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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Inflammatory markers and negative mood symptoms following exercise withdrawal.

Posted on March 3, 2012 by Maurice Preter MD

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]

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Depressive symptoms and metabolic syndrome: is inflammation the underlying link?

Posted on March 3, 2012 by Maurice Preter MD

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

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Relationship between inflammation and cognitive function in obstructive sleep apnea.

Posted on March 3, 2012 by Maurice Preter MD

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 ( = 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

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