Inflammatory mechanisms in major depressive disorder.

Posted on March 3, 2012 by Maurice Preter MD

Curr Opin Psychiatry. 2011 Nov;24(6):519-25.
Inflammatory mechanisms in major depressive disorder.
Raedler TJ.
Source

Department of Psychiatry, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. thomas.raedler@albertahealthservices.ca
Abstract
PURPOSE OF REVIEW:

As the ‘monoamine hypothesis of depression’ fails to explain all aspects of major depression, additional causes are being investigated. Several observations suggest that inflammatory mechanisms pay a role in the cause of major depressive disorder (MDD). This article reviews their role in major depression.
RECENT FINDINGS:

Recent studies support the concept that inflammatory mechanisms play a crucial role in the pathomechanisms of major depression. Major depression shares similarities with ‘sickness behavior’, a normal response to inflammatory cytokines. Elevations in proinflammatory cytokines and other inflammation-related proteins in major depression were found in plasma and cerebrospinal fluid (CSF) as well as in postmortem studies. Elevated levels of proinflammatory cytokines persist after clinical symptoms of depression are in remission and can also predict the onset of a depressive episode. Antidepressant treatment can lead to a normalization of elevated cytokine levels in major depression. Finally, we understand how inflammatory mechanisms affect the metabolism of tryptophan and how nonsteroidal antiinflammatory drugs (NSAIDs) can interfere with the effects of antidepressants.
SUMMARY:

Further studies are needed to fully understand the role of inflammatory mechanisms in major depression and the potential treatment implications.

PMID:
21897249
[PubMed – indexed for MEDLINE]

Posted in News | Tagged , |

Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial.

Posted on March 3, 2012 by Maurice Preter MD

Brain Behav Immun. 2011 Nov;25(8):1725-34. Epub 2011 Jul 19.
Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial.
Kiecolt-Glaser JK, Belury MA, Andridge R, Malarkey WB, Glaser R.
Source

Institute for Behavioral Medicine Research, Ohio State University College of Medicine, OH 43210, USA. Janice.Kiecolt-Glaser@osumc.edu
Abstract

Observational studies have linked lower omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and higher omega-6 (n-6) PUFAs with inflammation and depression, but randomized controlled trial (RCT) data have been mixed. To determine whether n-3 decreases proinflammatory cytokine production and depressive and anxiety symptoms in healthy young adults, this parallel group, placebo-controlled, double-blind 12-week RCT compared n-3 supplementation with placebo. The participants, 68 medical students, provided serial blood samples during lower-stress periods as well as on days before an exam. The students received either n-3 (2.5 g/d, 2085 mg eicosapentaenoic acid and 348 mg docosahexanoic acid) or placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Compared to controls, those students who received n-3 showed a 14% decrease in lipopolysaccharide (LPS) stimulated interleukin 6 (IL-6) production and a 20% reduction in anxiety symptoms, without significant change in depressive symptoms. Individuals differ in absorption and metabolism of n-3 PUFA supplements, as well as in adherence; accordingly, planned secondary analyses that used the plasma n-6:n-3 ratio in place of treatment group showed that decreasing n-6:n-3 ratios led to lower anxiety and reductions in stimulated IL-6 and tumor necrosis factor alpha (TNF-α) production, as well as marginal differences in serum TNF-α. These data suggest that n-3 supplementation can reduce inflammation and anxiety even among healthy young adults. The reduction in anxiety symptoms associated with n-3 supplementation provides the first evidence that n-3 may have potential anxiolytic benefits for individuals without an anxiety disorder diagnosis. ClinicalTrials.gov identifier: NCT00519779.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21784145
[PubMed – indexed for MEDLINE]
PMCID:
PMC3191260
[Available on 2012/11/1]

Posted in News | Tagged |

Pro- and anti-inflammatory cytokines expression in rat’s brain and spleen exposed to chronic mild stress: involvement in depression.

Posted on March 3, 2012 by Maurice Preter MD

Behav Brain Res. 2011 Nov 20;225(1):135-41. Epub 2011 Jul 8.
Pro- and anti-inflammatory cytokines expression in rat’s brain and spleen exposed to chronic mild stress: involvement in depression.
You Z, Luo C, Zhang W, Chen Y, He J, Zhao Q, Zuo R, Wu Y.
Source

Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China. youzili@uestc.edu.cn
Abstract

The association between pro-inflammatory cytokines and depression has been reported by many studies. However, the mechanisms by which inflammation affects mood are only partially understood. In this study, we detected depression-like behavior in a rat animal model which was induced inflammation in the spleen and brain by chronic mild stress (CMS). Wistar rats receiving CMS treatment for four weeks showed a variety of depression-like behavioral changes, including a significant reduction in sucrose preference and locomotion. Real-time RT-PCR was used to analyze the transcriptional regulation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-18) and anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) in hippocampus, cortex, hypothalamus and spleen. The result showed high expression of pro-inflammatory cytokines IL-1β, TNF-α and IL-6, and low expression of anti-inflammatory cytokines TGF-β and IL-10, thus higher ratio of TNF-α/IL-10 and IL-6/IL-10 in the brain of animal exposed to CMS. Simultaneously, brain derived neurotrophic factor mRNA decreased significantly in the hippocampus and hypothalamus of stressed rats. Immunofluorescence found that the BrdU Positive cells after CMS treatment significantly decreased in the hippocampus. These data suggested a crucial role of dysregulation between pro- and anti-inflammatory in CMS-induced depression, possibly because the imbalance of cytokines affects regeneration of neurons.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID:
21767575
[PubMed – indexed for MEDLINE]

Posted in Uncategorized | Tagged |

Inflammatory biomarkers in depression: an opportunity for novel therapeutic interventions.

Posted on March 3, 2012 by Maurice Preter MD

Curr Psychiatry Rep. 2011 Oct;13(5):316-20.
Inflammatory biomarkers in depression: an opportunity for novel therapeutic interventions.
Li M, Soczynska JK, Kennedy SH.
Source

Psychosocial Oncology and Palliative Care, University Health Network/Princess Margaret Hospital and University of Toronto, Toronto, ON M5G 2M9, Canada. madeline.li@uhn.on.ca
Abstract

Currently available antidepressants are effective in less than two thirds of depressed patients, with even lower remission rates in the context of co-morbid medical illness. A rapidly expanding evidence base suggests that maladaptive inflammatory immune responses may be a common pathophysiology underlying depression, particularly in the presence of a general medical condition. The inflammatory hypothesis of depression marks a significant shift away from monoamine-based approaches and is a major step towards developing novel treatments that directly target causal factors of depression. Many antidepressants exert anti-inflammatory effects and there is an emerging literature documenting the efficacy of anti-inflammatory agents as adjunctive treatments for depression. Identification of inflammatory biomarkers in depression will require a re-conceptualization of both the diagnostic phenomenology and the experimental approaches to studying multi-determined psychiatric disorders. In addition to their application in diagnosis, predicting prognosis, and monitoring severity and response to treatment, inflammatory biomarkers may serve as novel therapeutic targets in the treatment of depression.

PMID:
21671010
[PubMed – indexed for MEDLINE]

Posted in Psychiatry/Neurology | Tagged |

Inflammation and depression: why poststroke depression may be the norm and not the exception.

Posted on March 3, 2012 by Maurice Preter MD

Int J Stroke. 2011 Apr;6(2):128-35. doi: 10.1111/j.1747-4949.2010.00565.x. Epub 2011 Jan 19.
Inflammation and depression: why poststroke depression may be the norm and not the exception.
Pascoe MC, Crewther SG, Carey LM, Crewther DP.
Source

Brain Sciences Institute, Swinburne University, Melbourne, Vic, Australia.
Abstract

Ischaemic stroke often precedes the appearance of clinical depression. Poststroke depression in turn influences the prognostic outcome. In the interest of advancing our understanding of the biological mechanisms underlying the development of poststroke depression, this systematic review explores the immunological processes driving the development of inflammation-related cell death in mood-related brain regions. Particular attention has been paid to cytokine-driven intrinsic apoptosis factors, including intracellular calcium, glutamate excitotoxicity and free radicals that appear in the brain following ischaemic damage and whose presence significantly increases the likelihood of clinically defined depression.

© 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.
Comment in

* Int J Stroke. 2011 Dec;6(6):567-8.

PMID:
21371275
[PubMed – indexed for MEDLINE]

Posted in Aging | Tagged , |