The older people, omega-3, and cognitive health (EPOCH) trial design and methodology: a randomised, double-blind, controlled trial investigating the effect of long-chain omega-3 fatty acids on cognitive ageing and wellbeing in cognitively healthy older adults.

Posted on March 3, 2012 by Maurice Preter MD

Nutr J. 2011 Oct 20;10:117.
The older people, omega-3, and cognitive health (EPOCH) trial design and methodology: a randomised, double-blind, controlled trial investigating the effect of long-chain omega-3 fatty acids on cognitive ageing and wellbeing in cognitively healthy older adults.
Danthiir V, Burns NR, Nettelbeck T, Wilson C, Wittert G.
Source

Preventative Health Research Flagship, Commonwealth Scientific and Industrial Research Organisation – Food and Nutritional Sciences, Adelaide, South Australia, Australia. vanessa.danthiir@csiro.au
Abstract

BACKGROUND: Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and better cognitive outcomes in older adults. To date, only two randomised, controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy populations. Of these trials only one found a benefit, in the subgroup carrying the ApoE-ε4 allele. The benefits of n-3 LC PUFA supplementation on cognitive function in older normal populations thus still remain unclear. The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people, and included ApoE-ε4 allele carriage as a potential moderating factor. The detailed methodology of the trial is reported herein. METHODS: The study was a parallel, 18-month, randomised, double-blind, placebo-controlled intervention with assessment at baseline and repeated 6-monthly. Participants (N = 391, 53.7% female) aged 65-90 years, English-speaking and with normal cognitive function, were recruited from metropolitan Adelaide, South Australia. Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules. The primary outcome is rate of change in cognitive performance, as measured by latent variables for the cognitive constructs (encompassing Reasoning, Working Memory, Short-term Memory, Retrieval Fluency, Inhibition, Simple and Choice-Reaction Time, Perceptual Speed, Odd-man-out Reaction Time, Speed of Memory Scanning, and Psychomotor Speed) and assessed by latent growth curve modeling. Secondary outcomes are change in the Mini-mental State Examination, functional capacity and well-being (including health status, depression, mood, and self-report cognitive functioning), blood pressure, and biomarkers of n-3 LC PUFA status, glucose, lipid metabolism, inflammation, oxidative stress, and DNA damage. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000278437.

PMID:
22011460
[PubMed – indexed for MEDLINE]
PMCID:
PMC3210089

Free PMC Article

Posted in Aging, Health, metabolic, new treatments | Tagged , , |

Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior.

Posted on March 3, 2012 by Maurice Preter MD

Neuropsychopharmacology. 2012 Jan;37(1):137-62. doi: 10.1038/npp.2011.205. Epub 2011 Sep 14.
Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior.
Haroon E, Raison CL, Miller AH.
Source

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Abstract

The potential contribution of chronic inflammation to the development of neuropsychiatric disorders such as major depression has received increasing attention. Elevated biomarkers of inflammation, including inflammatory cytokines and acute-phase proteins, have been found in depressed patients, and administration of inflammatory stimuli has been associated with the development of depressive symptoms. Data also have demonstrated that inflammatory cytokines can interact with multiple pathways known to be involved in the development of depression, including monoamine metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits relevant to mood regulation. Further understanding of mechanisms by which cytokines alter behavior have revealed a host of pharmacologic targets that may be unique to the impact of inflammation on behavior and may be especially relevant to the treatment and prevention of depression in patients with evidence of increased inflammation. Such targets include the inflammatory signaling pathways cyclooxygenase, p38 mitogen-activated protein kinase, and nuclear factor-κB, as well as the metabolic enzyme, indoleamine-2,3-dioxygenase, which breaks down tryptophan into kynurenine. Other targets include the cytokines themselves in addition to chemokines, which attract inflammatory cells from the periphery to the brain. Psychosocial stress, diet, obesity, a leaky gut, and an imbalance between regulatory and pro-inflammatory T cells also contribute to inflammation and may serve as a focus for preventative strategies relevant to both the development of depression and its recurrence. Taken together, identification of mechanisms by which cytokines influence behavior may reveal a panoply of personalized treatment options that target the unique contributions of the immune system to depression.

PMID:
21918508
[PubMed – in process]
PMCID:
PMC3238082
[Available on 2013/1/1]

Posted in Psychiatry/Neurology |

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 |