Age at onset and familial risk for major depression in a Swedish national twin sample.
BACKGROUND
In many biomedical disorders, early age at onset (AAO) is an index of high liability to illness which is manifest by an increased risk of illness in relatives. Most but not all prior studies report such a pattern for major depression (MD).


METHODS
Lifetime MD and AAO were assessed at personal interview using modified DSM-III-R criteria in 13864 twin pairs, including 4229 onsets of MD, from the Swedish National Twin Registry. Analyses were conducted using Cox proportional hazards models.


RESULTS
Controlling for year of birth, gender, zygosity, co-twin history of MD and the interaction of zygosity and co-twin history, the best-fit model showed a significant main effect and a quadratic effect of AAO of MD in the co-twin on the log hazard ratio for MD in the index twin. When examined together, these effects predicted that from the ages of 15 to approximately 35 years, AAO of MD is moderately negatively related to risk of illness in relatives. However, past age 35, the function flattens out, with little change of risk in relatives with further increases of AAO. Even when the co-twin had a late AAO, the risk in the index twin substantially exceeded that seen when the co-twin had no history of MD.


CONCLUSIONS
In this large sample, AAO is a meaningful, albeit modest, index of familial liability to MD. The relationship is nonlinear and results largely from an increased liability in individuals with an early AAO. These results should be interpreted in the context of the limitations of long-term recall.
Kendler
Kenneth S
KS
Department of Psychiatry, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA 23298-0126, USA. kendler@hsc.vcu.edu
Gatz
Margaret
M
Gardner
Charles O
CO
Pedersen
Nancy L
NL
D017668:Age of Onset; D003866:Depressive Disorder / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016016:Proportional Hazards Models; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic