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      C-Reactive Protein Gene Variants in Depressive Symptoms & Antidepressants Efficacy

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          Abstract

          Objective

          Although the pathogenesis of depression remains unclear, C-reactive protein (CRP) levels are commonly elevated in depressed patients. Thus, CRP single-nucleotide polymorphisms (SNPs) that influence CRP levels may be associated with depression. In the present study, we explored whether CRP SNPs are related to depressive symptoms and antidepressants efficacy in Han Chinese patients.

          Methods

          We analyzed data from 440 patients with first-episode depression. We obtained genome CRP SNPs, scores of the 17-item Hamilton Rating Scale for Depression 17 (HAMD17) and its four-factor at baseline and after 6 weeks. Quantitative trait analysis was performed using UNPHASED software and curative effects were analyzed using SPSS software.

          Results

          Male patients with SNP rs1800947G exhibited lower insomnia scores and rs2794521CC exhibited lower scores of anxiety/ physical symptoms, total HAMD17 score. Female patients with rs2794521TT exhibited higher scores of insomnia and lower antidepressants efficacy.

          Conclusion

          CRP SNPs rs1800947 and rs2794521 may be associated with depressive symptoms in patients with depression in a sex-specific fashion. Furthermore, rs2794521 may be a predictor of the efficacy of antidepressants in female patients.

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          Most cited references35

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          Diagnostic and statistical manual of mental disorders.

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            Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis.

            Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory cytokines and C-reactive protein. In addition, previous meta-analyses suggest that antidepressant drug treatment may decrease peripheral levels of interleukin-1 beta (IL-1β) and IL-6. Recently, several new studies examining the effect of antidepressants on these cytokines have been published, and so we performed an updated meta-analysis of studies that measured peripheral levels of cytokines and chemokines during antidepressant treatment in patients with MDD. The PubMed/MEDLINE, EMBASE, and PsycInfo databases were searched from inception through March 9, 2017. Forty-five studies met inclusion criteria (N = 1517). Peripheral levels of IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, IL-10, IL-2, IL-4, interferon-γ, IL-8, the C-C motif ligand 2 chemokine (CCL-2), CCL-3, IL-1 receptor antagonist, IL-13, IL-17, IL-5, IL-7, and the soluble IL-2 receptor were measured in at least three datasets and thus were meta-analyzed. Antidepressant treatment significantly decreased peripheral levels of IL-6 (Hedges g = -0.454, P <0.001), TNF-α (g = -0.202, P = 0.015), IL-10 (g = -0.566, P = 0.012), and CCL-2 (g = -1.502, P = 0.006). These findings indicate that antidepressants decrease several markers of peripheral inflammation. However, this meta-analysis did not provide evidence that reductions in peripheral inflammation are associated with antidepressant treatment response although few studies provided separate data for treatment responders and non-responders.
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              What does plasma CRP tell us about peripheral and central inflammation in depression?

              Peripheral blood C-reactive protein (CRP) is a biomarker used clinically to measure systemic inflammation and is reproducibly increased in a subset of patients with major depressive disorder (MDD). Furthermore, increased peripheral blood CRP in MDD has been associated with altered reward circuitry and increased brain glutamate in relation with symptoms of anhedonia. Nevertheless, the relationship between peripheral CRP and other peripheral and central markers of inflammation in depressed patients has not been established. Plasma (n=89) and CSF (n=73) was collected from medically-stable, currently-unmedicated adult outpatients with MDD. Associations among plasma and CSF CRP and plasma and CSF inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF] and IL-1beta) and their soluble receptors/antagonists were examined. Relationships between plasma and CSF inflammatory markers and depressive symptoms including anhedonia and reduced motivation (RM) were also explored. Plasma CRP was correlated with multiple plasma inflammatory markers (all p 3mg/L) and correlated with depressive symptom severity. These findings were driven by CSF TNF, which correlated with RM (r=0.236, p=0.045), and CSF IL-6 soluble receptor, which correlated with anhedonia (r=0.301, p=0.010) in the sample as a whole and particularly females. CRP appears to be a peripheral biomarker that reflects peripheral and central inflammation and seems well-suited for guiding immunotherapies targeting TNF and IL-6 in patients with MDD.
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                Author and article information

                Journal
                Psychiatry Investig
                Psychiatry Investig
                PI
                Psychiatry Investigation
                Korean Neuropsychiatric Association
                1738-3684
                1976-3026
                December 2019
                13 November 2019
                : 16
                : 12
                : 940-947
                Affiliations
                [1 ]Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
                [2 ]Shanxi Medical University, Taiyuan, China
                Author notes
                Correspondence: Kerang Zhang, MD, PhD Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, People’s Republic of China Tel: +86-351-4639869, Fax: +86-351-4639956, E-mail: atomsxmu@ 123456vip.163.com
                Author information
                http://orcid.org/0000-0002-6296-4409
                http://orcid.org/0000-0002-7397-2738
                Article
                pi-2019-0117
                10.30773/pi.2019.0117
                6933135
                31711279
                51f54148-4700-4c5a-bfff-be92e79cdf4d
                Copyright © 2019 Korean Neuropsychiatric Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 May 2019
                : 3 July 2019
                : 5 September 2019
                Categories
                Original Article

                Clinical Psychology & Psychiatry
                depression,single-nucleotide polymorphism,antidepressant,c-reactive protein,6-week follow-up

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