TY  - JOUR
AB  - In a subset of patients with mental disorders, such as depression, low-grade inflammation and altered immune marker concentrations are observed. However, these immune alterations are often assessed by only one data type and small marker panels. Here, we used a transdiagnostic approach and combined data from two cohorts to define subgroups of depression symptoms across the diagnostic spectrum through a large-scale multi-omics clustering approach in 237 individuals. The method incorporated age, body mass index (BMI), 43 plasma immune markers and RNA-seq data from peripheral mononuclear blood cells (PBMCs). Our initial clustering revealed four clusters, including two immune-related depression symptom clusters characterized by elevated BMI, higher depression severity and elevated levels of immune markers such as interleukin-1 receptor antagonist (IL-1RA), C-reactive protein (CRP) and C-C motif chemokine 2 (CCL2 or MCP-1). In contrast, the RNA-seq data mostly differentiated a cluster with low depression severity, enriched in brain related gene sets. This cluster was also distinguished by electrocardiography data, while structural imaging data revealed differences in ventricle volumes across the clusters. Incorporating predicted cell type proportions into the clustering resulted in three clusters, with one showing elevated immune marker concentrations. The cell type proportion and genes related to cell types were most pronounced in an intermediate depression symptoms cluster, suggesting that RNA-seq and immune markers measure different aspects of immune dysregulation. Lastly, we found a dysregulation of the SERPINF1/VEGF-A pathway that was specific to dendritic cells by integrating immune marker and RNA-seq data. This shows the advantages of combining different data modalities and highlights possible markers for further stratification research of depression symptoms.
AU  - Hagenberg, J.
AU  - Brückl, T.M.*
AU  - Erhart, M.*
AU  - Kopf-Beck, J.*
AU  - Ködel, M.*
AU  - Rehawi, G.
AU  - Röh-Karamihalev, S.*
AU  - Sauer, S.*
AU  - Yusupov, N.*
AU  - Rex-Haffner, M.*
AU  - Spoormaker, V.I.*
AU  - Samann, P.*
AU  - Binder, E.*
AU  - Knauer-Arloth, J.
C1  - 73656
C2  - 56848
SP  - 353-369
TI  - Dissecting depression symptoms: Multi-omics clustering uncovers immune-related subgroups and cell-type specific dysregulation.
JO  - Brain Behav. Immun.
VL  - 123
PY  - 2025
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - Background: During gestation, the brain development of the fetus is affected by many biological markers, where inflammatory processes and neurotrophic factors have been of particular interest in the past decade. Aim: This exploratory study is the first attempt to explore the relationships between biomarker levels in maternal and cord-blood samples and human fetal brain activity measured with non-invasive fetal magnetoencephalography (fMEG). Method: Twenty-three women were enrolled in this study for collection of maternal serum and fMEG tracings immediately prior to their scheduled cesarean delivery. Twelve of these women had a preexisting diabetic condition. At the time of delivery, umbilical cord blood was also collected. Biomarker levels from both maternal and cord blood were measured and subsequently analyzed for correlations with fetal brain activity in four frequency bands extracted from fMEG power spectral densities. Results: Relative power in the delta, alpha, and beta frequency bands exhibited moderate-sized correlations with maternal BDNF and cord-blood CRP levels before and after adjusting for confounding diabetic status. These correlations were negative for the delta band, and positive for the alpha and beta bands. Maternal CRP and cord-blood BDNF and IL-6 exhibited negligible correlations with relative power in all four bands. Diabetes did not appear to be a strong confounding factor affecting the studied biomarkers. Conclusions: Maternal BDNF levels and cord-blood CRP levels appear to have a direct correlation to fetal brain activity. Our findings indicate the potential use of these biomarkers in conjunction with fetal brain electrophysiology to track fetal neurodevelopment.
AU  - Mercado, L.*
AU  - Rose, S.*
AU  - Escalona-Vargas, D.*
AU  - Dajani, N.*
AU  - Siegel, E.R.*
AU  - Preissl, H.
AU  - Eswaran, H.*
C1  - 70876
C2  - 55774
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
SP  - 399-405
TI  - Correlating maternal and cord-blood inflammatory markers and BDNF with human fetal brain activity recorded by magnetoencephalography: An exploratory study.
JO  - Brain Behav. Immun.
VL  - 52
IS  - 4
PB  - Elsevier
PY  - 2024
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - BACKGROUND: Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Netherlands Study of Depression and Anxiety (NESDA) study. In this study, we aimed to replicate these immunometabolic associations and to characterize the metabolomic correlates of each of the three MDD dimensions. METHODS: Using three clinical rating scales, Melancholic, and Anxious distress, and Immunometabolic (IMD) dimensions were characterized in 158 patients who participated in the Predictors of Remission to Individual and Combined Treatments (PReDICT) study and from whom plasma and serum samples were available. The NESDA-defined inflammatory index, a composite measure of interleukin-6 and C-reactive protein, was measured from pre-treatment plasma samples and a metabolomic profile was defined using serum samples analyzed on three metabolomics platforms targeting fatty acids and complex lipids, amino acids, acylcarnitines, and gut microbiome-derived metabolites among other metabolites of central metabolism. RESULTS: The IMD clinical dimension and the inflammatory index were positively correlated (r=0.19, p=.019) after controlling for age, sex, and body mass index, whereas the Melancholic and Anxious distress dimensions were not, replicating the previous NESDA findings. The three symptom dimensions had distinct metabolomic signatures using both univariate and set enrichment statistics. IMD severity correlated mainly with gut-derived metabolites and a few acylcarnitines and long chain saturated free fatty acids. Melancholia severity was significantly correlated with several phosphatidylcholines, primarily the ether-linked variety, lysophosphatidylcholines, as well as several amino acids. Anxious distress severity correlated with several medium and long chain free fatty acids, both saturated and polyunsaturated ones, sphingomyelins, as well as several amino acids and bile acids. CONCLUSION: The IMD dimension of depression appears reliably associated with markers of inflammation. Metabolomics provides powerful tools to inform about depression heterogeneity and molecular mechanisms related to clinical dimensions in MDD, which include a link to gut microbiome and lipids implicated in membrane structure and function.
AU  - Brydges, C.R.*
AU  - Bhattacharyya, S.*
AU  - Dehkordi, S.M.*
AU  - Milaneschi, Y.*
AU  - Penninx, B.*
AU  - Jansen, R.*
AU  - Kristal, B.S.*
AU  - Han, X.*
AU  - Arnold, M.
AU  - Kastenmüller, G.
AU  - Bekhbat, M.*
AU  - Mayberg, H.S.*
AU  - Craighead, W.E.*
AU  - Rush, A.J.*
AU  - Fiehn, O.*
AU  - Dunlop, B.W.*
AU  - Kaddurah-Daouk, R.*
C1  - 64242
C2  - 52120
SP  - 42-52
TI  - Metabolomic and inflammatory signatures of symptom dimensions in major depression.
JO  - Brain Behav. Immun.
VL  - 102
PY  - 2022
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - BACKGROUND: About 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. METHODS: This 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=1,058) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D, n=1,143) 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. RESULTS: Network 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. CONCLUSIONS: Genetic 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.
AU  - Kappelmann, N.*
AU  - Czamara, D.*
AU  - Rost, N.*
AU  - Moser, S.*
AU  - Schmoll, V.*
AU  - Trastulla, L.*
AU  - Stochl, J.*
AU  - Lucae, S.*
AU  - Binder, E.B.*
AU  - Khandaker, G.M.*
AU  - Knauer-Arloth, J.
C1  - 61749
C2  - 50442
CY  - 525 B St, Ste 1900, San Diego, Ca 92101-4495 Usa
SP  - 256-268
TI  - Polygenic risk for immuno-metabolic markers and specific depressive symptoms: A multi-sample network analysis study.
JO  - Brain Behav. Immun.
VL  - 95
PB  - Academic Press Inc Elsevier Science
PY  - 2021
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - Loss of appetite (anorexia) is a typical behavioral response to infectious diseases that often reduces body weight. Also, anorexia can be observed in cancer and trauma patients, causing poor quality of life and reduced prospects of positive therapeutic outcomes. Although anorexia is an acute symptom, its initiation and endocrine regulation during antiviral immune responses are poorly understood. During viral infections, plasmacytoid dendritic cells (pDCs) produce abundant type I interferon (IFN-I) to initiate first-line defense mechanisms. Here, by targeted ablation of pDCs and various in vitro and in vivo mouse models of viral infection and inflammation, we identified that IFN-I is a significant driver of somatostatin (SST). Consequently, SST suppressed the hunger hormone ghrelin that led to severe metabolic changes, anorexia, and rapid bodyweight loss. Furthermore, during vaccination with Modified Vaccinia Ankara virus (MVA), the SST-mediated suppression of ghrelin was critical to viral immune response, as ghrelin restrained the production of early cytokines by natural killer (NK) cells and pDCs, and impaired the clonal expansion of CD8+ T cells. Thus, the hormonal modulation of ghrelin through SST and the cytokine IFN-I is fundamental for optimal antiviral immunity, which comes at the expense of calorie intake.
AU  - Stutte, S.*
AU  - Ruf, J.*
AU  - Kugler, I.*
AU  - Ishikawa-Ankerhold, H.*
AU  - Parzefall, A.
AU  - Marconi, P.*
AU  - Maeda, T.*
AU  - Kaisho, T.*
AU  - Krug, A.*
AU  - Popper, B.*
AU  - Lauterbach, H.*
AU  - Colonna, M.*
AU  - von Andrian, U.*
AU  - Brocker, T.*
C1  - 61880
C2  - 50497
CY  - 525 B St, Ste 1900, San Diego, Ca 92101-4495 Usa
SP  - 429-443
TI  - Type I interferon mediated induction of somatostatin leads to suppression of ghrelin and appetite thereby promoting viral immunity in mice.
JO  - Brain Behav. Immun.
VL  - 95
PB  - Academic Press Inc Elsevier Science
PY  - 2021
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - Detailed knowledge about the patterns of molecular alterations during epileptogenesis is a presupposition for identifying targets for preventive or disease-modifying approaches, as well as biomarkers of the disease. Large-scale differential proteome analysis can provide unique and novel perspectives based on comprehensive data sets informing about the complex regulation patterns in the disease proteome. Thus, we have completed an elaborate differential proteome analysis based on label-free LC-MS/MS in a rat model of epileptogenesis. Hippocampus and parahippocampal cortex tissues were sampled and analyzed separately at three key time points chosen for monitoring disease development following electrically-induced status epilepticus, namely, the early post-insult phase, the latency phase, and the chronic phase with spontaneous recurrent seizures. We focused the bioinformatics analysis on proteins linked to immune and inflammatory responses, because of the emerging evidence of the specific pathogenic role of inflammatory signalings during epileptogenesis. In the early post-insult and the latency phases, pathway enrichment analysis revealed an extensive over-representation of Toll-like receptor signaling, pro-inflammatory cytokines, heat shock protein regulation, and transforming growth factor beta signaling and leukocyte transendothelial migration. The inflammatory response in the chronic phase proved to be more moderate with differential expression in the parahippocampal cortex exceeding that in the hippocampus. The data sets provide novel information about numerous differentially expressed proteins, which serve as interaction partners or modulators in key disease-associated inflammatory signaling events. Noteworthy, a set of proteins which act as modulators of the ictogenic Toll-like receptor signaling proved to be differentially expressed. In addition, we report novel data demonstrating the regulation of different Toll-like receptor ligands during epileptogenesis. Taken together, the findings deepen our understanding of modulation of inflammatory signaling during epileptogenesis providing an excellent and comprehensive basis for the identification of target and biomarker candidates.
AU  - Walker, A.*
AU  - Russmann, V.*
AU  - Deeg, C.A.*
AU  - von Toerne, C.
AU  - Kleinwort, K.J.*
AU  - Szober, C.M.*
AU  - Rettenbeck, M.L.*
AU  - von Rüden, E.L.*
AU  - Goc, J.*
AU  - Ongerth, T.*
AU  - Boes, K.*
AU  - Salvamoser, J.D.*
AU  - Vezzani, A.*
AU  - Hauck, S.M.
AU  - Potschka, H.*
C1  - 47576
C2  - 40314
SP  - 138-158
TI  - Proteomic profiling of epileptogenesis in a rat model: Focus on inflammation.
JO  - Brain Behav. Immun.
VL  - 53
PY  - 2016
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - Tumor necrosis factor (TNF) is considered a key molecule in the regulation of sleep in health and disease. Conversely, sleep compared to sleep deprivation can modulate TNF release, but overall results are conflicting. In this study we focused on the influence of sleep on spontaneous, i.e., unstimulated TNF production, which might be involved in sleep regulation under normal non-infectious conditions, and on lipopolysaccharide (LPS)-stimulated TNF production, which reflects the capacity of the immune system to respond to a pathogen. To this end, we monitored 10 healthy men during a regular sleep-wake cycle and during 24h of wakefulness while blood was sampled repeatedly to analyze circulating TNF levels in serum as well as intracellular TNF production in monocytes spontaneously and after stimulation with LPS employing whole blood cell cultures. In addition we assessed numbers of monocyte subsets and levels of various hormones in blood. In comparison with nocturnal wakefulness, sleep acutely decreased serum TNF levels, with no parallel decrease in spontaneous monocytic TNF production, but was associated with a striking nighttime increase in the percentage of TNF producing monocytes after stimulation with LPS. The following day circulating TNF showed a reverse pattern with higher levels after regular sleep than after the nocturnal vigil. The mechanisms mediating the differential effects of sleep on circulating TNF (acutely decreased) vs. stimulated monocytic TNF production (acutely increased) remain unclear, although explorative correlational analyses pointed to a regulatory involvement of cortisol, norepinephrine and prolactin. The acute enhancing effect of sleep on LPS stimulated monocytic TNF production adds to the notion that nocturnal sleep favors immune defense to a microbial challenge.
AU  - Dimitrov, S.*
AU  - Besedovsky, L.*
AU  - Born, J.
AU  - Lange, T.*
C1  - 43052
C2  - 36000
CY  - San Diego
SP  - 201-210
TI  - Differential acute effects of sleep on spontaneous and stimulated production of tumor necrosis factor in men.
JO  - Brain Behav. Immun.
VL  - 47
PB  - Academic Press Inc Elsevier Science
PY  - 2015
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - The immune system is known to essentially contribute to the regulation of sleep. Whereas research in this regard focused on the pro-inflammatory cytokines interleukin-1 and tumor necrosis factor, the role of interleukin-6 (IL-6) in sleep regulation has been less intensely studied, probably due to the so far seemingly ambiguous results. Yet, this picture might simply reflect that the effects of IL-6 are conveyed via two different pathways (with possibly different actions), i.e., in addition to the 'classical' signaling pathway via the membrane bound IL-6 receptor (IL-6R), IL-6 stimulates cells through the alternative 'trans-signaling' pathway via the soluble IL-6R. Here, we concentrated on the contributions of the trans-signaling pathway to sleep regulation. To characterize this contribution, we compared the effect of blocking IL-6 trans-signaling (by the soluble gp130Fc fusion protein) in the brain versus body periphery. Thus, we compared sleep in transgenic mice expressing the soluble gp130Fc protein only in the brain (GFAP mice) or in the body periphery (PEPCK mice), and in wild type mice (WT) during a 24-h period of undisturbed conditions and during 18h following a 6-h period of sleep deprivation. Compared with WT mice, PEPCK mice displayed less sleep, particularly during the late light phase, and this was accompanied by decreases in slow wave sleep (SWS) and rapid eye movement (REM) sleep. Following sleep deprivation PEPCK mice primarily recovered REM sleep rather than SWS. GFAP mice showed a slight decrease in REM sleep in combination with a profound and persistent increase in EEG theta activity. In conclusion, peripheral and central nervous IL-6 trans-signaling differentially influences brain activity. Peripheral IL-6 trans-signaling appears to more profoundly contribute to sleep regulation, mainly by supporting SWS.
AU  - Oyanedel, C.N.*
AU  - Kelemen, E.
AU  - Scheller, J.*
AU  - Born, J.
AU  - Rose-John, S.*
C1  - 46290
C2  - 37458
SP  - 178-185
TI  - Peripheral and central blockade of interleukin-6 trans-signaling differentially affects sleep architecture.
JO  - Brain Behav. Immun.
VL  - 50
PY  - 2015
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - Pro-inflammatory cytokines like interleukin-1 beta (IL-1) are major players in the interaction between the immune system and the central nervous system. Various animal studies report a sleep-promoting effect of IL-1 leading to enhanced slow wave sleep (SWS). Moreover, this cytokine was shown to affect hippocampus-dependent memory. However, the role of IL-1 in human sleep and memory is not yet understood. We administered the synthetic IL-1 receptor antagonist anakinra (IL-1ra) in healthy humans (100mg, subcutaneously, before sleep; n=16) to investigate the role of IL-1 signaling in sleep regulation and sleep-dependent declarative memory consolidation. Inasmuch monocytes have been considered a model for central nervous microglia, we monitored cytokine production in classical and non-classical blood monocytes to gain clues about how central nervous effects of IL-1ra are conveyed. Contrary to our expectation, IL-1ra increased EEG slow wave activity during SWS and non-rapid eye movement (NonREM) sleep, indicating a deepening of sleep, while sleep-associated memory consolidation remained unchanged. Moreover, IL-1ra slightly increased prolactin and reduced cortisol levels during sleep. Production of IL-1 by classical monocytes was diminished after IL-1ra. The discrepancy to findings in animal studies might reflect species differences and underlines the importance of studying cytokine effects in humans.
AU  - Schmidt, E.*
AU  - Linz, B.*
AU  - Diekelmann, S.*
AU  - Besedovsky, L.*
AU  - Lange, T.*
AU  - Born, J.
C1  - 43034
C2  - 36004
CY  - San Diego
SP  - 178-185
TI  - Effects of an interleukin-1 receptor antagonist on human sleep, sleep-associated memory consolidation, and blood monocytes.
JO  - Brain Behav. Immun.
VL  - 47
PB  - Academic Press Inc Elsevier Science
PY  - 2015
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - Background: Psychological stress at work is considered a cardiac risk factor, yet whether it acts directly through neuroimmune processes, or indirectly by increasing behavioral risk factors, is uncertain. Cross-sectional associations between job strain and serum biomarkers of inflammation and endothelial dysfunction were investigated. Secondary analyses explored the role of psychosocial/cardiometabolic risk factors as mediators of job stress associated inflammation in healthy workers. Methods: Information on risk factors was obtained in standardized personal interviews of a subcohort of working participants in the MONICA/KORA population (n = 951). Work stress was measured by the Karasek job strain index. Biomarkers were measured from non-fasting venous blood. Multivariate regression analyses were used to examine the association of job strain with inflammatory biomarkers. Mediation analysis (Sobel test) was used to determine the effect of psychosocial risk factors on the association between job strain and C-reactive protein (CRP). Results: High job strain was reported by half (n = 482, 50.7%) of the study participants. While workers with high job strain were more likely to have adverse workplace conditions (competition with coworkers, job dissatisfaction and insecurity), sleeping problems, depressive symptoms, a Type A personality, and be physically inactive, no differences in cardiometabolic risk factors were detected. A strong and robust association between job strain and CRP was observed in age and sex adjusted models, as well as models adjusted for classic coronary heart disease risk factors (beta = 0.39, p = 0.006 and beta = 0.27, p = 0.03, respectively). Adjustment for physical activity abrogated this effect (beta = 0.23, p = 0.07), and a mediating effect of physical activity on stress-associated inflammation was demonstrated (p = 0.04). Conclusions: The analyses provide evidence for both a direct and an indirect effect of job strain on inflammation.
AU  - Emeny, R.T.
AU  - Lacruz, M.-E.
AU  - Baumert, J.J.
AU  - Zierer, A.
AU  - von Eisenhart Rothe, A.
AU  - Autenrieth, C.
AU  - Herder, C.*
AU  - Koenig, W.*
AU  - Thorand, B.
AU  - Ladwig, K.-H.
C1  - 10619
C2  - 30378
SP  - 1077-1084
TI  - Job strain associated CRP is mediated by leisure time physical activity: Results from the MONICA/KORA study.
JO  - Brain Behav. Immun.
VL  - 26
IS  - 7
PB  - Elsevier
PY  - 2012
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - INTRODUCTION: Depressed individuals not only suffer from chronic low grade inflammation, but also exhibit an inflammatory hyper-responsiveness to acute stress. We investigate whether chronic stress also induces an exaggerated inflammatory response in individuals with increased depression features. As model for chronic stress, social isolation was chosen. METHODS: Interleukin (IL)-6 and hs-CRP levels were assessed in 1547 subjects (847 men and 700 women), derived from the population-based MONICA/KORA study. Standardized questionnaires were used to assess depressed mood (depression and exhaustion subscale) and social isolation (social network index). The relationship between the two inflammatory markers, social isolation and depressed mood was examined taking into account interactions social isolation × depressed mood using multivariable linear regression models, adjusted for age, BMI, smoking, alcohol, and physical activity. Analyses were performed in men and women separately. RESULTS: We observed a significant interaction between depressed mood and social isolation regarding IL-6 and hs-CRP, respectively in men (p-value=0.02 for IL-6 and <0.01 for hs-CRP), evidencing a substantial synergistic effect of social isolation, and depressed mood on inflammatory responses. Furthermore, depressed and socially isolated men had highly significantly elevated IL-6 levels (geometric mean: 3.76 vs. 1.92 pg/ml, p-value <0.01) and heightened hs-CRP levels (geometric mean: 2.01 vs. 1.39 mg/l, p=0.08) in comparison with non-depressed and socially integrated men. In women, no significant associations were seen. CONCLUSION: The interaction of depressed mood and social isolation elicits a substantial synergistic impact on inflammatory markers in men, but not in depressed women.
AU  - Häfner, S.
AU  - Emeny, R.T.
AU  - Lacruz, M.E.
AU  - Baumert, J.J.
AU  - Herder, C.*
AU  - Koenig, W.*
AU  - Thorand, B.
AU  - Ladwig, K.-H.
AU  - KORA Study Group (*)
C1  - 5636
C2  - 29388
SP  - 1701-1707
TI  - Association between social isolation and inflammatory markers in depressed and non-depressed individuals: Results from the MONICA/KORA study.
JO  - Brain Behav. Immun.
VL  - 25
IS  - 8
PB  - Elsevier
PY  - 2011
SN  - 0889-1591
ER  - 

TY  - JOUR
AB  - In response to infectious stimuli, enhanced non-rapid eye movement sleep (NREMS) occurs, which is driven by pro-inflammatory cytokines. Those cytokines further elicit the release of corticotropin-releasing hormone (CRH), resulting in the activation of the hypothalamic-pituitary-adrenocortical axis. Signals of CRH are mediated by two receptor types, namely CRH-R1 and -R2. The role of CRH-R1 in wake-promoting effects of CRH has been rather clarified, whereas the involvement of CRH-R2 in sleep-wake regulation is poorly understood. To investigate whether CRH-R2 interferes with sleep responses to immune challenge, this study examined effects of bacterial lipopolysaccharide (LPS) on sleep in CRH-R2 deficient (KO) mice. CRH-R2 KO mice and control littermates (CL) were implanted with electrodes for recording electroencephalogram (EEG) and electromyogram. After recovery, LPS was applied by intraperitoneal injection at doses of 0.1, 1.0, or 10 μg at dark onset. In response to LPS injection NREMS of both genotypes was enhanced in a dose-dependent manner. However, CRH-R2 KO mice showed a larger increase, in particular after 10 μg of LPS compared to CL mice. During postinjection, reduced delta power for NREMS was detected in both genotypes after each dose, but the highest dose evoked a marked elevation of EEG activity in a limited frequency band (4 Hz). However, the EEG power of lower frequencies (1-2 Hz) increased more in CRH-R2 KO than in CL mice. The results indicated that CRH-R2 KO mice show greater NREMS responses to LPS, providing evidence that CRH-R2 participates in sleep-wake regulation via an interaction with the activated immune system.
AU  - Jakubcakova, V.*
AU  - Flachskamm, C.*
AU  - Deussing, J.M.
AU  - Kimura, M.*
C1  - 6927
C2  - 29454
CY  - San Diego
SP  - 1626-1636
TI  - Deficiency of corticotropin-releasing hormone type-2 receptor alters sleep responses to bacterial lipopolysaccharide in mice.
JO  - Brain Behav. Immun.
VL  - 25
IS  - 8
PB  - Academic Press
PY  - 2011
SN  - 0889-1591
ER  -