Psychological and biological mechanisms of cytokine induced depression.

Posted on March 3, 2012 by Maurice Preter MD

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]

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Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.

Posted on March 3, 2012 by Maurice Preter MD

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

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Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.

Posted on March 3, 2012 by Maurice Preter MD

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]

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The relationship between depression, anxiety, and cardiovascular outcomes in patients with acute coronary syndromes.

Posted on March 3, 2012 by Maurice Preter MD

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

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Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.

Posted on March 3, 2012 by Maurice Preter MD

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

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