Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood.

Posted on March 3, 2012 by Maurice Preter MD

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

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Depression and Alzheimer’s disease: neurobiological links and common pharmacological targets.

Posted on March 3, 2012 by Maurice Preter MD

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 1 (TGF-1) 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]

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Neurobiology of depression, fibromyalgia and neuropathic pain.

Posted on March 3, 2012 by Maurice Preter MD

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]

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Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity.

Posted on March 3, 2012 by Maurice Preter MD

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

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Allergy: a risk factor for suicide?

Posted on March 3, 2012 by Maurice Preter MD

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

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