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Chemokines in depression in health and in inflammatory illness: a systematic review and meta-analysis.

ABSTRACT: Inflammatory illness is associated with depression. Preclinical work has shown that chemokines are linked with peripheral-central crosstalk and may be important in mediating depressive behaviours. We sought to establish what evidence exists that differences in blood or cerebrospinal fluid chemokine concentration discriminate between individuals with depression and those without. Following PRISMA guidelines, we systematically searched Embase, PsycINFO and Medline databases. We included participants with physical illness for subgroup analysis, and excluded participants with comorbid psychiatric diagnoses. Seventy-three studies met the inclusion criteria for the meta-analysis. Individuals with depression had higher levels of blood CXCL4 and CXCL7 and lower levels of blood CCL4. Sensitivity analysis of studies with only physically healthy participants identified higher blood levels of CCL2, CCL3, CCL11, CXCL7 and CXCL8 and lower blood levels of CCL4. All other chemokines examined did not reveal significant differences (blood CCL5, CCL7, CXCL9, CXCL10 and cerebrospinal fluid CXCL8 and CXCL10). Analysis of the clinical utility of the effect size of plasma CXCL8 in healthy individuals found a negative predictive value 93.5%, given the population prevalence of depression of 10%. Overall, our meta-analysis finds evidence linking abnormalities of blood chemokines with depression in humans. Furthermore, we have demonstrated the possibility of classifying individuals with depression based on their inflammatory biomarker profile. Future research should explore putative mechanisms underlying this association, attempt to replicate existing findings in larger populations and aim to develop new diagnostic and therapeutic strategies.

SUBMITTER: Leighton SP

PROVIDER: S-EPMC5754468 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Chemokines in depression in health and in inflammatory illness: a systematic review and meta-analysis.

Leighton S P SP Nerurkar L L Krishnadas R R Johnman C C Graham G J GJ Cavanagh J J

Molecular psychiatry 20171114 1

Inflammatory illness is associated with depression. Preclinical work has shown that chemokines are linked with peripheral-central crosstalk and may be important in mediating depressive behaviours. We sought to establish what evidence exists that differences in blood or cerebrospinal fluid chemokine concentration discriminate between individuals with depression and those without. Following PRISMA guidelines, we systematically searched Embase, PsycINFO and Medline databases. We included participan ...[more]

PMID: 29133955

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Project description:The innate immune system is dysregulated in depression; however, less is known about the longitudinal associations of depression and inflammatory biomarkers. We investigated the prospective associations of depression and inflammatory biomarkers [interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-α), and C-reactive protein (CRP)] in community samples, both unadjusted and adjusted for covariates. The review, registered with PROSPERO, searched for published and unpublished studies via MEDLINE/PsycINFO/PsycARTICLES/EMBASE/Proquest Dissertation. Standardized Fisher transformations of the correlation/beta coefficients, both unadjusted and adjusted for covariates, were extracted from studies examining the prospective associations of depression and inflammatory biomarkers. Systematic review conducted in January, 2019 included 38 studies representing 58,256 participants, with up to 27 studies included in random-effects meta-analysis. Higher CRP/IL-6 were associated with future depressive symptoms, and higher depressive symptoms were associated with higher future CRP/IL-6 in both unadjusted and adjusted analyses - this is the first meta-analysis reporting an adjusted association of IL-6 with future depression. The adjusted prospective associations of depression with CRP/CRP with depression were substantially attenuated and small in magnitude. No significant associations were observed for TNF-α. No conclusive results were observed in studies of clinical depression. Meta-regression indicated that the association of CRP and future depression was larger in older samples and in studies not controlling for possible infection. Small, prospective associations of depression and inflammatory biomarkers are observed in both directions, particularly for IL-6; however, the strength and importance of this relationship is likely obscured by the heterogeneity in depression and profound study/methodological differences. Implications for future studies are discussed.

Project description:BackgroundThe Canadian Task Force on Preventive Health Care has a guideline on screening for depression among adults 18 years of age or older at average or high risk for depression. To provide evidence for an update of this guideline, we evaluated the literature on the effectiveness of screening for depression in adults.MethodsFor the period 1994 to May 23, 2012, we searched the following electronic databases: MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Randomized controlled trials, observational studies and systematic reviews with evidence for the benefits or harms of screening for depression were eligible for inclusion. We performed screening for relevance, extraction of data, analysis of risk of bias and quality assessments in duplicate. We used the generic inverse variance method to conduct a meta-analysis. To determine confidence in the effect, we analyzed the results according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.ResultsFive quasi-experimental studies (before-after design with a nonrandomized control group) met the inclusion criteria for this review. These studies reported on the effect of community-based screening for depression, with follow-up on the risk of suicide completion, for older residents in regions of rural Japan with high suicide rates. Meta-analysis showed that the screening program had a protective effect on the overall incidence of suicide completion (ratio of rate ratios [RRR] 0.50, 95% confidence interval [CI], 0.32-0.78). When sex was considered, the RRR indicated a significantly lower rate of suicide among women (RRR 0.37, 95% CI 0.21-0.66) but not among men (RRR 0.67, 95% CI 0.35-1.27). The overall GRADE rating applied to this evidence indicated very low quality. No studies addressing the harms of screening for depression met the inclusion criteria for the review.InterpretationThere is very limited research evidence allowing conclusions about the effectiveness of screening for depression in either average-risk or high-risk populations.

Project description:BackgroundPsychiatric comorbidity is known to impact upon use of nonpsychiatric health services. The aim of this systematic review and meta-analysis was to assess the specific impact of severe mental illness (SMI) on the use of inpatient, emergency, and primary care services for nonpsychiatric medical disorders.Methods and findingsPubMed, Web of Science, PsychINFO, EMBASE, and The Cochrane Library were searched for relevant studies up to October 2018. An updated search was carried out up to the end of February 2020. Studies were included if they assessed the impact of SMI on nonpsychiatric inpatient, emergency, and primary care service use in adults. Study designs eligible for review included observational cohort and case-control studies and randomised controlled trials. Random-effects meta-analyses of the effect of SMI on inpatient admissions, length of hospital stay, 30-day hospital readmission rates, and emergency department use were performed. This review protocol is registered in PROSPERO (CRD42019119516). Seventy-four studies were eligible for review. All were observational cohort or case-control studies carried out in high-income countries. Sample sizes ranged from 27 to 10,777,210. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies. The majority of studies (n = 45) were deemed to be of good quality. Narrative analysis showed that SMI led to increases in use of inpatient, emergency, and primary care services. Meta-analyses revealed that patients with SMI were more likely to be admitted as nonpsychiatric inpatients (pooled odds ratio [OR] = 1.84, 95% confidence interval [CI] 1.21-2.80, p = 0.005, I2 = 100%), had hospital stays that were increased by 0.59 days (pooled standardised mean difference = 0.59 days, 95% CI 0.36-0.83, p < 0.001, I2 = 100%), were more likely to be readmitted to hospital within 30 days (pooled OR = 1.37, 95% CI 1.28-1.47, p < 0.001, I2 = 83%), and were more likely to attend the emergency department (pooled OR = 1.97, 95% CI 1.41-2.76, p < 0.001, I2 = 99%) compared to patients without SMI. Study limitations include considerable heterogeneity across studies, meaning that results of meta-analyses should be interpreted with caution, and the fact that it was not always possible to determine whether service use outcomes definitively excluded mental health treatment.ConclusionsIn this study, we found that SMI impacts significantly upon the use of nonpsychiatric health services. Illustrating and quantifying this helps to build a case for and guide the delivery of system-wide integration of mental and physical health services.

Dataset Information

Chemokines in depression in health and in inflammatory illness: a systematic review and meta-analysis.

Publications

Chemokines in depression in health and in inflammatory illness: a systematic review and meta-analysis.

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