Neuroactive steroid biosynthesis during pregnancy predicts future postpartum depression: a role for the 3α and/or 3β-HSD neurosteroidogenic enzymes?
Related Articles
A network analysis of postpartum depression and mother-to-infant bonding shows common and unique symptom-level connections across three postpartum periods
Postpartum depression and mother-to-infant bonding difficulties (MIBD), two issues crucial to maternal and infant mental health, often coexist and affect each other. Our study aims to dissect their complex relationship through a graphical LASSO network analysis of individual symptoms in 5594 Japanese postpartum women, whose geographical distribution was nationally representative. We identified ‘fear’, ‘enjoyment’, ‘overwhelm’, and ‘insomnia’ as common bridge symptoms linking postpartum depression and MIBD across three distinct postpartum periods. Moreover, ‘self-harm’ emerged as a bridge symptom in the first 6 months and the 7–12 month period, while ‘laugh’ was a bridge symptom in the first 6 months and the 13–24 month period. Notably, ‘self-blame’ was identified as a unique bridge symptom specific to the 13–24 month period. Our analysis highlights the complexities of symptom connectivity across postpartum stages and underscores the critical need for interventions that address both common and stage-specific bridge symptoms to effectively support maternal mental health and strengthen mother-to-infant bonding.
Hypertension inhibition by Dubosiella newyorkensis via reducing pentosidine synthesis
Gut dysbiosis has been associated with hypertension. Herein, we aimed to discover the potential association between gut microbiota and high-salt diet (HSD) induced endothelial dysfunction in conventional hypertensive mice. Dubosiella newyorkensis was found highly sensitive to salt in HSD-induced hypertension. The salt-sensitive nature of Dubosiella newyorkensis was confirmed by bacteria culture in vitro. Oral Dubosiella newyorkensis in HSD-induced hypertensive mice decreased blood pressure, inhibited activation of vascular endothelium, attenuated inflammation and alleviated intestinal vascular barrier injury. Similar effects of Dubosiella newyorkensis were observed in germ-free mice. Interestingly, serum pentosidine was found to function as a biomarker for Dubosiella newyorkensis in response to HSD in both metabolic modes. Supplement of pentosidine, deteriorated hypertension and vascular endothelial damage. Differential genes enriched in the glycerophospholipid metabolism were markedly altered in cultured bacteria. Our study has identified Dubosiella newyorkensis as a new salt-sensitive gut microbe that inhibits pentosidine production thereby alleviating hypertension.
Genome-wide analysis identifies novel shared loci between depression and white matter microstructure
Depression, a complex and heritable psychiatric disorder, is associated with alterations in white matter microstructure, yet their shared genetic basis remains largely unclear. Utilizing the largest available genome-wide association study (GWAS) datasets for depression (N = 674,452) and white matter microstructure (N = 33,224), assessed through diffusion tensor imaging metrics such as fractional anisotropy (FA) and mean diffusivity (MD), we employed linkage disequilibrium score regression method to estimate global genetic correlations, local analysis of [co]variant association approach to pinpoint genomic regions with local genetic correlations, and conjunctional false discovery rate analysis to identify shared variants. Our findings revealed that depression showed significant local genetic correlations with FA in 37 genomic regions and with MD in 59 regions, while global genetic correlations were weak. Variant-level analysis identified 78 distinct loci jointly associated with depression (25 novel loci) and FA (35 novel loci), and 41 distinct loci associated with depression (17 novel loci) and MD (25 novel loci). Further analyses showed that these shared loci exhibited both concordant and discordant effect directions between depression and white matter traits, as well as distinct yet overlapping hemispheric patterns in their genetic architecture. Enrichment analysis of these shared loci implicated biological processes related to metabolism and regulation. This study provides evidence of a mixed-direction shared genetic architecture between depression and white matter microstructure. The identification of specific loci and pathways offers potential insights for developing targeted interventions to improve white matter integrity and alleviate depressive symptoms.
Cardiovascular health (“Life’s Essential 8”), risk of depression and anxiety: a prospective cohort study
There is a growing interest in the linkage of cardiovascular health (CVH) with depression/anxiety but the evidence of “Life’s Essential 8” CVH score is scarce. We evaluated the associations of CVH score with risk of incident depression/anxiety among ~0.4 million participants. During follow-up, 17,554 incident events with symptoms of either disorder were recorded. Per 100-point decrease in CVH score was associated with an increased risk of incident either disorder (Hazard ratio [HR] = 1.133, 95% confidence interval [CI]:1.114–1.153), depression (HR = 1.205, 95% CI:1.180–1.231), and anxiety (HR = 1.042, 95% CI:1.017–1.069). Per 100-point decrease in health assessments or health behaviors was associated with an increased risk of incident either disorder (HRhealth assessments = 1.085, 95% CI: 1.058–1.113, HRhealth behaviors = 1.217, 95% CI: 1.186–1.250). Poor CVH is a risk factor for the incident late-life depression/anxiety symptoms of middle-aged and older adults, and healthy behaviors could be targeted for the risk assessment and intervention of depression/anxiety.
Depression symptom-specific genetic associations in clinically diagnosed and proxy case Alzheimer’s disease
Depression is a risk factor for the later development of Alzheimer’s disease (AD), but evidence for the genetic relationship is mixed. Assessing depression symptom-specific genetic associations may better clarify this relationship. To address this, we conducted genome-wide meta-analysis (a genome-wide association study, GWAS) of the nine depression symptom items, plus their sum score, on the Patient Health Questionnaire (PHQ-9) (GWAS-equivalent N: 224,535–308,421) using data from UK Biobank, the GLAD study and PROTECT, identifying 37 genomic risk loci. Using six AD GWASs with varying proportions of clinical and proxy (family history) case ascertainment, we identified 20 significant genetic correlations with depression/depression symptoms. However, only one of these was identified with a clinical AD GWAS. Local genetic correlations were detected in 14 regions. No statistical colocalization was identified in these regions. However, the region of the transmembrane protein 106B gene (TMEM106B) showed colocalization between multiple depression phenotypes and both clinical-only and clinical + proxy AD. Mendelian randomization and polygenic risk score analyses did not yield significant results after multiple testing correction in either direction. Our findings do not demonstrate a causal role of depression/depression symptoms on AD and suggest that previous evidence of genetic overlap between depression and AD may be driven by the inclusion of family history-based proxy cases/controls. However, colocalization at TMEM106B warrants further investigation.
Responses