An inflamed mood: studies on the role of inflammation in the pathophysiology and treatment outcome of major depressive disorder

Chenghao Yang

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    The unclear etiology and diverse presentations of major depressive disorder (MDD) generate substantial obstacles for an accurate diagnosis and effective treatment. Here we aimed to explore the pathophysiology of MDD, and specifically treatment Resistant Depression (TRD), with a specific interest in the role of dysregulated inflammatory system.

    In the first review study we describe that increased values of serum interleukin (IL)-6 and 1β tend to be more common in the melancholic subtype compared to the non-melancholic subtype or healthy controls, while C-reactive protein (CRP) may be a pointer for the non-melancholic subtype. The second paper covers that IL-6 and CRP/high sensitivity (hs)-CRP are promising markers for predicting treatment response in TRD.

    Then two genetic association studies are presented in Han Chinese persons, which zoom into the FKBP5 and CNR1 genes, both involved in regulation of inflammatory response. We found that CNR1 gene variants, including rs806367, rs6454674 and the haplotype C-T-T-C of rs806366, rs806367, rs806368, and rs806370, are associated with an increased risk for MDD but also with antidepressant treatment resistance between cases/TRD patients/non-TRD patients and healthy controls. This was not the case for FKBP5 alleles, genotypes and haplotypes.

    Lastly, an ongoing antidepressant augmentation trial with N-acetylcysteine is presented, that was designed to target TRD patients with inflammatory dysregulation. The design, with strengths and limitations are discussed, in attendance of the later results of this trial.

    In conclusion, we propose that specific inflammatory markers and genetic variants could be promising pointers in diagnosing and predicting antidepressant treatment response for MDD/TRD.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • Schoevers, Robert, Supervisor
    • Bosker, Fokko, Co-supervisor
    Award date9-Oct-2019
    Place of Publication[Groningen]
    Print ISBNs978-94-034-1974-9
    Electronic ISBNs978-94-034-1973-2
    Publication statusPublished - 2019

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