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]
Saturday, March 3, 2012
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]
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
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
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]
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]
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]
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]
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]
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]
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]
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]
Immune activation by casein dietary antigens in bipolar disorder.
Bipolar Disord. 2010 Dec;12(8):834-42. doi: 10.1111/j.1399-5618.2010.00879.x.
Immune activation by casein dietary antigens in bipolar disorder.
Severance EG, Dupont D, Dickerson FB, Stallings CR, Origoni AE, Krivogorsky B, Yang S, Haasnoot W, Yolken RH.
Source
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA. eseverance@jhmi.edu
Abstract
OBJECTIVES:
Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized different epitopes of the casein protein than control individuals.
METHODS:
Anti-bovine casein immunoglobulin G (IgG) levels were measured with solid-phase immunoassays in 75 individuals with bipolar disorder and 65 controls. Epitope recognition was evaluated in immunoassays by cross neutralization with anti-bovine casein polyclonal antibodies of defined reactivity. Group-specific reactivity and associations with symptom severity scores were detected with age-, gender-, and race-controlled regression models.
RESULTS:
Individuals with bipolar disorder had significantly elevated anti-casein IgG (t-test, p ≤0.001) compared to controls. Casein IgG seropositivity conferred odds ratios of 3.97 for bipolar disorder [n=75, 95% confidence interval (CI): 1.31-12.08, p ≤0.015], 5.26 for the bipolar I subtype (n=56, 95% CI: 1.66-16.64, p ≤0.005), and 3.98 for bipolar disorder with psychosis (n=54, 95% CI: 1.32-12.00, p ≤0.014). Lithium and/or antipsychotic medication did not significantly affect anti-casein IgG levels. Casein IgG measures correlated with severity of manic (R(2) =0.15, 95% CI: 0.05-0.24, p ≤0.02) but not depressive symptoms. Unlike controls, sera from individuals with bipolar disorder did not inhibit binding of casein-reactive animal sera (t-test/χ(2) , p ≤0.0001).
CONCLUSIONS:
Anti-casein IgG associations with bipolar I diagnoses, psychotic symptom history, and mania severity scores suggest that casein-related immune activation may relate to the psychosis and mania components of this mood disorder. Case-control differences in epitope recognition implicate disease-related alterations in how the casein molecule is digested and/or how resulting casein-derived structures are rendered immunogenic.
© 2010 John Wiley and Sons A/S.
PMID:
21176030
[PubMed - indexed for MEDLINE]
Immune activation by casein dietary antigens in bipolar disorder.
Severance EG, Dupont D, Dickerson FB, Stallings CR, Origoni AE, Krivogorsky B, Yang S, Haasnoot W, Yolken RH.
Source
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA. eseverance@jhmi.edu
Abstract
OBJECTIVES:
Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized different epitopes of the casein protein than control individuals.
METHODS:
Anti-bovine casein immunoglobulin G (IgG) levels were measured with solid-phase immunoassays in 75 individuals with bipolar disorder and 65 controls. Epitope recognition was evaluated in immunoassays by cross neutralization with anti-bovine casein polyclonal antibodies of defined reactivity. Group-specific reactivity and associations with symptom severity scores were detected with age-, gender-, and race-controlled regression models.
RESULTS:
Individuals with bipolar disorder had significantly elevated anti-casein IgG (t-test, p ≤0.001) compared to controls. Casein IgG seropositivity conferred odds ratios of 3.97 for bipolar disorder [n=75, 95% confidence interval (CI): 1.31-12.08, p ≤0.015], 5.26 for the bipolar I subtype (n=56, 95% CI: 1.66-16.64, p ≤0.005), and 3.98 for bipolar disorder with psychosis (n=54, 95% CI: 1.32-12.00, p ≤0.014). Lithium and/or antipsychotic medication did not significantly affect anti-casein IgG levels. Casein IgG measures correlated with severity of manic (R(2) =0.15, 95% CI: 0.05-0.24, p ≤0.02) but not depressive symptoms. Unlike controls, sera from individuals with bipolar disorder did not inhibit binding of casein-reactive animal sera (t-test/χ(2) , p ≤0.0001).
CONCLUSIONS:
Anti-casein IgG associations with bipolar I diagnoses, psychotic symptom history, and mania severity scores suggest that casein-related immune activation may relate to the psychosis and mania components of this mood disorder. Case-control differences in epitope recognition implicate disease-related alterations in how the casein molecule is digested and/or how resulting casein-derived structures are rendered immunogenic.
© 2010 John Wiley and Sons A/S.
PMID:
21176030
[PubMed - indexed for MEDLINE]
Overnight changes of immune parameters and catecholamines are associated with mood and stress.
Psychosom Med. 2010 Oct;72(8):755-62. Epub 2010 Sep 14.
Overnight changes of immune parameters and catecholamines are associated with mood and stress.
Rief W, Mills PJ, Ancoli-Israel S, Ziegler MG, Pung MA, Dimsdale JE.
Source
Department of Psychiatry, University of California, San Diego, San Diego, California, USA. rief@staff.uni-marburg.de
Abstract
OBJECTIVES:
To test the hypothesis that a nocturnal decrease of secretion of inflammation markers and catecholamines would be associated with mood and stress variables even after controlling for objective sleep variables.
METHODS:
A total of 130 healthy volunteers participated in this study, spending 2 nights in the Gillin Laboratory of Sleep and Chronobiology at the University of California, San Diego, General Clinical Research Center. Blood samples were obtained before sleep (10:30 PM) and after awakening (6:30 AM) on the first day, and these samples were assayed for inflammatory biomarkers and catecholamines. On the second night, polysomnographic records were scored for objective sleep variables, e.g., total sleep time and wake after sleep onset. Self-rating scales for mood, stress, depression, and daily hassles were administered the second day.
RESULTS:
The nocturnal decrease in interleukin-6 was smaller in people who reported more negative mood or fatigue and greater in those who reported more uplift events (e.g., with Profile of Mood States fatigue r(p) = -.25 to -.30). People with high stress or high depression levels had smaller nocturnal decreases of epinephrine. That relationship was even stronger when partial correlations were used to control for morning level and sleep variables. The associations between nocturnal changes of C-reactive protein, soluble tumor necrosis factor-receptor I, and norepinephrine with psychological states were nonremarkable.
CONCLUSIONS:
The analyses of nocturnal change scores (difference scores) add substantial information compared with the traditional analyses of morning levels of immune variables and catecholamines alone. Subjective well-being is significantly associated with a greater nocturnal decrease of interleukin-6 and epinephrine. More research on nocturnal adaptation processes is warranted.
PMID:
20841563
[PubMed - indexed for MEDLINE]
PMCID:
PMC3162345
Free PMC Article
Overnight changes of immune parameters and catecholamines are associated with mood and stress.
Rief W, Mills PJ, Ancoli-Israel S, Ziegler MG, Pung MA, Dimsdale JE.
Source
Department of Psychiatry, University of California, San Diego, San Diego, California, USA. rief@staff.uni-marburg.de
Abstract
OBJECTIVES:
To test the hypothesis that a nocturnal decrease of secretion of inflammation markers and catecholamines would be associated with mood and stress variables even after controlling for objective sleep variables.
METHODS:
A total of 130 healthy volunteers participated in this study, spending 2 nights in the Gillin Laboratory of Sleep and Chronobiology at the University of California, San Diego, General Clinical Research Center. Blood samples were obtained before sleep (10:30 PM) and after awakening (6:30 AM) on the first day, and these samples were assayed for inflammatory biomarkers and catecholamines. On the second night, polysomnographic records were scored for objective sleep variables, e.g., total sleep time and wake after sleep onset. Self-rating scales for mood, stress, depression, and daily hassles were administered the second day.
RESULTS:
The nocturnal decrease in interleukin-6 was smaller in people who reported more negative mood or fatigue and greater in those who reported more uplift events (e.g., with Profile of Mood States fatigue r(p) = -.25 to -.30). People with high stress or high depression levels had smaller nocturnal decreases of epinephrine. That relationship was even stronger when partial correlations were used to control for morning level and sleep variables. The associations between nocturnal changes of C-reactive protein, soluble tumor necrosis factor-receptor I, and norepinephrine with psychological states were nonremarkable.
CONCLUSIONS:
The analyses of nocturnal change scores (difference scores) add substantial information compared with the traditional analyses of morning levels of immune variables and catecholamines alone. Subjective well-being is significantly associated with a greater nocturnal decrease of interleukin-6 and epinephrine. More research on nocturnal adaptation processes is warranted.
PMID:
20841563
[PubMed - indexed for MEDLINE]
PMCID:
PMC3162345
Free PMC Article
Psychological and biological mechanisms of cytokine induced depression.
Epidemiol Psichiatr Soc. 2010 Apr-Jun;19(2):98-102.
Psychological and biological mechanisms of cytokine induced depression.
Hepgul N, Mondelli V, Pariante CM.
Abstract
Depression is frequently seen in patients with medical illnesses yet the link between medical illnesses and depression remains unclear. There is increasing data to suggest that the array of depressive symptoms experienced by the medically-ill may involve inflammation. The activation of the immune system and the subsequent release of innate immune products such as cytokines can have important effects on behaviour. The treatment of choice for chronic viral hepatitis C, interferon-alpha IFN-alpha, acutely induces the production and release of other innate immune cytokines, and has been indicated to cause clinically significant depression in 30% of patients receiving treatment. This in turn can impair quality of life and affect treatment compliance. We and others use IFN-alpha induced depression as a model to identify alterations in psychological and biological pathways that predispose to depression in the medically-ill, and thus provide an explanatory link between inflammation and the subsequent behavioural changes. In this editorial, we aim to describe the main biological pathways involved in IFN-induced depression and to discuss psychological, clinical and biological factors that have been found to predict those who will develop more severe psychiatric symptoms during treatment with IFN-alpha. Among these, particular attention would be given to psychological traits, genetic polymorphisms regulating inflammation and serotonergic function, and changes in plasma levels of pro-inflammatory cytokines.
PMID:
20815291
[PubMed - indexed for MEDLINE]
Psychological and biological mechanisms of cytokine induced depression.
Hepgul N, Mondelli V, Pariante CM.
Abstract
Depression is frequently seen in patients with medical illnesses yet the link between medical illnesses and depression remains unclear. There is increasing data to suggest that the array of depressive symptoms experienced by the medically-ill may involve inflammation. The activation of the immune system and the subsequent release of innate immune products such as cytokines can have important effects on behaviour. The treatment of choice for chronic viral hepatitis C, interferon-alpha IFN-alpha, acutely induces the production and release of other innate immune cytokines, and has been indicated to cause clinically significant depression in 30% of patients receiving treatment. This in turn can impair quality of life and affect treatment compliance. We and others use IFN-alpha induced depression as a model to identify alterations in psychological and biological pathways that predispose to depression in the medically-ill, and thus provide an explanatory link between inflammation and the subsequent behavioural changes. In this editorial, we aim to describe the main biological pathways involved in IFN-induced depression and to discuss psychological, clinical and biological factors that have been found to predict those who will develop more severe psychiatric symptoms during treatment with IFN-alpha. Among these, particular attention would be given to psychological traits, genetic polymorphisms regulating inflammation and serotonergic function, and changes in plasma levels of pro-inflammatory cytokines.
PMID:
20815291
[PubMed - indexed for MEDLINE]
Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.
Biol Psychiatry. 2010 Oct 15;68(8):748-54. Epub 2010 Aug 16.
Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.
Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR.
Source
Department of Psychology, Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, California 90095-1563, USA. neisenbe@ucla.edu
Abstract
BACKGROUND:
Although inflammatory activity is known to play a role in depression, no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia, a key diagnostic symptom of depression. To investigate this, we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia-namely, reduced ventral striatum (VS) activity to reward cues. We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood.
METHODS:
Participants (n = 39) were randomly assigned to receive either placebo or low-dose endotoxin, which increases proinflammatory cytokine levels in a safe manner. Cytokine levels were repeatedly assessed through hourly blood draws; self-reported and observer-rated depressed mood were assessed regularly as well. Two hours after drug administration, neural activity was recorded as participants completed a task in which they anticipated monetary rewards.
RESULTS:
Results demonstrated that subjects exposed to endotoxin, compared with placebo, showed greater increases in self-reported and observer-rated depressed mood over time, as well as significant reductions in VS activity to monetary reward cues. Moreover, the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward.
CONCLUSIONS:
The data reported here show, for the first time, that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood. As such, these findings have implications for understanding risk of depression in persons with underlying inflammation.
Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
PMID:
20719303
[PubMed - indexed for MEDLINE]
PMCID:
PMC3025604
Free PMC Article
Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.
Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR.
Source
Department of Psychology, Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, California 90095-1563, USA. neisenbe@ucla.edu
Abstract
BACKGROUND:
Although inflammatory activity is known to play a role in depression, no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia, a key diagnostic symptom of depression. To investigate this, we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia-namely, reduced ventral striatum (VS) activity to reward cues. We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood.
METHODS:
Participants (n = 39) were randomly assigned to receive either placebo or low-dose endotoxin, which increases proinflammatory cytokine levels in a safe manner. Cytokine levels were repeatedly assessed through hourly blood draws; self-reported and observer-rated depressed mood were assessed regularly as well. Two hours after drug administration, neural activity was recorded as participants completed a task in which they anticipated monetary rewards.
RESULTS:
Results demonstrated that subjects exposed to endotoxin, compared with placebo, showed greater increases in self-reported and observer-rated depressed mood over time, as well as significant reductions in VS activity to monetary reward cues. Moreover, the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward.
CONCLUSIONS:
The data reported here show, for the first time, that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood. As such, these findings have implications for understanding risk of depression in persons with underlying inflammation.
Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
PMID:
20719303
[PubMed - indexed for MEDLINE]
PMCID:
PMC3025604
Free PMC Article
Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):730-43. Epub 2010 Aug 5.
Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.
Gardner A, Boles RG.
Source
Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden. agtorndal@odenhall.se
Abstract
For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression. High degrees of overlapping comorbidities and common drug efficacies suggest that depression is one of a family of related conditions sometimes referred to as the "affective spectrum disorders", and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others. Herein, we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders. The three concepts of monoamines, energy metabolism and inflammatory pathways are inter-related in many complex manners. For example, the major categories of drugs used to treat depression have been demonstrated to exert effects on mitochondria and inflammation, as well as on monoamines. Furthermore, commonly-used mitochondrial-targeted treatments exert effects on mitochondria and inflammation, and are increasingly being shown to demonstrate efficacy in the affective spectrum disorders. We propose that interactions among monoamines, mitochondrial dysfunction and inflammation can inspire explanatory, rather than mere descriptive, models of these disorders.
Copyright © 2010 Elsevier Inc. All rights reserved.
PMID:
20691744
[PubMed - indexed for MEDLINE]
Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.
Gardner A, Boles RG.
Source
Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden. agtorndal@odenhall.se
Abstract
For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression. High degrees of overlapping comorbidities and common drug efficacies suggest that depression is one of a family of related conditions sometimes referred to as the "affective spectrum disorders", and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others. Herein, we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders. The three concepts of monoamines, energy metabolism and inflammatory pathways are inter-related in many complex manners. For example, the major categories of drugs used to treat depression have been demonstrated to exert effects on mitochondria and inflammation, as well as on monoamines. Furthermore, commonly-used mitochondrial-targeted treatments exert effects on mitochondria and inflammation, and are increasingly being shown to demonstrate efficacy in the affective spectrum disorders. We propose that interactions among monoamines, mitochondrial dysfunction and inflammation can inspire explanatory, rather than mere descriptive, models of these disorders.
Copyright © 2010 Elsevier Inc. All rights reserved.
PMID:
20691744
[PubMed - indexed for MEDLINE]
The relationship between depression, anxiety, and cardiovascular outcomes in patients with acute coronary syndromes.
Neuropsychiatr Dis Treat. 2010 May 6;6:123-36.
The relationship between depression, anxiety, and cardiovascular outcomes in patients with acute coronary syndromes.
Huffman JC, Celano CM, Januzzi JL.
Source
Department of Psychiatry, Massachusetts General Hospital, 55 Fruit Street/Blake 11, Boston, MA, USA. jhuffman@partners.org
Abstract
Depression and anxiety occur at high rates among patients suffering an acute coronary syndrome (ACS). Both depressive symptoms and anxiety appear to adversely affect in-hospital and long term cardiac outcomes of post-ACS patients, independent of traditional risk factors. Despite their high prevalence and serious impact, mood and anxiety symptoms go unrecognized and untreated in most ACS patients and such symptoms (rather than being transient reactions to ACS) persist for months and beyond. The mechanisms by which depression and anxiety are linked to these negative medical outcomes are likely a combination of the effects of these conditions on inflammation, catecholamines, heart rate variability, and endothelial function, along with effects on health-promoting behavior. Fortunately, standard treatments for these disorders appear to be safe, well-tolerated and efficacious in this population; indeed, selective serotonin reuptake inhibitors may actually improve cardiac outcomes. Future research goals include gaining a better understanding of the combined effects of depression and anxiety, as well as definitive prospective studies of the impact of treatment on cardiac outcomes. Clinically, protocols that allow for efficient and systematic screening, evaluation, and treatment for depression and anxiety in cardiac patients are critical to help patients avoid the devastating effects of these illnesses on quality of life and cardiac health.
PMID:
20505844
[PubMed]
PMCID:
PMC2874336
Free PMC Article
The relationship between depression, anxiety, and cardiovascular outcomes in patients with acute coronary syndromes.
Huffman JC, Celano CM, Januzzi JL.
Source
Department of Psychiatry, Massachusetts General Hospital, 55 Fruit Street/Blake 11, Boston, MA, USA. jhuffman@partners.org
Abstract
Depression and anxiety occur at high rates among patients suffering an acute coronary syndrome (ACS). Both depressive symptoms and anxiety appear to adversely affect in-hospital and long term cardiac outcomes of post-ACS patients, independent of traditional risk factors. Despite their high prevalence and serious impact, mood and anxiety symptoms go unrecognized and untreated in most ACS patients and such symptoms (rather than being transient reactions to ACS) persist for months and beyond. The mechanisms by which depression and anxiety are linked to these negative medical outcomes are likely a combination of the effects of these conditions on inflammation, catecholamines, heart rate variability, and endothelial function, along with effects on health-promoting behavior. Fortunately, standard treatments for these disorders appear to be safe, well-tolerated and efficacious in this population; indeed, selective serotonin reuptake inhibitors may actually improve cardiac outcomes. Future research goals include gaining a better understanding of the combined effects of depression and anxiety, as well as definitive prospective studies of the impact of treatment on cardiac outcomes. Clinically, protocols that allow for efficient and systematic screening, evaluation, and treatment for depression and anxiety in cardiac patients are critical to help patients avoid the devastating effects of these illnesses on quality of life and cardiac health.
PMID:
20505844
[PubMed]
PMCID:
PMC2874336
Free PMC Article
Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.
Psychosom Med. 2010 May;72(4):365-9. Epub 2010 Apr 21.
Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.
Kiecolt-Glaser JK.
Source
Department of Psychiatry, The Ohio State Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, Ohio 43210-1228, USA. Janice.Kiecolt-Glaser@osumc.edu
Abstract
Inflammation is the common link among the leading causes of death. Mechanistic studies have shown how various dietary components can modulate key pathways to inflammation, including sympathetic activity, oxidative stress, transcription factor nuclear factor-kappaB activation, and proinflammatory cytokine production. Behavioral studies have demonstrated that stressful events and depression can also influence inflammation through these same processes. If the joint contributions of diet and behavior to inflammation were simply additive, they would be important. However, several far more intriguing interactive possibilities are discussed: stress influences food choices; stress can enhance maladaptive metabolic responses to unhealthy meals; and diet can affect mood as well as proinflammatory responses to stressors. Furthermore, because the vagus nerve innervates tissues involved in the digestion, absorption, and metabolism of nutrients, vagal activation can directly and profoundly influence metabolic responses to food, as well as inflammation; in turn, both depression and stress have well-documented negative effects on vagal activation, contributing to the lively interplay between the brain and the gut. As one example, omega-3 fatty acid intake can boost mood and vagal tone, dampen nuclear factor-kappaB activation and responses to endotoxin, and modulate the magnitude of inflammatory responses to stressors. A better understanding of how stressors, negative emotions, and unhealthy meals work together to enhance inflammation will benefit behavioral and nutritional research, as well as the broader biomedical community.
PMID:
20410248
[PubMed - indexed for MEDLINE]
PMCID:
PMC2868080
Free PMC Article
Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.
Kiecolt-Glaser JK.
Source
Department of Psychiatry, The Ohio State Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, Ohio 43210-1228, USA. Janice.Kiecolt-Glaser@osumc.edu
Abstract
Inflammation is the common link among the leading causes of death. Mechanistic studies have shown how various dietary components can modulate key pathways to inflammation, including sympathetic activity, oxidative stress, transcription factor nuclear factor-kappaB activation, and proinflammatory cytokine production. Behavioral studies have demonstrated that stressful events and depression can also influence inflammation through these same processes. If the joint contributions of diet and behavior to inflammation were simply additive, they would be important. However, several far more intriguing interactive possibilities are discussed: stress influences food choices; stress can enhance maladaptive metabolic responses to unhealthy meals; and diet can affect mood as well as proinflammatory responses to stressors. Furthermore, because the vagus nerve innervates tissues involved in the digestion, absorption, and metabolism of nutrients, vagal activation can directly and profoundly influence metabolic responses to food, as well as inflammation; in turn, both depression and stress have well-documented negative effects on vagal activation, contributing to the lively interplay between the brain and the gut. As one example, omega-3 fatty acid intake can boost mood and vagal tone, dampen nuclear factor-kappaB activation and responses to endotoxin, and modulate the magnitude of inflammatory responses to stressors. A better understanding of how stressors, negative emotions, and unhealthy meals work together to enhance inflammation will benefit behavioral and nutritional research, as well as the broader biomedical community.
PMID:
20410248
[PubMed - indexed for MEDLINE]
PMCID:
PMC2868080
Free PMC Article
Polyunsaturated fatty acids, neuroinflammation and well being.
Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):295-303. Epub 2010 Mar 15.
Polyunsaturated fatty acids, neuroinflammation and well being.
Layé S.
Source
Psychoneuroimmunology, Nutrition and Genetic (PsyNuGen), UMR INRA 1286, CNRS 5226, University Bordeaux 2, Bordeaux, France. sophie.laye@bordeaux.inra.fr
Abstract
The innate immune system of the brain is principally composed of microglial cells and astrocytes, which, once activated, protect neurons against insults (infectious agents, lesions, etc.). Activated glial cells produce inflammatory cytokines that act specifically through receptors expressed by the brain. The functional consequences of brain cytokine action (also called neuroinflammation) are alterations in cognition, mood and behaviour, a hallmark of altered well-being. In addition, proinflammatory cytokines play a key role in depression and neurodegenerative diseases linked to aging. Polyunsaturated fatty acids (PUFA) are essential nutrients and essential components of neuronal and glial cell membranes. PUFA from the diet regulate both prostaglandin and proinflammatory cytokine production. n-3 fatty acids are anti-inflammatory while n-6 fatty acids are precursors of prostaglandins. Inappropriate amounts of dietary n-6 and n-3 fatty acids could lead to neuroinflammation because of their abundance in the brain and reduced well-being. Depending on which PUFA are present in the diet, neuroinflammation will, therefore, be kept at a minimum or exacerbated. This could explain the protective role of n-3 fatty acids in neurodegenerative diseases linked to aging.
Copyright 2010 Elsevier Ltd. All rights reserved.
PMID:
20227866
[PubMed - indexed for MEDLINE]
Polyunsaturated fatty acids, neuroinflammation and well being.
Layé S.
Source
Psychoneuroimmunology, Nutrition and Genetic (PsyNuGen), UMR INRA 1286, CNRS 5226, University Bordeaux 2, Bordeaux, France. sophie.laye@bordeaux.inra.fr
Abstract
The innate immune system of the brain is principally composed of microglial cells and astrocytes, which, once activated, protect neurons against insults (infectious agents, lesions, etc.). Activated glial cells produce inflammatory cytokines that act specifically through receptors expressed by the brain. The functional consequences of brain cytokine action (also called neuroinflammation) are alterations in cognition, mood and behaviour, a hallmark of altered well-being. In addition, proinflammatory cytokines play a key role in depression and neurodegenerative diseases linked to aging. Polyunsaturated fatty acids (PUFA) are essential nutrients and essential components of neuronal and glial cell membranes. PUFA from the diet regulate both prostaglandin and proinflammatory cytokine production. n-3 fatty acids are anti-inflammatory while n-6 fatty acids are precursors of prostaglandins. Inappropriate amounts of dietary n-6 and n-3 fatty acids could lead to neuroinflammation because of their abundance in the brain and reduced well-being. Depending on which PUFA are present in the diet, neuroinflammation will, therefore, be kept at a minimum or exacerbated. This could explain the protective role of n-3 fatty acids in neurodegenerative diseases linked to aging.
Copyright 2010 Elsevier Ltd. All rights reserved.
PMID:
20227866
[PubMed - indexed for MEDLINE]
Black sheep get the blues: a psychobiological model of social rejection and depression.
Black sheep presumably also get less Vitamin D.
Neurosci Biobehav Rev. 2010 Sep;35(1):39-45. Epub 2010 Jan 18.
Black sheep get the blues: a psychobiological model of social rejection and depression.
Slavich GM, O'Donovan A, Epel ES, Kemeny ME.
Source
Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0848, USA. george.slavich@ucsf.edu
Abstract
Major life events involving social rejection are strongly associated with onset of depression. To account for this relation, we propose a psychobiological model in which rejection-related stressors elicit a distinct and integrated set of cognitive, emotional, and biological changes that may evoke depression. In this model, social rejection events activate brain regions involved in processing negative affect and rejection-related distress (e.g., anterior insula, dorsal anterior cingulate cortex). They also elicit negative self-referential cognitions (e.g., "I'm undesirable," "Other people don't like me") and related self-conscious emotions (e.g., shame, humiliation). Downstream biological consequences include upregulation of the hypothalamic-pituitary-adrenal axis, sympathetic-adrenal-medullary axis, and inflammatory response. Pro-inflammatory cytokines play an important role in this process because they induce a constellation of depressotypic behaviors called sickness behaviors. Although these changes can be short-lived, sustained inflammation may occur via glucocorticoid resistance, catecholamines, sympathetic innervation of immune organs, and immune cell aging. This response also may be moderated by several factors, including prior life stress, prior depression, and genes implicated in stress reactivity.
PMID:
20083138
[PubMed - indexed for MEDLINE]
PMCID:
PMC2926175
Free PMC Article
Neurosci Biobehav Rev. 2010 Sep;35(1):39-45. Epub 2010 Jan 18.
Black sheep get the blues: a psychobiological model of social rejection and depression.
Slavich GM, O'Donovan A, Epel ES, Kemeny ME.
Source
Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0848, USA. george.slavich@ucsf.edu
Abstract
Major life events involving social rejection are strongly associated with onset of depression. To account for this relation, we propose a psychobiological model in which rejection-related stressors elicit a distinct and integrated set of cognitive, emotional, and biological changes that may evoke depression. In this model, social rejection events activate brain regions involved in processing negative affect and rejection-related distress (e.g., anterior insula, dorsal anterior cingulate cortex). They also elicit negative self-referential cognitions (e.g., "I'm undesirable," "Other people don't like me") and related self-conscious emotions (e.g., shame, humiliation). Downstream biological consequences include upregulation of the hypothalamic-pituitary-adrenal axis, sympathetic-adrenal-medullary axis, and inflammatory response. Pro-inflammatory cytokines play an important role in this process because they induce a constellation of depressotypic behaviors called sickness behaviors. Although these changes can be short-lived, sustained inflammation may occur via glucocorticoid resistance, catecholamines, sympathetic innervation of immune organs, and immune cell aging. This response also may be moderated by several factors, including prior life stress, prior depression, and genes implicated in stress reactivity.
PMID:
20083138
[PubMed - indexed for MEDLINE]
PMCID:
PMC2926175
Free PMC Article
Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood.
As usual, Eisenberger is way ahead of the pack. The relationship between inflammation and social rejection is bi-directional.
Brain Behav Immun. 2010 May;24(4):558-63. Epub 2010 Jan 4.
Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood.
Eisenberger NI, Inagaki TK, Mashal NM, Irwin MR.
Source
Department of Psychology, University of California, Los Angeles, CA 90095-1563, USA. neisenbe@ucla.edu
Abstract
Although research has established links between feelings of social isolation and inflammation, the direction of these effects is unclear. Based on the role that proinflammatory cytokines play in initiating "sickness behavior," which includes symptoms such as social withdrawal, it is possible that inflammatory processes heighten feelings of 'social disconnection.' Here, we examined whether exposure to an inflammatory challenge increased self-reported feelings of social disconnection. In addition, because both inflammatory processes and feelings of social disconnection contribute to depressive symptoms, we also explored whether increases in feelings of social disconnection played a role in the link between inflammation and depressed mood. Participants were randomly assigned to either receive endotoxin, an inflammatory challenge, or placebo. Proinflammatory cytokines (IL-6, TNF-alpha) were collected at baseline and then hourly for 6h. Participants completed self-reports of sickness symptoms ("fatigue"), social disconnection ("I feel disconnected from others"), and depressed mood ("unhappy") hourly. Results revealed that endotoxin led to significant increases (from baseline) in IL-6 and TNF-alpha levels as well as feelings of social disconnection and depressed mood. Moreover, controlling for increases in social disconnection eliminated the relationship between exposure to inflammatory challenge and depressed mood. This study demonstrates that inflammation can have social psychological consequences, which may play a role in cytokine-related depressive symptoms.
Copyright 2009 Elsevier Inc. All rights reserved.
PMID:
20043983
[PubMed - indexed for MEDLINE]
PMCID:
PMC2856755
Free PMC Article
Brain Behav Immun. 2010 May;24(4):558-63. Epub 2010 Jan 4.
Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood.
Eisenberger NI, Inagaki TK, Mashal NM, Irwin MR.
Source
Department of Psychology, University of California, Los Angeles, CA 90095-1563, USA. neisenbe@ucla.edu
Abstract
Although research has established links between feelings of social isolation and inflammation, the direction of these effects is unclear. Based on the role that proinflammatory cytokines play in initiating "sickness behavior," which includes symptoms such as social withdrawal, it is possible that inflammatory processes heighten feelings of 'social disconnection.' Here, we examined whether exposure to an inflammatory challenge increased self-reported feelings of social disconnection. In addition, because both inflammatory processes and feelings of social disconnection contribute to depressive symptoms, we also explored whether increases in feelings of social disconnection played a role in the link between inflammation and depressed mood. Participants were randomly assigned to either receive endotoxin, an inflammatory challenge, or placebo. Proinflammatory cytokines (IL-6, TNF-alpha) were collected at baseline and then hourly for 6h. Participants completed self-reports of sickness symptoms ("fatigue"), social disconnection ("I feel disconnected from others"), and depressed mood ("unhappy") hourly. Results revealed that endotoxin led to significant increases (from baseline) in IL-6 and TNF-alpha levels as well as feelings of social disconnection and depressed mood. Moreover, controlling for increases in social disconnection eliminated the relationship between exposure to inflammatory challenge and depressed mood. This study demonstrates that inflammation can have social psychological consequences, which may play a role in cytokine-related depressive symptoms.
Copyright 2009 Elsevier Inc. All rights reserved.
PMID:
20043983
[PubMed - indexed for MEDLINE]
PMCID:
PMC2856755
Free PMC Article
Depression and Alzheimer's disease: neurobiological links and common pharmacological targets.
Eur J Pharmacol. 2010 Jan 10;626(1):64-71. Epub 2009 Oct 18.
Depression and Alzheimer's disease: neurobiological links and common pharmacological targets.
Caraci F, Copani A, Nicoletti F, Drago F.
Source
Department of Pharmaceutical Sciences, University of Catania, 95125, Catania, Italy.
Abstract
Depression is one of the most prevalent and life-threatening forms of mental illnesses, whereas Alzheimer's disease is a neurodegenerative disorder that affects more than 37 million people worldwide. Recent evidence suggests a strong relationship between depression and Alzheimer's disease. A lifetime history of major depression has been considered as a risk factor for later development of Alzheimer's disease. The presence of depressive symptoms can affect the conversion of mild cognitive impairment into Alzheimer's disease. Neuritic plaques and neurofibrillary tangles, the two major hallmarks of Alzheimer's disease brain, are more pronounced in the brains of Alzheimer's disease patients with comorbid depression as compared with Alzheimer's disease patients without depression. On the other hand, neurodegenerative phenomena have been observed in different brain regions of patients with a history of depression. Recent evidence suggests that molecular mechanisms and cascades that underlie the pathogenesis of major depression, such as chronic inflammation and hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis, are also involved in the pathogenesis of Alzheimer's disease. In particular, a specific impairment in the signaling of some neurotrophins such as transforming-growth-factor beta1 (TGF-beta1) and brain-derived neurotrophic factor (BDNF) has been observed both in depression and Alzheimer's disease. In the present review we will examine the evidence on the common molecular pathways between depression and Alzheimer's disease and we will discuss these pathways as new pharmacological targets for the treatment of both major depression and Alzheimer's disease.
PMID:
19837057
[PubMed - indexed for MEDLINE]
Depression and Alzheimer's disease: neurobiological links and common pharmacological targets.
Caraci F, Copani A, Nicoletti F, Drago F.
Source
Department of Pharmaceutical Sciences, University of Catania, 95125, Catania, Italy.
Abstract
Depression is one of the most prevalent and life-threatening forms of mental illnesses, whereas Alzheimer's disease is a neurodegenerative disorder that affects more than 37 million people worldwide. Recent evidence suggests a strong relationship between depression and Alzheimer's disease. A lifetime history of major depression has been considered as a risk factor for later development of Alzheimer's disease. The presence of depressive symptoms can affect the conversion of mild cognitive impairment into Alzheimer's disease. Neuritic plaques and neurofibrillary tangles, the two major hallmarks of Alzheimer's disease brain, are more pronounced in the brains of Alzheimer's disease patients with comorbid depression as compared with Alzheimer's disease patients without depression. On the other hand, neurodegenerative phenomena have been observed in different brain regions of patients with a history of depression. Recent evidence suggests that molecular mechanisms and cascades that underlie the pathogenesis of major depression, such as chronic inflammation and hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis, are also involved in the pathogenesis of Alzheimer's disease. In particular, a specific impairment in the signaling of some neurotrophins such as transforming-growth-factor beta1 (TGF-beta1) and brain-derived neurotrophic factor (BDNF) has been observed both in depression and Alzheimer's disease. In the present review we will examine the evidence on the common molecular pathways between depression and Alzheimer's disease and we will discuss these pathways as new pharmacological targets for the treatment of both major depression and Alzheimer's disease.
PMID:
19837057
[PubMed - indexed for MEDLINE]
Neurobiology of depression, fibromyalgia and neuropathic pain.
Front Biosci. 2009 Jun 1;14:5291-338.
Neurobiology of depression, fibromyalgia and neuropathic pain.
Maletic V, Raison CL.
Source
University of South Carolina, School of Medicine, Department of Neuropsychiatry and Behavioral Sciences, Columbia, SC, USA. vmaletic@bellsouth.net
Abstract
This article synthesizes recent data suggesting that the high rates of comorbidity observed between major depression, fibromyalgia and neuropathic pain likely result from the fact that these disorders share multiple biological and environmental underpinnings. This perspective suggests that these biologically complex conditions result from similar genetic vulnerabilities interacting with environmental adversity. Shared genetic determinants include poorly functional alleles regulating monoaminergic, glutamatergic, neurotrophic, opioid and inflammatory cytokine signaling. Chief among environmental risk factors are psychosocial stress and illness, both of which promote, in vulnerable individuals, relative resistance to glucocorticoids, increased sympathetic/decreased parasympathetic activity and increased production and release of proinflamnmatory mediators. Dysregulation of stress/inflammatory pathways promotes alterations in brain circuitry that modulates mood, pain and the stress response. Over time, these functional changes likely promote disruptions in neurotrophic support and disturbances of glia-neuronal communication. These changes, in turn, have been associated with the related processes of central sensitization in pain disorders and "kindling" in depression, both of which may account for the progressive and self-perpetuating nature of these disorders, especially when inadequately treated.
PMID:
19482616
[PubMed - indexed for MEDLINE]
Free full text
Neurobiology of depression, fibromyalgia and neuropathic pain.
Maletic V, Raison CL.
Source
University of South Carolina, School of Medicine, Department of Neuropsychiatry and Behavioral Sciences, Columbia, SC, USA. vmaletic@bellsouth.net
Abstract
This article synthesizes recent data suggesting that the high rates of comorbidity observed between major depression, fibromyalgia and neuropathic pain likely result from the fact that these disorders share multiple biological and environmental underpinnings. This perspective suggests that these biologically complex conditions result from similar genetic vulnerabilities interacting with environmental adversity. Shared genetic determinants include poorly functional alleles regulating monoaminergic, glutamatergic, neurotrophic, opioid and inflammatory cytokine signaling. Chief among environmental risk factors are psychosocial stress and illness, both of which promote, in vulnerable individuals, relative resistance to glucocorticoids, increased sympathetic/decreased parasympathetic activity and increased production and release of proinflamnmatory mediators. Dysregulation of stress/inflammatory pathways promotes alterations in brain circuitry that modulates mood, pain and the stress response. Over time, these functional changes likely promote disruptions in neurotrophic support and disturbances of glia-neuronal communication. These changes, in turn, have been associated with the related processes of central sensitization in pain disorders and "kindling" in depression, both of which may account for the progressive and self-perpetuating nature of these disorders, especially when inadequately treated.
PMID:
19482616
[PubMed - indexed for MEDLINE]
Free full text
Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity.
Biol Psychiatry. 2009 Sep 1;66(5):407-14. Epub 2009 May 7.
Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity.
Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD.
Source
Wellcome Trust, Centre for Neuroimaging, Institute of Cognitive Neuroscience, UCL, 17 Queen Square, London WC1N 3AR, UK. n.harrison@fil.ion.ucl.ac.uk
Abstract
BACKGROUND:
Inflammatory cytokines are implicated in the pathophysiology of depression. In rodents, systemically administered inflammatory cytokines induce depression-like behavior. Similarly in humans, therapeutic interferon-alpha induces clinical depression in a third of patients. Conversely, patients with depression also show elevated pro-inflammatory cytokines.
OBJECTIVES:
To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing.
METHODS:
In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Mood questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed an implicit emotional face perception task during functional magnetic resonance imaging. Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression.
RESULTS:
Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours. Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex (sACC) (a region implicated in the etiology of depression) during emotional face processing. Furthermore, inflammation-associated mood change reduced connectivity of sACC to amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus, which was modulated by peripheral interleukin-6.
CONCLUSIONS:
Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli. Peripheral cytokines modulate this mood-dependent sACC connectivity, suggesting a common pathophysiological basis for major depressive disorder and sickness-associated mood change and depression.
PMID:
19423079
[PubMed - indexed for MEDLINE]
PMCID:
PMC2885494
Free PMC Article
Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity.
Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD.
Source
Wellcome Trust, Centre for Neuroimaging, Institute of Cognitive Neuroscience, UCL, 17 Queen Square, London WC1N 3AR, UK. n.harrison@fil.ion.ucl.ac.uk
Abstract
BACKGROUND:
Inflammatory cytokines are implicated in the pathophysiology of depression. In rodents, systemically administered inflammatory cytokines induce depression-like behavior. Similarly in humans, therapeutic interferon-alpha induces clinical depression in a third of patients. Conversely, patients with depression also show elevated pro-inflammatory cytokines.
OBJECTIVES:
To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing.
METHODS:
In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Mood questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed an implicit emotional face perception task during functional magnetic resonance imaging. Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression.
RESULTS:
Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours. Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex (sACC) (a region implicated in the etiology of depression) during emotional face processing. Furthermore, inflammation-associated mood change reduced connectivity of sACC to amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus, which was modulated by peripheral interleukin-6.
CONCLUSIONS:
Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli. Peripheral cytokines modulate this mood-dependent sACC connectivity, suggesting a common pathophysiological basis for major depressive disorder and sickness-associated mood change and depression.
PMID:
19423079
[PubMed - indexed for MEDLINE]
PMCID:
PMC2885494
Free PMC Article
Allergy: a risk factor for suicide?
Curr Treat Options Neurol. 2008 Sep;10(5):363-76.
Allergy: a risk factor for suicide?
Postolache TT, Komarow H, Tonelli LH.
Source
Teodor T. Postolache, MD Mood and Anxiety Program (MAP), Department of Psychiatry, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF Building Room 930, Baltimore, MD 21201, USA. tpostolache@psych.umaryland.edu.
Abstract
The rates of depression, anxiety, and sleep disturbance (suicide risk factors) are greater in patients with allergic rhinitis than in the general population. The rate of allergy is also greater in patients with depression. Preliminary data suggest that patients with a history of allergy may have an increased rate of suicide. Clinicians should actively inquire to diagnose allergy in patients with depression and depression in patients with allergy. Spring peaks of suicide are highly replicated, but their origin is poorly understood. Preliminary epidemiologic data suggest that seasonal spring peaks in aeroallergens are associated with seasonal spring peaks in suicide. Our research in Brown Norway rats demonstrates that sensitization and exposure to aeroallergens induces anxiety-like and aggressive behaviors as well as allergy-related helper T-cell type 2 (Th2) cytokine gene expression in the prefrontal cortex. Thus, it is possible that sensitization and exposure to aeroallergens, which peak in spring, may be conducive to seasonal exacerbation of suicide risk factors such as anxiety, depression, hostility/aggression, and sleep disturbance. Connecting allergy with suicide and suicide risk factors adds to previous neurologic literature connecting allergy with migraines and seizure disorders. Our recent report of Th2 (allergy-mediating) cytokine expression in the orbitofrontal cortex of suicide victims should lead to future studies to test the hypothesis that mediators of allergic inflammation in the nasal cavities may result in Th2 cytokine expression in the brain, influencing affect and behavioral modulation. Certain medications used to treat allergy can exacerbate suicide risk factors, potentially worsening suicide risk and even triggering suicide. Systemic (but not topical) corticosteroids have been associated with manic and depressive episodes and mixed mood states. Recently, the US Food and Drug Administration started investigating the possibility that montelukast may trigger suicide. Although this association requires further exploration and confirmation, clinicians should err on the side of caution, inquiring about past suicide attempts; hopelessness; reasons for living; and suicidal ideation, intent, or plan; and referring the patient to a mental health professional for evaluation if appropriate.
PMID:
18782509
[PubMed - in process]
PMCID:
PMC2592251
Free PMC Article
Allergy: a risk factor for suicide?
Postolache TT, Komarow H, Tonelli LH.
Source
Teodor T. Postolache, MD Mood and Anxiety Program (MAP), Department of Psychiatry, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF Building Room 930, Baltimore, MD 21201, USA. tpostolache@psych.umaryland.edu.
Abstract
The rates of depression, anxiety, and sleep disturbance (suicide risk factors) are greater in patients with allergic rhinitis than in the general population. The rate of allergy is also greater in patients with depression. Preliminary data suggest that patients with a history of allergy may have an increased rate of suicide. Clinicians should actively inquire to diagnose allergy in patients with depression and depression in patients with allergy. Spring peaks of suicide are highly replicated, but their origin is poorly understood. Preliminary epidemiologic data suggest that seasonal spring peaks in aeroallergens are associated with seasonal spring peaks in suicide. Our research in Brown Norway rats demonstrates that sensitization and exposure to aeroallergens induces anxiety-like and aggressive behaviors as well as allergy-related helper T-cell type 2 (Th2) cytokine gene expression in the prefrontal cortex. Thus, it is possible that sensitization and exposure to aeroallergens, which peak in spring, may be conducive to seasonal exacerbation of suicide risk factors such as anxiety, depression, hostility/aggression, and sleep disturbance. Connecting allergy with suicide and suicide risk factors adds to previous neurologic literature connecting allergy with migraines and seizure disorders. Our recent report of Th2 (allergy-mediating) cytokine expression in the orbitofrontal cortex of suicide victims should lead to future studies to test the hypothesis that mediators of allergic inflammation in the nasal cavities may result in Th2 cytokine expression in the brain, influencing affect and behavioral modulation. Certain medications used to treat allergy can exacerbate suicide risk factors, potentially worsening suicide risk and even triggering suicide. Systemic (but not topical) corticosteroids have been associated with manic and depressive episodes and mixed mood states. Recently, the US Food and Drug Administration started investigating the possibility that montelukast may trigger suicide. Although this association requires further exploration and confirmation, clinicians should err on the side of caution, inquiring about past suicide attempts; hopelessness; reasons for living; and suicidal ideation, intent, or plan; and referring the patient to a mental health professional for evaluation if appropriate.
PMID:
18782509
[PubMed - in process]
PMCID:
PMC2592251
Free PMC Article
Inflammatory markers and negative mood symptoms following exercise withdrawal.
Brain Behav Immun. 2008 Nov;22(8):1190-6. Epub 2008 Jul 10.
Inflammatory markers and negative mood symptoms following exercise withdrawal.
Kop WJ, Weinstein AA, Deuster PA, Whittaker KS, Tracy RP.
Source
Department of Medicine, University of Maryland Medical Center, 22 South Greene Street, S3B04, Baltimore, MD 21201, USA. wkop@medicine.umaryland.edu
Abstract
OBJECTIVE:
Physical inactivity is associated with elevated inflammatory markers, but little is known about the time trajectories of reduced physical activity and inflammatory markers. Changes in inflammatory markers in response to withholding regular aerobic exercise were prospectively examined and correlated with increased negative mood symptoms and fatigue that accompany exercise withdrawal.
METHODS:
Participants with regular exercise habits (N=40, mean age of 31.3+/-7.5 years, 55% women) were randomized to aerobic exercise withdrawal or to continue regular exercise for 2 weeks. Protocol adherence was documented using ambulatory actigraphy. Inflammatory markers (interleukin-6, C-reactive protein, fibrinogen and soluble intercellular adhesion molecule-1) were assessed at weekly intervals. Negative mood was measured with the Profile of Mood States (POMS) and the Beck Depression Inventory (BDI), and fatigue with the Multidimensional Fatigue Inventory (MFI). Autonomic nervous system activity was examined using heart rate variability-based indices.
RESULTS:
Changes in inflammatory markers did not differ between exercise withdrawal and control groups (multivariate p interaction=0.25). Exercise withdrawal resulted in increased negative mood symptoms and fatigue from baseline to day 14 compared to controls (p DeltaPOMS=0.008, p DeltaBDI=0.002; p DeltaMFI=0.003), but these responses were not associated with changes in inflammatory markers (p-values >0.10). Inflammatory markers were also not correlated with autonomic nervous system dysregulation (p-values >0.10).
CONCLUSION:
Inflammatory markers were not increased following 2 weeks of exercise withdrawal. Negative mood symptoms and fatigue were not accounted for by changes in inflammatory markers. Compensatory feedback mechanisms may operate among healthy individuals to promote resilience from the effects of reduced exercise.
PMID:
18619772
[PubMed - indexed for MEDLINE]
Inflammatory markers and negative mood symptoms following exercise withdrawal.
Kop WJ, Weinstein AA, Deuster PA, Whittaker KS, Tracy RP.
Source
Department of Medicine, University of Maryland Medical Center, 22 South Greene Street, S3B04, Baltimore, MD 21201, USA. wkop@medicine.umaryland.edu
Abstract
OBJECTIVE:
Physical inactivity is associated with elevated inflammatory markers, but little is known about the time trajectories of reduced physical activity and inflammatory markers. Changes in inflammatory markers in response to withholding regular aerobic exercise were prospectively examined and correlated with increased negative mood symptoms and fatigue that accompany exercise withdrawal.
METHODS:
Participants with regular exercise habits (N=40, mean age of 31.3+/-7.5 years, 55% women) were randomized to aerobic exercise withdrawal or to continue regular exercise for 2 weeks. Protocol adherence was documented using ambulatory actigraphy. Inflammatory markers (interleukin-6, C-reactive protein, fibrinogen and soluble intercellular adhesion molecule-1) were assessed at weekly intervals. Negative mood was measured with the Profile of Mood States (POMS) and the Beck Depression Inventory (BDI), and fatigue with the Multidimensional Fatigue Inventory (MFI). Autonomic nervous system activity was examined using heart rate variability-based indices.
RESULTS:
Changes in inflammatory markers did not differ between exercise withdrawal and control groups (multivariate p interaction=0.25). Exercise withdrawal resulted in increased negative mood symptoms and fatigue from baseline to day 14 compared to controls (p DeltaPOMS=0.008, p DeltaBDI=0.002; p DeltaMFI=0.003), but these responses were not associated with changes in inflammatory markers (p-values >0.10). Inflammatory markers were also not correlated with autonomic nervous system dysregulation (p-values >0.10).
CONCLUSION:
Inflammatory markers were not increased following 2 weeks of exercise withdrawal. Negative mood symptoms and fatigue were not accounted for by changes in inflammatory markers. Compensatory feedback mechanisms may operate among healthy individuals to promote resilience from the effects of reduced exercise.
PMID:
18619772
[PubMed - indexed for MEDLINE]
Depressive symptoms and metabolic syndrome: is inflammation the underlying link?
Biol Psychiatry. 2008 Nov 15;64(10):896-900. Epub 2008 Jul 2.
Depressive symptoms and metabolic syndrome: is inflammation the underlying link?
Capuron L, Su S, Miller AH, Bremner JD, Goldberg J, Vogt GJ, Maisano C, Jones L, Murrah NV, Vaccarino V.
Source
Laboratory of Psychoneuroimmunology, Nutrition and Genetics, INRA-University Victor Segalen Bordeaux 2, Bordeaux, France. lucile.capuron@bordeaux.inra.fr
Abstract
BACKGROUND:
Behavioral alterations, including depression, are frequent in individuals with the metabolic syndrome (MetS). Recent findings suggest that chronic activation of innate immunity might be involved. The objective of this study was to examine the relationship between MetS and depressive symptoms and to elucidate the involvement of inflammation in this relationship.
METHODS:
Participants were 323 male twins, with and without MetS and free of symptomatic cardiovascular disease, drawn from the Vietnam Era Twin Registry. Depressive symptoms were measured with the Beck Depression Inventory (BDI). Inflammatory status was assessed using C-reactive protein (CRP) and interleukin-6 (IL-6); twins with both CRP and IL-6 levels above the median were classified as having an elevated inflammatory status. Factor analysis was performed on individual BDI items to extract specific symptom dimensions (neurovegetative, mood, affective-cognitive).
RESULTS:
Subjects with MetS had more depressive symptoms than those without. Depressive symptoms with neurovegetative features were more common and more robustly associated with MetS. Both the BDI total score and each symptom subscore were associated with inflammatory biomarkers. After adjusting for age, education, and smoking status, the MetS was significantly associated with the BDI total score and the neurovegetative score. After further adjusting for inflammation, the coefficient for MetS decreased somewhat but remained statistically significant for the BDI neurovegetative subscore. When controlling for the MetS, inflammation remained significantly associated with the BDI mood subscore.
CONCLUSIONS:
The MetS is associated with higher depressive symptomatology characterized primarily by neurovegetative features. Inflammation is one determinant of depressive symptoms in individuals with MetS.
PMID:
18597739
[PubMed - indexed for MEDLINE]
PMCID:
PMC2621309
Free PMC Article
Depressive symptoms and metabolic syndrome: is inflammation the underlying link?
Capuron L, Su S, Miller AH, Bremner JD, Goldberg J, Vogt GJ, Maisano C, Jones L, Murrah NV, Vaccarino V.
Source
Laboratory of Psychoneuroimmunology, Nutrition and Genetics, INRA-University Victor Segalen Bordeaux 2, Bordeaux, France. lucile.capuron@bordeaux.inra.fr
Abstract
BACKGROUND:
Behavioral alterations, including depression, are frequent in individuals with the metabolic syndrome (MetS). Recent findings suggest that chronic activation of innate immunity might be involved. The objective of this study was to examine the relationship between MetS and depressive symptoms and to elucidate the involvement of inflammation in this relationship.
METHODS:
Participants were 323 male twins, with and without MetS and free of symptomatic cardiovascular disease, drawn from the Vietnam Era Twin Registry. Depressive symptoms were measured with the Beck Depression Inventory (BDI). Inflammatory status was assessed using C-reactive protein (CRP) and interleukin-6 (IL-6); twins with both CRP and IL-6 levels above the median were classified as having an elevated inflammatory status. Factor analysis was performed on individual BDI items to extract specific symptom dimensions (neurovegetative, mood, affective-cognitive).
RESULTS:
Subjects with MetS had more depressive symptoms than those without. Depressive symptoms with neurovegetative features were more common and more robustly associated with MetS. Both the BDI total score and each symptom subscore were associated with inflammatory biomarkers. After adjusting for age, education, and smoking status, the MetS was significantly associated with the BDI total score and the neurovegetative score. After further adjusting for inflammation, the coefficient for MetS decreased somewhat but remained statistically significant for the BDI neurovegetative subscore. When controlling for the MetS, inflammation remained significantly associated with the BDI mood subscore.
CONCLUSIONS:
The MetS is associated with higher depressive symptomatology characterized primarily by neurovegetative features. Inflammation is one determinant of depressive symptoms in individuals with MetS.
PMID:
18597739
[PubMed - indexed for MEDLINE]
PMCID:
PMC2621309
Free PMC Article
Relationship between inflammation and cognitive function in obstructive sleep apnea.
Sleep Breath. 2009 Mar;13(1):35-41. Epub 2008 Jun 13.
Relationship between inflammation and cognitive function in obstructive sleep apnea.
Haensel A, Bardwell WA, Mills PJ, Loredo JS, Ancoli-Israel S, Morgan EE, Heaton RK, Dimsdale JE.
Source
Department of General Internal Medicine, University Hospital Berne, Berne, Switzerland.
Abstract
OBJECTIVES:
Obstructive sleep apnea (OSA) can have adverse effects on cognitive functioning, mood, and cardiovascular functioning. OSA brings with it disturbances in sleep architecture, oxygenation, sympathetic nervous system function, and inflammatory processes. It is not clear which of these mechanisms is linked to the decrease in cognitive functioning. This study examined the effect of inflammatory parameters on cognitive dysfunction.
MATERIALS AND METHODS:
Thirty-nine patients with untreated sleep apnea were evaluated by polysomnography and completed a battery of neuropsychological tests. After the first night of evaluation in the sleep laboratory, blood samples were taken for analysis of interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1).
RESULTS:
sTNF-R1 significantly correlated with cognitive dysfunction. In hierarchical linear regression analysis, measures of obstructive sleep apnea severity explained 5.5% of the variance in cognitive dysfunction (n.s.). After including sTNF-R1, percentage of variance explained by the full model increased more than threefold to 19.6% (F = 2.84, df = 3, 36, p = 0.05). Only sTNF-R1 had a significant individual relationship with cognitive dysfunction (beta = 0.376 t = 2.48, p = 0.02).
CONCLUSIONS:
sTNF-R1 as a marker of chronic inflammation may be associated with diminished neuropsychological functioning in patients with OSA.
PMID:
18551328
[PubMed - indexed for MEDLINE]
PMCID:
PMC3175694
Free PMC Article
Relationship between inflammation and cognitive function in obstructive sleep apnea.
Haensel A, Bardwell WA, Mills PJ, Loredo JS, Ancoli-Israel S, Morgan EE, Heaton RK, Dimsdale JE.
Source
Department of General Internal Medicine, University Hospital Berne, Berne, Switzerland.
Abstract
OBJECTIVES:
Obstructive sleep apnea (OSA) can have adverse effects on cognitive functioning, mood, and cardiovascular functioning. OSA brings with it disturbances in sleep architecture, oxygenation, sympathetic nervous system function, and inflammatory processes. It is not clear which of these mechanisms is linked to the decrease in cognitive functioning. This study examined the effect of inflammatory parameters on cognitive dysfunction.
MATERIALS AND METHODS:
Thirty-nine patients with untreated sleep apnea were evaluated by polysomnography and completed a battery of neuropsychological tests. After the first night of evaluation in the sleep laboratory, blood samples were taken for analysis of interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1).
RESULTS:
sTNF-R1 significantly correlated with cognitive dysfunction. In hierarchical linear regression analysis, measures of obstructive sleep apnea severity explained 5.5% of the variance in cognitive dysfunction (n.s.). After including sTNF-R1, percentage of variance explained by the full model increased more than threefold to 19.6% (F = 2.84, df = 3, 36, p = 0.05). Only sTNF-R1 had a significant individual relationship with cognitive dysfunction (beta = 0.376 t = 2.48, p = 0.02).
CONCLUSIONS:
sTNF-R1 as a marker of chronic inflammation may be associated with diminished neuropsychological functioning in patients with OSA.
PMID:
18551328
[PubMed - indexed for MEDLINE]
PMCID:
PMC3175694
Free PMC Article
Predictors of fatigue in obstructive sleep apnea.
Sleep Breath. 2008 Nov;12(4):397-9. Epub 2008 May 31.
Predictors of fatigue in obstructive sleep apnea.
Mills PJ, Kim JH, Bardwell W, Hong S, Dimsdale JE.
Source
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. pmills@ucsd.edu
Abstract
OBJECTIVE:
The objective of this study was to determine potential inflammatory predictors of fatigue in obstructive sleep apnea (OSA).
MATERIALS AND METHODS:
Fifty-six women and men untreated OSA patients had their sleep monitored with polysomnography. Fatigue was assessed by the Multidimensional Fatigue Symptom Inventory-Short Form. Depressed mood was assessed by the Center for Epidemiologic Studies-Depression Scale. Blood was drawn to assess circulating levels of Interleukin-6 (IL-6) and soluble tumor necrosis factor receptor I (sTNF-RI). Age, gender, body mass index (BMI), blood pressure, OSA severity, depressed mood, and inflammatory biomarkers were entered into a hierarchical multiple linear regression analysis predicting self-reported fatigue.
RESULTS:
Approximately 42% of the patients reported significant amounts of fatigue. Higher BMI (p = 0.014), greater depressed mood (p = 0.004), and higher sTNF-RI levels (p = 0.033) were independent predictors of fatigue in the final model (full model R2 = .571; p = .003). Age, gender, blood pressure and apnea severity were unrelated to fatigue.
CONCLUSION:
The findings suggest that in addition to depressed mood, fatigue in OSA may be associated with increased body weight and elevated levels of the proinflammatory cytokine receptor sTNF-RI. The findings support a linkage between the widely reported fatigue in OSA and a sleep-related component of inflammation.
PMID:
18516635
[PubMed - indexed for MEDLINE]
PMCID:
PMC2633300
Free PMC Article
Predictors of fatigue in obstructive sleep apnea.
Mills PJ, Kim JH, Bardwell W, Hong S, Dimsdale JE.
Source
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. pmills@ucsd.edu
Abstract
OBJECTIVE:
The objective of this study was to determine potential inflammatory predictors of fatigue in obstructive sleep apnea (OSA).
MATERIALS AND METHODS:
Fifty-six women and men untreated OSA patients had their sleep monitored with polysomnography. Fatigue was assessed by the Multidimensional Fatigue Symptom Inventory-Short Form. Depressed mood was assessed by the Center for Epidemiologic Studies-Depression Scale. Blood was drawn to assess circulating levels of Interleukin-6 (IL-6) and soluble tumor necrosis factor receptor I (sTNF-RI). Age, gender, body mass index (BMI), blood pressure, OSA severity, depressed mood, and inflammatory biomarkers were entered into a hierarchical multiple linear regression analysis predicting self-reported fatigue.
RESULTS:
Approximately 42% of the patients reported significant amounts of fatigue. Higher BMI (p = 0.014), greater depressed mood (p = 0.004), and higher sTNF-RI levels (p = 0.033) were independent predictors of fatigue in the final model (full model R2 = .571; p = .003). Age, gender, blood pressure and apnea severity were unrelated to fatigue.
CONCLUSION:
The findings suggest that in addition to depressed mood, fatigue in OSA may be associated with increased body weight and elevated levels of the proinflammatory cytokine receptor sTNF-RI. The findings support a linkage between the widely reported fatigue in OSA and a sleep-related component of inflammation.
PMID:
18516635
[PubMed - indexed for MEDLINE]
PMCID:
PMC2633300
Free PMC Article
Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.
Altern Med Rev. 2007 Sep;12(3):207-27.
Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.
Kidd PM.
Source
University of California, Berkeley, California, USA.
Abstract
The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.
PMID:
18072818
[PubMed - indexed for MEDLINE]
Free full text
Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.
Kidd PM.
Source
University of California, Berkeley, California, USA.
Abstract
The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.
PMID:
18072818
[PubMed - indexed for MEDLINE]
Free full text
Substance P at the nexus of mind and body in chronic inflammation and affective disorders.
Reductionistic but still of interest.
Psychol Bull. 2007 Nov;133(6):1007-37.
Substance P at the nexus of mind and body in chronic inflammation and affective disorders.
Rosenkranz MA.
Source
Department of Psychology, University of Wisconsin-Madison, WI 53705, USA. marosenk@wisc.edu
Abstract
For decades, research has demonstrated that chronic diseases characterized by dysregulation of inflammation are particularly susceptible to exacerbation by stress and emotion. Likewise, rates of depression and anxiety are overrepresented in individuals suffering from chronic inflammatory disease. In recent years, substance P has been implicated in both the pathophysiology of inflammatory disease and the pathophysiology of depression and anxiety by 2 parallel fields of study. This review integrates the literature from these 2 parallel fields and examines the possibility that substance P dysregulation may be a point of convergence underlying the overlap of chronic inflammatory disease and mood and anxiety disorders. First, the involvement of substance P in peripheral inflammation and in the immune events associated with chronic inflammatory disease is discussed, with a focus on inflammatory bowel disease and asthma. Next, the function of substance P in the communication of peripheral inflammation to the brain is considered. Finally, to complete the bidirectional loop of brain-immune interactions, substance P expression in anxiety and depression as well as its potential role in the neural regulation of peripheral inflammation is reviewed.
PMID:
17967092
[PubMed - indexed for MEDLINE]
Psychol Bull. 2007 Nov;133(6):1007-37.
Substance P at the nexus of mind and body in chronic inflammation and affective disorders.
Rosenkranz MA.
Source
Department of Psychology, University of Wisconsin-Madison, WI 53705, USA. marosenk@wisc.edu
Abstract
For decades, research has demonstrated that chronic diseases characterized by dysregulation of inflammation are particularly susceptible to exacerbation by stress and emotion. Likewise, rates of depression and anxiety are overrepresented in individuals suffering from chronic inflammatory disease. In recent years, substance P has been implicated in both the pathophysiology of inflammatory disease and the pathophysiology of depression and anxiety by 2 parallel fields of study. This review integrates the literature from these 2 parallel fields and examines the possibility that substance P dysregulation may be a point of convergence underlying the overlap of chronic inflammatory disease and mood and anxiety disorders. First, the involvement of substance P in peripheral inflammation and in the immune events associated with chronic inflammatory disease is discussed, with a focus on inflammatory bowel disease and asthma. Next, the function of substance P in the communication of peripheral inflammation to the brain is considered. Finally, to complete the bidirectional loop of brain-immune interactions, substance P expression in anxiety and depression as well as its potential role in the neural regulation of peripheral inflammation is reviewed.
PMID:
17967092
[PubMed - indexed for MEDLINE]
Mood-worsening with high-pollen-counts and seasonality: a preliminary report.
J Affect Disord. 2007 Aug;101(1-3):269-74. Epub 2007 Jan 12.
Mood-worsening with high-pollen-counts and seasonality: a preliminary report.
Guzman A, Tonelli LH, Roberts D, Stiller JW, Jackson MA, Soriano JJ, Yousufi S, Rohan KJ, Komarow H, Postolache TT.
Source
Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. aguzman@psych.umaryland.edu
Abstract
BACKGROUND:
Because aeroallergens produce inflammation in the respiratory airways, and inflammation triggers depression in vulnerable individuals, we hypothesized that mood sensitivity to pollen, the most seasonal aeroallergen, will be associated with a greater seasonality of mood. Since pollen is absent during winter, we specifically predicted that mood sensitivity to tree pollen will predict non-winter SAD but not winter SAD.
METHODS:
A convenience sample of African and African American college students who lived in the Washington DC metropolitan area for at least the past 3 years completed the Seasonal Pattern Assessment Questionnaire (SPAQ), from which the Global Seasonality Score (GSS) was calculated, a diagnosis of cumulative SAD (syndromal or subsyndromal SAD) was derived, a seasonal pattern (winter vs non-winter) identified, and self-reported mood changes during high pollen counts obtained. A Mann-Whitney test was used to compare GSS between participants with vs without mood worsening during high pollen counts. The capability of mood worsening with high pollen counts, gender, ethnicity, and age to predict non-winter SAD was analyzed with logistic regressions.
RESULTS:
GSS was greater (z=5.232, p<0.001) in those who reported mood worsening with high pollen counts. Mood sensitivity to pollen predicted non-winter SAD (p=0.017), but not winter SAD.
LIMITATIONS:
The SPAQ is not a definitive tool to assess seasonality, and self-reported mood worsening with high pollen counts relies on recollection. No direct measures of depression scores or pollen counts were collected. The non-winter SAD concept has not been previously established.
CONCLUSIONS:
Our study, which should be considered preliminary in light of its limitations, suggests that self-reported mood-worsening with high pollen count is associated with a greater seasonality of mood, and predicts SAD of non-winter type.
PMID:
17222915
[PubMed - indexed for MEDLINE]
PMCID:
PMC1949487
Free PMC Article
Mood-worsening with high-pollen-counts and seasonality: a preliminary report.
Guzman A, Tonelli LH, Roberts D, Stiller JW, Jackson MA, Soriano JJ, Yousufi S, Rohan KJ, Komarow H, Postolache TT.
Source
Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. aguzman@psych.umaryland.edu
Abstract
BACKGROUND:
Because aeroallergens produce inflammation in the respiratory airways, and inflammation triggers depression in vulnerable individuals, we hypothesized that mood sensitivity to pollen, the most seasonal aeroallergen, will be associated with a greater seasonality of mood. Since pollen is absent during winter, we specifically predicted that mood sensitivity to tree pollen will predict non-winter SAD but not winter SAD.
METHODS:
A convenience sample of African and African American college students who lived in the Washington DC metropolitan area for at least the past 3 years completed the Seasonal Pattern Assessment Questionnaire (SPAQ), from which the Global Seasonality Score (GSS) was calculated, a diagnosis of cumulative SAD (syndromal or subsyndromal SAD) was derived, a seasonal pattern (winter vs non-winter) identified, and self-reported mood changes during high pollen counts obtained. A Mann-Whitney test was used to compare GSS between participants with vs without mood worsening during high pollen counts. The capability of mood worsening with high pollen counts, gender, ethnicity, and age to predict non-winter SAD was analyzed with logistic regressions.
RESULTS:
GSS was greater (z=5.232, p<0.001) in those who reported mood worsening with high pollen counts. Mood sensitivity to pollen predicted non-winter SAD (p=0.017), but not winter SAD.
LIMITATIONS:
The SPAQ is not a definitive tool to assess seasonality, and self-reported mood worsening with high pollen counts relies on recollection. No direct measures of depression scores or pollen counts were collected. The non-winter SAD concept has not been previously established.
CONCLUSIONS:
Our study, which should be considered preliminary in light of its limitations, suggests that self-reported mood-worsening with high pollen count is associated with a greater seasonality of mood, and predicts SAD of non-winter type.
PMID:
17222915
[PubMed - indexed for MEDLINE]
PMCID:
PMC1949487
Free PMC Article
A study on symptom profiles of late-life depression: the influence of vascular, degenerative and inflammatory risk-indicators. Naarding P, Schoevers RA, Janzing JG, Jonker C, Koudstaal PJ, Beekman AT. Source
J Affect Disord. 2005 Oct;88(2):155-62.
A study on symptom profiles of late-life depression: the influence of vascular, degenerative and inflammatory risk-indicators.
Naarding P, Schoevers RA, Janzing JG, Jonker C, Koudstaal PJ, Beekman AT.
Source
Spatie, Center for Mental Health, PO box 926, 7300 BD Apeldoorn and Department of Psychiatry, University Medical Center St. Radboud, Nijmegen, The Netherlands. p.naarding@spatie.nl
Abstract
BACKGROUND:
If specific symptom profiles of depressive disorders in the elderly are related to a specific etiology, this could have implications for everyday clinical practice. We hypothesized that a "motivational" profile, with symptoms such as psychomotor change, loss of interest and loss of energy, could clinically separate patients with predominantly vascular or degenerative risk indicators from patients with inflammatory risk indicators.
METHODS:
A total of 4051 subjects participated in a study on mental health problems in community-dwelling elderly. Information on psychiatric symptoms, demographic and medical status, previous history and family history was obtained. We distinguished three subgroups according to predominant somatic risk-indicators; vascular, degenerative and inflammatory groups.
RESULTS:
Motivational symptoms were associated with vascular or degenerative risk-indicators for depression; psychomotor change with both indicators; loss of energy with vascular, though also with the inflammatory indicator, and thinking/concentration disturbance with the degenerative indicator. The so-called mood symptoms of depression, especially thoughts of death, were more strongly related with the inflammatory risk-indicator. Melancholic symptoms like appetite and sleep disturbances were more strongly associated with the inflammatory risk-indicator.
LIMITATIONS:
Etiological classification was not confirmed by additional investigations such as laboratory findings or MRI brain scans.
CONCLUSION:
This study showed that in patients with a late-life depression specific symptoms of the depressive disorder may reflect the predominant underlying pathogenic mechanism.
PMID:
16098601
[PubMed - indexed for MEDLINE]
A study on symptom profiles of late-life depression: the influence of vascular, degenerative and inflammatory risk-indicators.
Naarding P, Schoevers RA, Janzing JG, Jonker C, Koudstaal PJ, Beekman AT.
Source
Spatie, Center for Mental Health, PO box 926, 7300 BD Apeldoorn and Department of Psychiatry, University Medical Center St. Radboud, Nijmegen, The Netherlands. p.naarding@spatie.nl
Abstract
BACKGROUND:
If specific symptom profiles of depressive disorders in the elderly are related to a specific etiology, this could have implications for everyday clinical practice. We hypothesized that a "motivational" profile, with symptoms such as psychomotor change, loss of interest and loss of energy, could clinically separate patients with predominantly vascular or degenerative risk indicators from patients with inflammatory risk indicators.
METHODS:
A total of 4051 subjects participated in a study on mental health problems in community-dwelling elderly. Information on psychiatric symptoms, demographic and medical status, previous history and family history was obtained. We distinguished three subgroups according to predominant somatic risk-indicators; vascular, degenerative and inflammatory groups.
RESULTS:
Motivational symptoms were associated with vascular or degenerative risk-indicators for depression; psychomotor change with both indicators; loss of energy with vascular, though also with the inflammatory indicator, and thinking/concentration disturbance with the degenerative indicator. The so-called mood symptoms of depression, especially thoughts of death, were more strongly related with the inflammatory risk-indicator. Melancholic symptoms like appetite and sleep disturbances were more strongly associated with the inflammatory risk-indicator.
LIMITATIONS:
Etiological classification was not confirmed by additional investigations such as laboratory findings or MRI brain scans.
CONCLUSION:
This study showed that in patients with a late-life depression specific symptoms of the depressive disorder may reflect the predominant underlying pathogenic mechanism.
PMID:
16098601
[PubMed - indexed for MEDLINE]
Effects of seasonal mood changes on seasonal variations in coronary heart disease: role of immune system, infection, and inflammation.
Nice piece by Leo Sher from before the Vitamin D connection was on everyone's mind.
Med Hypotheses. 2001 Jan;56(1):104-6.
Effects of seasonal mood changes on seasonal variations in coronary heart disease: role of immune system, infection, and inflammation.
Sher L.
Abstract
Coronary heart disease shows a winter peak and summer trough in incidence and mortality. A substantial part of a general population experiences seasonal mood changes including winter depression. Many studies demonstrate that depression is associated with increased incidence, morbidity, and mortality of cardiovascular disease. Therefore, the author previously suggested that persons with high levels of seasonality may be at increased risk of developing or worsening of coronary heart disease in the winter. Some psychological factors promote the development of disorders of the cardiovascular system. The same psychological factors decrease immunity and promote infection. There is evidence that the infectious process is involved in the pathogenesis of coronary heart disease. Therefore, the author previously proposed that the development of infection and inflammation in the atherosclerotic plaque may be related to the psychological disorders that suppress the immune system. In this paper, the author suggests that winter depression-induced suppression of the immune system may contribute to the winter increase in incidence and mortality of cardiovascular disease.
PMID:
11133264
[PubMed - indexed for MEDLINE]
Med Hypotheses. 2001 Jan;56(1):104-6.
Effects of seasonal mood changes on seasonal variations in coronary heart disease: role of immune system, infection, and inflammation.
Sher L.
Abstract
Coronary heart disease shows a winter peak and summer trough in incidence and mortality. A substantial part of a general population experiences seasonal mood changes including winter depression. Many studies demonstrate that depression is associated with increased incidence, morbidity, and mortality of cardiovascular disease. Therefore, the author previously suggested that persons with high levels of seasonality may be at increased risk of developing or worsening of coronary heart disease in the winter. Some psychological factors promote the development of disorders of the cardiovascular system. The same psychological factors decrease immunity and promote infection. There is evidence that the infectious process is involved in the pathogenesis of coronary heart disease. Therefore, the author previously proposed that the development of infection and inflammation in the atherosclerotic plaque may be related to the psychological disorders that suppress the immune system. In this paper, the author suggests that winter depression-induced suppression of the immune system may contribute to the winter increase in incidence and mortality of cardiovascular disease.
PMID:
11133264
[PubMed - indexed for MEDLINE]
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