Alcoholism and inflammation: neuroimmunology of behavioral and mood disorders.

Posted on March 3, 2012 by Maurice Preter MD

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]

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Immune activation by casein dietary antigens in bipolar disorder.

Posted on March 3, 2012 by Maurice Preter MD

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]

Posted in Psychiatry/Neurology | Tagged , |

Overnight changes of immune parameters and catecholamines are associated with mood and stress.

Posted on March 3, 2012 by Maurice Preter MD

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

Posted in Psychiatry/Neurology |

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

Free PMC Article

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