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Family history of depression is associated with younger age of onset in patients with recurrent depression

  • F. Tozzi (a1), I. Prokopenko (a1), J. D. Perry (a2), J. L. Kennedy (a3), A. D. McCarthy (a2), F. Holsboer (a4), W. Berrettini (a5), L. T. Middleton (a2), H. D. Chilcoat (a6) (a7) and P. Muglia (a1) (a3)...



Genetic epidemiology data suggest that younger age of onset is associated with family history (FH) of depression. The present study tested whether the presence of FH for depression or anxiety in first-degree relatives determines younger age of onset for depression.


A sample of 1022 cases with recurrent major depressive disorder (MDD) was recruited at the Max Planck Institute and at two affiliated hospitals. Patients were assessed using the Schedules for Clinical Assessment in Neuropsychiatry and questionnaires including demographics, medical history, questions on the use of alcohol and tobacco, personality traits and life events. Survival analysis and the Cox proportional hazard model were used to determine whether FH of depression signals earlier age of onset of depression.


Patients who reported positive FH had a significantly earlier age of onset than patients who did not report FH of depression (log-rank=48, df=1, p<0.0001). The magnitude of association of FH varies by age of onset, with the largest estimate for MDD onset before age 20 years (hazard ratio=2.2, p=0.0009), whereas FH is not associated with MDD for onset after age 50 years (hazard ratio=0.89, p=0.5). The presence of feelings of guilt, anxiety symptoms and functional impairment due to depressive symptoms appear to characterize individuals with positive FH of depression.


FH of depression contributes to the onset of depression at a younger age and may affect the clinical features of the illness.


Corresponding author

*Address for correspondence: P. Muglia, M.D., Medical Genetics, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline R&D, Via A. Fleming, 4, 37135 Verona, Italy. (Email:


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