Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9: 46-56

Integrative Immunology & Behavior, Department of Animal Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois, Urbana-Champaign, Illinois 61801, USA.
Nature Reviews Neuroscience (Impact Factor: 31.43). 02/2008; 9(1):46-56. DOI: 10.1038/nrn2297
Source: PubMed


In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

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    • "Cytokines are important for brain development , and healthy brain function by supporting neuronal integrity, neurogenesis, and synaptic remodelling (Yirmiya and Goshen 2011), neurocircuitry and neurotransmitters to produce behavioural alterations (Haroon et al. 2012). The so-called " cytokine-induced sickness behaviour " (i.e., lethargy , depression, failure to concentrate, anorexia, sleep disturbances, decreased personal hygiene and social withdrawal) was shown to be mediated by proinfl ammatory cytokines IL-1, IL-6, and TNF-α (Dantzer et al. 2008). "
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    ABSTRACT: Suicidal behaviour (SB) entered the DSM-5, underlying a specific biological vulnerability. Then, recent findings suggested a possible role of the immune system in SB pathogenesis. The objective of this review is to present these main immune factors involved in SB pathogenesis. We conducted a review using Preferred Reporting Items for Systematic reviews and Meta-Analysis criteria, and combined ("Inflammation") AND ("Suicidal ideation" OR "Suicidal attempt" OR "suicide"). Post mortem studies demonstrated associations between suicide and inflammatory cytokines in the orbitofrontal cortex, a brain region involved in suicidal vulnerability. Also, microgliosis and monocyte-macrophage system activation may be a useful marker of suicide neurobiology. Kynurenine may influence inflammatory processes, and related molecular pathways may be involved in SB pathophysiology. Few recent studies associated inflammatory markers with suicidal vulnerability: serotonin dysfunction, impulsivity and childhood trauma. Interestingly, the perception of threat that leads suicidal individuals to contemplate suicide may activate biological stress responses, including inflammatory responses. Translational projects would be crucial to identify a specific marker in SB disorders, to investigate its clinical correlations, and the interaction between inflammatory cytokines and monoamine systems in SB. These researches might lead to new biomarkers and novel directions for therapeutic strategies.
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    • " TNFα was predictive of both atypical and prototypical profiles . The effect is small but could be explained by the fact that heightened levels of inflamma tion are on the one hand associated with antidepressant use ( Vogelzangs et al . , 2012 ) , which was found to be associated with atypical responding , and on the other hand with somatization ( Dantzer et al . , 2008 ) , which was found to be associated with prototypical responding . The person - fit statistic showed considerable consistency over time . Person - fit scores were positively correlated between baseline and two - year follow - up , the item - score patterns were similar and a substantial part of the baseline atypical subgroup also showe"
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    ABSTRACT: Atypical response behavior on depression questionnaires may invalidate depression severity measurements. This study aimed to identify and investigate atypical profiles of depressive symptoms using a data-driven approach based on the item response theory (IRT). A large cohort of participants completed the Inventory of Depressive Symptomatology self-report (IDS-SR) at baseline (n=2329) and two-year follow-up (n=1971). Person-fit statistics were used to quantify how strongly each patient׳s observed symptom profile deviated from the expected profile given the group-based IRT model. Identified atypical profiles were investigated in terms of reported symptoms, external correlates and temporal consistency. Compared to others, atypical responders (6.8%) showed different symptom profiles, with higher 'mood reactivity' and 'suicidal ideation' and lower levels of mild symptoms like 'sad mood'. Atypical responding was associated with more medication use (especially tricyclic antidepressants: OR=1.5), less somatization (OR=0.8), anxiety severity (OR=0.8) and anxiety diagnoses (OR=0.8-0.9), and was shown relatively stable (29.0%) over time. This is a methodological proof-of-principal based on the IDS-SR in outpatients. Implementation studies are needed. Person-fit statistics can be used to identify patients who report atypical patterns of depressive symptoms. In research and clinical practice, the extra diagnostic information provided by person-fit statistics could help determine if respondents׳ depression severity scores are interpretable or should be augmented with additional information. Copyright © 2015 Elsevier B.V. All rights reserved.
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    • "The knowledge of the functional role of the central nervous system in the genesis of fever has greatly improved over the last decade. It is clear that the febrile process, which develops in the sick individual, is just one of many diverse brain-controlled symptoms, most of which are collectively termed ''sickness behavior'' (Dantzer et al., 2008; McCusker and Kelley, 2013; Pecchi et al., 2009). These include anorexia, fatigue, loss of interest in usual daily activities, social withdrawal, listlessness or malaise, hyperalgesia, sleep disturbances and cognitive dysfunction. "
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    ABSTRACT: Fever has been recognized as an important symptom of disease since ancient times. For many years, fever was treated as a putative life-threatening phenomenon. More recently, it has been recognized as an important part of the body's defense mechanisms; indeed at times it has even been used as a therapeutic agent. The knowledge of the functional role of the central nervous system in the genesis of fever has greatly improved over the last decade. It is clear that the febrile process, which develops in the sick individual, is just one of many brain-controlled sickness symptoms. Not only will the sick individual appear "feverish" but they may also display a range of behavioral changes, such as anorexia, fatigue, loss of interest in usual activities, social withdrawal, listlessness or malaise, hyperalgesia, sleep disturbances and cognitive dysfunction, collectively termed "sickness behavior". In this review we consider the issue of whether fever and sickness behaviors are friend or foe during: a critical illness, the common cold or influenza, in pregnancy and in the newborn. Deciding whether these sickness responses are beneficial or harmful will very much shape our approach to the use of antipyretics during illness. Copyright © 2015. Published by Elsevier Inc.
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