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Saturday, March 3, 2012

Pain affect in the absence of pain sensation: evidence of asomaesthesia after somatosensory cortex lesions in the rat.

Pain. 2012 Feb 23. [Epub ahead of print]
Pain affect in the absence of pain sensation: evidence of asomaesthesia after somatosensory cortex lesions in the rat.
Uhelski ML, Davis MA, Fuchs PN.
Source

Department of Diagnostic and Biological Sciences, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Abstract

Multidimensional models of pain processing distinguish the sensory, motivational, and affective components of the pain experience. Efforts to understand underlying mechanisms have focused on isolating the roles of specific brain structures, including both limbic and non-limbic cortical areas, in the processing of nociceptive stimuli. The purpose of this study was to examine the role of the somatosensory cortex in both sensory and affective aspects of pain processing. It was hypothesized that animals with lesions of the hind limb area of the somatosensory cortex would demonstrate altered sensory processing (asomaesthesia, a deficit in the ability to detect and identify somatic sensation) in the presence of an inflammatory state when compared to animals with sham lesions. The level of pain affect produced by an inflammatory pain condition was not expected to change, as this region has not demonstrated a role in processing the affective component of pain. Seventy-nine adult female Sprague-Dawley rats were randomly assigned to receive bilateral lesions or a sham procedure. The results showed that somatosensory lesions to the hindlimb region altered responses to mechanical stimulation in the presence of experimentally-induced inflammation, but did not attenuate the inflammation-induced paw volume changes or the level of pain affect, as demonstrated by escape/avoidance behavior in response to mechanical stimulation. Overall, these results support previous evidence suggesting that the somatosensory cortex is primarily involved in the processing the sensory/discriminative aspect of pain, and the current study is the first to demonstrate the presence of pain affect in the absence of somatosensory processing.

Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

PMID:
22365310
[PubMed - as supplied by publisher]

Inflammation during fetal and neonatal life: Implications for neurologic and neuropsychiatric disease in children and adults.

Ann Neurol. 2011 Sep 2. doi: 10.1002/ana.22620. [Epub ahead of print]
Inflammation during fetal and neonatal life: Implications for neurologic and neuropsychiatric disease in children and adults.
Hagberg H, Gressens P, Mallard C.
Source

Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, United Kingdom. henrik.hagberg@obgyn.gu.se.
Abstract

Inflammation is increasingly recognized as being of both physiological and pathological importance in the immature brain. The rationale of this review is to present an update on this topic with focus on long-term consequences of inflammation during childhood and in adults. The immature brain can be exposed to inflammation in connection with viral or bacterial infection during pregnancy or as a result of sterile central nervous system (CNS) insults. Through efficient anti-inflammatory and reparative processes, inflammation may resolve without any harmful effects on the brain. Alternatively, inflammation contributes to injury or enhances CNS vulnerability. Acute inflammation can also be shifted to a chronic inflammatory state and/or adversely affect brain development. Hypothetically, microglia are the main immunocompetent cells in the immature CNS, and depending on the stimulus, molecular context, and timing, these cells will acquire various phenotypes, which will be critical regarding the CNS consequences of inflammation. Inflammation has long-term consequences and could speculatively modify the risk of a variety of neurological disorders, including cerebral palsy, autism spectrum disorders, schizophrenia, multiple sclerosis, cognitive impairment, and Parkinson disease. So far, the picture is incomplete, and data mostly experimental. Further studies are required to strengthen the associations in humans and to determine whether novel therapeutic interventions during the perinatal period can influence the occurrence of neurological disease later in life. Ann Neurol 2012;

Copyright © 2012 American Neurological Association.

PMID:
22334391
[PubMed - as supplied by publisher]

Psychosocial stress and cardiovascular risk : current opinion.

Swiss Med Wkly. 2012 Jan 20;142:0. doi: 10.4414/smw.2012.13502.
Psychosocial stress and cardiovascular risk : current opinion.
von Känel R.
Source

Division of Psychosomatic Medicine, Department of General Internal Medicine, Inselspital, Bern University Hospital, and University of Bern, Switzerland. roland.vonkaenel@insel.ch
Abstract

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Epidemiologic research of the last half-century has clearly shown that psychosocial factors related to the social environment, personality characteristics, and negative affect increase the risk of incident CVD and also impact prognosis of cardiac patients. Several mechanisms may explain this link, including a genetic predisposition, poor lifestyle choices, low adherence to health recommendations, and direct pathophysiologic perturbations. The latter include alteration of the hypothalamic-pituitary adrenal axis and autonomic dysfunction resulting in endothelial dysfunction, inflammation, and a prothrombotic state further downstream. Screening for psychosocial factors seems appropriate as part of the standard history and based on the clinician's knowledge of the patient and the purpose of the visit. Psychological interventions generally alleviate distress in cardiac patients, but whether they reduce the risk of hard cardiovascular endpoints and all-cause mortality is less evident. Cardiac patients with more severe depression may particularly profit from antidepressant medications. Due to their pharmacologic properties, selective serotonin reuptake inhibitors were shown to improve cardiovascular outcome. The most effective psychosocial treatment is multicomponent therapy that combines elements of cognitive behaviour therapy ("stress management") and changes in health behaviours, including the adoption of a regular exercise regimen. Gender-specific issues should probably be considered. The field of behavioural cardiology has accumulated a wealth of epidemiological, mechanistic and clinical knowledge that undoubtedly has furthered our understanding about the important role of psychosocial risk factors in patients with a heart disease.

PMID:
22271452
[PubMed - in process]

Free full text

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.

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

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

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]

Inflammatory mechanisms in major depressive disorder.

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]

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

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]

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

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]

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

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]

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

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]

Alcoholism and inflammation: neuroimmunology of behavioral and mood disorders.

Brain Behav Immun. 2011 Jun;25 Suppl 1:S13-20. Epub 2010 Dec 28.
Alcoholism and inflammation: neuroimmunology of behavioral and mood disorders.
Kelley KW, Dantzer R.
Source

Integrative Immunology and Behavior Program, Department of Animal Sciences, College of ACES, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. kwkelley@illinois.edu
Abstract

Alcohol abuse changes behavior and can induce major mood disorders such as depression. Recent evidence in pre-clinical rodent models and humans now supports the conclusion that the innate immune system is an important physiological link between alcoholism and major depressive disorders. Deficiency of toll-like receptor 4 (TLR4), a protein that has been known to immunologists for 50 years, not only prevents lipopolysaccharide (LPS)-induced sickness behavior but recently has been demonstrated to induce resistance to chronic alcohol ingestion. Activation of the immune system by acute administration of LPS, a TLR4 agonist, as well as chronic infection with Bacille Calmette-Guérin (BCG), causes development of depressive-like behaviors in pre-clinical rodent models. Induction of an enzyme expressed primarily in macrophages and microglia, 2,3 indoleamine dioxygenase, shunts tryptophan catabolism to form kynurenine metabolites. This enzyme is both necessary and sufficient for expression of LPS and BCG-induced depressive-like behaviors in mice. New findings have extended these concepts to humans by showing that tryptophan catabolites of 2,3 indoleamine dioxygenase are elevated in the cerebrospinal fluid of hepatitis patients treated with the recombinant cytokine interferon-α. The remarkable conservation from mice to humans of the impact of inflammation on mood emphasizes the ever-expanding role for cross-talk among diverse physiological symptoms that are likely to be involved in the pathogenesis of alcohol abuse. These findings present new and challenging opportunities for scientists who are engaged in brain, behavior and immunity research.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID:
21193024
[PubMed - indexed for MEDLINE]