Background. Major depressive disorder (MDD) is highly co-morbid with other Axis I disorders, which commonly precede its onset. We sought to determine the level and periods of risk for MDD posed by prior or co-occurring psychiatric disorders.

Method. Using retrospective data from a longitudinal, population-based sample of 2926 male and 1929 female adult twin subjects, we predicted the hazard rates for MDD from a Cox proportional hazards model with same-year or prior onsets of co-morbid Axis I disorders as time-dependent covariates.

Results. All axis I disorders studied (generalized anxiety disorder, panic disorder, phobia, alcohol dependence, psychoactive substance use disorders and conduct disorder) significantly predicted increased risk for developing MDD. The highest hazard rates occurred for MDD onsets that co-occurred with those of the co-morbid disorder. However, the risk for onset of MDD subsequent to that of prior disorders is also significantly increased and remains relatively unchanged over time. Although the risk for onset of MDD is significantly higher in women than men, this was not explained by gender differences in prior disorder prevalence or increased sensitivity in women to the effects of prior disorders on risk for depression.

Conclusions. Prior psychiatric disorders are significant risk factors for the development of MDD, independent of the length of the intervening period between the onset of the first disorder and that of MDD.