1. 1 Alcohol Use and Psychiatric Comorbidity: A Phenotypic perspective K. Thennarasu, Kathleen K Bucholz and Rosalind J Neuman Department of Psychiatry, Washington University School of Medicine, St. Louis, MO

2. 2 Objectives To establish homogeneous alcohol user classes based on comorbidities using latent class analysis.To establish homogeneous alcohol user classes based on comorbidities using latent class analysis. To validate latent phenotypic classes using external covariates.To validate latent phenotypic classes using external covariates. To find similarity between latent phenotypic classes using multi dimensional scaling.To find similarity between latent phenotypic classes using multi dimensional scaling.

3. 3 Data Source National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), 2000-2001.National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), 2000-2001. 43,093 non-institutionalized household residents43,093 non-institutionalized household residents aged >=18 years aged >=18 years NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV)NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV)

4. 4 NESARC data were divided in to five discrete groupsNESARC data were divided in to five discrete groups  Abstainers  No alcohol diagnosis  Abuse only  Dependence only  Abuse and dependence only Used the following 9 comorbid diagnosis to determine latent structure of each of the above groupsUsed the following 9 comorbid diagnosis to determine latent structure of each of the above groups  Major Depressive Disorder  Panic Disorder and Agoraphobia  Social Phobia  Specific Phobia  Generalized Anxiety Disorder  Obsessive Compulsive Disorder  Antisocial Personality Disorder  Nicotine dependence  Other drug dependence Methods* I * All diagnosis are based on DSM IV

5. 5 Methods II External validatorsExternal validators  Gender  Age  Education  Ethnicity  Mental health scale  Physical function scale*  Family history of alcohol problem  Age at onset of alcohol use*  Age at onset of everyday smoking * Results not shown in this display

6. 6 Prevalence of co-morbidities in each group

7. 7 Model selection: BIC comparison TwoThreeFourFivesixSeven Abstainers21682.5921693.6521708.0821735.8621773.13- No alcohol Dx 82689.8182388.1182323.4782310.5582336.9282391.98 Abuse only 36101.1636058.2736032.8136078.9-- Dependence only 4568.354599.014639.24682.99-- Abuse & Dependence32118.6232001.4231892.6631914.5831952.54- Number of Latent classes

8. 8 Abstainers 4 latent classes Group baseline prevalence

9. 9 No alcohol Dx group 5 latent classes Group baseline prevalence

10. 10 Abuse only group 4 latent classes Group baseline prevalence

11. 11 Dependence only group 3 latent classes Group baseline prevalence

12. 12 Abuse & Dependence group 5 latent classes Group baseline prevalence

13. 13 % of Males Many5.74 MDD+Phobia+Anx17.34 MDD+Anx19.94 Many21.13 MDD21.87 Phobia26.42 Phobia+OCD29.48 Many30.41 fewer33.02 MDD34.64 Nic+MDD39.31 MDD+Anx43.96 Fewer44.98 Severe48.33 MDD51.88 Fewer53.92 All-NIC56.26 Nic+MDD57.44 Fewer70.40 Nic+MDD75.25 Fewer77.13 ██ Abstainers, ██ No alcohol Dx, ██ Abuse only, ██ Dependence only, ██ Abuse & dependence Validator: Sex Distribution by latent class

14. 14 Age (years) Fewer34.84 Nic+MDD36.81 Nic+MDD37.09 Severe37.93 Many38.44 Fewer40.44 Nic+MDD41.35 MDD41.36 MDD41.58 All-NIC41.85 MDD+Phobia+Anx42.07 Many42.95 Many43.63 Phobia+OCD44.96 Fewer46.00 MDD+Anx46.16 MDD+Anx46.62 Fewer47.42 Phobia47.61 MDD48.41 fewer49.85 ██ Abstainers, ██ No alcohol Dx, ██ Abuse only, ██ Dependence only, ██ Abuse & dependence Validator: Age Distribution by latent class

15. 15 Education (Years) MDD+Phobia+Anx8.29MDD8.54 fewer8.57 Phobia8.64 Severe9.18 MDD9.33 Many9.40 Nic+MDD9.42 Many9.50 Many9.53 Nic+MDD9.53 Fewer9.56 Nic+MDD9.62 All-NIC9.65 Fewer9.74 Phobia+OCD9.76 Fewer9.83 MDD+Anx9.92 Fewer9.93 MDD10.02 MDD+Anx10.14 ██ Abstainers, ██ No alcohol Dx, ██ Abuse only, ██ Dependence only, ██ Abuse & dependence Validator: Education Distribution by latent class

16. 16 % Whites fewer71.82Phobia74.95 MDD78.34 Fewer79.18 Fewer82.68 Phobia+OCD82.76 MDD+Phobia+Anx82.83 Nic+MDD86.77 MDD87.20 Nic+MDD87.25 Many87.25 MDD+Anx87.35 Fewer89.22 Nic+MDD89.29 All-NIC89.45 Fewer89.80 Many91.36 MDD92.02 Severe92.05 MDD+Anx92.97 Many96.82 ██ Abstainers, ██ No alcohol Dx, ██ Abuse only, ██ Dependence only, ██ Abuse & dependence Validator: Ethnicity Distribution by latent class

17. 17 fewer32.01 Fewer40.55 Fewer50.00 Fewer55.75 Phobia57.71 MDD+Anx62.59 Phobia+OCD62.71 MDD64.67 MDD65.04 Fewer65.53 MDD+Phobia+Anx65.89 MDD+Anx68.78 Nic+MDD71.75 Many73.16 Nic+MDD73.22 Many80.88 Nic+MDD82.36 MDD82.58 All-NIC83.12 Severe85.67 Many92.81 Family History % ██ Abstainers, ██ No alcohol Dx, ██ Abuse only, ██ Dependence only, ██ Abuse & dependence Validator: Family History Distribution by latent class

18. 18 MDD+Phobia+Anx36.88 Many37.78 Severe38.30 Many38.44 Many42.36 MDD42.95 MDD+Anx44.94 Nic+MDD45.47 All-NIC45.53 MDD+Anx45.58 MDD45.71 Phobia46.75 Nic+MDD46.98 Phobia+OCD47.48 MDD47.54 Nic+MDD47.89 Fewer50.88 Fewer51.20 Fewer53.16 fewer53.41 Fewer53.47 Validator: Mental Health Scale Distribution by latent class ██ Abstainers, ██ No alcohol Dx, ██ Abuse only, ██ Dependence only, ██ Abuse & dependence Norm based Mental Health Scale

19. 19 Biplot using Multi Dimensional Scaling based on principal normalization Dimension 1 Dimension 2 29.4% 84.3% 54.9% Total Variance Accounted:

20. 20 Summary Need to include comorbidities when defining alcohol phenotypesNeed to include comorbidities when defining alcohol phenotypes Phenotypic characteristics of some latent classes are uniquePhenotypic characteristics of some latent classes are unique Biplot results shows existence of similar latent classes across groupsBiplot results shows existence of similar latent classes across groups Latent class phenotypes will reduce heterogeneityLatent class phenotypes will reduce heterogeneity