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Knapp, J. D.

Publications and source records attributed to Knapp, J. D..

2 recordsLinked to original sources

The lipidome of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women develop PTSD at twice the rate of men, despite greater trauma exposure in men. Lipids and their metabolites (lipidome) regulate a myriad of key biological processes and pathways such as membrane integrity, oxidative stress, and neuroinflammation in the brain by maintaining neuronal connectivity and homeostasis. In this study, we analyzed the lipidome of 40 individuals with PTSD and 40 trauma-exposed non-PTSD individuals. Plasma samples were analyzed for lipidomics using Quadrupole Time-of-Flight (QToF) mass spectrometry. Additionally, [~] 90 measures were collected, on sleep, mental and physical health indices. Sleep quality worsened as PTSD severity increased in both sexes. The lipidomics analysis identified a total of 348 quantifiable known lipid metabolites and 1951 lipid metabolites that are yet unknown; known metabolites were part of 13 classes of lipids. After adjusting for sleep quality, in women with PTSD, only one lipid subclass, phosphatidylethanolamine (PE) was altered, whereas, in men with PTSD, 9 out of 13 subclasses were altered compared to non-PTSD women and men, respectively. Severe PTSD was associated with 22% and 5% of altered lipid metabolites in men and women, respectively. Of the changed metabolites, only 0.5% measures (2 PEs and cholesterol) were common between women and men with PTSD. Several sphingomyelins, PEs, ceramides, and triglycerides were increased in men with severe PTSD. The triglycerides and ceramide metabolites that were most highly increased were correlated with cholesterol metabolites and systolic blood pressure in men but not always in women with PTSD. Alterations in triglycerides and ceramides are linked with cardiac health and metabolic function in humans. Thus, disturbed sleep and higher weight may have contributed to changes in the lipidome found in PTSD.

systems biology↗

BNT162b2 mRNA vaccine-induced sex differences in the single-cell transcriptome of peripheral blood mononuclear cells in healthy adults

IntroductionMen reportedly experience more severe disease and adverse outcomes from COVID-19, including death. Women report more adverse events (AEs) after vaccination in general. While few studies have addressed sex-specific risk factors or molecular mechanisms behind COVID-19, none have examined sex differences in the response to COVID-19 vaccination. MethodsWe searched AE reporting databases to find sex differences specific to COVID-19 vaccines. We analyzed public datasets to identify baseline sex differences in gene expression across cell types and time points, and sex differences in the response to the second BNT162b2 mRNA vaccine dose. ResultsSex differences in AE rates for mRNA vaccines equaled those for other non-mRNA vaccines. T cells and monocytes showed the greatest number of sexually dimorphic genes. Platelet counts in the study population differed significantly before vaccination (3.6% in females vs 1.8% in males) but not after the second BNT162b2 dose (7.2% vs 7.3%). There were no notable sex differences in the expression of key genes induced by the second dose after exclusion of platelets. BNT162b2 dose 2-specific APOBEC3Ahigh monocytes and the dose 2-induced gene signature persisted for longer in women. Glucocorticoid-responsive TSC22D3, CEBPB/D and DDIT4 were specifically induced in females; the voltage-gated potassium channel regulatory subunit KCNE3 was specifically induced in males. ConclusionsThis sexual dimorphism in both X-linked and autosomal gene transcriptome in PBMCs after mRNA COVID-19 vaccination might explain fatigue, autoimmune, and neurological AEs reported after vaccination at different rates in women and men.

systems biology↗