Blood mononuclear cell gene expression signature of postpartum depression

Abstract

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.

The Influence of genetic factors on peripartum depression: A systematic review

“…In contrast, none of the studies performed during the first trimester reported any significant associations. The findings from population studies and studies of SNPs are consistent with those from gene expression studies (Katz et al, 2012;Segman et al, 2010), which reported increased gene expression during the course of pregnancy and a reduction in genes that were differentially transcribed during the course of the puerperal period in women exhibiting depressive symptoms than in those who did not. Building upon these findings, Mehta et al (2014) found that transcripts that are differentially expressed during the third trimester of pregnancy are more effective in predicting the status of postpartum depression than are transcripts that are differentially expressed during the third trimester.…”

“…Segman et al (2010) observed differences in gene expression in peripheral blood mononuclear cells of 19 women according to the presence of depressive symptoms. On the second day of the puerperium, 73 genes exhibited differential expression in women who were depressed compared to those who were not.…”

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

“…Additionally, glucocorticoids have effects on peripheral blood cells and the hypothalamus-pituitary adrenal (HPA) axis, which is perturbed during depressive episodes of many patients (Gladkevich et al, 2004). Transcriptional profiling in whole blood has been used in the search for biomarkers for patients with neurological and other psychiatric disorders including patients with Parkinson's (Scherzer et al, 2007) and Huntington's disease (Borovecki et al, 2005), post-traumatic stress disorder Segman et al, 2005;Yehuda et al, 2009), schizophrenia (Kurian et al, 2011), bipolar disorder (Le-Niculescu et al, 2009;Padmos et al, 2008) and major depression (Segman et al, 2010;Spijker et al, 2010). Most of these studies have analyzed baseline gene expression profiles.…”

In Search of Neural Endophenotypes of Postpartum Psychopathology and Disrupted Maternal Caregiving

“…A genetic study compared nine women with PPD and ten postpartum nondepressed women (197). Gene expression profiles correctly classified 84% of patients as depressed or nondepressed, and gene expression was correlated with the severity of depressive symptoms and clinical course of illness.…”