Alcohol Use and Psychiatric Comorbidity: A Phenotypic perspective

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Alcohol Use and Psychiatric Comorbidity: Alcohol Use and Psychiatric Comorbidity: A Phenotypic perspectiveA Phenotypic perspective

K. Thennarasu, Kathleen K Bucholz and Rosalind J K. Thennarasu, Kathleen K Bucholz and Rosalind J NeumanNeuman

Department of Psychiatry, Department of Psychiatry, Washington University School of Medicine,Washington University School of Medicine,

St. Louis, MOSt. Louis, MO

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ObjectivesObjectives

• To establish homogeneous alcohol user To establish homogeneous alcohol user classes based on comorbidities using latent classes based on comorbidities using latent class analysis.class analysis.

• To validate latent phenotypic classes using To validate latent phenotypic classes using external covariates.external covariates.

• To find similarity between latent phenotypic To find similarity between latent phenotypic classes using multi dimensional scaling. classes using multi dimensional scaling.

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Data SourceData Source• National Epidemiologic Survey on Alcohol and National Epidemiologic Survey on Alcohol and

Related Conditions (NESARC), 2000-2001.Related Conditions (NESARC), 2000-2001.

• 43,093 non-institutionalized household 43,093 non-institutionalized household residentsresidents

• aged >=18 yearsaged >=18 years

• NIAAA Alcohol Use Disorder and Associated NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV)(AUDADIS-IV)

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• 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 Used the following 9 comorbid diagnosis to determine latent structure of each of the above groupslatent 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* IMethods* I

* All diagnosis are based on DSM IV

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Methods IIMethods 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

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Prevalence of co-morbiditiesPrevalence of co-morbiditiesin each groupin each group

0

10

20

30

40

50

60

MDD Panic Social Phobia SpecificPhobia

Anxity OCD Nicotinedependence

ASPD Otherdependence

Abstainers No alco Dx Abuse Depend Abuse&dep Total

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Model selection: BIC comparisonModel selection: BIC comparison

Two Two ThreeThree FourFour FiveFive sixsix SevenSeven

AbstainersAbstainers 21682.5921682.59 21693.6521693.65 21708.0821708.08 21735.8621735.86 21773.1321773.13 --No alcohol DxNo alcohol Dx 82689.8182689.81 82388.1182388.11 82323.4782323.47 82310.5582310.55 82336.9282336.92 82391.9882391.98

Abuse onlyAbuse only 36101.1636101.16 36058.2736058.27 36032.8136032.81 36078.936078.9 -- --Dependence onlyDependence only 4568.354568.35 4599.014599.01 4639.24639.2 4682.994682.99 -- --

Abuse &Abuse &DependenceDependence 32118.6232118.62 32001.4232001.42 31892.6631892.66 31914.5831914.58 31952.5431952.54 --

Number of Latent classesNumber of Latent classes

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Abstainers Abstainers 4 latent classes4 latent classes

0

0.2

0.4

0.6

0.8

1

1.2

MDD Panic Soc Phobia Spe Phobia Anxiety OCD Nicotine ASPD oth depend

Est

imat

ed P

roba

bilit

y

MDD(6.1) so+sp phobia(1.7) Fewer(91.3) Mdd+pho+anx(0.9)

Group baseline prevalence

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No alcohol Dx groupNo alcohol Dx group5 latent classes5 latent classes

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1


Est

ima

ted

Pro

ba

bili

ty

nico+MDD(5.6) MDD+anx(5.0) Many(1.6) Fewer(85.7) phob+ocd(2.1)


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Abuse only groupAbuse only group4 latent classes4 latent classes

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1


Est

imat

ed P

roba

bilit

y

many(1.8) Fewer(80.1) nicot+mdd(7.6) mdd+anx+(7.9)


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Dependence only groupDependence only group3 latent classes3 latent classes

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1


Est

ima

ted

Pro

ba

bili

ty

many(3.7) Fewer(67.2) MDD+nico(29.1)


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Abuse & Dependence group Abuse & Dependence group 5 latent classes5 latent classes

0

0.2

0.4

0.6

0.8

1

1.2


Est

imat

ed p

roba

bilit

y

MDD(17.2) too many(5.8) nico+MDD(12.0) All-nic(6.0) Fewer(59.0)


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% of Males% of Males

ManyMany 5.745.74

MDD+Phobia+AnxMDD+Phobia+Anx 17.3417.34

MDD+AnxMDD+Anx 19.9419.94

ManyMany 21.1321.13

MDDMDD 21.8721.87

PhobiaPhobia 26.4226.42

Phobia+OCDPhobia+OCD 29.4829.48

ManyMany 30.4130.41

fewerfewer 33.0233.02

MDDMDD 34.6434.64

Nic+MDDNic+MDD 39.3139.31


FewerFewer 44.9844.98

SevereSevere 48.3348.33

MDDMDD 51.8851.88


All-NICAll-NIC 56.2656.26





0

10

20

30

40

50

60

70

80

Abstainers No alco Dx Abuse Depend Abuse&dep

██ Abstainers, ██ No alcohol Dx, ██ Abuse only,

██ Dependence only, ██ Abuse & dependence

Validator: SexValidator: SexDistribution by latent classDistribution by latent class

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Age (years)Age (years)FewerFewer 34.8434.84




ManyMany 38.4438.44



MDDMDD 41.3641.36

MDDMDD 41.5841.58



ManyMany 42.9542.95

ManyMany 43.6343.63







MDDMDD 48.4148.41




0

5

10

15

20

25

30

35

40

45

50


Validator: AgeValidator: AgeDistribution by latent classDistribution by latent class

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Education (Years)Education (Years)

7.8

8

8.2

8.4

8.6

8.8

9

9.2

9.4

9.6

9.8

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MDDMDD 8.548.54

fewerfewer 8.578.57



MDDMDD 9.339.33

ManyMany 9.409.40


ManyMany 9.509.50

ManyMany 9.539.53


FewerFewer 9.569.56



FewerFewer 9.749.74


FewerFewer 9.839.83


FewerFewer 9.939.93

MDDMDD 10.0210.02




Validator: EducationValidator: EducationDistribution by latent classDistribution by latent class

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% Whites% Whites

0

10

20

30

40

50

60

70

80

90

100




MDDMDD 78.3478.34






MDDMDD 87.2087.20


ManyMany 87.2587.25






ManyMany 91.3691.36

MDDMDD 92.0292.02



ManyMany 96.8296.82



Validator: EthnicityValidator: EthnicityDistribution by latent classDistribution by latent class

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MDDMDD 64.6764.67

MDDMDD 65.0465.04





ManyMany 73.1673.16


ManyMany 80.8880.88


MDDMDD 82.5882.58



ManyMany 92.8192.81

0

10

20

30

40

50

60

70

80


Family History %Family History %



Validator: Family HistoryValidator: Family HistoryDistribution by latent classDistribution by latent class

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ManyMany 37.7837.78


ManyMany 38.4438.44

ManyMany 42.3642.36

MDDMDD 42.9542.95





MDDMDD 45.7145.71




MDDMDD 47.5447.54







Validator: Mental Health ScaleValidator: Mental Health ScaleDistribution by latent classDistribution by latent class



46

47

48

49

50

51

52

53


Norm based Mental Norm based Mental Health ScaleHealth Scale

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Biplot using Multi Dimensional ScalingBiplot using Multi Dimensional Scaling based on principal normalizationbased on principal normalization

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-1.5

-1

-0.5

0

0.5

1

1.5

-1 -0.5 0 0.5 1 1.5 2 2.5 3

Abstainer(MDD+Phobia+Anx)

Abstainer(MDD)

No alco Dx (Many)Abuse

(Many)

Dependence(Many)

Abuse&dep(Severe)

No alco Dx (MDD) No alco Dx

(MDD+Anx) Abstainer(Phobia)

Abstainer(fewer)

No alco Dx (Phobia+OCD)

Abuse(MDD+Anx)

Abuse&dep(MDD)

Abuse&dep(Nic+MDD)

Abuse(Nic+MDD) Dependence(Nic+MDD)

Abuse&dep(All-NIC)

Abuse&dep(Fewer)

Abuse(Fewer)

Dependence(Fewer)No alco Dx

(Fewer)

Dimension 1

Dim

ensi

on 2

29.4

%

84.3%54.9%

Total Variance Accounted:

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SummarySummary

• Need to include comorbidities when Need to include comorbidities when defining alcohol phenotypesdefining alcohol phenotypes

• Phenotypic characteristics of some Phenotypic characteristics of some latent classes are uniquelatent classes are unique

• Biplot results shows existence of Biplot results shows existence of similar latent classes across groupssimilar latent classes across groups

• Latent class phenotypes will reduce Latent class phenotypes will reduce heterogeneityheterogeneity

Documents

Alcohol Use and Psychiatric Comorbidity: A Phenotypic perspective