Depression and markers of inflammation as predictors of all-cause mortality in heart failure

BackgroundIn patients with heart failure (HF) depressive symptoms have been associated with mortality, as well as biological risk factors, including inflammation, nitric oxide (NO) regulation, and oxidative stress. We investigated the joint predictive value of depressive symptoms, inflammation and NO regulation on all-cause mortality in patients with HF, adjusted for covariates.MethodsSerum levels of inflammation (TNFα, sTNFr1, sTNFr2, IL-6, hsCRP, NGAL), NO regulation (l-arginine, ADMA, and SDMA), and oxidative stress (isoprostane 8-Epi Prostaglandin F2 Alpha) were measured in 104 patients with HF (mean age 65.7 ± SD 8.4 years, 28% women). Depressive symptoms (Beck Depression Inventory, BDI) were measured as continuous total, cognitive, and somatic symptoms, as well as categorized presence of mild/moderate depression (cut-off BDI ⩾10). In Cox proportional hazard models we adjusted for age, sex, poor exercise tolerance and comorbidity.ResultsAfter on average 6.1 years follow-up (SD = 2.9, range 0.4–9.2), 49 patients died. Total and somatic depressive symptoms, mild/moderate depression, higher NGAL, sTNFr2, IL-6, hsCRP and SDMA serum levels were significantly associated with a higher all-cause mortality rate, adjusted for covariates. The findings were most consistent for CRP level and somatic depressive symptoms. When combined, both depressive symptoms and markers of inflammation and NO regulation remained significantly associated with all-cause mortality. These associations were not confounded by age, sex, poor exercise tolerance and comorbidity.ConclusionDepressive symptoms and markers of inflammation and NO regulation are codominant risk factors for all-cause mortality in heart failure.     

Increased soluble TNF receptor 2 in antidepressant-free patients with late-life depression

Increased pro-inflammatory state has been implicated in the pathophysiology of major depressive disorder. The aim of this study was to determine serum levels of TNF-α and soluble TNF-α receptors 1 and 2 (sTNFR1 and sTNFR2) in anti-depressant free depressed elderly patients as compared to healthy controls. Sixty-seven older adults (28 with major depression and 39 controls) were enrolled to this study. Participants were assessed by the SCID and diagnosis of major depressive episode was made according to the DSM-IV criteria. Serum TNF-α, sTNFR1 and sTNFR2 were determined by ELISA. Anti-depressant free patients with late-life depression showed an increased level of the sTNFR2 as compared to controls (p = 0.03). No significant differences were found in serum TNF-α and sTNFR1 levels (p = 0.1 and p = 0.4, respectively). There was no correlation between serum levels of these inflammatory markers and the severity of depression. Our findings provide additional evidence of the involvement of abnormal pro-inflammatory state in late-life depression.     

Subtypes of depressive symptoms and inflammatory biomarkers: An exploratory study on a sample of HIV-positive patients

Depressive symptoms cause major impairment and may accelerate HIV progression despite the use of antiretroviral medication. The somatic symptoms criteria for HIV infection and depression partially overlap, which can make differential diagnosis challenging. Because of chronic inflammation caused by HIV infection, HIV-positive patients may develop somatic and affective-cognitive symptoms of depression. Inflammation-related depression is primarily characterized with severe somatic symptoms such as fatigue and sleep disturbance. This study sought to explore the patterns of somatic and cognitive-affective depressive symptoms that characterize HIV-positive patients. Our specific aims were (1) to identify subtypes of depressive symptoms in a sample of HIV-positive patients; and (2) to test the subtypes’ difference on inflammatory and HIV disease progression biomarkers. HIV-positive men and women (N = 102) with and without depressive symptoms were randomly selected from an Italian HIV clinic. Depressive symptoms (PHQ-9), viral load (VL), CD4+, Il-6, TNF-α, and monocytes were assessed. The three subtypes formed using Latent Class Analysis (LCA) identified patients with (1) severe cognitive-affective and somatic depressive symptoms; (2) severe/moderate somatic symptoms; and (3) absent or low depressive symptoms. The subtype with severe/moderate somatic symptoms was characterized with elevated levels of Il-6 and monocytes. No difference on HIV progression biomarkers was found. The subtypes of depressive symptoms might help differentiating depressive symptoms from HIV- and inflammatory-related somatic symptoms. When present, cognitive-affective and/or somatic symptoms cause significant impairment to patients’ lives and thus warrant further assessment and treatment.     

Increased soluble tumor necrosis factor-α receptors in patients with major depressive disorder

Aim:  Several lines of evidence suggest that major depressive disorder is associated with an inflammatory status. Tumor necrosis factor-α has been investigated as a potential molecular target in mood disorders. Tumor necrosis factor-α exerts its activity through binding to specific cell membrane receptors named as TNFR1 and TNFR2. The aim of the present study was to investigate soluble plasma TNFR1 (sTNFR1) and TNFR2 levels (sTNFR2) in major depressive disorder patients.
Methods:  Female outpatients with major depressive disorder ( n  = 30) were compared with a healthy control group ( n  = 19). Severity of depressive symptoms was evaluated on Beck Depression Inventory; post-traumatic stress disorder (PTSD) symptoms were evaluated on PTSD Checklist–Civilian Version; and childhood abuse and neglect on the Childhood Trauma Questionnaire. Plasma tumor necrosis factor-α and its soluble receptors were measured by ELISA.
Results:  Patients had no changes in tumor necrosis factor-α concentrations but did have increased sTNFR1 ( P  < 0.001) and sTNFR2 ( P  < 0.001) levels compared to controls. Plasma level of sTNFR1 was positively predicted by age (B = 0.25, P  = 0.05) and PTSD-like symptoms (B = 0.41, P  = 0.002) and plasma levels of sTNFR2 by depression severity (B = 0.67, P  < 0.001).
Conclusions:  Soluble tumor necrosis factor-α receptors could be reliable markers of inflammatory activity in major depression.     

Longitudinal association between inflammatory markers and specific symptoms of depression in a prospective birth cohort

BackgroundLow-grade inflammation is associated with depression, but studies of specific symptoms are relatively scarce. Association between inflammatory markers and specific symptoms may provide insights into potential mechanism of inflammation-related depression. Using longitudinal data, we have tested whether childhood serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels are associated with specific depressive symptoms in early adulthood.MethodsIn the ALSPAC birth cohort, serum IL-6 and CRP levels were assessed at age 9 years and 19 depressive symptoms were assessed at age 18 years. We used modified Poisson generalised linear regression with robust error variance to estimate the risk ratio (RR) and 95% confidence interval (95% CI) for each depressive symptom. In addition, we used confirmatory factor analysis to create two continuous latent variables representing somatic/neurovegetative and psychological dimension scores. Structural equation modelling was used to test the associations between IL-6 and these dimension scores.ResultsBased on data from 2731 participants, IL-6 was associated with diurnal mood variation, concentration difficulties, fatigue and sleep disturbances. The adjusted RRs for these symptoms at age 18 years for participants in top, compared with bottom, third of IL-6 at age 9 years were 1.75 (95% CI, 1.13–2.69) for diurnal mood variation, 1.50 (95% CI, 1.11–2.02) for concentration difficulties, 1.31 (95% CI, 1.12–1.54) for fatigue, and 1.24 (95% CI, 1.01–1.52) for sleep disturbances. At dimension level, IL-6 was associated with both somatic/neurovegetative (β = 0.059, SE = 0.024, P = 0.013) and psychological (β = 0.056, SE = 0.023, P = 0.016) scores.ConclusionsInflammation is associated with specific symptoms of depression. Associations with so-called somatic/neurovegetative symptoms of depression such as fatigue, sleep disturbances and diurnal mood variation indicate that these symptoms could be useful treatment targets and markers of treatment response in clinical trials of anti-inflammatory treatment for depression.     

Neutrophil Gelatinase-Associated Lipocalin and depression in patients with chronic heart failure

Depression adversely affects prognosis in heart failure (HF) patients. Inflammation is indicated as potential biological pathway in this co-morbidity. Since increased levels of the cytokine Neutrophil Gelatinase-Associated Lipocalin (NGAL) are predictive for HF prognosis, and recently indicated in patients with major depression, this study examined the association of serum NGAL levels with symptoms of depression in patients with HF. Serum NGAL levels were measured in 104 patients with HF (left ventricular ejection fraction, LVEF ⩽ 40). Depression, evaluated using the Beck Depression Inventory (BDI; total score, somatic and cognitive component), and the Hamilton Depression Rating scale (HAMD), at baseline and 12 months follow-up, was associated with NGAL levels using mixed model analysis. Analyses were adjusted for demographics measures, disease severity indicators, inflammation, comorbidity and medication. Increased serum NGAL levels were significantly associated with depression measured by HAMD (baseline: r = 0.25, p < .05) and BDI (baseline: r = 0.22, p < .05; 12 months: r = 0.37, p < .01). This association remained significant after adjustment for covariates; age, sex, time, LVEF, and creatinine (HAMD, t = 2.01, p = .047; BDI, t = 2.28, p = .024). NGAL was significantly associated with somatic- (p = 0.004), but not cognitive depressive symptoms (p = 0.32). NGAL levels were associated with the experienced HF-related functional limitations (6 min walk test), rather than the severity of cardiac dysfunction (LVEF). This study indicates that depression in patients with chronic HF is associated with elevated NGAL levels, independent of clinical severity of the underlying disease.     

Polygenic risk for immuno-metabolic markers and specific depressive symptoms: A multi-sample network analysis study

BackgroundAbout every fourth patient with major depressive disorder (MDD) shows evidence of systemic inflammation. Previous studies have shown inflammation-depression associations of multiple serum inflammatory markers and multiple specific depressive symptoms. It remains unclear, however, if these associations extend to genetic/lifetime predisposition to higher inflammatory marker levels and what role metabolic factors such as Body Mass Index (BMI) play. It is also unclear whether inflammation-symptom associations reflect direct or indirect associations, which can be disentangled using network analysis.MethodsThis study examined associations of polygenic risk scores (PRSs) for immuno-metabolic markers (C-reactive protein [CRP], interleukin [IL]-6, IL-10, tumour necrosis factor [TNF]-α, BMI) with seven depressive symptoms in one general population sample, the UK Biobank study (n = 110,010), and two patient samples, the Munich Antidepressant Response Signature (MARS, n = 1058) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D, n = 1143) studies. Network analysis was applied jointly for these samples using fused graphical least absolute shrinkage and selection operator (FGL) estimation as primary analysis and, individually, using unregularized model search estimation. Stability of results was assessed using bootstrapping and three consistency criteria were defined to appraise robustness and replicability of results across estimation methods, network bootstrapping, and samples.ResultsNetwork analysis results displayed to-be-expected PRS-PRS and symptom-symptom associations (termed edges), respectively, that were mostly positive. Using FGL estimation, results further suggested 28, 29, and six PRS-symptom edges in MARS, STAR*D, and UK Biobank samples, respectively. Unregularized model search estimation suggested three PRS-symptom edges in the UK Biobank sample. Applying our consistency criteria to these associations indicated that only the association of higher CRP PRS with greater changes in appetite fulfilled all three criteria. Four additional associations fulfilled at least two consistency criteria; specifically, higher CRP PRS was associated with greater fatigue and reduced anhedonia, higher TNF-α PRS was associated with greater fatigue, and higher BMI PRS with greater changes in appetite and anhedonia. Associations of the BMI PRS with anhedonia, however, showed an inconsistent valence across estimation methods.ConclusionsGenetic predisposition to higher systemic inflammatory markers are primarily associated with somatic/neurovegetative symptoms of depression such as changes in appetite and fatigue, consistent with previous studies based on circulating levels of inflammatory markers. We extend these findings by providing evidence that associations are direct (using network analysis) and extend to genetic predisposition to immuno-metabolic markers (using PRSs). Our findings can inform selection of patients with inflammation-related symptoms into clinical trials of immune-modulating drugs for MDD.     

Lifetime depressive and somatic symptoms as preclinical markers of late-onset depression

Background: Several risk factors of depression, i. e., female gender and life-stress, have been identified. Few studies have focussed on symptoms as preclinical markers of depression. In these studies current symptoms like dysphoria, tiredness and increased appetite predicted later depression. Even though of possible interest for treatment, no study focussed on lifetime symptoms as preclinical markers of depression. Consequently, we examined lifetime depressive and somatic symptoms with respect to later development of late-onset depression. Methods: 664 non-depressed elderly subjects without lifetime diagnoses of depression at the initial examination were selected for a prospective follow-up study (mean follow-up ± SD: 5.02 ± 2.44 years). 51 subjects (mean age ± SD: 66.6 ± 11.3) developing late-onset depression (defined as depression starting after age 60) were compared to those remaining non-depressed (mean age ± SD: 59.1 ± 16.0) during follow-up using the CIDI. To determine the influence of lifetime symptoms on the development of depression, chi-square statistics and multivariate logistic regression analyses were performed. Results: The following symptoms being present over a period longer than two weeks were individual preclinical markers of late-onset depression: dysphoria, increased appetite, insomnia, lack of energy, morning depth, lack of joy and interest, inferiority feeling, lack of self-confidence, poor concentration, indecisiveness, thinking about death, wish to die and joint pain. The most important symptoms elevating the risk of late-onset depression in a multivariate model were lack of joy and interest, poor concentration, increased appetite, lack of energy and joint pain. Conclusions: Different symptoms can be used individually and in combination to predict later depression. This might allow early treatment. Received: 6 September 2002 / Accepted: 5 December 2002 Correspondence to Prof. Dr. Reinhard Heun     

Circulating tumour necrosis factor is highly correlated with brainstem serotonin transporter availability in humans

Preclinical studies demonstrate that pro-inflammatory cytokines increase serotonin transporter availability and function, leading to depressive symptoms in rodent models. Herein we investigate associations between circulating inflammatory markers and brainstem serotonin transporter (5-HTT) availability in humans. We hypothesised that higher circulating inflammatory cytokine concentrations, particularly of tumour necrosis factor (TNF-α), would be associated with greater 5-HTT availability, and that TNF-α inhibition with etanercept (sTNFR:Fc) would in turn reduce 5-HTT availability. In 13 neurologically healthy adult women, plasma TNF-α correlated significantly with 5-HTT availability (rho = 0.6; p = 0.03) determined by [¹²³I]-beta-CIT SPECT scanning. This association was replicated in an independent sample of 12 patients with psoriasis/psoriatic arthritis (rho = 0.76; p = 0.003). Indirect effects analysis, showed that there was a significant overlap in the variance explained by 5-HTT availability and TNF-α concentrations on BDI scores. Treatment with etanercept for 6–8 weeks was associated with a significant reduction in 5-HTT availability (Z = 2.09; p = 0.03; r = 0.6) consistent with a functional link. Our findings confirm an association between TNF-α and 5-HTT in both the basal physiological and pathological condition. Modulation of both TNF-α and 5-HTT by etanercept indicate the presence of a mechanistic pathway whereby circulating inflammatory cytokines are related to central nervous system substrates underlying major depression.     

Inflammatory markers in women with postpartum depressive symptoms

Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.     

Impact of Inflammation on Cognitive Functioning After Electroconvulsive Therapy in Older Patients with Depression with and Without White Matter Hyperintensities

ObjectiveShould we treat older, patients with depression with white matter hyperintensities (WMH) with electroconvulsive therapy (ECT)? WMH, inflammation, depression and cognitive functioning are suggested to be intertwined. Hence, this study investigates whether the association between inflammation and cognition is different in patients with depression with or without WMH.MethodsCognitive functioning was assessed using the Mini–Mental State Examination during and after a course of ECT in 77 older patients with depression. Serum samples (C–reactive protein [CRP], interleukin-6 [IL-6], interleukin-10 [IL-10] and tumour necrosis factor–alpha [TNF-α]) and 3T magnetic resonance imaging were obtained prior to ECT.ResultsAn interaction effect was found for IL-10, but not for CRP, IL-6 or TNF-α.ConclusionIn general, the association between inflammatory markers and cognition in patients with depression treated with ECT is not different in patients with WMH compared to patients without WMH.     

Inflammation in psychotic disorders: a population-based study

We investigated inflammatory markers in psychotic disorders and their association with metabolic comorbidity, antipsychotic medication, smoking, alcohol use, physical condition, and mood. From the population-based Finnish Health 2000 study, we identified all persons with schizophrenia (n = 45), other nonaffective psychosis (ONAP) (n = 57), affective psychosis (n = 37) and chose controls matched by age, sex, and region of residence. We found that persons with schizophrenia had significantly higher sIL-2Rα, IL-1RA and C-reactive protein (CRP), persons with ONAP significantly higher IL-1RA and CRP and persons with affective psychosis almost significantly higher TNF-α compared to their matched controls. Current antipsychotic use was associated with elevated IL-1RA and CRP. After taking metabolic and lifestyle-related variables that associated with inflammatory markers into account, only antipsychotic medication remained associated with elevated IL-1RA and TNF-α which are markers related to the activation of innate immune system. CRP was influenced by both antipsychotic medication and nonaffective psychosis. sIL-2Rα, a marker of T-cell activation, was associated with depressive symptoms, schizophrenia, and affective psychosis. We conclude that in persons with psychotic disorders, activation of mononuclear phagocyte system was mostly related to metabolic comorbidity and antipsychotic medication use, whereas T-cell activation had a more direct relationship with both psychotic disorders and depressive symptoms.     

Leukocyte activation: relation to cardiovascular mortality after cerebrovascular ischemia

Activated leukocytes are believed to be involved in the pathogenesis and progression of atherosclerotic vascular disease and its consequences. In a 4-year observational follow-up study, we investigated whether markers for systemic leukocyte activation (leukocyte-derived inflammatory mediators) were related to cardiovascular mortality after cerebrovascular ischemia. Using enzyme-linked immunosorbent assays, we measured the plasma levels of soluble tumor necrosis factor receptor protein-1 (sTNFR-1), neutrophil gelatinase-associated lipocalin (NGAL) and neutrophil protease-4 (NP4) in 144 patients (90 stroke, 54 transient ischemic attack) 1-3 days after cerebral ischemia. During the 4 years of follow-up, 42 (29%) of the 144 patients died; 38 of cardiovascular causes and 4 of other causes. Patients with evidence of higher leukocyte activation (n = 47) had a higher 4-year cardiovascular mortality rate than those without evidence of leukocyte activation (n = 97; p < 0.005). Logistic regression analysis with age, sex and other significant predictors as covariates showed higher plasma levels of sTNFR1 and NGAL both to be significant independent predictors of cardiovascular mortality, the respective odds ratio, 95% confidence intervals, and p values being 2.0, 1.2-3.4, p < 0.01, and 3.6, 1.2-10.5, p = 0.02, respectively. We concluded that in patients with acute cerebral ischemia, plasma markers of leukocyte activation were significant predictors of long-term cardiovascular mortality. This may indicate an important role of activated leukocytes in the progression of these diseases.     

Cerebrospinal fluid inflammatory markers in Parkinson’s disease – Associations with depression,fatigue, and cognitive impairment

Neuroinflammation may be involved in the pathophysiology of Parkinson’s disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. The aim of this study was to measure inflammatory markers in cerebrospinal fluid (CSF) samples from PD patients and a reference group, and to investigate correlations between non-motor symptoms and inflammation.We quantified C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein 1-β in CSF samples from PD patients (N = 87) and the reference group (N = 33). Sixteen of the PD patients had a dementia diagnosis (PDD). We assessed symptoms of fatigue, depression, anxiety and cognitive function using the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and the Mini Mental State Examination, respectively.There were no significant differences in mean levels of inflammatory markers between PD patients and the reference group. After controlling for age, gender and somatic illness, patients with PDD had significantly higher levels of CRP compared to non-demented PD patients (p = 0.032) and the reference group (p = 0.026). Increased levels of inflammatory markers in CSF were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition in the entire PD group. After controlling for PD duration, age, gender, somatic illness and dementia diagnosis, high CRP levels were significantly associated with more severe symptoms of depression (p = 0.010) and fatigue (p = 0.008), and high MCP-1 levels were significantly associated with more severe symptoms of depression (p = 0.032).Our results indicate that non-motor features of PD such as depression, fatigue, and cognitive impairment are associated with higher CSF levels of inflammatory markers.     

Val66Met polymorphism association with serum BDNF and inflammatory biomarkers in major depression

Objectives: Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients.

Methods: All participants (n?=?73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele.

Results: In our sample (84.9% female, mean age 52.4?±?10.3 years), 24.7% (n?=?18) were Met-carriers. After Bonferroni correction, the Met allele was significantly associated with higher BDNF and lower TNF-α. These associations persisted after adjusting for potential confounders.

Conclusions: The pattern of low BDNF and high inflammation in MDD may be influenced by the Val66Met polymorphism. The association of a polymorphism in the BDNF gene with inflammatory markers in addition to BDNF levels suggests an interaction between these systems.     

Inflammatory cytokines,complement factor H and anhedonia in drug-naïve major depressive disorder

ObjectiveAnhedonia is a core symptom of major depressive disorder (MDD) and often associated with poor prognosis. The main objective of the present study was to explore the relationship between complement factor H (CFH), inflammatory cytokines and anhedonia in drug-naïve MDD patients.MethodsA total of 215 participants (61 MDD patients with anhedonia, 78 MDD patients without anhedonia, and 76 control subjects) were included. Severity of depression and levels of anhedonia were evaluated by Hamilton Rating Scale for Depression-17 (HAMD-17) and SHAPS (Snaith-Hamilton Pleasure Scale). Plasma levels of CFH, interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) were measured.ResultsThe plasma levels of CFH, IL-10 and TNF-α were higher in drug-naïve MDD patients than control subjects. Compared to MDD patients without anhedonia, patients with anhedonia showed higher levels of CFH and IL-6. The stepwise regression analysis revealed that IL-10, TNF-α, as well as IL-10 × TNF-α were associated with depressive symptoms measured by HAMD-17 in drug-naïve MDD patients, while only CFH levels were identified as a mediator factor for the severity of anhedonia in the patients.ConclusionMDD patients with anhedonia showed different inflammatory characteristics compared to patients without anhedonia. Our results provide novel evidence suggesting that increased plasma CFH levels may be a potential biomarker of anhedonia of subtyping MDD.     

Dissociation of inflammatory markers and natural killer cell activity in major depressive disorder

Major depressive disorder is associated with increases in infectious disease risk as well as the incidence of inflammatory disorders. Declines of natural killer (NK) cell activity are reliably found in depression, whereas other studies report evidence of inflammation in depressed patients. The potential association between NK activity and circulating markers of immune activation has not been previously examined in the context of major depression. In this study, we measured levels of NK activity, circulating levels of interleukin-6 (IL-6), soluble interleukin-2 receptor, and acute phase proteins in 25 male patients with current major depressive disorder and 25 age, gender, and body weight comparable controls. As compared to controls, patients with major depressive disorder showed lower NK activity (p = .05) and higher circulating levels of IL-6 (p < .05). Levels of NK activity were not correlated with IL-6 or with other markers of immune activation. The independent effect of depression on inflammatory markers and natural killer immune responses has implications for understanding individual differences in the adverse health effects of major depressive disorder.     

Higher serum sTNFR1 level predicts conversion from mild cognitive impairment to Alzheimer's disease

The activation of inflammatory cascades has been consistently demonstrated in the pathophysiology of Alzheimer's disease (AD). Among several putative neuroinflammatory mechanisms, the tumor necrosis factor α (TNF-α) signaling system has a central role in this process. Recent evidence indicates that the abnormal production of inflammatory factors may accompany the progression from mild cognitive impairment (MCI) to dementia. We aimed to examine serum levels of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in patients with MCI and AD as compared to cognitively unimpaired elderly subjects. We further aimed to investigate whether abnormal levels of these cytokines predict the progression from MCI to AD upon follow-up. We utilized cross-sectional determination of serum levels of TNF-α, sTNFR1, and sTNFR2 (ELISA method) in a test group comprising 167 older adults (31 AD, 72 MCI, and 64 healthy controls), and longitudinal reassessment of clinical status after 18.9 ± 10.0 months. At baseline, there were no statistically significant differences in serum TNF-α, sTNFR1, and sTNFR2 between patients with MCI and AD as compared to controls. Nevertheless, patients with MCI who progressed to AD had significantly higher serum sTNFR1 levels as opposed to patients who retained the diagnosis of MCI upon follow-up (p = 0.03). Cox regression analysis showed that high serum sTNFR1 levels predicted the conversion from MCI to AD (p = 0.003), whereas no significant differences were found with respect to serum levels of TNF-α and sTNFR2. Abnormal activation of TNF-α signaling system, represented by increased expression of sTNFR1, is associated with a higher risk of progression from MCI to AD.     

血清YKL-40蛋白水平与颈动脉斑块内新生血管形成的关系

目的 探讨血清YKL-40蛋白水平与颈动脉斑块内新生血管形成的关系。方法 收集2015年1月～2016年12月本院超声科首次发现有颈动脉斑块者575例为研究组,以同期无动脉斑块者500例为对照组; 应用超微血管成像(SMI)技术判断斑块内新生血管分级,并检测研究对象的血清YKL-40蛋白、血脂、炎性因子TNF-α、hsCRP、IL-6等指标水平。结果 ①与对照组比较,研究组TC、TG、LDLC水平明显升高,HDLC明显降低(P均<0.05); ②研究组的IL-6、TNF-α、hsCRP、Lp-PLA2、YKL-40蛋白水平与对照组存在明显差异(P<0.05); ③按SMI分级将研究组患者分为4组,4组患者的YKL-40蛋白、IL-6、TNF-α、hsCRP、Lp-PLA2、血脂水平存在明显差异(P均<0.05); ④YKL-40蛋白与炎性因子及血脂指标水平存在相关性(P均<0.05)。结论 血清YKL-40蛋白水平与颈动脉斑块内新生血管形成的严重程度有关,检测YKL-40蛋白水平对判断斑块的稳定性有益。     

What does the beck depression inventory measure in myocardial infarction patients? a psychometric approach using item response theory and person‐fit

Observed associations between depression following myocardial infarction (MI) and adverse cardiac outcomes could be overestimated due to patients’ tendency to over report somatic depressive symptoms. This study was aimed to investigate this issue with modern psychometrics, using item response theory (IRT) and person‐fit statistics to investigate if the Beck Depression Inventory (BDI) measures depression or something else among MI‐patients. An IRT‐model was fit to BDI‐data of 1135 MI patients. Patients’ adherence to this IRT‐model was investigated with person‐fit statistics. Subgroups of “atypical” (low person‐fit) and “prototypical” (high person‐fit) responders were identified and compared in terms of item‐response patterns, psychiatric diagnoses, socio‐demographics and somatic factors. In the IRT model, somatic items had lower thresholds compared to depressive mood/cognition items. Empirically identified “atypical” responders (n = 113) had more depressive mood/cognitions, scored lower on somatic items and more often had a Comprehensive International Diagnostic Interview (CIDI) depressive diagnosis than “prototypical” responders (n = 147). Additionally, “atypical” responders were younger and more likely to smoke. In conclusion, the BDI measures somatic symptoms in most MI patients, but measures depression in a subgroup of patients with atypical response patterns. The presented approach to account for interpersonal differences in item responding could help improve the validity of depression assessments in somatic patients. Copyright © 2015 John Wiley & Sons, Ltd.