Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder

Grosse, Laura; Carvalho, Lívia A.; Wijkhuijs, Annemarie J.M.; Bellingrath, Silja; Ruland, Tillmann; Ambrée, Oliver; Alferink, Judith; Ehring, Thomas; Drexhage, Hemmo A.; Arolt, Volker

doi:10.1016/j.bbi.2014.08.004

Cited by 65 publications

(43 citation statements)

References 34 publications

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“…Alternative splicing of exon 9 of the NR3C1 gene primary transcript generates two GR isoforms: GRα, which mediates classical glucocorticoid-induced transcriptional activity, and GRβ, which does not exhibit transcriptional activity and inhibits GRα (Oakley and Cidlowski, 2013). Although GRα is much more abundant than GRβ in almost all tissues and cell types, it has been shown that GRα/GRβ ratio is decreased in monocytes or the frontal cortex and amygdala of major depression patients (Pandey et al, 2013; Grosse et al, 2015). Moreover, Maiaru et al (2016) reported that spinal GRβ mRNA was increased in rats with CFA-induced chronic inflammatory pain.…”

Section: Discussionmentioning

confidence: 99%

Impaired Spinal Glucocorticoid Receptor Signaling Contributes to the Attenuating Effect of Depression on Mechanical Allodynia and Thermal Hyperalgesia in Rats with Neuropathic Pain

Xiao

Sun

Luo

2017

Front. Cell. Neurosci.

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Although depression-induced altered pain perception has been described in several laboratory and clinical studies, its neurobiological mechanism in the central nervous system (CNS), particularly in the spinal dorsal horn, remains unclear. Therefore, in this study, we aimed to clarify whether nociceptive sensitivity of neuropathic pain is altered in the olfactory bulbectomy (OB) model of depression and whether glucocorticoid receptor (GR), which is involved in the etio-pathologic mechanisms of both major depression and neuropathic pain, contributes to these processes in the spinal dorsal horn of male Sprague-Dawley rats. The results showed that mechanical allodynia and thermal hyperalgesia induced by spinal nerve ligation (SNL) were attenuated in OB-SNL rats with decreased spinal GR expression and nuclear translocation, whereas non-olfactory bulbectomy (NOB)-SNL rats showed increased spinal GR nuclear translocation. In addition, decreased GR nuclear translocation with normal mechanical nociception and hypoalgesia of thermal nociception were observed in OB-Sham rats. Intrathecal injection (i.t.) of GR agonist dexamethasone (Dex; 4 μg/rat/day for 1 week) eliminated the attenuating effect of depression on nociceptive hypersensitivity in OB-SNL rats and aggravated neuropathic pain in NOB-SNL rats, which was associated with the up-regulation of brain-derived neurotrophic factor (BDNF), TrkB and NR2B expression in the spinal dorsal horn. The present study shows that depression attenuates the mechanical allodynia and thermal hyperalgesia of neuropathic pain and suggests that altered spinal GR-BDNF-TrkB signaling may be one of the reasons for depression-induced hypoalgesia.

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Section: Discussionmentioning

confidence: 99%

Impaired Spinal Glucocorticoid Receptor Signaling Contributes to the Attenuating Effect of Depression on Mechanical Allodynia and Thermal Hyperalgesia in Rats with Neuropathic Pain

Xiao

Sun

Luo

2017

Front. Cell. Neurosci.

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“…The GenPod/NEWMEDS and Harvard i2b2 studies, which appeared in the replication of the primary analysis of this dataset, did not have AAO data available and were not included. Four new replication studies were available: 1) a collection of samples available through the University of Mu¨nster (38, 39); 2) a combination of RADIANT cases from Denmark (40), the Danish DEMO and PRISME studies of MDD (41, 42), and a set of Danish population control subjects; 3) the CONVERGE (China Oxford and VCU Experimental Research on Genetic Epidemiology) study of MDD cases and control subjects recruited in China (18, 43, 44); and 4) the Generation Scotland study, which included measures on MDD (45). These are outlined, alongside the definitions of AAO, in Supplemental Methods.…”

Section: Methodsmentioning

confidence: 99%

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Power

Tansey

Buttenschøn

et al. 2017

Biological Psychiatry

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177

140

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BackgroundMajor depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset.MethodsDiscovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer’s disease, and coronary artery disease.ResultsWe identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11–1.21, p = 5.2 × 10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD.ConclusionsWe demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder.

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“…An increasing body of literature demonstrates the involvement of immune dysregulation in MDD (Baumeister et al 2014;Carvalho et al 2014;Dantzer et al 2008;Eyre and Baune 2012;Grosse et al 2015;Miller et al 2009;Zunszain et al 2013). Meta-analysis has shown that, among others, the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin (IL)-6, and Creactive protein (CRP) are consistently elevated in the serum of patients with MDD (Dowlati et al 2010).…”

Section: Introductionmentioning

confidence: 98%

Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy

et al. 2015

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Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder

Cited by 65 publications

References 34 publications

Impaired Spinal Glucocorticoid Receptor Signaling Contributes to the Attenuating Effect of Depression on Mechanical Allodynia and Thermal Hyperalgesia in Rats with Neuropathic Pain

Impaired Spinal Glucocorticoid Receptor Signaling Contributes to the Attenuating Effect of Depression on Mechanical Allodynia and Thermal Hyperalgesia in Rats with Neuropathic Pain

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy

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