Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression
Richard C. Shelton,J Claiborne,M Sidoryk-Wegrzynowicz,Rakesh Reddy,Michael Aschner,David A. Lewis,Karoly Mirnics +6 more
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TLDR
The results of this study indicate that post-mortem brain tissue samples from BA10, a region that is involved in reward-related behavior, show evidence of local inflammatory, apoptotic, and oxidative stress in MDD.Abstract:
The etiology of major depression (MDD), a common and complex disorder, remains obscure. Gene expression profiling was conducted on post-mortem brain tissue samples from Brodmann Area 10 (BA10) in the prefrontal cortex from psychotropic drug-free persons with a history of MDD and age, gender, and post-mortem interval-matched normal controls (n=14 pairs of subjects). Microarray analysis was conducted using the Affymetrix Exon 1.0 ST arrays. A set of differential expression changes was determined by dual-fold change-probability criteria (∣average log ratios∣>0.585 [equivalent to a 1.5-fold difference in either direction], P<0.01), whereas molecular pathways of interest were evaluated using Gene Set Enrichment Analysis software. The results strongly implicate increased apoptotic stress in the samples from the MDD group. Three anti-apoptotic factors, Y-box-binding protein 1, caspase-1 dominant-negative inhibitor pseudo-ICE, and the putative apoptosis inhibitor FKGS2, were over-expressed. Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1α (IL-1α), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNγ), and lymphotoxin α (TNF superfamily member 1). The genes showing reduced expression included metallothionein 1M (MT1M), a zinc-binding protein with a significant function in the modulation of oxidative stress. The results of this study indicate that post-mortem brain tissue samples from BA10, a region that is involved in reward-related behavior, show evidence of local inflammatory, apoptotic, and oxidative stress in MDD.read more
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Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes.
Elaine Setiawan,Alan A. Wilson,Alan A. Wilson,Romina Mizrahi,Pablo Rusjan,Laura Miler,Grazyna Rajkowska,Ivonne Suridjan,Ivonne Suridjan,James L. Kennedy,P. Vivien Rekkas,Sylvain Houle,Sylvain Houle,Jeffrey H. Meyer +13 more
TL;DR: This finding is important for improving treatment because it implies that therapeutics that reduce microglial activation should be promising for MDE and is consistent with the concept that neuroinflammation in specific regions may contribute to sickness behaviors that overlap with the symptoms of MDE.
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The GABAergic deficit hypothesis of major depressive disorder
TL;DR: Clinical and preclinical evidence supporting a central and causal role of GABAergic deficits in the etiology of depressive disorders is summarized and the GABAergic hypothesis of MDD suggests that alterations in GABAergic transmission represent fundamentally important aspects of the etiological sequelae of MDDs that are reversed by monoaminergic AD action.
Journal ArticleDOI
The Bidirectional Relationship of Depression and Inflammation: Double Trouble.
TL;DR: How the immune system regulates mood and the potential causes of the dysregulated inflammatory responses in depressed patients are described, and inflammation is likely a critical disease modifier, promoting susceptibility to depression.
Journal ArticleDOI
Integrating neuroimmune systems in the neurobiology of depression
TL;DR: Interventions targeting immune-related cellular and molecular pathways may benefit subsets of MDD patients with immune dysregulation and ongoing studies examining neuroimmune mechanisms that influence neuronal activity as well as synaptic plasticity are discussed.
Journal ArticleDOI
Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study
Michael E. Benros,Michael E. Benros,Berit Lindum Waltoft,Merete Nordentoft,Merete Nordentoft,Søren Dinesen Østergaard,William W. Eaton,Jesper Krogh,Preben Bo Mortensen,Preben Bo Mortensen +9 more
TL;DR: Autoimmune diseases and infections are risk factors for subsequent mood disorder diagnosis and seem compatible with an immunologic hypothesis for the development of mood disorders in subgroups of patients.
References
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Statistical significance for genomewide studies
John D. Storey,Robert Tibshirani +1 more
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Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
TL;DR: Preliminary data from patients with inflammatory disorders, as well as medically healthy depressed patients, suggest that inhibiting proinflammatory cytokines or their signaling pathways may improve depressed mood and increase treatment response to conventional antidepressant medication.
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Cytokines sing the blues: inflammation and the pathogenesis of depression
TL;DR: These findings suggest that targeting proinflammatory cytokines and their signaling pathways might represent a novel strategy to treat depression.
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Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression
TL;DR: Because the MPFC and related limbic structures provide forebrain modulation over visceral control structures in the hypothalamus and brainstem, their dysfunction can account for the disturbances in autonomic regulation and neuroendocrine responses that are associated with mood disorders.