Is there a genetic relationship between alcoholism and depression? - Research Update

Alcohol Research & Health, Fall, 2002 by John I. Nurnberger, Jr., Tatiana Foroud, Leah Flury, Eric Meyer, T., Ryan Wiegand

Table 1 Hypotheses About the Relationship Between Alcoholism and
Affective Disorders (e.g., Depression)

If it is                 Relative risk of          Relative risk of
hypothesized    Then:    affective disorder        alcoholism  in
that:                    in alcoholics             affective patients

Alcoholism is the        Increases                 Is unchanged
primary disorder and
affective disorder
is secondary

The affective disorder   Is unchanged              Increases
is primary and
alcoholism is
secondary

Alcoholism and           Increases                 Increases
affective disorders
develop from a
common genetic
predisposition

Genetic Subtype I        Is unchanged              Is unchanged
(depressive spectrum
disorder)

Genetic Subtype II       Increases, specifically   Is unchanged
(alcoholism with         for depressive syndrome
depression)

Alcoholism and           Is unchanged              Is unchanged
affective disorder
develop as separate
illnesses

If it is                 Relatives of alcoholics   Relatives of
hypothesized    Then:    would be at increased     affective patients
that:                    risk for:                 would be at
                                                   increased risk for:

Alcoholism is the        Alcoholism with           Affective disorder
primary disorder and     secondary affective       only
affective disorder       disorder
is secondary

The affective disorder   Alcoholism only           Affective disorder
is primary and                                     with secondary
alcoholism is                                      alcoholism
secondary

Alcoholism and           Both alcoholism and       Both alcoholism and
affective disorders      affective disorder        affective disorder
develop from a
common genetic
predisposition

Genetic Subtype I        Alcoholism only           Both alcoholism and
(depressive spectrum                               affective disorder
disorder)

Genetic Subtype II       Both alcoholism and       Affective disorder
(alcoholism with         depression                only
depression)

Alcoholism and           Alcoholism only           Affective disorder
affective disorder                                 only
develop as separate
illnesses

Table 2 Prevalence of DSM-III-R Depression and Depressive Syndrome in
Adult COGA Probands and Their Alcoholic and Nonalcoholic Relatives

                         COGA Probands
                           and their          Nonalcoholic
                       Alcoholic Relatives     Relatives

Males

Major Depression      11.0% (257/2,337)       10.5% (151/1,436)
Depressive Syndrome   30.3% (a) (707/2,337)    6.0% (86/1,436)
Total                 41.2% (a) (964/2,337)   16.5% (237/1,436)

Females

Major Depression      24.2% (b) (311/1,288)   22.4% (c) (704/3,138)
Depressive Syndrome   32.8% (a) (423/1,288)   11.3% (c) (356/3,138)
Total                 57.0% (b) (734/1,288)   33.8% (c) (1,060/3,138)

                         Relative Risk
                      Among COGA Probands
                           and their
                      Alcoholic Relatives

Males

Major Depression             1.05
Depressive Syndrome          5.05
Total                        2.50

Females

Major Depression             1.08
Depressive Syndrome          2.90
Total                        1.69

(a) [chi square] [greater than or equal to] 204 (actual values 315.4,
250.9, 290.9, 204.0, from top to bottom), df= 1, p < [10.sup.-45] vs.
nonalcoholic subjects.

(b) [chi square] [greater than or equal to] 82 (actual values 108.6,
82.6), df= 1, p < [10.sup.-18] vs. males.

(c) [chi square] [greater than or equal to] 32 (actual values 92.1,
32.4, 144.7), df= 1, p < [10.sup.-7] vs. males.

NOTE: The data are from COGA Master File 86 (1999).

Table 3 Prevalence and Risk of Alcoholism and Depression in the
Relatives of Alcoholic Probands and Control Subjects in the
COGA Study

                                  Diagnosis in Relatives

                        All Types of                    Relative Risk
Proband Diagnosis        Alcoholism                     of Alcoholism

Control               14.2% (144/1,014)
Alcoholism Only       29.2% (971/3,331)                      2.1
Alcoholism with
  Depressive
  Syndrome            31.6% * (1,059/3,357)                  2.2
Alcoholism with
  Major Depression    32.8% * (306/934)                      2.3

                                  Diagnosis in Relatives

                         All Types of                   Relative Risk
Proband Diagnosis         Depression                    of Depression

Control               20.9% (212/1,014)
Alcoholism Only       28.6% (952/3,331)                      1.4
Alcoholism with
  Depressive
  Syndrome            33.5% * (1,123/3,357)                  1.6
Alcoholism with
  Major Depression    39.0% ([dagger]) (364/934)             1.9

* p < .05 vs. alcoholism only

([dagger]) p < .05 vs. alcoholism with depressive syndrome

All comparisons significant vs. control

NOTE: The data were derived from COGA Master file 86 (1999).

Table 4 Prevalence of Alcoholism and Depression in the Relatives of
Alcoholic and Control Probands in the COGA Study

                                   Diagnosis in Relatives

                        Alcoholism with or
Proband Diagnosis       without Depressive        Major Depression Only
                             Syndrome

Control                 10.2% (74/725)            14.6% (106/725)

Alcoholism with or
  without Depressive
  Syndrome              25.6% (a) (1,112/4,348)   13.1% (571/4,348)
Alcoholism with Major
  Depression            24.0% (a) (132/549)       14.2% (78/549)

                        Diagnosis in Relatives

                        Alcoholism and
Proband Diagnosis       Major Depression

Control                 2.2% (16/725)

Alcoholism with or
  without Depressive
  Syndrome              4.4% (a) (191/4,348)
Alcoholism with Major
  Depression            8.4% ([dagger]) (46/549)

* p < .01 vs. control

([dagger]) p < .001 vs. alcoholism only and control

NOTE: The data were derived from COGA Master File 86 (1999).

Table 5 Chronological Order of Disease Development in COGA Participants
with Alcoholism and an Affective Disorder (i.e., Major Depression or
Mania)

                                                        Same Time
                             Onset of      Onset of      of Onset
                            Alcoholism    Depression     for Both
                              First         First       Disorders

Alcoholism and Depression

Males (N = 267)             143 (53.6%)   104 (39.0%)   20 (7.5%)
Females (N = 325)           115 (35.4%)   193 (59.4%)   17 (5.2%)
Total (N = 592)             258 (43.6%)   297 (50.2%)   37 (6.3%)

Alcoholism and Mania

Males (N = 33)               22 (66.7%)    9 (23.7%)     2 (6.1%)
Females (N = 33)             13 (39.4%)   19 (57.6%)     1 (3.0%)
Total (N = 66)               35 (53.0%)   28 (42.4%)     3 (4.5%)

NOTE: The diagnoses and age of onset are based on data from COGA
Master File 118 (2002).