Families at high and low risk for depression: a 3-generation study.
BACKGROUND
The familial nature of early-onset major depressive disorder (MDD) has been documented in numerous family studies of adults and is supported by studies of offspring of parents with MDD, for whom the risk is more than 3-fold. None of the published high-risk studies have gone beyond 2 generations, and few have a longitudinal design. We report results of an approximately 20-year follow-up of families at high and low risk for depression. The first 2 generations were interviewed 4 times during this period. The offspring from the second generation are now adults and have children of their own, the third generation of the original cohort.


OBJECTIVE
To examine the familial aggregation of psychiatric disorders and functioning in grandchildren by their parents' and grandparents' depression status.


METHODS
Longitudinal, retrospective cohort, family study.


METHODS
One hundred sixty-one grandchildren and their parents and grandparents.


METHODS
Lifetime rate of psychiatric disorder and functioning in grandchildren, stratified by parental and by grandparental depression status, collected by clinicians blind to diagnoses of previous generations and to previous interviews.


RESULTS
There were high rates of psychiatric disorders, particularly anxiety disorders, in the grandchildren with 2 generations of major depression, with 59.2% of these grandchildren (mean age, 12 years) already having a psychiatric disorder. The effect of parental depression on grandchildren's outcomes differed significantly with grandparental depression status. Among families with a depressed grandparent, increased risk of anxiety (relative risk, 5.17; 95% confidence interval, 1.4-18.7; P = .01) and increased risk of any disorder (relative risk, 5.52; 95% confidence interval, 2.0-15.4; P = .002) were observed in grandchildren with a depressed parent as compared with those with nondepressed parents. The severity of parental depression, as measured by impairment, significantly increased the rate of a mood disorder in these grandchildren (relative risk, 2.44; 95% confidence interval, 1.1-5.5; P = .03). In contrast, among grandchildren with nonfamilial depression, ie, depressed parents with no depressed grandparents, there was no significant effect of parental MDD on grandchildren diagnoses. However, parental MDD, regardless of whether families had a depressed grandparent, had a significant impact on the grandchildren's overall functioning. Potential confounding variables did not affect the strength of the association with parental and grandparental depression.


CONCLUSIONS
The association between parental MDD and child diagnosis is moderated by grandparental MDD status. The rates of psychopathology are highest in grandchildren of parents and grandparents with a moderately to severely impairing depression. Anxiety disorders are the early sign of psychopathology in the young grandchildren. Early interventions in the offspring of 2 generations affected with moderately to severely impairing MDD seem warranted. This familial group may be the target for neuroimaging, genetic, and other biological studies.
Weissman
Myrna M
MM
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. mmw3@columbia.edu
Wickramaratne
Priya
P
Nomura
Yoko
Y
Warner
Virginia
V
Verdeli
Helen
H
Pilowsky
Daniel J
DJ
Grillon
Christian
C
Bruder
Gerard
G
D000328:Adult; D017668:Age of Onset; D001008:Anxiety Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D002648:Child; D016241:Child of Impaired Parents; D015331:Cohort Studies; D003866:Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005190:Family; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012307:Risk Factors; D012720:Severity of Illness Index