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      Association Between Mood Disorder Severity, Treatment Response and Systemic Inflammatory Markers: Exploring the Role of NLR, PLR, MLR, and SII

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          Abstract

          Background:

          In this study, the relationship between treatment response, clinical features of episodes such as psychosis, suicidal behavior, and agitation, duration of hospitalization, and systemic inflammation markers Systemic Inflammatory Index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in bipolar affective disorder manic episode (BAD-M), bipolar affective disorder—depressive episode (BAD-D), and major depressive disorder (MDD) were investigated.

          Methods:

          TheNLR, MLR, PLR, and log SII were measured using parameters from a complete blood count. Admission and discharge Young Mania Rating Scale and Hamilton Depression Rating Scale scores were evaluated. This is a retrospective study conducted with a total of 451 inpatients, 122 (27.10%) of whom were diagnosed with BAD-M, 60 (13.20%) with BAD-D, and 269 (56.60%) with MDD.

          Results:

          The patients with manic episodes have higher levels of NLR ( P = .019), MLR ( P = .002), and log SII ( P = .007). In the bipolar depression and mania groups, the patients with and without treatment responses did not differ in terms of inflammation markers; the log PLR value was found to be higher in the unipolar depression group in the patients who did not reach remission ( P = .048).

          Conclusion:

          This study reveals associations between inflammation markers and different types of mood episodes. Higher NLR, MLR, and log SII levels in bipolar mania and lower NLR levels in agitated unipolar depression provide clues about changes in inflammation across different episodes. Studies with larger samples are needed to evaluate the relationship between inflammatory markers, the severity of mania and depression, and the response to treatment.

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          Most cited references48

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          Severity classification on the Hamilton Depression Rating Scale.

          Symptom severity as a moderator of treatment response has been the subject of debate over the past 20 years. Each of the meta- and mega-analyses examining the treatment significance of depression severity used the Hamilton Depression Rating Scale (HAMD), wholly, or in part, to define severity, though the cutoff used to define severe depression varied. There is limited empirical research establishing cutoff scores for bands of severity on the HAMD. The goal of the study is to empirically establish cutoff scores on the HAMD in their allocation of patients to severity groups. Six hundred twenty-seven outpatients with current major depressive disorder were evaluated with a semi-structured diagnostic interview. Scores on the 17-item HAMD were derived from ratings according to the conversion method described by Endicott et al. (1981). The patients were also rated on the Clinical Global Index of Severity (CGI). Receiver operating curves were computed to identify the cutoff that optimally discriminated between patients with mild vs. moderate and moderate vs. severe depression. HAMD scores were significantly lower in patients with mild depression than patients with moderate depression, and patients with moderate depression scored significantly lower than patients with severe depression. The cutoff score on the HAMD that maximized the sum of sensitivity and specificity was 17 for the comparison of mild vs. moderate depression and 24 for the comparison of moderate vs. severe depression. The present study was conducted in a single outpatient practice in which the majority of patients were white, female, and had health insurance. Although the study was limited to a single site, a strength of the recruitment procedure was that the sample was not selected for participation in a treatment study, and exclusion and inclusion criteria did not reduce the representativeness of the patient groups. The analyses were based on HAMD scores extracted from ratings on the SADS. However, we used Endicott et al.'s (1981) empirically established formula for deriving a HAMD score from SADS ratings, and our results concurred with other small studies of the mean and median HAMD scores in severity groups. Based on this large study of psychiatric outpatients with major depressive disorder we recommend the following severity ranges for the HAMD: no depression (0-7); mild depression (8-16); moderate depression (17-23); and severe depression (≥24). Copyright © 2013 Elsevier B.V. All rights reserved.
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            Neuroinflammation and psychiatric illness

            Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence supporting the pathogenic role of neuroinflammation in selected classical psychiatric disorders. Understanding how psychosocial, genetic, immunological and neurotransmitter systems interact can reveal pathogenic clues and help target new preventive and symptomatic therapies.
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              Cytokine production and treatment response in major depressive disorder.

              In a controlled study, such immunological parameters as whole blood production of the cytokines interleukin-6 (IL-6) and tumor-necrosis factor-alpha (TNF-alpha) were assessed in 24 inpatients with a major depressive disorder (MDD) both before and again under treatment. After a 6-week treatment period with amitriptyline, patients were classified as responders or nonresponders according to their psychopathological outcome as evaluated by the Hamilton and the Montgomery-Asberg Depression Rating Scales. Pre-treatment levels of c-reactive protein (CRP) were significantly higher in both patient subgroups than in the control subjects. In comparison to the controls, unstimulated pretreatment production of IL-6 was significantly decreased in the responders; whereas it was significantly increased in the nonresponder subgroup. Post-treatment values did not differ significantly among the patient and control groups. Pretreatment levels of TNF-alpha were increased in both patient subgroups, with a significant decrease during treatment only in the responder subgroup. Pretreatment levels of IL-6/10(5) mononuclear cells and the ratio between lymphocytes and monocytes acted as independent variables with regard to the clinical response. Our data indicate that unstimulated secretion of TNF-alpha is related to the psychopathological improvement; whereas, IL-6 levels might dichotomize the patients into subsequent responders and nonresponders already at admission.
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                Author and article information

                Journal
                Psychiatry Clin Psychopharmacol
                Psychiatry Clin Psychopharmacol
                Psychiatry and Clinical Psychopharmacology
                Mesut Çetin
                2475-0581
                March 2024
                01 March 2024
                : 34
                : 1
                : 19-28
                Affiliations
                Department of Psychiatry , Gazi University, Faculty of Medicine, Ankara, Turkey
                Author notes
                Corresponding author: Melike Kucukkarapinar or Filiz Karadag, e-mail: melikekkpinar@ 123456gazi.edu.tr or filizkaradag@ 123456gazi.edu.tr

                Cite this article as: Kucukkarapinar M, Erbil D, Keles İ, Karadag F. Association between mood disorder severity, treatment response and systemic inflammatory markers: Exploring the role of NLR, PLR, MLR, and SII. Psychiatry Clin Psychopharmacol. 2024; 34(1): 19-28.

                Author information
                http://orcid.org/0000-0001-8067-4029
                http://orcid.org/0000-0001-9991-2891
                http://orcid.org/0000-0001-9975-1194
                http://orcid.org/0000-0001-8631-7049
                Article
                pcp-34-1-19
                10.5152/pcp.2024.23760
                11177661
                38883883
                b297ebca-6e61-4828-a739-0605b7b17da1
                2024 authors

                Content of this journal is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 26 August 2023
                : 5 December 2023
                Funding
                The authors declare that this study has received no financial support.
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