Karabatsiakis 2023 MiP2023

Karabatsiakis 2023 MiP2023

Combined metabolite and lipid fingerprinting of blood serum reveals biomarker candidates of altered mitochondrial bioenergetics in peripheral blood mononuclear cells of female patients with depression.

Link: MiP2023 Obergurgl AT

Karabatsiakis Alexander (2023)

Event: MiP2023 Obergurgl AT

Authors: Karabatsiakis Alexander, Manrique Juan-Salinas, Stoll Thomas, Hennessy Thomas, Hill Michelle M, Dietrich Detlef E

Major depressive disorder (MDD) is characterized by impairments in mental and physical performance. Despite intensified hypothesis-driven research, applicable biomarkers for MDD are missing. Research showed that MD is associated with impaired mitochondrial bioenergetic functioning in peripheral blood mononuclear cells (PBMC). However, deeper biomolecular insights into bioenergetic and associated biochemical changes in blood underlying the pathophysiology of MDD are necessary to identify new biomarker candidates. Here, the biochemistry of PBMC-surrounding blood was analyzed using a hypothesis-free biomarker identification approach combining metabolite and lipid fingerprinting. Biochemical fingerprints of serum were compared between female individuals (N = 44) with and without MDD. Serum extracts were separated by liquid chromatography and detected with time-of-flight mass spectrometry. The data was analyzed by multiple group comparisons and correlations, as well as two multivariate classification procedures. Next, our previously identified alterations in mitochondrial bioenergetics in PBMC were co-considered as an outcome for our biomarker identification approach. Consequently, the most promising compound was tested for correlation with mitochondrial respiration. Nine biomarker candidates discriminated between MDD and non-MDD with high predictive accuracy (90.9 %). The detected compounds are involved in lipid and amino acid-metabolism. 9,10-dihydroxy-octadenedioic acid was revealed as a robust biomarker candidate with a predictive accuracy of 81.8 % and significant mean positive correlation with parameters of mitochondrial respiration (r = 0.31-0.48, p<0.01). Our fingerprinting results highlight novel biomarker candidates and associated pathways for MDD research. The unraveled biochemical pathways indicate a modulated association of MDD with inflammation, oxidative stress, and mitochondrial bioenergetics. The biomarker candidates have to be replicated in independent cohorts of all ages & sexes.

Affiliations

Karabatsiakis Alexander ¹, Manrique Juan-Salinas², Stoll Thomas³, Hennessy Thomas⁴, Hill Michelle M³, Dietrich Detlef E²

1. 1 Department of Clinical Psychology II, Institute of Psychology, University of Innsbruck, Innsbruck, Austria
2. AMEOS Clinics Hildesheim, Hildesheim, Germany
3. The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia
4. Agilent Technologies Australia Pty Ltd, 679 Springvale Road, Mulgrave, VIC, 3170 Australia

Labels:

Organism: Human  Tissue;cell: Blood cells 

Event: Oral