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Untersuchung von Haarproteinspiegeln des mitochondrialen Energiestoffwechsels bei Personen mit und ohne Majore Depression und Suizidenten

eine Analyse zum Projekt GerontoTel
Authors: Zacharias, Marta Carlota;

Untersuchung von Haarproteinspiegeln des mitochondrialen Energiestoffwechsels bei Personen mit und ohne Majore Depression und Suizidenten

Abstract

Chronischer Stress ist ein ätiologisch bedeutsamer Risikofaktor für das Auftreten einer Depression. Ein Symptom der Depression ist Suizidalität. Bislang gibt es keine fundierten labordiagnostischen Möglichkeiten, um Depressionen und Suizidalität eindeutig zu erfassen, Vielversprechende Biomarker hierfür könnten Metabolite und Proteine bioenergetischer Prozesse in den Mitochondrien sein. Vorhergehende Studien konnten bereits eine verringerte mitochondriale Atmung sowie verringerte ATP-Level in Immunzellen von depressiven Personen feststellen. Die Verwendung von Haaren erlaubt auch Einblicke in die Stressbiologie der Depression. Es konnten unterschiedliche Haarkortisollevel bei Personen mit und ohne Depression sowie bei Personen nach komplettiertem Suizid aufgezeigt werden. Ziel dieser Arbeit war es, die verfügbaren Proteine des zellulären Energiestoffwechsels in Haaren zu messen und diese auf Unterschiede bezogen auf den zellulären Energiestoffwechsel zwischen Personen mit Majorer Depression (n=19) und Personen ohne depressive Vorerkrankungen (n=20) sowie nach komplettiertem Suizid (SC) (n=55) zu untersuchen. Die Haarproben wurden mittels LC-MS/MS-Analyse für einen Proteomics-Ansatz eingesetzt und analysiert. Es konnten insgesamt zehn Proteine gemessen werden, die für den Energiestoffwechsel im Citratzyklus relevant waren. Des Weiteren zeigten sich signifikante Gruppenunterschiede zwischen Kontrollgruppe und depressiver Experimentalgruppe (MDD). Hierbei können signifikante Unterschiede zwischen MDD-Gruppe und KG hinsichtlich einer größtenteils erhöhten Proteinausprägung gezeigt werden. Es sind keine Gruppenunterschiede zwischen SC-Gruppe und KG-Gruppe festzustellen. Im Vergleich zur MDD-Gruppe waren die Proteine der SC-Gruppe nicht signifikant verringert. Zudem konnte ein Zusammenhang zwischen der Symptomschwere der Depression, gemessen durch die klinischen Messinstrumente Beck Depressionsinventar-II (BDI, Selbstbericht) und Montgomery Asberg Depression rating scale (MADRS, Fremdbeurteilung) und den Proteinspiegeln in Haar gezeigt werden. Die Proteine des Citratzyklus könnten potenzielle Biomarker im Kontext der 3PM darstellen, jedoch bedarf es an weitere Forschungen, welche den ganzen Energiestoffwechselpfad untersuchen sollte, um die Ergebnisse zu replizieren und zu validieren. Zudem sollten longitudinale Daten untersucht werden.

Chronic stress is a significant risk factor for the occurrence of depression. Suicidal behaviour is a symptom of depression. To date, there are no well-founded laboratory diagnostic options to clearly identify depression and suicidality. Promising biomarkers for this could be metabolites and proteins of bioenergetic processes in the mitochondria. Previous studies have already identified reduced mitochondrial respiration and reduced ATP levels in immune cells of depressed individuals. The use of hair also provides insights into the stress biology of depression. Different hair cortisol levels were shown in people with and without depression and in people who had completed suicide. The aim of this study was to measure the available proteins of the cellular energy metabolism in hair and to analyse these for differences in cellular energy metabolism between individuals with major depression (n=19) and individuals without previous depressive disorders (n=20) as well as after completed suicide (SC) (n=55). The hair samples were used and analysed using LC-MS/MS analysis for a proteomics approach. A total of ten proteins relevant for energy metabolism in the citric acid cycle were measured. Furthermore, significant group differences were found between the control group and the depressive experimental group (MDD). Significant differences can be shown between the MDD group and the SC group with regard to a largely increased protein expression. There are no group differences between the SC group and the KG group. Compared to the MDD group, the proteins of the SC group were not significantly reduced. In addition, a correlation between the symptom severity of depression, measured by the clinical measurement instruments Beck Depression Inventory-II (BDI, self-report) and Montgomery Asberg Depression Rating Scale (MADRS, external assessment) and the protein levels in hair could be shown. The proteins of the citrate cycle could be potential biomarkers in the context of 3PM, but further research is needed to investigate the whole energy metabolism pathway to replicate and validate the results. In addition, longitudinal data should be analysed.

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Keywords

3PM, Depression, Personalisierte Medizin, personalised medicine, Omics, biomarkers, Biomarker, prediction, Prädiktion, Prävention, Stress, Suizid, bioenergetics, omics, Citratzyklus, stress, Haarproben, prevention, depression, citric acid cycle, Bioenergetik, suicide, hair samples

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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