OBJECTIVES/SPECIFIC AIMS: Smoking during pregnancy (SDP) is associated with negative health outcomes, both proximal (e.g., preterm labor, cardiovascular changes, low birth weight) and distal (e.g., increased child externalizing behaviors and attention deficit/hyperactivity disorder (ADHD) symptoms, increased risk of child smoking). As pregnancy provides a unique, strong incentive to quit smoking, investigating SDP allows analysis of individual predictive factors of recalcitrant smoking behaviors. Utilizing a female twin-pair cohort provides a model system for characterizing genotype×environment interactions using statistical approaches. METHODS/STUDY POPULATION: Using women from the Missouri Adolescent Female Twin Study, parental report of twin ADHD inattentive and hyperactive symptoms at twin median age 15, and twin report of DSM-IV lifetime diagnosis of major depressive disorder, trauma exposure (physical assault and childhood sexual abuse), collected at median age 22, were merged with Missouri birth record data for enrolled twins, leading to 1553 individuals of European ancestry and 163 individuals of African-American ancestry included in final analyses. A SDP propensity score was calculated from sociodemographic variables (maternal age, marital status, educational attainment, first born child) and used as a 6-level ordinal covariate in subsequent logistic regressions. RESULTS/ANTICIPATED RESULTS: For European ancestry individuals, parental report of hyperactive ADHD symptoms and exposure to childhood sexual abuse were predictive of SDP, while a lifetime diagnosis of major depressive disorder, parental report of inattentive ADHD symptoms, and exposure to assaultive trauma were all not significantly predictive of future SDP. For African-American individuals, none of these variables were significant in predicting future SDP. DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding this relationship of risk-mechanisms is important for clinical understanding of early predictors of SDP and tailoring interventions to at risk individuals. Ultimately, the focus of this research is to mitigate risk to pregnant smokers and their children. Additionally, the cohort-ecological approach informs how well research and administrative (vital record) data agree. This allows for evaluation of whether administrative data improve prediction in research cohorts, and conversely if research data improve prediction over standard sociodemographic variables available in administrative data.

The current study examined a stage-based alcohol use trajectory model to test for potential causal effects of earlier drinking milestones on later drinking milestones in a combined sample of two cohorts of Australian monozygotic and same-sex dizygotic twins (N = 7,398, age M = 30.46, SD = 2.61, 61% male, 56% monozygotic twins). Ages of drinking, drunkenness, regular drinking, tolerance, first nontolerance alcohol use disorder symptom, and alcohol use disorder symptom onsets were assessed retrospectively. Ages of milestone attainment (i.e., age-of-onset) and time between milestones (i.e., time-to-event) were examined via frailty models within a multilevel discordant twin design. For age-of-onset models, earlier ages of onset of antecedent drinking milestones increased hazards for earlier ages of onset for more proximal subsequent drinking milestones. For the time-to-event models, however, earlier ages of onset for the “starting” milestone decreased risk for a shorter time period between the starting and the “ending” milestone. Earlier age of onset of intermediate milestones between starting and ending drinking milestones had the opposite effect, increasing risk for a shorter time period between the starting and ending milestones. These results are consistent with a causal effect of an earlier age of drinking milestone onset on temporally proximal subsequent drinking milestones.

Migraine frequently co-occurs with depression. Using a large sample of Australian twin pairs, we aimed to characterize the extent to which shared genetic factors underlie these two disorders. Migraine was classified using three diagnostic measures, including self-reported migraine, the ID migraine™ screening tool, or migraine without aura (MO) and migraine with aura (MA) based on International Headache Society (IHS) diagnostic criteria. Major depressive disorder (MDD) and minor depressive disorder (MiDD) were classified using the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Univariate and bivariate twin models, with and without sex-limitation, were constructed to estimate the univariate and bivariate variance components and genetic correlation for migraine and depression. The univariate heritability of broad migraine (self-reported, ID migraine, or IHS MO/MA) and broad depression (MiDD or MDD) was estimated at 56% (95% confidence interval [CI]: 53–60%) and 42% (95% CI: 37–46%), respectively. A significant additive genetic correlation (rG = 0.36, 95% CI: 0.29–0.43) and bivariate heritability (h2 = 5.5%, 95% CI: 3.6–7.8%) was observed between broad migraine and depression using the bivariate Cholesky model. Notably, both the bivariate h2 (13.3%, 95% CI: 7.0–24.5%) and rG (0.51, 95% CI: 0.37–0.69) estimates significantly increased when analyzing the more narrow clinically accepted diagnoses of IHS MO/MA and MDD. Our results indicate that for both broad and narrow definitions, the observed comorbidity between migraine and depression can be explained almost entirely by shared underlying genetically determined disease mechanisms.

Objectives: This research examined the familial aggregation of migraine, depression, and their co-occurrence.

Methods: Diagnoses of migraine and depression were determined in a sample of 5,319 Australian twins. Migraine was diagnosed by either self-report, the ID migraine™ Screener, or International Headache Society (IHS) criteria. Depression was defined by fulfilling either major depressive disorder (MDD) or minor depressive disorder (MiDD) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. The relative risks (RR) for migraine and depression were estimated in co-twins of twin probands reporting migraine or depression to evaluate their familial aggregation and co-occurrence.

Results: An increased RR of both migraine and depression in co-twins of probands with the same trait was observed, with significantly higher estimates within monozygotic (MZ) twin pairs compared to dizygotic (DZ) twin pairs. For cross-trait analysis, the RR for migraine in co-twins of probands reporting depression was 1.36 (95% CI: 1.24–1.48) in MZ pairs and 1.04 (95% CI: 0.95–1.14) in DZ pairs; and the RR for depression in co-twins of probands reporting migraine was 1.26 (95% CI: 1.14–1.38) in MZ pairs and 1.02 (95% CI: 0.94–1.11) in DZ pairs. The RR for strict IHS migraine in co-twins of probands reporting MDD was 2.23 (95% CI: 1.81–2.75) in MZ pairs and 1.55 (95% CI: 1.34–1.79) in DZ pairs; and the RR for MDD in co-twins of probands reporting IHS migraine was 1.35 (95% CI: 1.13–1.62) in MZ pairs and 1.06 (95% CI: 0.93–1.22) in DZ pairs.

Conclusions: We observed significant evidence for a genetic contribution to familial aggregation of migraine and depression. Our findings suggest a bi-directional association between migraine and depression, with an increased risk for depression in relatives of probands reporting migraine, and vice versa. However, the observed risk for migraine in relatives of probands reporting depression was considerably higher than the reverse. These results add further support to previous studies suggesting that patients with comorbid migraine and depression are genetically more similar to patients with only depression than patients with only migraine.

Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10, 000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10-8) for ND (rs964170 in ARHGAPlOon chromosome 4, p = 4.43 x 10”8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10-9), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10-9) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10-8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepre-sentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be requirec before the detailed causes of comorbidity between AC and ND are understood.

Breastfeeding has been an important survival trait during human history, though it has long been recognized that individuals differ in their exact breastfeeding behavior. Here our aims were, first, to explore to what extent genetic and environmental influences contributed to the individual differences in breastfeeding behavior; second, to detect possible genetic variants related to breastfeeding; and lastly, to test if the genetic variants associated with breastfeeding have been previously found to be related with breast size. Data were collected from a large community-based cohort of Australian twins, with 3,364 women participating in the twin modelling analyses and 1,521 of them included in the genome-wide association study (GWAS). Monozygotic (MZ) twin correlations (rMZ = 0.52, 95% CI 0.46–0.57) were larger than dizygotic (DZ) twin correlations (rDZ = 0.35, 95% CI 0.25–0.43) and the best-fitting model was the one composed by additive genetics and unique environmental factors, explaining 53% and 47% of the variance in breastfeeding behavior, respectively. No breastfeeding-related genetic variants reached genome-wide significance. The polygenic risk score analyses showed no significant results, suggesting breast size does not influence breastfeeding. This study confers a replication of a previous one exploring the sources of variance of breastfeeding and, to our knowledge, is the first one to conduct a GWAS on breastfeeding and look at the overlap with variants for breast size.

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD prevalence, symptomatology, and risk factors, and (2) genetic and/or environmental liability to MDD, we analyzed data from a large population-representative sample of twins ascertained from birth records (n = 550 AA and n = 3226 EA female twins) aged 18–28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (odds ratio = 0.88, 95% confidence interval [CI]: 0.67–1.15). Most MDD risk factors identified among AA women were also associated with MDD at similar magnitudes among EA women. Although the MDD heritability point estimate was higher among AA women than EA women in a model with paths estimated separately by race (56%, 95% CI: 29–78% vs. 41%, 95% CI: 29–52%), the best fitting model was one in which additive genetic and non-shared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33–53% and E = 57%, 47–67%). In spite of a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women.

Aspects of disordered eating and personality traits, such as neuroticism, are correlated and individually heritable. We examined the phenotypic correlation between binge eating episodes and indices of personality (neuroticism, extraversion, openness to experience, agreeableness, conscientiousness, and control/impulsivity). For correlations ≥|0.20|, we estimated the extent to which genetic and environmental factors contributed to this correlation. Participants included 3,446 European American same-sex female twins from the Missouri Adolescent Female Twin Study (median age = 22 years). Binge eating episode was assessed via interview questions. Personality traits were assessed by self-report questionnaires. There was a significant moderate phenotypic correlation between binge eating episode and neuroticism (r = 0.33) as well as conscientiousness (r = -0.21), while other correlations were significant but smaller (r ranging from -0.14 to 0.14). Individual differences in binge eating episodes, neuroticism, and conscientiousness were attributed to additive genetic influences (38% [95% CI: 21–53%], 45% [95% CI: 38–52%], and 44% [95% CI: 0.33–0.55%] respectively), with the remaining variance attributed to individual-specific environmental influences. Covariance was attributable to genetic (neuroticism rg = 0.37; conscientiousness rg = -0.22) and individual-specific environmental (neuroticism re = 0.28; conscientiousness re = -0.19) influences. Personality traits may be an early indicator of genetic vulnerability to a variety of pathological behaviors, including binge eating episode. Furthermore, prior research documenting phenotypic correlations between eating disorder diagnoses and personality may have stemmed from etiological overlap between these personality traits and aspects of disordered eating, such as binge eating episode.

Cannabis is the most widely used illicit drug throughout the developed world and there is consistent evidence of heritable influences on multiple stages of cannabis involvement including initiation of use and abuse/dependence. In this paper, we describe the methodology and preliminary results of a large-scale interview study of 3,824 young adult twins (born 1972–1979) and their siblings. Cannabis use was common with 75.2% of males and 64.7% of females reporting some lifetime use of cannabis while 24.5% of males and 11.8% of females reported meeting criteria for DSM-IV cannabis abuse or dependence. Rates of other drug use disorders and common psychiatric conditions were highly correlated with extent of cannabis involvement and there was consistent evidence of heritable influences across a range of cannabis phenotypes including early (≤15 years) opportunity to use (h2 = 72%), early (≤16 years) onset use (h2 = 80%), using cannabis 11+ times lifetime (h2 = 76%), and DSM abuse/dependence (h2 = 72%). Early age of onset of cannabis use was strongly associated with increased rates of subsequent use of other illicit drugs and with illicit drug abuse/dependence; further analyses indicating that some component of this association may have been mediated by increasing exposure to and opportunity to use other illicit drugs.

Both genetic and environmental factors affect smoking initiation and maintenance, but less is known about the genetic architecture of various other smoking-related behaviors. The aim of this study is to examine the genetic architecture of smoking behavior in a large twin cohort. Questionnaires with an extensive smoking history section were mailed to same-sex adult twins of the Finnish twin cohort. The final study population included 2923 monozygotic and 6018 dizygotic twin pairs aged 24 to 88 years. Two-stage bivariate genetic modeling of age at initiation with amount smoked (less than 20 cigarettes per day vs. 20 or more) and age at initiation with smoking cessation was done by using the Mx statistical package. For men the heritability estimate for age at initiation was .59 (95% confidence interval [CI] .49–.69), for amount smoked .54 (95% CI .45–.62) and for smoking cessation .58 (95% CI .50–.65). For women the heritability estimates were .36 (95% CI .28–.43), .61 (95% CI .46–.70) and .50 (95% CI .39–.60), respectively. The genetic correlations between age at initiation and amount smoked or smoking cessation were at most .22 in magnitude, indicating that genetic influences in age at initiation accounted for at most about 4% of the genetic factors in amount smoked or in cessation. Genetic factors are important in amount smoked and smoking cessation and they are largely independent of genetic influences on age at initiation. This has implications for defining phenotypes in searches for genes underlying smoking behaviors.

Many studies have found strong peer correlations for a variety of problem behaviors that begin in adolescence (e.g. substance use). Such correlations are commonly attributed to peer influences, but could also be explained by selective (‘assortative’) friendship: the tendency for those with similar patterns of behavior to become friends. Here we show how, under certain assumptions, cross-sectional data from pairs of siblings or twins and their peers may be used to resolve the contributions of peer selection and reciprocal peer environmental influences to peer resemblance. We performed power calculations to determine necessary sample sizes for rejecting with 80% power, at the 5% significance level, the hypothesis of only peer selection effects, or only reciprocal peer environmental effects. A false hypothesis of only selective friendship effects was always easier to reject than a false hypothesis of only reciprocal peer environmental influences. Limitations of these simulations, including uncertainty about the most appropriate way to model peer selection, are discussed.

Alcohol dependence symptoms and consumption measures were examined for stability and heritability. Data were collected from 12,045 individuals (5376 twin pairs, 1293 single twins) aged 19 to 90 years in telephone interviews conducted in three collection phases. Phases 1 and 2 were independent samples, but Phase 3 targeted families of smokers and drinkers from the Phase 1 and 2 samples. The stability of dependence symptoms and consumption was examined for 1158 individuals interviewed in both Phases 1 and 3 (mean interval = 11.0 years). For 1818 individuals interviewed in Phases 2 and 3 (mean interval = 5.5 years) the stability of consumption was examined. Heritability was examined for each collection phase and retest samples from the selected Phase 3 collection. The measures examined were a dependence score, based on DSM-IIIR and DSM-IV criteria for substance dependence, and a quantity × frequency measure. Measures were moderately stable, with test–retest correlations ranging from .58 to .61 for dependence and from .55 to .64 for consumption. However, the pattern of changes over time for dependence suggested that the measure may more strongly reflect recent than lifetime experience. Similar to previous findings, heritabilities ranged from .42 to .51 for dependence and from .31 to .51 for consumption. Consumption was significantly less heritable in the younger Phase 2 cohort (23–39 years) compared to the older Phase 1 cohort (28–90 years).

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions, recovery of simulated genetic and environmental correlations becomes possible. Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

Individuals who experience one type of trauma often experience other types, yet few studies have examined the clustering of trauma. This study examines the clustering of traumatic events and associations of trauma with risk for single and co-occurring major depressive disorder (MDD) and panic attack for 20 years after first trauma. Lifetime histories of MDD, panic attack, and traumatic events were obtained from participants in an Australian twin sample. Latent class analysis was used to derive trauma classes based on each respondent's trauma history. Associations of the resulting classes and of parental alcohol problems and familial effects with risk for a first onset of single and co-occurring MDD and panic attack were examined from the year of first trauma to 20 years later. Traumatic events clustered into three distinct classes characterized by endorsement of little or no trauma, primarily nonassaultive, and primarily assaultive events. Individuals in the assaultive class were characterized by a younger age at first trauma, a greater number of traumatic events, and high rates of parental alcohol problems. Members of the assaultive trauma class had the strongest and most enduring risk for single and co-occurring lifetime MDD and panic attack. Assaultive trauma outweighed associations of familial effects and nonassaultive trauma with risk for 10 years following first trauma.

We examined whether there are crosscultural differences in the magnitude of genetic and environmental contributions to risk of becoming a regular smoker and of persistence in smoking in men and women. Standard methods of epidemio-logic and genetic analysis were applied to questionnaire data on history of cigarette use obtained from large samples of male and female like-sex twins from three different countries: Australia (N = 2284 pairs), Sweden (N = 8651 pairs), and Finland (N = 10,948 pairs). Samples were subdivided into three age groups (AG), 18–25 years, 26–35 years, and 36–46 years of age. The magnitude of genetic influence for lifetime smoking was found to be consistent across country and AG for women (46%) and men (57%), and estimates of the contribution from environmental influences shared by twin and co-twin could be equated across all countries by AG for the women (from youngest to oldest AG: 45%, 35%, and 26%), but not for men, with separate estimates obtained for the Scandinavian (33%, 29%, and 19%) and the Australian men (26%, 9%, and 11%). There was no evidence for an important role for shared environmental influences on persistent smoking, and the genetic contribution was found to be consistent in magnitude in men and women, and the same acrosscountry and AG (52%). There are strong genetic influences on smoking behavior, and that risk of becoming a smoker (but not persistence in smoking) may be modified by experiences shared by twins that differ by AG and, at least for men, cultural background.

Female twin pairs were identified from birth records, and their families invited to participate in a prospective study of the determinants of alcohol problems in women. We investigated sampling biases arising because of failure to locate families, or non-cooperation of families. Out of 2644 families with a live-born pair (born between July 1975 and December 1986) who survived beyond infancy, contact was established and a brief screening interview completed with 90% (N = 2380). Fewer than 6% of located families declined to participate in the initial screening interview. Predictors of failure to locate a family or to obtain a screening interview were identified from information recorded in birth records, and from neighborhood characteristics identified from 1990 US Census block group data for the family residence when the twins were born. African-American families were under-represented in the final sample, but this effect was barely significant when other variables were controlled for. Under-represented were families where the mother was 19 or younger at the birth of the twins, where the mother herself was born out-of-state, or where information about biological father was not reported in the birth record. Non-participating families on average came from neighborhoods with a higher proportion of residents living in poverty, and with a higher proportion of African-American residents. Sampling biases were however small. The unusual cooperativeness in research of families with twins persists.

The aim of this study is to characterize the relationship between major depression and the metabolic syndrome in a large community based sample of Australian men and women aged 26–90 years. A lifetime history of major depression was assessed by telephone interview following the DSM–III-R. A current history of metabolic syndrome was assessed following the United States National Cholesterol Education Program Adult Treatment Panel III (NCEP AP-III) guidelines 1 to 3 years later. Logistic regression was used to estimate the association between depression and the metabolic syndrome, and its component criteria, controlling for age, sex and alcohol dependence. There was no association between a lifetime history of major depression and the presence of the metabolic syndrome. There was a weak association between depression and low high-density lipoprotein cholesterol but not with other component criteria of the metabolic syndrome. Despite calls for interventions directed at depression to reduce the onset of the metabolic syndrome there are important failures to replicate in large samples such as this, no consensus regarding the threshold at which depression may pose a significant risk even allowing for heterogeneity across populations, and no consensus regarding confounders that may explain inter-study differences. The absence of any dosage effect of depression on the associated risk for the metabolic syndrome in other unselected samples does not support a direct causal relationship. The call for intervention studies on the basis of the currently published evidence base is unwarranted.

Childhood sexual abuse (CSA) and physical abuse (CPA) are well-established risk-factors for a wide of range of proximal and distal outcomes. The lack of availability of an optimal design for examining abuse and its consequences has resulted in the use of various approaches, each having its own limitations. We describe the Childhood Trauma Study, which ascertained families from a large young adult Australian twin cohort on the basis of twins' responses to screening questions assessing CSA and CPA. We report data from 3407 participants including twins, non-twin siblings, and their parents. Our data demonstrate the feasibility of using a comprehensive assessment to evaluate retrospective history of childhood abuse in an adult sample. We observed that risk for each form of abuse increased incrementally with the number of parents with alcohol problems. Psychometric properties of our measures of CSA and CPA including reasonable long-term stability, construct validity, and evidence of familial corroboration compare favorably with those of other reports in which samples were considerably younger and assessments were repeated over shorter intervals.

For zygosity diagnosis in the absence of genotypic data, or in the recruitment phase of a twin study where only single twins from same-sex pairs are being screened, or to provide a test for sample duplication leading to the false identification of a dizygotic pair as monozygotic, the appropriate analysis of respondents' answers to questions about zygosity is critical. Using data from a young adult Australian twin cohort (N = 2094 complete pairs and 519 singleton twins from same-sex pairs with complete responses to all zygosity items), we show that application of latent class analysis (LCA), fitting a 2-class model, yields results that show good concordance with traditional methods of zygosity diagnosis, but with certain important advantages. These include the ability, in many cases, to assign zygosity with specified probability on the basis of responses of a single informant (advantageous when one zygosity type is being oversampled); and the ability to quantify the probability of misassignment of zygosity, allowing prioritization of cases for genotyping as well as identification of cases of probable laboratory error. Out of 242 twins (from 121 like-sex pairs) where genotypic data were available for zygosity confirmation, only a single case was identified of incorrect zygosity assignment by the latent class algorithm. Zygosity assignment for that single case was identified by the LCA as uncertain (probability of being a monozygotic twin only 76%), and the co-twin's responses clearly identified the pair as dizygotic (probability of being dizygotic 100%). In the absence of genotypic data, or as a safeguard against sample duplication, application of LCA for zygosity assignment or confirmation is strongly recommended.

This article applies methods of latent class analysis (LCA) to data on lifetime illicit drug use in order to determine whether qualitatively distinct classes of illicit drug users can be identified. Self-report data on lifetime illicit drug use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids and solvents) collected from a sample of 6265 Australian twins (average age 30 years) were analyzed using LCA. Rates of childhood sexual and physical abuse, lifetime alcohol and tobacco dependence, symptoms of illicit drug abuse/dependence and psychiatric comorbidity were compared across classes using multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%) had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine, other stimulant and hallucinogen use but lower risks for the use of sedatives or opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other stimulant or hallucinogen use but high rates of sedative and opioid use. Finally, Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates of psychiatric comorbidity were highest in the polydrug class although the sedative/opioid class had elevated rates of depression/suicidal behaviors and exposure to childhood abuse. Aggregation of population-level data may obscure important subgroup differences in patterns of illicit drug use and psychiatric comorbidity. Further exploration of a ‘self-medicating’ subgroup is needed.