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Abstract
Postpartum depressive symptom (PDS) is a common psychological and mental disorder after giving birth. Our previous studies showing the application of dexmedetomidine, an α2-AR agonist, can significantly improve maternal sleep, as well as relieve and reduce the incidence of PDS. This study investigated the association between α2AAR gene polymorphisms and PDS. A total of 568 cesarean section patients were enrolled; the incidence of PDS is 18.13% (103 with PDS, 465 with non-PDS). The Edinburgh Postpartum Depression Scale score ≥10 was used to diagnose PDS at 42 days after delivery. The single-nucleotide polymorphisms of α2AR were sequenced by pyrosequencing. The effect of rs13306146 A > G polymorphism on α2AR transcription and the regulation of miR-646 on α2AR expression were assessed by dual luciferase reporter assays or gene transfection. Increased stress during pregnancy, poor relationship between mother-in-law and daughter-in-law, spousal relationship, domestic violence, antenatal depression, self-harm ideation, and stressful life events were all associated with increased PDS incidence (p < 0.05). The logistic regression analysis found that the α2AAR rs13306146 polymorphism was associated with PDS after adjusting confounding variables. The transcriptional function of the α2AAR rs13306146 A allele was decreased compared with the G allele, and the α2AAR expression level was correspondingly decreased (p < 0.05), as the strongest binding ability of miR-646 to the α2AAR rs13306146 AA genotype. The effect of α2AAR rs13306146 A > G polymorphism may change the binding ability of miR-646 at the 3′UTR of the α2AAR gene, affecting the expression of α2AAR. This study supports the involvement of the norepinephrine system in the pathogenesis of PDS. Genotypes of α2AAR may be novel and useful biomarkers for PDS.
Highlights
Postpartum depressive symptoms (PDS) are common among women, with an incidence of between 10 and 20% (Gavin et al, 2005)
The results showed that (1) α2AAR rs13316046 polymorphism was associated with PDS. (2) PDS risk in women with the α2AAR rs13316046AA genotype was significantly higher vs. women with AG and GG genotypes
NE neurons is scattered across different brain regions, the highest concentration of NE neurons is in the locus coeruleus, there is evidence of NE nuclei in the hippocampus, frontal cortex, lateral reticular nucleus, and other brain regions (Borodovitsyna et al, 2017)
Summary
Postpartum depressive symptoms (PDS) are common among women, with an incidence of between 10 and 20% (Gavin et al, 2005). Preclinical data clearly shows chronic stress-induced depression to involve alterations in locus coeruleus NE release (Kitayama et al, 2004; Seki et al, 2018), which in the lipopolysaccharide (LPS) preclinical model can be prevented by blocking α1 central noradrenergic receptors (Sekio and Seki, 2015). Butler and Leonard (1986) reported an increased density of lymphocyte adrenergic receptors in PDS patients, which decreased following 6 weeks of antidepressant treatment Such data show that alterations in systemic α2AAR levels and function may be evident in depression. Preclinical data indicate that antidepressant treatment efficacy is mediated by treatment-induced decreases in α2AAR, following chronic stress-induced elevations in the presynaptic α2AAR that arise from stress-mediated rise in central NE (Wang B. et al, 2017) Overall, such data would suggest that α2AAR is an important regulator of depressive responses to chronic stress, with relevance to PDS pathobiology. We showed that SNPs of the metabolic enzymes monoamine oxidase (MAO)-A and catechol-
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