Investigating mitochondrial bioenergetics in peripheral blood mononuclear cells of women with childhood maltreatment from post-parturition period to one-year follow-up

Abstract

Background: Childhood maltreatment (CM) exerts various long-lasting psychological and biological changes in affected individuals, with inflammation being an interconnecting element. Besides chronic low-grade inflammation, CM might also affect the energy production of cells by altering the function and density of mitochondria, i.e. the body's main energy suppliers. Here, we compared mitochondrial respiration and density in intact peripheral blood mononuclear cells (PBMC), from women with and without CM between two time points, i.e. at the highly inflammatory phase within 1 week after parturition (t₀) and again after 1 year (t₂).

Methods: CM exposure was assessed with the Childhood Trauma Questionnaire. Whole blood was collected from n = 52 healthy women within the study 'My Childhood - Your Childhood' at both time points to isolate and cryopreserve PBMC. Thawed PBMC were used to measure mitochondrial respiration and density by high-resolution respirometry followed by spectrophotometric analyses of citrate-synthase activity.

Results: Over time, quantitative respiratory parameters increased, while qualitative flux control ratios decreased, independently of CM. Women with CM showed higher mitochondrial respiration and density at t₀, but not at t₂. We found significant CM group × time interaction effects for ATP-turnover-related respiration and mitochondrial density.

Conclusions: This is the first study to longitudinally investigate mitochondrial bioenergetics in postpartum women with and without CM. Our results indicate that CM-related mitochondrial alterations reflect allostatic load, probably due to higher inflammatory states during parturition, which normalize later. However, later inflammatory states might moderate the vulnerability for a second-hit on the level of mitochondrial bioenergetics, at least in immune cells.

Keywords: Bioenergetics; PBMC; childhood maltreatment; mitochondria; mitochondrial density; postpartum.

Fig. 1.

The change in mitochondrial respiration and density from 1 week postpartum (t₀) to 1 year postpartum (t₂) in n = 52 women with a history of childhood maltreatment (CM+, n = 23) and without (CM−, n = 29). Results of the linear mixed effect models are presented as predicted mean ± model-based 95% confidence intervals on the background of raw data. Mitochondrial respiration (a–e) was measured by high-resolution respirometry in pmol O₂/s per Million living cells. Flux control ratios (f–i) were calculated based on the measured respiratory values. As a marker for mitochondrial density (mitochondrial biogenesis), Citrate-synthase activity in pmol/s per Million shock-frozen cells was spectrophotometrically measured. Significant post-hoc tests are denoted by *p < 0.050, **p < 0.010, ***p < 0.001.