1 alcohol use and psychiatric comorbidity: a phenotypic perspective k. thennarasu, kathleen k...
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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
9
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
MDD Panic Soc Phobia Spe Phobia Anxiety OCD Nicotine ASPD oth depend
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)
Group baseline prevalence
10
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
MDD Panic Soc Phobia Spe Phobia Anxiety OCD Nicotine ASPD oth depend
Est
imat
ed P
roba
bilit
y
many(1.8) Fewer(80.1) nicot+mdd(7.6) mdd+anx+(7.9)
Group baseline prevalence
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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
MDD Panic Soc Phobia Spe Phobia Anxiety OCD Nicotine ASPD oth depend
Est
ima
ted
Pro
ba
bili
ty
many(3.7) Fewer(67.2) MDD+nico(29.1)
Group baseline prevalence
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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
MDD Panic Soc Phobia Spe Phobia Anxiety OCD Nicotine ASPD oth depend
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)
Group baseline prevalence
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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
MDD+AnxMDD+Anx 43.9643.96
FewerFewer 44.9844.98
SevereSevere 48.3348.33
MDDMDD 51.8851.88
FewerFewer 53.9253.92
All-NICAll-NIC 56.2656.26
Nic+MDDNic+MDD 57.4457.44
FewerFewer 70.4070.40
Nic+MDDNic+MDD 75.2575.25
FewerFewer 77.1377.13
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
Nic+MDDNic+MDD 36.8136.81
Nic+MDDNic+MDD 37.0937.09
SevereSevere 37.9337.93
ManyMany 38.4438.44
FewerFewer 40.4440.44
Nic+MDDNic+MDD 41.3541.35
MDDMDD 41.3641.36
MDDMDD 41.5841.58
All-NICAll-NIC 41.8541.85
MDD+Phobia+AnxMDD+Phobia+Anx 42.0742.07
ManyMany 42.9542.95
ManyMany 43.6343.63
Phobia+OCDPhobia+OCD 44.9644.96
FewerFewer 46.0046.00
MDD+AnxMDD+Anx 46.1646.16
MDD+AnxMDD+Anx 46.6246.62
FewerFewer 47.4247.42
PhobiaPhobia 47.6147.61
MDDMDD 48.4148.41
fewerfewer 49.8549.85
██ Abstainers, ██ No alcohol Dx, ██ Abuse only,
██ Dependence only, ██ Abuse & dependence
0
5
10
15
20
25
30
35
40
45
50
Abstainers No alco Dx Abuse Depend Abuse&dep
Validator: AgeValidator: AgeDistribution by latent classDistribution by latent class
15
Education (Years)Education (Years)
7.8
8
8.2
8.4
8.6
8.8
9
9.2
9.4
9.6
9.8
10
Abstainers No alco Dx Abuse Depend Abuse&dep
MDD+Phobia+AnxMDD+Phobia+Anx 8.298.29
MDDMDD 8.548.54
fewerfewer 8.578.57
PhobiaPhobia 8.648.64
SevereSevere 9.189.18
MDDMDD 9.339.33
ManyMany 9.409.40
Nic+MDDNic+MDD 9.429.42
ManyMany 9.509.50
ManyMany 9.539.53
Nic+MDDNic+MDD 9.539.53
FewerFewer 9.569.56
Nic+MDDNic+MDD 9.629.62
All-NICAll-NIC 9.659.65
FewerFewer 9.749.74
Phobia+OCDPhobia+OCD 9.769.76
FewerFewer 9.839.83
MDD+AnxMDD+Anx 9.929.92
FewerFewer 9.939.93
MDDMDD 10.0210.02
MDD+AnxMDD+Anx 10.1410.14
██ Abstainers, ██ No alcohol Dx, ██ Abuse only,
██ Dependence only, ██ Abuse & dependence
Validator: EducationValidator: EducationDistribution by latent classDistribution by latent class
16
% Whites% Whites
0
10
20
30
40
50
60
70
80
90
100
Abstainers No alco Dx Abuse Depend Abuse&dep
fewerfewer 71.8271.82
PhobiaPhobia 74.9574.95
MDDMDD 78.3478.34
FewerFewer 79.1879.18
FewerFewer 82.6882.68
Phobia+OCDPhobia+OCD 82.7682.76
MDD+Phobia+AnxMDD+Phobia+Anx 82.8382.83
Nic+MDDNic+MDD 86.7786.77
MDDMDD 87.2087.20
Nic+MDDNic+MDD 87.2587.25
ManyMany 87.2587.25
MDD+AnxMDD+Anx 87.3587.35
FewerFewer 89.2289.22
Nic+MDDNic+MDD 89.2989.29
All-NICAll-NIC 89.4589.45
FewerFewer 89.8089.80
ManyMany 91.3691.36
MDDMDD 92.0292.02
SevereSevere 92.0592.05
MDD+AnxMDD+Anx 92.9792.97
ManyMany 96.8296.82
██ Abstainers, ██ No alcohol Dx, ██ Abuse only,
██ Dependence only, ██ Abuse & dependence
Validator: EthnicityValidator: EthnicityDistribution by latent classDistribution by latent class
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fewerfewer 32.0132.01
FewerFewer 40.5540.55
FewerFewer 50.0050.00
FewerFewer 55.7555.75
PhobiaPhobia 57.7157.71
MDD+AnxMDD+Anx 62.5962.59
Phobia+OCDPhobia+OCD 62.7162.71
MDDMDD 64.6764.67
MDDMDD 65.0465.04
FewerFewer 65.5365.53
MDD+Phobia+AnxMDD+Phobia+Anx 65.8965.89
MDD+AnxMDD+Anx 68.7868.78
Nic+MDDNic+MDD 71.7571.75
ManyMany 73.1673.16
Nic+MDDNic+MDD 73.2273.22
ManyMany 80.8880.88
Nic+MDDNic+MDD 82.3682.36
MDDMDD 82.5882.58
All-NICAll-NIC 83.1283.12
SevereSevere 85.6785.67
ManyMany 92.8192.81
0
10
20
30
40
50
60
70
80
Abstainers No alco Dx Abuse Depend Abuse&dep
Family History %Family History %
██ Abstainers, ██ No alcohol Dx, ██ Abuse only,
██ Dependence only, ██ Abuse & dependence
Validator: Family HistoryValidator: Family HistoryDistribution by latent classDistribution by latent class
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MDD+Phobia+AnxMDD+Phobia+Anx 36.8836.88
ManyMany 37.7837.78
SevereSevere 38.3038.30
ManyMany 38.4438.44
ManyMany 42.3642.36
MDDMDD 42.9542.95
MDD+AnxMDD+Anx 44.9444.94
Nic+MDDNic+MDD 45.4745.47
All-NICAll-NIC 45.5345.53
MDD+AnxMDD+Anx 45.5845.58
MDDMDD 45.7145.71
PhobiaPhobia 46.7546.75
Nic+MDDNic+MDD 46.9846.98
Phobia+OCDPhobia+OCD 47.4847.48
MDDMDD 47.5447.54
Nic+MDDNic+MDD 47.8947.89
FewerFewer 50.8850.88
FewerFewer 51.2051.20
FewerFewer 53.1653.16
fewerfewer 53.4153.41
FewerFewer 53.4753.47
Validator: Mental Health ScaleValidator: Mental Health ScaleDistribution by latent classDistribution by latent class
██ Abstainers, ██ No alcohol Dx, ██ Abuse only,
██ Dependence only, ██ Abuse & dependence
46
47
48
49
50
51
52
53
Abstainers No alco Dx Abuse Depend Abuse&dep
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
-2
-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