08:30 Uhr
Die Rolle des Mineralokortikoid-Rezeptors bei depressiven Verläufen und dem Ansprechen auf eine antidepressive Pharmakotherapie – Ergebnisse aus der EMC-Studie
J. Engelmann (Mainz, DE)
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Autor:innen:
J. Engelmann (Mainz, DE)
H. Murck (Marburg, DE)
S. Wagner (Mainz, DE)
D. Herzog (Mainz, DE)
A. Tadic (Liebenburg, DE)
M. Müller (Mainz, DE)
K. Lieb (Mainz, DE)
Veränderungen in der Hypothalamus-Hypophysen-Nebennierenrinden-Achse (HPA) sind die am häufigsten reproduzierten Befunden bei Depressionen. Der Mineralokortikoidrezeptor (MR) gilt als wichtiger Stressmodulator, der sowohl die basale als auch die Stress-induzierten Aktivität der HPA-Achse beeinflusst. Mehreren Studien deuten auf einen Zusammenhang zwischen autonomen Funktionen des MRs sowohl bei der Pathophysiologie als auch beim Ansprechen auf Antidepressiva hin. Ziel dieser sekundären Analyse war es, periphere Marker des MRs (systolischer RR und Elektrolyte) sowie Cortisol- und Aldosteronkonzentrationen bei einer großen Kohorte von antidepressiv behandelten Patienten zu untersuchen. 826 MDD Patienten, die im Rahmen der Early Medication Change (EMC) Studie antidepressiv behandelt wurden, wurden in die sekundäre Analyse eingeschlossen. Die Depressionsschwere und die MR-assoziierten Marker (Blutdruck und Elektrolyte) wurde wöchentlich bestimmt. In 560 Patienten erfolgten longitudinale Kortisol- und Aldosteron-Messungen. Wir konnten früheren Beobachtungen einer veränderten peripheren MR-Sensitivität bei schwergradig Depressiven bestätigen. Patienten mit niedrigerem systolischen Blutdruck waren schwerer depressiv und sprachen schlechter auf die Pharmakotherapie an. Auch Veränderungen im Natrium/Kalium Haushalt korrelierten mit der Depressionsschwere und dem Ansprechen. Die Ergebnisse der Gesamtgruppe bestätigten sich in Subgruppenanalysen, vor allem zwischen suizidalen und nicht-suizidalen Patienten. Weiterhin werden vorläufige Ergebnisse von longitudinalen Kortisol- und Aldosteronmessungen präsentiert. Zusammenfassend konnten wir frühere Beobachtungen einer veränderten MR-Sensitivität bei Patienten mit schwergradiger depressiver Symptomatik in einem großen MDD Studienkollektiv bestätigen. Die leicht verfügbaren peripheren MR-Marker sollte als potentielle Biomarker für depressive Subgruppen in weiteren Kohorten untersucht werden.
08:42 Uhr
Temporal dynamics of depressive symptomatology: an idiographic time series analysis applying dynamic network models to patients with depressive disorders
B. Siepe (Frankfurt am Main, DE)
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Autor:innen:
B. Siepe (Frankfurt am Main, DE)
C. Sander (Leipzig, DE)
M. Schultze (Frankfurt am Main, DE)
A. Kliem (Dortmund, DE)
S. Ludwig (Leipzig, DE)
H. Reich de Paredes (Frankfurt am Main, DE)
U. Hegerl (Frankfurt am Main, DE)
Background: As phenotypes of depressive disorders (DD) are highly heterogenous, a growing number of studies investigate person-specific associations of depressive symptoms in time series data. Most available methods for estimating applicable models rely on the assumption that the associations between variables stay constant over time, which can be unrealistic in clinical contexts. To circumvent this limitation, we used a recently developed technique to estimate time-varying vector autoregressive models. Methods: In daily diary data of 20 participants with DD with a mean length of 274 days (SD = 82.4, range = 154-539), we modeled idiographic associations between core depressive symptoms, rumination, sleep, and social contacts as idiographic time-varying dynamical networks. Results: Resulting models showed marked inter- as well as intraindividual differences. For some participants, associations between variables changed fast over time, whereas for others they showed more stability. Our results further indicate nonstationarity in all time series. Discussion: Changes in symptom networks of depression can be of interest to clinicians and researchers. The assumption of stationarity can hinder insights into important change processes. Idiographic time-varying network models are a promising approach to capture changes over time and provide detailed insights into the temporal course of mental disorders. We further discuss limitations, their possible solutions, and recommendations for further use of the modeling technique.
08:54 Uhr
The steroid hormone dehydroepiandrosterone (DHEA) counteracts the consequences of psychological trauma on immunocellular aging
K. de Punder (Innsbruck, AT)
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Autor:innen:
K. de Punder (Innsbruck, AT)
J. Salinas-Manrique (Hildesheim, DE)
I. Kolassa (Ulm, DE)
D. Dietrich (Hildesheim, DE)
A. Karabatsiakis (Innsbruck, AT)
Exposure to psychological trauma is related to the development of a wide range of age-related physical and mental disorders, including depression. Emerging studies have highlighted the role of the telomere biology system as an aging mechanism underlying this association. An area of interest and investigation is the identification of biological resilience factors that target the telomere biology system and thereby possibly counteract the negative consequences of psychological trauma on accelerated cellular aging and the development of psychopathology. Therefore, in the present study, we investigated the proposed anti-ageing effects of endogenous circulating levels of the steroid hormone dehydroepiandrosterone (DHEA) in n=22 inpatients with MDD and n=22 non-depressed controls of whom lifetime traumatic events were assessed by self-report using the Essener Trauma Inventory. DHEA levels were measured by immunoassay and immune cell TL was quantified in kilobases using quantitative fluorescent in situ hybridization in total peripheral blood mononuclear cells (PBMC) and in specific T-cell subpopulations. We found that higher trauma load related to lower DHEA concentration and that lower DHEA concentration was associated with more depression-related fatigue symptoms. DHEA concentration mediated the effect of trauma load on depression-related fatigue only among women with depression. In addition, we observed that DHEA levels were positively associated with TL in memory CD4+ T-cells as well as in naïve and memory CD8+ T cells but not in naïve CD4+ T-cells and in total PBMC. Mediational analysis suggested that the effect of trauma load on memory CD8+ T-cell TL was mediated by DHEA concentration. In conclusion, the current findings highlight the role of DHEA as an endogenous biological resilience factor that was demonstrated here to attenuate the adverse consequences of trauma exposure on immunocellular aging.
09:06 Uhr
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
A. Karabatsiakis (Innsbruck, AT)
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Autor:innen:
A. Karabatsiakis (Innsbruck, AT)
J. Salinas-Manrique (DE)
T. Stoll (AU)
T. Hennessy (AU)
I. Kolassa (DE)
M. Hill (AU)
D. Dietrich (DE)
Major depression (MD) is characterized by impairments in mental and physical performance. Despite intensified hypothesis-driven research, applicable biomarkers for MD remain missing. Research demonstrated 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 MD 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 MD. 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 MD and non-MD 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 MD research. The unraveled biochemical pathways indicate a modulated association of MD with inflammation, oxidative stress, and mitochondrial bioenergetics. The biomarker candidates have to be replicated in independent cohorts.