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

Posted on March 3, 2012 by Maurice Preter MD

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]

Posted in Psychiatry/Neurology | Tagged |

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

Posted on March 3, 2012 by Maurice Preter MD

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]

Posted in Aging | Tagged , |

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]

Posted in News | Tagged |

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 |