Blood mononuclear cell gene expression signature of postpartum depression.

In sorrow thou shalt bring forth children (Genesis 3:16) seems as relevant today, with one of seven mothers afflicted by a depressive episode, constituting the most common medical complication after delivery. Why mothers are variably affected by mood symptoms postpartum remains unclear, and the pathogenesis and early molecular indicators of this divergent outcome have not been described. We applied a case-control design comparing differential global gene expression profiles in blood mononuclear cells sampled shortly after delivery at the time of inception of postpartum depression (PD). Nine antidepressant naive mothers showing high depressive scores and developing a persisting major depressive episode with postpartum onset were compared with 10 mothers showing low depressive scores and no depressive symptoms on prospective follow-up. A distinctive gene expression signature was observed after delivery among mothers with an emergent PD, with a significant overabundance of transcripts showing a high-fold differential expression between groups, and correlating with depressive symptom severity among all mothers. Early expression signatures correctly classified the majority of PD patients and controls. Those developing persisting PD exhibit a relative downregulation of transcription after delivery, with differential immune activation, and decreased transcriptional engagement in cell proliferation, and DNA replication and repair processes. Our data provide initial evidence indicating that blood cells sampled shortly after delivery may harbor valuable prognostic information for identifying the onset of persisting PD. Some of the informative transcripts and pathways may be implicated in the differential vulnerability that underlies depression pathogenesis.

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors.

Trauma survivors show marked differences in the severity and persistence of post-traumatic stress disorder (PTSD) symptoms. Early symptoms subside in most, but persist as acute and chronic PTSD in a significant minority. The underlying molecular mechanisms or outcome predictors determining these differences are not known. Molecular markers for identifying any mental disorder are currently lacking. Gene expression profiling during the triggering and development of PTSD may be informative of its onset and course. We used oligonucleotide microarrays to measure peripheral blood mononuclear cell (PBMC) gene expression of trauma survivors at the emergency room and 4 months later. Gene expression signatures at both time points distinguished survivors who met DSM-IV diagnostic criteria for PTSD at 1 and 4 months, from those who met no PTSD criterion. Expression signatures at both time points correlated with the severity of each of the three PTSD symptom clusters assessed 4 months following exposure among all survivors. Results demonstrate a general reduction in PBMCs' expression of transcription activators among psychologically affected trauma survivors. Several differentiating genes were previously described as having a role in stress response. These findings provide initial evidence that peripheral gene expression signatures following trauma identify an evolving neuropsychiatric disorder and are informative of its key clinical features and outcome. Replications in larger samples, as well as studies focusing on specific markers within the signatures discovered, are warranted to confirm and extend the diagnostic utility and pathogenetic implications of our results.