Peripheral C-reactive Protein Research Articles

196. Associations Between Peripheral C-Reactive Protein and Individual Symptoms of Depression in a Lower-Middle Income Country

196. Associations Between Peripheral C-Reactive Protein and Individual Symptoms of Depression in a Lower-Middle Income Country

Obesity Is Associated with a Weakened Gingival Inflammatory Cytokine Response.

Background and Objectives: An obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and to examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis-resistant obese individuals. Materials and Methods: Thirty-nine participants in good periodontal health were recruited. Twenty patients were classified as lean and nineteen as obese based on their BMI levels. A thorough periodontal assessment was carried out. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were analyzed for interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A), and CRP. Results: GCF CRP levels were significantly higher in the obese than in the lean individuals. No statistically significant differences were noted between the two groups in either GCF or blood in terms of any of the inflammatory cytokine levels. IL-17A was not detected in the GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, and the association tended to be stronger in the obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels were positively associated with multiple GCF inflammatory cytokines (e.g., IL-1β, IL-6, IL-8, and TNF-α) in all subjects, the associations tended to be weaker in the obese individuals (e.g., IL-1β, IL-6, and TNF-α). Furthermore, the levels of the GCF inflammatory cytokines IL-6 and TNF-α were decreased in the obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a weakened inflammatory cytokine response in the gingival tissues of obese individuals.

Inflammatory biomarkers and delirium: a Mendelian randomization study.

The association between inflammatory biomarkers and individual delirium symptoms remains controversial in observational studies. We investigated the relationship between inflammatory biomarkers and the risk of developing delirium. A bidirectional two-sample Mendelian randomization (MR) was performed. Genetic instruments associated with peripheral tumor necrosis factor-a (TNF-a) C-reactive protein (CRP), interleukin (IL)-1α, IL-1β, IL-2, IL-8, IL-6, soluble IL-6 receptor alpha (sIL-6Rα), and soluble gp130 were identified in three different large summary genome-wide association studies (GWAS) conducted in the European population. Summary-level statistics for delirium not induced by alcohol and other psychoactive substances were obtained from the FinnGen consortium (2,612 cases and 325,306 controls). The estimated causal effects were performed using instruments' variants at the genome-wide significant level (P < 5e-8 and P < 5e-6), applying a linkage disequilibrium clumping approach with a threshold of r2 < 0.001 for each of the exposures. Reverse causation was also performed. The inverse-variance weighted method (IVW), MR-Egger method, weighted median method, MR-Egger regression, and MR Pleiotropy RESidual Sum were used for MR analyses. At the genome-wide significant level (P < 5e-8, r2 < 0.001), genetically predicted sIL-6Rα was significantly associated with a decreased risk of delirium with less than three single-nucleotide polymorphisms (SNPs) in all three GWAS data sources (ORWaldratio = 0.89, 95% CI: 0.79-0.96, PWaldratio = 0.0016; ORIVW = 0.88, 95% CI: 0.79-0.97, PIVW = 0.008; ORIVW = 0.88, 95% CI: 0.80-0.96, PIVW = 0.004). The causal relationship between sIL-6Rα and delirium became non-significant when a more liberal threshold of P of < 5e-6 was applied (all PIVW > 0.05). At the two genome-wide significance levels (P < 5e-8 and P < 5e-6), we found no evidence for the causal effects of peripheral TNF-α, CRP, IL-1α, IL-1β, IL-2, IL-6, IL-8, and soluble gp130 on delirium (all P > 0.05). The MR-Egger intercept and MR-PRESSO results indicated that no SNP had possible pleiotropy (all P > 0.05). Regarding the reverse, no evidence for an effect of delirium on these inflammatory biomarkers could be found (all P > 0.05). The results of this MR analysis did not support that peripheral TNF-α, CRP, IL-1α, IL-1β, IL-2, IL-6, sIL-6Rα, soluble gp130, and IL-8 were causally associated with delirium. More research is needed to explore the role of inflammatory factors in the pathogenesis of delirium.

C-Reactive Protein Levels and Cognitive Decline following Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Cognitive decline (CD) is devastating with a high incidence in patients after stroke. Although some studies have explored underlying associations between C-reactive protein (CRP) levels and cognitive decline after stroke, consistent results have not been obtained. Therefore, this meta-analysis aimed to explore whether or not higher levels of C-reactive proteins were associated with an increased risk of cognitive decline after stroke. To this end, PubMed, Embase, the Cochrane Library, and Web of Science were searched for eligible studies, and pooled effect sizes from eligible studies were calculated using random effect models. Furthermore, subgroups were established and meta-regression analyses were performed to explain the causes of heterogeneity. Eventually, nine studies with 3893 participants were included. Our statistical results suggested that the concentrations of peripheral CRP may be significantly increased for CD patients after stroke, compared to those of non-CD patients. Subgroup analyses showed that CRP was higher in CD than that in non-CD patients when the mini-mental state examination was used. A higher level of CRP in the acute phase of ischemic stroke may suggest an increased risk of CD after stroke. However, these results should be cautiously interpreted because of the limited sample sizes and the diversity of potential confounders in the studies included in this meta-analysis.

Elevated serum leptin is associated with attenuated reward anticipation in major depressive disorder independent of peripheral C-reactive protein levels

Major depressive disorder (MDD) is associated with immunologic and metabolic alterations linked to central processing dysfunctions, including attenuated reward processing. This study investigated the associations between inflammation, metabolic hormones (leptin, insulin, adiponectin), and reward-related brain processing in MDD patients with high (MDD-High) and low (MDD-Low) C-reactive protein (CRP) levels compared to healthy comparison subjects (HC). Participants completed a blood draw and a monetary incentive delay task during functional magnetic resonance imaging. Although groups did not differ in insulin or adiponectin concentrations, both MDD-High (Wilcoxon p = 0.004, d = 0.65) and MDD-Low (Wilcoxon p = 0.046, d = 0.53) showed higher leptin concentrations than HC but did not differ from each other. Across MDD participants, higher leptin levels were associated with lower brain activation during reward anticipation in the left insula (r = − 0.30, p = 0.004) and left dorsolateral putamen (r = -− 0.24, p = 0.025). In contrast, within HC, higher leptin concentrations were associated with higher activation during reward anticipation in the same regions (insula: r = 0.40, p = 0.007; putamen: r = 0.37, p = 0.014). Depression may be characterized by elevated pro-inflammatory signaling via leptin concentrations through alternate inflammatory pathways distinct to CRP.

Relationship between Peripheral Blood Inflammatory Factors and Prognosis of Subarachnoid Hemorrhage: A Meta-Analysis

Introduction: Subarachnoid hemorrhage (SAH) is a severe cerebrovascular event with high mortality and disability rate. Neuroinflammation is involved in the brain injury after SAH, but the exact association between SAH progression and peripheral blood inflammatory factors is unknown. Therefore, to determine the relationship between inflammatory factors and the prognosis of SAH, we performed a meta-analysis. Method: A systematic literature review was conducted in PubMed, Embase, and the Cochrane Library. Studies comparing the relationship between inflammatory factors (C-reactive protein [CRP], interleukin-6 [IL-6], interleukin-10 [IL-10], and tumor necrosis factor [TNF-α]) and prognosis of SAH were included in the study. A random-effects meta-analysis was conducted based on mRS, GOS, and the occurrence of cerebral vasospasm, delayed cerebral ischemia, and delayed ischemic neurologic deficits. Sensitivity analysis was performed using the leave-one-out method. The Newcastle-Ottawa Scale (NOS) for case-control studies was used to assess the quality of included studies. For continuous variables, we calculated the mean difference with a 95% confidence interval (CI). Results: 1,469 patients from 18 case-control studies met the inclusion criteria. The results found that patients in the good outcome group had significantly lower CRP levels than those in the poor outcome group (SMD: −1.15, 95% CI: −1.64 to −0.66, p < 0.00001, I2 = 87%), and peripheral IL-6 levels were significantly lower in SAH patients with the good functional outcome than those with the poor functional outcome (SMD: −0.99, 95% CI: −1.48 to −0.51, p < 0.0001, I2 = 88%). As for IL-10 (SMD: −0.28, 95% CI: −0.97 to 0.42, p = 0.43, I2 = 88%) and TNF-α (SMD: −0.40, 95% CI: −0.98 to 0.19, p = 0.18, I2 = 79%), due to the small number of studies, heterogeneity, and uncontrollable factors, robust conclusions cannot be drawn. Conclusion: SAH patients with good prognoses have significantly lower peripheral CRP and IL-6 levels. In addition, due to the small number of studies, heterogeneity, and uncontrollable factors, robust conclusions cannot be drawn for IL-10 and TNF-α. More high-quality studies are needed in the future to provide more specific recommendations for the clinical practice of inflammatory factors.

Peripheral apolipoprotein E proteins and their binding to LRP1 antagonize Alzheimer’s disease pathogenesis in the brain during peripheral chronic inflammation

C-reactive protein (CRP) impacts apolipoprotein E4 (ApoE4) allele to increase Alzheimer’s disease (AD) risk. However, it is unclear how the ApoE protein and its binding to LRP1 are involved. We found that ApoE2 carriers had the highest but ApoE4 carriers had the lowest concentrations of blood ApoE in both humans and mice; blood ApoE concentration was negatively associated with AD risk. Elevation of peripheral monomeric CRP (mCRP) reduced the expression of ApoE in ApoE2 mice, while it decreased ApoE-LRP1 binding in the brains of ApoE4 mice that was characterized by Proximity Ligation Assay. Both serum ApoE and brain ApoE-LRP1 binding were positively associated with the expression of pericytes that disappeared after mCRP treatment, and negatively associated with brain tauopathy and neuroinflammation in the presence of mCRP. In ApoE-/- mice, mCRP reduced the brain expression levels of synaptophysin and PSD95 and the positive relationship between ApoE-LRP1 binding and synaptophysin or PSD95 expression disappeared. Our study suggests that blood ApoE protects against AD pathogenesis by binding to LRP1 during peripheral chronic inflammation.

The impact of increasing levels of blood C-reactive protein on the inflammatory loci SPI1 and CD33 in Alzheimer’s disease

Apolipoprotein ε4 (APOE ε4) is the most significant genetic risk factor for late-onset Alzheimer’s disease (AD). Elevated blood C-reactive protein (CRP) further increases the risk of AD for people carrying the APOE ε4 allele. We hypothesized that CRP, as a key inflammatory element, could modulate the impact of other genetic variants on AD risk. We selected ten single nucleotide polymorphisms (SNPs) in reported AD risk loci encoding proteins related to inflammation. We then tested the interaction effects between these SNPs and blood CRP levels on AD incidence using the Cox proportional hazards model in UK Biobank (n = 279,176 white participants with 803 incident AD cases). The five top SNPs were tested for their interaction with different CRP cutoffs for AD incidence in the Framingham Heart Study (FHS) Generation 2 cohort (n = 3009, incident AD = 156). We found that for higher concentrations of serum CRP, the AD risk increased for SNP genotypes in 3 AD-associated genes (SPI1, CD33, and CLU). Using the Cox model in stratified genotype analysis, the hazard ratios (HRs) for the association between a higher CRP level (≥10 vs. <10 mg/L) and the risk of incident AD were 1.94 (95% CI: 1.33–2.84, p < 0.001) for the SPI1 rs1057233-AA genotype, 1.75 (95% CI: 1.20–2.55, p = 0.004) for the CD33 rs3865444-CC genotype, and 1.76 (95% CI: 1.25–2.48, p = 0.001) for the CLU rs9331896-C genotype. In contrast, these associations were not observed in the other genotypes of these genes. Finally, two SNPs were validated in 321 Alzheimer’s Disease Neuroimaging (ADNI) Mild Cognitive Impairment (MCI) patients. We observed that the SPI1 and CD33 genotype effects were enhanced by elevated CRP levels for the risk of MCI to AD conversion. Furthermore, the SPI1 genotype was associated with CSF AD biomarkers, including t-Tau and p-Tau, in the ADNI cohort when the blood CRP level was increased (p < 0.01). Our findings suggest that elevated blood CRP, as a peripheral inflammatory biomarker, is an important moderator of the genetic effects of SPI1 and CD33 in addition to APOE ε4 on AD risk. Monitoring peripheral CRP levels may be helpful for precise intervention and prevention of AD for these genotype carriers.

Peripheral vitamin D levels in ankylosing spondylitis: A systematic review and meta-analysis

ObjectivesPrevious studies showed conflicting results regarding peripheral vitamin D levels in ankylosing spondylitis (AS). We performed this systemic review and meta-analysis to explore whether vitamin D may influence AS process.MethodsArticles published until March 2022 were searched in databases as follows: PubMed, Web of Science, and Google Scholar. The present study included cross-sectional and case-control studies regarding vitamin D levels in patients with AS. Studies were excluded according to the following exclusion criteria: (1) we excluded studies which did not provide sufficient information regarding the comparison of vitamin D levels in AS patients and healthy controls (HC). Vitamin D levels in the two group studies should be reported or could be calculated in included studies; (2) meta-analysis, reviews and case reports. STATA 12.0 software was used to make a meta-analysis. Standard mean differences (SMDs) and 95% confidence intervals (CIs) were computed as effect size.ResultsThe present meta-analysis showed no significant difference in peripheral 1,25-dihydroxyvitamin D3 (1,25OHD) levels between AS and healthy controls (HCs) in Caucasians with a random effects model [SMD: −0.68, 95% CI (−1.90, 0.54)]. Patients with AS had lower peripheral 25-hydroxyvitamin D (25OHD) levels compared with HC with a random effects model [SMD: −0.45, 95% CI: (−0.70, −0.20)]. Patients with AS had higher peripheral C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels compared with HC in Caucasian population with random effects models [CRP: SMD: 1.08, 95% CI: (0.78, 1.37); ESR: SMD: 0.86, 95% CI: (0.39, 1.34)]. However, no significant difference in alkaline phosphatase (ALP), parathyroid hormone (PTH) or calcium levels were indicated between AS and HC in Caucasian with random effects models [ALP: SMD: 0.07, 95% CI: (−0.41, 0.55); PTH: SMD: −0.15, 95% CI: (−0.56, 0.26); calcium: SMD: −0.06, 95% CI: (−0.39, 0.26)].ConclusionIn conclusion, the study showed an inverse association between 25OHD and AS, which suggests that vitamin D may have a protective effect on AS. ESR and C-reactive protein (CRP) are important biomarkers for AS.

Cognitive impairment, childhood trauma, sedentary behaviour, and elevated C-reactive protein levels in major affective disorders

Elevated C-reactive protein (CRP) levels were associated with cognitive decline, sedentary behaviour, and childhood trauma in patients with major affective disorders. This study aims to examine the association of peripheral CRP levels, cognitive function, childhood trauma, sedentary behaviour, and quality of life in individuals with major affective disorders, including bipolar disorder (BD), major depressive disorder (MDD), and individuals without mood disorders (controls). We included outpatients with BD (n = 42), MDD (n = 27), and healthy controls (n = 40). All participants were assessed by a questionnaire, structured clinical interview, and the following scales: international physical activity questionnaire, childhood trauma questionnaire, 17-item Hamilton Depression Rating Scale (HDRS17), and World Health Organization Quality of Life instrument, brief version (WHOQOL-BREF). Other measures were included: hs-CRP levels, anthropometric measures, and cognitive tests (Trail-making test part A and part B, Stroop test, phonemic verbal fluency test, and semantic verbal fluency test). Our results indicated that BD outpatients were less significantly physically active on leisure domain than controls. Levels of hs-CRP ≥ 5 mg/L were significantly linked with a history of childhood sexual abuse and childhood physical abuse, as well as worse neurocognitive performance in major depressive disorders, mainly in BD. There was a significant negative correlation between Trail-making part B score and WHOQOL-BREF total score. The findings support the hypothesis that levels of hs-CRP ≥ 5 mg/L may be a possible predictor of cognitive dysfunction, childhood sexual abuse and sedentary behaviour in major affective disorders.

Peripheral Immune Cell Numbers and C-Reactive Protein in Parkinson's Disease: Results from a Population-Based Study.

Background:The immune system is known to be involved in Parkinson’s disease (PD) pathogenesis, but the temporal relationship between peripheral immune responses and PD remains unknown.Objective:We determined the association between peripheral immune cell numbers, C-reactive protein (CRP), and prevalent as well as incident PD.Methods:This study was embedded in the population-based setting of the Rotterdam Study. We repeatedly measured peripheral immune cell numbers (differential leukocyte count and platelet count, granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], and adapted systemic immune-inflammation index [adapted SII]) and CRP between 1990 and 2016. Participants were continuously followed-up for PD until 2018. We estimated the association of the markers with prevalent and incident PD using logistic regression models and joint models, respectively. Models were adjusted for age, sex, smoking, body mass index, and medication use. Odds ratios (OR) and hazard ratios (HR) are shown per doubling of the marker.Results:A total of 12,642 participants were included in this study. The mean age (standard deviation) was 65.1 (9.8) years and 57.5%were women. Participants with a higher lymphocyte count were less likely to have prevalent PD (adjusted OR: 0.34, 95%CI 0.17–0.68). Participants with a higher GLR, PLR, and adapted SII were more likely to have prevalent PD, but these effects were explained by the lymphocyte count. The peripheral immune cell numbers and CRP were not significantly associated with the risk of incident PD.Conclusion:We found participants with a higher lymphocyte count to be less likely to have prevalent PD, but we did not find an association between peripheral immune cell numbers nor CRP and the risk of incident PD.

Inflammatory biomarkers in older adults with frailty: a systematic review and meta-analysis of cross-sectional studies.

Systemic chronic inflammation has been proposed as an essential mediating factor in frailty, and several studies tested its relationship with frailty. However, the issue is still controversial. We identified observational studies and pooled their results to assess whether abnormal expression of inflammatory biomarkers is present in the blood of older adults with frailty. We conducted a systematic search on the Medline, Embase, and Web of Science database from inception to 1st September 2021. The quality of included studies was assessed using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies (JBI-MAStARI). Study heterogeneity was assessed with the Cochran Q test and I2 statistic. Pooled estimates were obtained through random-effect models. Sensitivity analyses were conducted by excluding one of the studies. Egger's regression test and observation of funnel plots were used to detect small-study effects and publication bias. PROSPERO registration: CRD42020172853. A total of 53 cross-sectional studies corresponding to 56 independent study populationswere included in this analysis. There were 31 study populations with three frailty categories (3144 frailty, 14,023 pre-frailty, 10,989 robust) and 25 study populations with two frailty categories (2576 frailty, 8368 non-frailty). This meta-analysisperformed pooled analyses for the inflammatory biomarker leukocyte, lymphocytes, CRP, IL-6, IL-10, and TNF-α. Older adults with frailty had lower lymphocytes and higher interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels compared with the control group. However, there was no significant difference in leukocyte and IL-10 levels in the two groups. These findings suggest that peripheral inflammatory biomarkers lymphocytes, IL-6, CRP, and TNF-α are related to frailty status. Our findings are not conclusive regarding the causal relationship between chronic inflammation and frailty, so the development of further longitudinal and well-designed studies focused on this is necessary.

The effects of atorvastatin on emotional processing, reward learning, verbal memory and inflammation in healthy volunteers: An experimental medicine study.

Background:Growing evidence from clinical trials and epidemiological studies suggests that statins can have clinically significant antidepressant effects, potentially related to anti-inflammatory action on several neurobiological structures. However, the underlying neuropsychological mechanisms of these effects remain unexplored.Aims:In this experimental medicine trial, we investigated the 7-day effects of the lipophilic statin, atorvastatin on a battery of neuropsychological tests and inflammation in healthy volunteers.Methods:Fifty healthy volunteers were randomised to either 7 days of atorvastatin 20 mg or placebo in a double-blind design. Participants were assessed with psychological questionnaires and a battery of well-validated behavioural tasks assessing emotional processing, which is sensitive to putative antidepressant effects, reward learning and verbal memory, as well as the inflammatory marker, C-reactive protein.Results:Compared to placebo, 7-day atorvastatin increased the recognition (p = 0.006), discriminability (p = 0.03) and misclassifications (p = 0.04) of fearful facial expression, independently from subjective states of mood and anxiety, and C-reactive protein levels. Otherwise, atorvastatin did not significantly affect any other psychological and behavioural measure, nor peripheral C-reactive protein.Conclusions:Our results reveal for the first time the early influence of atorvastatin on emotional cognition by increasing the processing of anxiety-related stimuli (i.e. increased recognition, discriminability and misclassifications of fearful facial expression) in healthy volunteers, in the absence of more general effects on negative affective bias. Further studies exploring the effects of statins in depressed patients, especially with raised inflammatory markers, may clarify this finding and inform future clinical trials.

Alterations in Peripheral C-Reactive Protein and Inflammatory Cytokine Levels in Patients with Panic Disorder: A Systematic Review and Meta-Analysis.

BackgroundAccumulating evidence has shown the important role of the inflammatory process in the pathophysiology of mental disorders. However, the relative levels of inflammatory markers in patients with panic disorder (PD) have rarely been evaluated. The aim of the present study was to conduct a systematic review to determine the correlation of peripheral C-reactive protein (CRP) and inflammatory cytokine profiles with PD.MethodsThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for quantitative research studies published up to July 31, 2021 that measured peripheral levels of CRP and inflammatory cytokines in people with PD compared with controls. Meta-analysis using a random-effects model was performed for the levels of CRP and inflammatory cytokines with data from three or more studies.ResultsFourteen identified studies met the inclusion criteria. In total, 18 cytokines were evaluated. Markers that were reported in more than 3 studies were included in this meta-analysis. The results showed that peripheral levels of CRP, IL-6, IL-2 and TNF-α were significantly higher in PD patients than in healthy controls, while there was no significant difference in peripheral levels of IL-1β, IL-10 and IFN-γ between groups. Notably, the relevant studies involving IL-6, IL-1β, IL-10 and IFN-γ in PD patients were highly heterogeneous. Similar to meta-analyses of other inflammatory factors in mental disorders, our meta-analysis also reflected differences in participant medication use, comorbid anxiety or depression, sampling methods and detection methods. Eight inflammatory cytokines were reported in only one study, and their expression levels were higher, lower, or unchanged compared with those in healthy controls.ConclusionThere is preliminary evidence to suggest a significant inflammatory response in PD patients, but the role of inflammatory markers in PD remains unclear. Studying inflammatory markers in PD will help to clarify the etiology and pathophysiological mechanisms of the disorder.

Investigation of C-reactive protein and AIM2 methylation as a marker for PTSD in Australian Vietnam veterans.

Chronic inflammation is a key factor in symptomology and comorbidities of post-traumatic stress disorder (PTSD). Levels of a proinflammatory marker, C-reactive protein (CRP) are increased in individuals with PTSD but it is not clear if this is due to trauma exposure or PTSD. Our study aimed to assess the relationship between serum CRP levels, CRP SNPs, methylation, mRNA expression and PTSD in a homogenous trauma exposed Australian Vietnam veteran cohort. We hypothesized that decreased DNA methylation would be associated with increased gene expression and increased peripheral CRP levels in PTSD patients and that this would be independent of trauma. Participants were 299 Vietnam veterans who had all been exposed to trauma and approximately half were diagnosed with PTSD. We observed higher levels of serum CRP in the PTSD group compared to the non-PTSD group but after controlling for BMI and triglycerides the association did not remain significant. No association was found between CRP SNPs and PTSD or CRP levels. Absent in Melanoma 2 (AIM2) which is a mediator of inflammatory response and a determinant of CRP levels was analysed for DNA methylation and mRNA expression. We observed a trend level association between PTSD and AIM2 methylation after controlling for age, smoking, triglycerides, BMI and cell types. There was no significant interaction between PTSD and CRP levels on AIM2 methylation after controlling for covariates. We observed that as AIM2 methylation levels decreased, AIM2 mRNA expression increased. Elevated CRP levels were associated with AIM2 mRNA in the trauma exposed cohort but there was no significant interaction effect with PTSD. Our results could not confirm that CRP is a marker of PTSD independent of trauma in this group of older veterans. CRP may be a broad marker of disease risk, or a marker of PTSD in younger cohorts than those in this study.

Increased C-reactive protein concentration and suicidal behavior in people with psychiatric disorders: A systematic review and meta-analysis.

ObjectiveSuicide is a leading cause of death worldwide. Identifying factors associated with suicidality (suicidal ideation [SI]/suicidal behavior) could increase our understanding of the pathophysiological underpinnings of suicide and improve its prevention.MethodsWe conducted a systematic review (PubMed/PsycInfo/Cochrane databases, up to September 2020) and random‐effect meta‐analysis including observational studies comparing peripheral C‐reactive protein (CRP) levels in suicidal versus non‐suicidal patients affected by any psychiatric disorder and healthy controls (HC). Primary outcome was the CRP standardized mean difference (SMD) between patients with high suicidality versus those with absent or low suicidality. Secondary outcomes were SMD of CRP levels between those with suicide attempt versus no suicide attempt, as well as between those with (high) versus low or absent SI. Quality of included studies was measured with Newcastle‐Ottawa scale.ResultsOut of initial 550 references, 21 observational studies involving 7682 subjects (7445 with mood disorders or first‐episode psychosis, 237 HC) were included. A significant association of CRP levels with suicidality (SMD 0.688, 95% CI 0.476–0.9, p < 0.001) emerged. CRP levels were higher in individuals with high SI (SMD 1.145, 95% CI 0.273–2.018, p = 0.010) and in those with suicide attempt (SMD 0.549, 95%CI 0.363–0.735, p < 0.001) than non‐suicidal individuals (either patients or HC). Main analyses were confirmed in sensitivity analysis (removing HC), and after adjusting for publication bias. The cross‐sectional design of included studies, and the high heterogeneity of diagnosis and treatment limit the generalizability of these results. Median quality of included studies was high.ConclusionCRP is associated with higher suicidality in patients with mental disorders. Large cohort studies longitudinally monitoring CRP levels are needed to explore its longitudinal association with suicidality.

Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents.

Introduction: Increased peripheral inflammation has been consistently documented in both adult and pediatric depression. However, elevated levels of C-reactive protein (CRP), a nonspecific biomarker for inflammation, have been primarily reported in adults; whether CRP plays a similar role in adolescent depression has not been conclusively established. In our prior work, we identified relationships between CRP and reward neurocircuitry in adolescents with psychiatric symptoms (N = 64) but not with depressive symptoms. Extending this work, we sought to examine CRP across the full range of mood and anxiety symptom severity in a larger, clinically diverse cohort of psychotropic medication-free adolescents and healthy controls (HCs). Methods: Subjects were adolescents (N = 127, age: 15.17 ± 2.19 years, 78 female) with psychiatric symptoms (n = 96, including previous cohort of 64) and HC (n = 31). All completed a semi-structured psychiatric evaluation and dimensional assessments for depression, anxiety, anhedonia, and suicidality. Group-comparison and correlation analyses utilized nonparametric statistics controlled for body mass index, sex, and age at pFWE < 0.05. Results: No group differences were identified in CRP levels between the clinical cohort and HCs. In addition, correlations between CRP and clinical symptomatology were not significant in either the whole sample or the psychiatric group. Conclusions: We found that, unlike in adults, CRP was not associated with depressive symptoms. This suggests that inflammation in pediatric depression is more narrowly delimited at the onset of psychiatric symptoms and may only become systemic with chronicity.

Bipolar disorder: an association between body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation.

To investigate associations between body mass index (BMI), white matter fractional anisotropy (FA), and C-reactive protein (CRP) in a group of individuals with bipolar disorder (BD) during euthymia and compare them with a control group of healthy subjects (CTR). The sample consisted of 101 individuals (BD n = 35 and CTR n = 66). Regions of interest (ROI) were defined using a machine learning approach. For each ROI, a regression model tested the association between FA and BMI, controlling for covariates. Peripheral CRP levels were assayed, correlated with BMI, and included in a mediation analysis. BMI predicted the FA of the right cingulate gyrus in BD (AdjR2 = 0.312 F(3) = 5.537 p = 0.004; β = -0.340 p = 0.034), while there was no association in CTR. There was an interaction effect between BMI and BD diagnosis (F(5) = 3.5857 p = 0.012; Fchange = 0.227 AdjR2 = 0.093; β = -1.093, p = 0.048). Furthermore, there was a positive correlation between BMI and CRP in both groups (AdjR2 = 0.170 F(3) = 7.337 p < 0.001; β = 0.364 p = 0.001), but it did not act as a mediator of the effect on FA. Higher BMI is associated with right cingulate microstructure in BD, but not in CTR, and this effect could not be explained by inflammatory mediation alone.

C-Reactive Protein: Marker of risk for post-traumatic stress disorder and its potential for a mechanistic role in trauma response and recovery.

Increasing evidence indicates that inflammation plays a role in PTSD and stress disorder pathophysiology. PTSD is consistently associated with higher circulating inflammatory protein levels. Rodent models demonstrate that inflammation promotes enduring avoidance and arousal behaviors after severe stressors (e.g., predator exposure and social defeat), suggesting that inflammation may play a mechanistic role in trauma disorders. C-reactive protein (CRP) is an innate acute phase reactant produced by the liver after acute infection and chronic disease. A growing number of investigations report associations with PTSD diagnosis and elevated peripheral CRP, CRP gene mutations, and CRP gene expression changes in immune signaling pathways. CRP is reasonably established as a potential marker of PTSD and trauma exposure, but if and how it may play a mechanistic role is unclear. In this review, we discuss the current understanding of immune mechanisms in PTSD with a particular focus on the innate immune signaling factor, CRP. We found that although there is consistent evidence of an association of CRP with PTSD symptoms and risk, there is a paucity of data on how CRP might contribute to CNS inflammation in PTSD, and consequently, PTSD symptoms. We discuss potential mechanisms through which CRP could modulate enduring peripheral and CNS stress responses, along with future areas of investigation probing the role of CRP and other innate immune signaling factors in modulating trauma responses. Overall, we found that CRP likely contributes to central inflammation, but how it does so is an area for further study.

Abstract 15156: Comparison of Left Atrial D - dimer Level in Patients With Atrial Fibrillation Administering Dabigatran, Apixaban and Edoxaban

Introduction: Atrial fibrillation causes cerebral infarction and systemic embolism. Increased D-dimer level indicates the hyperactivation of secondary fibrinolysis, showing thrombosis tendency in the vessel. Hypothesis: To clarify the effects of anticoagulation therapy, we planned to compare the D-dimer levels of peripheral and left atrial (LA) blood in patients scheduled for atrial fibrillation ablation during administration of dabigatran (D), apixaban (A) and edoxaban (E). Methods and Results: We analyzed 141 patients with non-valvular atrial fibrillation (D, n=30; A, n= 47; E, n=64; median age: 68[38-84] years, male: 60%) after exclusion of patients on dialysis. Peripheral venous blood was collected immediately before ablation and LA blood was collected immediately after the Brockenbrough method. We examined laboratory and echocardiographic parameters such as D-dimer and protein C levels, and LA diameter. Anticoagulation therapy was discontinued on the day of ablation. There were no significant differences in ejection fraction, LA diameter and peripheral C-reactive protein levels among the three groups treated with D, A and E. After adjusting for baseline characteristics, D-dimer level in the left atrium treated with E was significantly higher among the three groups (D, 0.550±0.078 vs. A, 0.603±0.052 vs. E, 0.774±0.046), although there were no significant differences in peripheral D-dimer levels (Table). Protein C levels of peripheral blood in group E were significantly suppressed among the three groups (D, 130.17±4.84 vs. A, 102.13±3.59 vs. E, 91.92±2.11, p&lt;0.001). Conclusions: In the edoxaban group, the D-dimer level in the left atrium was higher than that in the apixaban group, suggesting that the anticoagulatory effect of left atrium is better in apixaban as compared to edoxaban in patient with non-valvular atrial fibrillation.