that may be an appropriate target for prevention efforts. Although it is widely accepted that individuals with mood disorders should receive appropriate treatment, there is a large group of individuals with subthreshold mood symptoms who may be at equal risk for dependence and generally do not receive treatment. Individuals with subclinical or subthreshold symptoms are unlikely to seek mental health treatment but may attempt to cope with their early mood symptoms with alternative strategies. They may not be aware of the importance of avoiding alleviation of mood symptoms with alcohol. Early identification and educational efforts, particularly in clinical settings where at-risk individuals potentially are more readily targeted, may have an effect on reducing the development and chronicity of alcohol dependence.

Corresponding Author: Rosa M. Crum, MD, MHS, Johns Hopkins Health Institutions, Welch Center for Prevention, Epidemiology and Clinical Research, 2024 E Monument St, Ste 2-500, Baltimore, MD 21205 (rcrum@jhsph.edu).

Submitted for Publication: February 4, 2012; final revision received August 17, 2012; accepted October 30, 2012.

Published Online: May 1, 2013. doi: 10.1001/jamapsychiatry.2013.1098

Author Contributions: Dr Crum had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of Interest Disclosures: None reported.

Funding/Support: The analyses and preparation of this project were supported by grants AA016346 from the National Institute on Alcohol Abuse and Alcoholism and DA030460 from the National Institute on Drug Abuse. Preparation of the manuscript was supported by New Investigator Award 152348 from the Canadian Institutes of Health Research, a Manitoba Health Research Council Chair award (Dr Sareen), and a Johns Hopkins School of Medicine Clinician Scientist Award (Dr Alvanzo).

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Regier  DA, Farmer  ME, Rae  DS,  et al.  Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264(19):2511-2518.
PubMed   |  Link to Article
Kessler  RC, Crum  RM, Warner  LA, Nelson  CB, Schulenberg  J, Anthony  JC.  Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch Gen Psychiatry. 1997;54(4):313-321.
PubMed   |  Link to Article
Ross  HE.  DSM-III-R alcohol abuse and dependence and psychiatric comorbidity in Ontario: results from the Mental Health Supplement to the Ontario Health Survey. Drug Alcohol Depend. 1995;39(2):111-128.
PubMed   |  Link to Article
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):807-816.
PubMed   |  Link to Article
Hasin  DS, Goodwin  RD, Stinson  FS, Grant  BF.  Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry. 2005;62(10):1097-1106.
PubMed   |  Link to Article
Husky  MM, Mazure  CM, Paliwal  P, McKee  SA.  Gender differences in the comorbidity of smoking behavior and major depression. Drug Alcohol Depend. 2008;93(1-2):176-179.
PubMed   |  Link to Article
Fergusson  DM, Boden  JM, Horwood  LJ.  Tests of causal links between alcohol abuse or dependence and major depression. Arch Gen Psychiatry. 2009;66(3):260-266.
PubMed   |  Link to Article
Hasin  DS, Grant  BF.  Major depression in 6050 former drinkers: association with past alcohol dependence. Arch Gen Psychiatry. 2002;59(9):794-800.
PubMed   |  Link to Article
Kuo  PH, Gardner  CO, Kendler  KS, Prescott  CA.  The temporal relationship of the onsets of alcohol dependence and major depression: using a genetically informative study design. Psychol Med. 2006;36(8):1153-1162.
PubMed   |  Link to Article
Boden  JM, Fergusson  DM.  Alcohol and depression. Addiction. 2011;106(5):906-914.
PubMed   |  Link to Article
Wang  JC, Hinrichs  AL, Stock  H,  et al.  Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet. 2004;13(17):1903-1911.
PubMed   |  Link to Article
Khantzian  EJ.  Self-regulation and self-medication factors in alcoholism and the addictions: similarities and differences. Recent Dev Alcohol.1990;8:255-271.
PubMed
Holahan  CJ, Moos  RH, Holahan  CK, Cronkite  RC, Randall  PK.  Drinking to cope and alcohol use and abuse in unipolar depression: a 10-year model. J Abnorm Psychol. 2003;112(1):159-165.
PubMed   |  Link to Article
Cohen  E, Feinn  R, Arias  A, Kranzler  HR.  Alcohol treatment utilization: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. Drug Alcohol Depend. 2007;86(2-3):214-221.
PubMed   |  Link to Article
Persson  J, Magnusson  P-H.  Comparison between different methods of detecting patients with excessive consumption of alcohol. Acta Med Scand. 1988;223(2):101-109.
PubMed   |  Link to Article
Swendsen  JD, Tennen  H, Carney  MA, Affleck  G, Willard  A, Hromi  A.  Mood and alcohol consumption: an experience sampling test of the self-medication hypothesis. J Abnorm Psychol. 2000;109(2):198-204.
PubMed   |  Link to Article
Bolton  JM, Robinson  J, Sareen  J.  Self-medication of mood disorders with alcohol and drugs in the National Epidemiologic Survey on Alcohol and Related Conditions. J Affect Disord. 2009;115(3):367-375.
PubMed   |  Link to Article
Robinson  JA, Sareen  J, Cox  BJ, Bolton  JM.  Correlates of self-medication for anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Nerv Ment Dis. 2009;197(12):873-878.
PubMed   |  Link to Article
Robinson  J, Sareen  J, Cox  BJ, Bolton  J.  Self-medication of anxiety disorders with alcohol and drugs: results from a nationally representative sample. J Anxiety Disord. 2009;23(1):38-45.
PubMed   |  Link to Article
Lazareck  S, Robinson  JA, Crum  RM, Mojtabai  R, Sareen  J, Bolton  JM.  A longitudinal investigation of the role of self-medication in the development of comorbid mood and drug use disorders: findings from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). J Clin Psychiatry. 2012;73(5):e588-e593. doi:10.4088/JCP.11m07345.
PubMed   |  Link to Article
Bolton  J, Cox  B, Clara  I, Sareen  J.  Use of alcohol and drugs to self-medicate anxiety disorders in a nationally representative sample. J Nerv Ment Dis. 2006;194(11):818-825.
PubMed   |  Link to Article
Grant  BF, Goldstein  RB, Chou  SP,  et al.  Sociodemographic and psychopathologic predictors of first incidence of DSM-IV substance use, mood and anxiety disorders: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Mol Psychiatry. 2009;14(11):1051-1066.
PubMed   |  Link to Article
Grant  BF, Harford  TC, Dawson  DA, Chou  PS, Pickering  RP.  The Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS): reliability of alcohol and drug modules in a general population sample. Drug Alcohol Depend. 1995;39(1):37-44.
PubMed   |  Link to Article
Ruan  WJ, Goldstein  RB, Chou  SP,  et al.  The Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV (AUDADIS-IV): reliability of new psychiatric diagnostic modules and risk factors in a general population sample. Drug Alcohol Depend. 2008;92(1-3):27-36.
PubMed   |  Link to Article
Rubin  DB.  Estimating causal effects from large data sets using propensity scores. Ann Intern Med. 1997;127(8 Pt 2):757-763.
PubMed   |  Link to Article
Rubin  DB.  Propensity score methods. Am J Ophthalmol. 2010;149(1):7-9.
PubMed   |  Link to Article
Curtis  LH, Hammill  BG, Eisenstein  EL, Kramer  JM, Anstrom  KJ.  Using inverse probability-weighted estimators in comparative effectiveness analyses with observational databases. Med Care. 2007;45(10)(suppl 2):S103-S107.
PubMed   |  Link to Article
Xu  S, Ross  C, Raebel  MA, Shetterly  S, Blanchette  C, Smith  D.  Use of stabilized inverse propensity scores as weights to directly estimate relative risk and its confidence intervals. Value Health. 2010;13(2):273-277.
PubMed   |  Link to Article
Stuart  EA.  Matching methods for causal inference: a review and a look forward. Stat Sci. 2010;25(1):1-21.
PubMed   |  Link to Article
Newson R. PUNAF: Stata module to compute population attributable fractions for cohort studies. http://ideas.repec.org/c/boc/bocode/s457193.html. Published October 15, 2010. Accessed April 28, 2011.
Greenland  S, Drescher  K.  Maximum likelihood estimation of the attributable fraction from logistic models. Biometrics. 1993;49(3):865-872.
PubMed   |  Link to Article
Kelder  SH, Murray  NG, Orpinas  P,  et al.  Depression and substance use in minority middle-school students. Am J Public Health. 2001;91(5):761-766.
PubMed   |  Link to Article
Tomlinson  KL, Tate  SR, Anderson  KG, McCarthy  DM, Brown  SA.  An examination of self-medication and rebound effects: psychiatric symptomatology before and after alcohol or drug relapse. Addict Behav. 2006;31(3):461-474.
PubMed   |  Link to Article
Miller  BE, Miller  MN, Verhegge  R, Linville  HH, Pumariega  AJ.  Alcohol misuse among college athletes: self-medication for psychiatric symptoms? J Drug Educ. 2002;32(1):41-52.
PubMed   |  Link to Article
Feldstein Ewing  SW, Filbey  FM, Chandler  LD, Hutchison  KE.  Exploring the relationship between depressive and anxiety symptoms and neuronal response to alcohol cues. Alcohol Clin Exp Res. 2010;34(3):396-403.
PubMed   |  Link to Article
McEachin  RC, Keller  BJ, Saunders  EF, McInnis  MG.  Modeling gene-by-environment interaction in comorbid depression with alcohol use disorders via an integrated bioinformatics approach. BioData Min. 2008;1(1):2. doi:10.1186/1756-0381-1-2.
PubMed   |  Link to Article
Bruijnzeel  AW, Gold  MS.  The role of corticotropin-releasing factor–like peptides in cannabis, nicotine, and alcohol dependence. Brain Res Brain Res Rev. 2005;49(3):505-528.
PubMed   |  Link to Article
Rohde  P, Lewinsohn  PM, Kahler  CW, Seeley  JR, Brown  RA.  Natural course of alcohol use disorders from adolescence to young adulthood. J Am Acad Child Adolesc Psychiatry. 2001;40(1):83-90.
PubMed   |  Link to Article
Fergusson  DM, Woodward  LJ.  Mental health, educational, and social role outcomes of adolescents with depression. Arch Gen Psychiatry. 2002;59(3):225-231.
PubMed   |  Link to Article
Nellissery  M, Feinn  RS, Covault  J,  et al.  Alleles of a functional serotonin transporter promoter polymorphism are associated with major depression in alcoholics. Alcohol Clin Exp Res. 2003;27(9):1402-1408.
PubMed   |  Link to Article
Kendler  KS, Heath  AC, Neale  MC, Kessler  RC, Eaves  LJ.  Alcoholism and major depression in women: a twin study of the causes of comorbidity. Arch Gen Psychiatry. 1993;50(9):690-698.
PubMed   |  Link to Article
Dohrenwend  BP, Levav  I, Shrout  PE,  et al.  Socioeconomic status and psychiatric disorders: the causation-selection issue. Science. 1992;255(5047):946-952.
PubMed   |  Link to Article
Maier  W, Merikangas  K.  Co-occurrence and co-transmission of affective disorders and alcoholism in families. Br J Psychiatry Suppl. 1996;(30):93-100.
PubMed
Clark  DB, De Bellis  MD, Lynch  KG, Cornelius  JR, Martin  CS.  Physical and sexual abuse, depression and alcohol use disorders in adolescents: onsets and outcomes. Drug Alcohol Depend. 2003;69(1):51-60.
PubMed   |  Link to Article
Fu  Q, Heath  AC, Bucholz  KK,  et al.  Shared genetic risk of major depression, alcohol dependence, and marijuana dependence: contribution of antisocial personality disorder in men. Arch Gen Psychiatry. 2002;59(12):1125-1132.
PubMed   |  Link to Article
DuPont  RL, Gold  MS.  Comorbidity and “self-medication.” J Addict Dis. 2007;26(suppl 1):13-23.
PubMed   |  Link to Article
Brown  CG, Stewart  SH.  Exploring perceptions of alcohol use as self-medication for depression among women receiving community-based treatment for alcohol problems. J Prev Interv Community. 2008;35(2):33-47.
PubMed   |  Link to Article
De Bernardo  GL, Newcomb  M, Toth  A, Richey  G, Mendoza  R.  Comorbid psychiatric and alcohol abuse/dependence disorders: psychosocial stress, abuse, and personal history factors of those in treatment. J Addict Dis. 2002;21(3):43-59.
PubMed   |  Link to Article
Csikszentmihalyi  M, Larson  R.  Validity and reliability of the experience-sampling Method. J Nerv Ment Dis. 1987;175(9):526-536.
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1.  Characteristics of NESARC Participants With Mood Symptoms at the Wave 1 (Baseline) Interview With Incidence and Persistence of Alcohol Dependence at the Time of the Follow-up Interview (Wave 2)
Table Graphic Jump LocationTable 2.  Association of Self-medication Drinking With Alcohol Dependence Outcomes

References

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Driessen  M, Meier  S, Hill  A, Wetterling  T, Lange  W, Junghanns  K.  The course of anxiety, depression and drinking behaviours after completed detoxification in alcoholics with and without comorbid anxiety and depressive disorders. Alcohol Alcohol. 2001;36(3):249-255.
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Brown  SA, Inaba  RK, Gillin  JC, Schuckit  MA, Stewart  MA, Irwin  MR.  Alcoholism and affective disorder: clinical course of depressive symptoms. Am J Psychiatry. 1995;152(1):45-52.
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Salloum  IM, Mezzich  JE, Cornelius  J, Day  NL, Daley  D, Kirisci  L.  Clinical profile of comorbid major depression and alcohol use disorders in an initial psychiatric evaluation. Compr Psychiatry. 1995;36(4):260-266.
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Cornelius  JR, Salloum  IM, Mezzich  J,  et al.  Disproportionate suicidality in patients with comorbid major depression and alcoholism. Am J Psychiatry. 1995;152(3):358-364.
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Meyer  C, Rumpf  HJ, Hapke  U, John  U.  Impact of psychiatric disorders in the general population: satisfaction with life and the influence of comorbidity and disorder duration. Soc Psychiatry Psychiatr Epidemiol. 2004;39(6):435-441.
PubMed   |  Link to Article
Regier  DA, Farmer  ME, Rae  DS,  et al.  Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264(19):2511-2518.
PubMed   |  Link to Article
Kessler  RC, Crum  RM, Warner  LA, Nelson  CB, Schulenberg  J, Anthony  JC.  Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch Gen Psychiatry. 1997;54(4):313-321.
PubMed   |  Link to Article
Ross  HE.  DSM-III-R alcohol abuse and dependence and psychiatric comorbidity in Ontario: results from the Mental Health Supplement to the Ontario Health Survey. Drug Alcohol Depend. 1995;39(2):111-128.
PubMed   |  Link to Article
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):807-816.
PubMed   |  Link to Article
Hasin  DS, Goodwin  RD, Stinson  FS, Grant  BF.  Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry. 2005;62(10):1097-1106.
PubMed   |  Link to Article
Husky  MM, Mazure  CM, Paliwal  P, McKee  SA.  Gender differences in the comorbidity of smoking behavior and major depression. Drug Alcohol Depend. 2008;93(1-2):176-179.
PubMed   |  Link to Article
Fergusson  DM, Boden  JM, Horwood  LJ.  Tests of causal links between alcohol abuse or dependence and major depression. Arch Gen Psychiatry. 2009;66(3):260-266.
PubMed   |  Link to Article
Hasin  DS, Grant  BF.  Major depression in 6050 former drinkers: association with past alcohol dependence. Arch Gen Psychiatry. 2002;59(9):794-800.
PubMed   |  Link to Article
Kuo  PH, Gardner  CO, Kendler  KS, Prescott  CA.  The temporal relationship of the onsets of alcohol dependence and major depression: using a genetically informative study design. Psychol Med. 2006;36(8):1153-1162.
PubMed   |  Link to Article
Boden  JM, Fergusson  DM.  Alcohol and depression. Addiction. 2011;106(5):906-914.
PubMed   |  Link to Article
Wang  JC, Hinrichs  AL, Stock  H,  et al.  Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet. 2004;13(17):1903-1911.
PubMed   |  Link to Article
Khantzian  EJ.  Self-regulation and self-medication factors in alcoholism and the addictions: similarities and differences. Recent Dev Alcohol.1990;8:255-271.
PubMed
Holahan  CJ, Moos  RH, Holahan  CK, Cronkite  RC, Randall  PK.  Drinking to cope and alcohol use and abuse in unipolar depression: a 10-year model. J Abnorm Psychol. 2003;112(1):159-165.
PubMed   |  Link to Article
Cohen  E, Feinn  R, Arias  A, Kranzler  HR.  Alcohol treatment utilization: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. Drug Alcohol Depend. 2007;86(2-3):214-221.
PubMed   |  Link to Article
Persson  J, Magnusson  P-H.  Comparison between different methods of detecting patients with excessive consumption of alcohol. Acta Med Scand. 1988;223(2):101-109.
PubMed   |  Link to Article
Swendsen  JD, Tennen  H, Carney  MA, Affleck  G, Willard  A, Hromi  A.  Mood and alcohol consumption: an experience sampling test of the self-medication hypothesis. J Abnorm Psychol. 2000;109(2):198-204.
PubMed   |  Link to Article
Bolton  JM, Robinson  J, Sareen  J.  Self-medication of mood disorders with alcohol and drugs in the National Epidemiologic Survey on Alcohol and Related Conditions. J Affect Disord. 2009;115(3):367-375.
PubMed   |  Link to Article
Robinson  JA, Sareen  J, Cox  BJ, Bolton  JM.  Correlates of self-medication for anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Nerv Ment Dis. 2009;197(12):873-878.
PubMed   |  Link to Article
Robinson  J, Sareen  J, Cox  BJ, Bolton  J.  Self-medication of anxiety disorders with alcohol and drugs: results from a nationally representative sample. J Anxiety Disord. 2009;23(1):38-45.
PubMed   |  Link to Article
Lazareck  S, Robinson  JA, Crum  RM, Mojtabai  R, Sareen  J, Bolton  JM.  A longitudinal investigation of the role of self-medication in the development of comorbid mood and drug use disorders: findings from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). J Clin Psychiatry. 2012;73(5):e588-e593. doi:10.4088/JCP.11m07345.
PubMed   |  Link to Article
Bolton  J, Cox  B, Clara  I, Sareen  J.  Use of alcohol and drugs to self-medicate anxiety disorders in a nationally representative sample. J Nerv Ment Dis. 2006;194(11):818-825.
PubMed   |  Link to Article
Grant  BF, Goldstein  RB, Chou  SP,  et al.  Sociodemographic and psychopathologic predictors of first incidence of DSM-IV substance use, mood and anxiety disorders: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Mol Psychiatry. 2009;14(11):1051-1066.
PubMed   |  Link to Article
Grant  BF, Harford  TC, Dawson  DA, Chou  PS, Pickering  RP.  The Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS): reliability of alcohol and drug modules in a general population sample. Drug Alcohol Depend. 1995;39(1):37-44.
PubMed   |  Link to Article
Ruan  WJ, Goldstein  RB, Chou  SP,  et al.  The Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV (AUDADIS-IV): reliability of new psychiatric diagnostic modules and risk factors in a general population sample. Drug Alcohol Depend. 2008;92(1-3):27-36.
PubMed   |  Link to Article
Rubin  DB.  Estimating causal effects from large data sets using propensity scores. Ann Intern Med. 1997;127(8 Pt 2):757-763.
PubMed   |  Link to Article
Rubin  DB.  Propensity score methods. Am J Ophthalmol. 2010;149(1):7-9.
PubMed   |  Link to Article
Curtis  LH, Hammill  BG, Eisenstein  EL, Kramer  JM, Anstrom  KJ.  Using inverse probability-weighted estimators in comparative effectiveness analyses with observational databases. Med Care. 2007;45(10)(suppl 2):S103-S107.
PubMed   |  Link to Article
Xu  S, Ross  C, Raebel  MA, Shetterly  S, Blanchette  C, Smith  D.  Use of stabilized inverse propensity scores as weights to directly estimate relative risk and its confidence intervals. Value Health. 2010;13(2):273-277.
PubMed   |  Link to Article
Stuart  EA.  Matching methods for causal inference: a review and a look forward. Stat Sci. 2010;25(1):1-21.
PubMed   |  Link to Article
Newson R. PUNAF: Stata module to compute population attributable fractions for cohort studies. http://ideas.repec.org/c/boc/bocode/s457193.html. Published October 15, 2010. Accessed April 28, 2011.
Greenland  S, Drescher  K.  Maximum likelihood estimation of the attributable fraction from logistic models. Biometrics. 1993;49(3):865-872.
PubMed   |  Link to Article
Kelder  SH, Murray  NG, Orpinas  P,  et al.  Depression and substance use in minority middle-school students. Am J Public Health. 2001;91(5):761-766.
PubMed   |  Link to Article
Tomlinson  KL, Tate  SR, Anderson  KG, McCarthy  DM, Brown  SA.  An examination of self-medication and rebound effects: psychiatric symptomatology before and after alcohol or drug relapse. Addict Behav. 2006;31(3):461-474.
PubMed   |  Link to Article
Miller  BE, Miller  MN, Verhegge  R, Linville  HH, Pumariega  AJ.  Alcohol misuse among college athletes: self-medication for psychiatric symptoms? J Drug Educ. 2002;32(1):41-52.
PubMed   |  Link to Article
Feldstein Ewing  SW, Filbey  FM, Chandler  LD, Hutchison  KE.  Exploring the relationship between depressive and anxiety symptoms and neuronal response to alcohol cues. Alcohol Clin Exp Res. 2010;34(3):396-403.
PubMed   |  Link to Article
McEachin  RC, Keller  BJ, Saunders  EF, McInnis  MG.  Modeling gene-by-environment interaction in comorbid depression with alcohol use disorders via an integrated bioinformatics approach. BioData Min. 2008;1(1):2. doi:10.1186/1756-0381-1-2.
PubMed   |  Link to Article
Bruijnzeel  AW, Gold  MS.  The role of corticotropin-releasing factor–like peptides in cannabis, nicotine, and alcohol dependence. Brain Res Brain Res Rev. 2005;49(3):505-528.
PubMed   |  Link to Article
Rohde  P, Lewinsohn  PM, Kahler  CW, Seeley  JR, Brown  RA.  Natural course of alcohol use disorders from adolescence to young adulthood. J Am Acad Child Adolesc Psychiatry. 2001;40(1):83-90.
PubMed   |  Link to Article
Fergusson  DM, Woodward  LJ.  Mental health, educational, and social role outcomes of adolescents with depression. Arch Gen Psychiatry. 2002;59(3):225-231.
PubMed   |  Link to Article
Nellissery  M, Feinn  RS, Covault  J,  et al.  Alleles of a functional serotonin transporter promoter polymorphism are associated with major depression in alcoholics. Alcohol Clin Exp Res. 2003;27(9):1402-1408.
PubMed   |  Link to Article
Kendler  KS, Heath  AC, Neale  MC, Kessler  RC, Eaves  LJ.  Alcoholism and major depression in women: a twin study of the causes of comorbidity. Arch Gen Psychiatry. 1993;50(9):690-698.
PubMed   |  Link to Article
Dohrenwend  BP, Levav  I, Shrout  PE,  et al.  Socioeconomic status and psychiatric disorders: the causation-selection issue. Science. 1992;255(5047):946-952.
PubMed   |  Link to Article
Maier  W, Merikangas  K.  Co-occurrence and co-transmission of affective disorders and alcoholism in families. Br J Psychiatry Suppl. 1996;(30):93-100.
PubMed
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