Background Although PTSD-major depressive disorder (MDD) co-morbidity is well-established, the vast majority of studies have examined comorbidity at the level of PTSD total severity, rather than at the level of specific PTSD symptom clusters. This study aimed to examine the long-term associations between MDD and PTSD symptom clusters (intrusion, avoidance, hyperarousal), and the moderating role of gender in these associations. Methods 942 residents of urban Detroit neighborhoods were interviewed at 3 waves, 1 year apart. At each wave, they were assessed for PTSD, depression, trauma exposure, and stressful life events. Results At all waves, hyperarousal was the PTSD cluster most strongly correlated with MDD. For the full sample, a reciprocal relationship was found between MDD and all three PTSD clusters across time. Interestingly, the relative strength of associations between MDD and specific PTSD clusters changed over time. Women showed the same bidirectional MDD-PTSD pattern as in the entire sample, while men sometimes showed non-significant associations between early MDD and subsequent PTSD clusters. Limitations First, our analyses are based on DSM-IV criteria, as this was the existing edition at the time of this study. Second, although this is a longitudinal study, inferences regarding temporal precedence of one disorder over another must be made with caution. Conclusions Early identification of either PTSD or MDD following trauma may be crucial in order to prevent the development of the other disorder over time. The PTSD cluster of hyper-arousal may require special therapeutic attention. Also, professionals are encouraged to develop more gender-specific interventions post-trauma
