Assoziationen zwischen inflammatorischen Parametern und morphologischen Charakteristika des ZNS bei affektiv erkrankten Patienten – Eine experimentelle Studie im Rahmen der MACS-Kohorte –

Psychiatrische Erkrankungen aus dem affektiven Formenkreis verursachen neben erheblichem individuellem Leid ebenso immense gesamtgesellschaftliche Schäden. Zur weiteren Erforschung dieser multifaktoriell verursachten Störungen werden im Rahmen der DFG geförderten Marburg-Münster Affective Disorder C...

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Bibliographic Details
Main Author: Glandorf, Julian
Contributors: Pfefferle, Petra Ina (Prof. Dr. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2018
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Table of Contents: Psychiatric disorders of the affective spectrum not only cause serious individual suffering, but also tremendous socio-economic costs. Further research of the multifactorial genesis of these illnesses is provided by the DFG funded Marburg-Münster Affective Disorder Cohort Study (MACS). It focuses on the diverse genetical and molecular mechanisms underlying the genesis and maintaining of these disorders. Beside development of new treatment approaches, the research foundation strives to detect measurable biological parameters as a basis for diagnostical classification or as therapy control. This dissertation pursues the goal of detecting immunological and brain morphometric differences between healthy and ill subjects. Furthermore a statistically significant association between these parameters shall be detected. For this purpose peripheral venal blood of 609 participants of the MACS was incubated with lipopolysaccharide (LPS) and antiCD3/CD28-antibodies. LPS induces a general proinflammatory immune response, whereas antiCD3/CD28 gives rise to a specific T-cell response. The released cytokines were then quantified by a Cytometric Bead Array System (CBA). They reflect the general capacity and responsiveness of the immune system. Additionally, this dissertation incorporates volume data of multiple brain regions measured by a 3-tesla MRI. This data was provided by other members of the MACS. While healthy men and affected men show almost identical immune responses, healthy women show significantly higher concentrations of proinflammatory cytokines (IL1-β, TNF-α, IFN-γ, IL17-α und IL12p70) than their ill counterparts. Brain morphometric differences can be detected at the lateral ventricles, the thalamus, the amygdala, the left nucleus caudatus, the right nucleus accumbens und the left hippocampal region. The interaction factors related to the diagnoses, the age and/or the gender show significant values for these brain regions. Furthermore, in logistic regression model IL10 and TNF-α show significant influence on the target variables: Putamen, left nucleus accumbens and the right globus pallidus. These results strengthen the widely held assumption about a key role of the immune system in the etiopathogenesis of affective disorders. It goes in line with the findings of previous studies indicating various causes of elevated immune parameters, their diverse mechanisms of interaction with the brain and their broad effects on brain function and structure. The cross-sectional design of the present study does not allow for assuming a causal relationship between cytokines and brain volume. However, the results showing that cytokines are associated with the decreased brain volume are of great importance for the follow-up investigations or new longitudinal studies. In future research, it would be interesting to take into account the immune regulatory effects of antidepressant medication or smoking. Bioparameters measured in this work may contribute to the improvement of diagnostics and therapeutics of affective disorders in the future and thereby reduce the individual and social burden of this disease.