Major depressive disorder and hs-crp: comparative study of responsive and non-responsive to antidepressants MDD and its relationship with inflammatory biomarkers

Postgraduate Thesis uoadl:2943631 22 Read counter

Κατεύθυνση Προαγωγή ψυχικής υγείας - Πρόληψη ψυχιατρικών διαταραχών
Library of the School of Health Sciences
Deposit date:
Chliara Ioanna-Ilia
Supervisors info:
Αγγελόπουλος Ηλίας, Ιατρική Σχολή, ΕΚΠΑ
Παπαγεωργίου Χαράλαμπος, Ιατρική Σχολή, ΕΚΠΑ
Μασδράκης Βασίλειος, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Μείζων καταθλιπτική διαταραχή και hs-crp : συγκριτική μελέτη αποκρινόμενης και μη ΜΚΔ σε αντικαταθλιπτικά φάρμακα και συσχέτιση με φλεγμονώδεις δείκτες
Translated title:
Major depressive disorder and hs-crp: comparative study of responsive and non-responsive to antidepressants MDD and its relationship with inflammatory biomarkers
Introduction- Major depressive disorder is the most common severe mental disorder with a lifetime prevalence of up to 17% (Kessler et al., 2003). Evidence-based treatments are available to improve symptoms in most patients. However, according to the most important sequence study of The Sequenced Treatment Alternatives to Relieve Depression (STAR * D), in which the results were analyzed after several standardized stages of treatment, 33% of patients do not meet only the four, successive stages of their participation in the treatments, according to criteria(Rush et al 2006). The same results, regarding treatment-resistant depression (TRD), have been shown in more recent studies (Juan Qiao et. Al, 2019).

Over the past two decades, a growing area of preclinical and clinical research has been accumulating data linking psychiatric illness to inflammatory processes. Most of this data came from an attempt to link these disorders, in particular major depressive disorder (MDD), to the biology of stress. The data from these studies appear to enhance the possibility of an "initial common pathway" by which immune / inflammatory factors in combination with stress biomarkers cause changes in brain structure and function (Raison CL et al, 2006). Inflammation, and especially C-reactive protein (CRP), is associated with depression, and its levels have been shown to vary and even change after antidepressant treatment.

In terms of resistance to depression, comparative studies and meta-analyzes show that electroconvulsive therapy (ECT) is probably the most effective intervention (non-pharmacological) acute phase treatment for resistance to depression, but its clinical response varies. Despite studies evaluating the course of inflammatory change during ECT, both CRP and other inflammatory, pre-inflammatory, and anti-inflammatory markers, evaluation of biomarkers as prognostic markers of response to treatment is clearly absent (Jennifer L Kruse. Et al., 2018).

Aim- The present study investigated whether resistance to the treatment of depressed patients was associated with the inflammatory biomarker, hs-CRP. For this purpose, the levels of inflammatory factors in a group of patients who met the criteria for treatment-resistant depression, in which ECT was used as the treatment of choice, were compared with the levels of the same factors in a group of patients with MDDs responding to per os antidepressant.

Methodology - Evaluation is performed in patients (n = 43), 25 patients with TRD and 18 patients with drug-responsive MDD (control group) (diagnosed according to DSM-V criteria), taking a peripheral blood sample for blood factor analysis in specific time frames. The selected immune factor for analysis was hs-CRP, while the criteria for patient participation strictly included the symptoms of MDD, excluding organic or drug-induced / substance-induced etiology. Specifically, for patients with TRD, the first and last blood sampling was performed before the 1st and after the 12th ECT session(which took place at an academic referral center, Aeginiteio Hospital of Athens), while at the same time the control patients (MDD patients) underwent blood sampling at the beginning and at the end of their treatment in the same hospital. At the same time, their medication and its changes were recorded, their symptomatology assessments with the scales HAM-D-17 and MADRS, in the aforementioned time periods and the clinical picture of patients daily by trained medical staff. Personal data were collected during the period 10 / 2019-12 / 2020.

Results - In two-variable analysis, higher levels appeared on the HAM-D-17 and MADRS scales in the control group (n = 18) at the beginning, while at the end both scales showed improvement. These fluctuations in values were correlated with the corresponding fluctuations in hs-CRP levels (p <0.002). For the TRD group (n = 25), hs-CRP showed the same changes as the control group, with the HAM-D-17 and MADRS scales starting at high levels and showing a slight improvement, but not a complete absence of depression symptoms (p <0.001). The hs-CRP in the control group started at higher levels compared to the TRD group, and showed a greater decrease in prices, while a reasonable percentage was not lacking in the TRD group which made a small increase.

Conclusions - While the findings of the study yield statistically significant results, large fluctuations in values and small sample size do not allow the identification of hs-CRP prognostic factor of depression, on a substrate of inflammatory function. Acute changes in hs-CRP may reflect peaks in the inflammatory response when selecting antidepressants of choice, but not necessarily in the mood. Additional studies are needed to identify inflammatory biomarkers as guidelines for the treatment of TRD.
Main subject category:
Health Sciences
Major depressive disorder, Electroconvulsive therapy, hs-CRP, Biomarkers
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