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Objectives: Approximately one in five adults experiences chronic pain, often in co-occurrence with depression, insomnia, anxiety, and lower self-rated health. Elevated levels of cytokines, e.g. tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10), have been identified in patients with chronic pain. Depression, insufficient sleep, poor self-rated health, and pain intensity have also been associated with inflammatory biomarkers. This study aimed to investigate the interrelationships between inflammatory biomarkers and depression, insomnia, anxiety, self-rated health, sickness behavior, and pain intensity in patients with chronic pain., Methods: Self-report questionnaires and blood samples analyzed for plasma levels of inflammatory biomarkers were collected from 80 adult patients with chronic pain. Associations between inflammatory biomarkers (TNF-α, IL-6, IL-8, IL-10, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and depression, insomnia, anxiety, self-rated health, sickness behavior, and pain intensity, were analyzed using bivariate Spearman rank correlation coefficients and regression analyses., Results: Participants were mainly women (72.5 %), with a mean age of 50.8 years, and a reported mean pain duration of 16.7 years. There were significant correlations between insomnia and CRP (r s =.26, p <.05); sex and ESR (r s =.29, p <.05); age and IL-6 (r s =.29, p <.05) and IL-8 (r s =.30, p <.05); BMI and IL-6 (r s =.50, p <.001), CRP (r s =.63, p <.001) and ESR (r s =.42, p <.001). Ratings of depression were positively and significantly related to ratings of sickness behavior and anxiety (β =.32 and β =.40, respectively), explaining 49 % of the total variance in depression ratings. Insomnia was positively and significantly related to sickness behavior (β =.37) explaining 31 % of the total variance in insomnia ratings. Inflammatory biomarkers, however, did not contribute significantly to the models., Conclusions: Participants reported high levels of symptoms, yet the associations between these ratings and the inflammatory biomarkers were either absent or weak. Also, despite high levels of self-reported sickness behavior, overall the inflammatory status remained within the normal range. Ratings of sickness behavior contributed more than inflammatory markers in explaining ratings of depression and insomnia. The present results point to the complexity of chronic pain, and the challenges of identifying biomarkers that explain symptomatology., Competing Interests: Declaration of Competing Interest No conflict., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Exposure to light at night (LAN) can disrupt the circadian system, thereby altering neuroimmune reactivity and related behavior. Increased exposure to LAN affects people of all ages - and could have particularly detrimental effects during early-life and adolescence. Despite this, most research on the behavioral and physiological effects of LAN has been conducted in adult animals. Here we evaluated the effects of dim LAN during critical developmental windows on adulthood neuroimmune function and affective/sickness behaviors. Male and female C57BL/6 J mice were exposed to dim LAN [12:12 light (150 lx)/dim (15 lx) cycle] during early life (PND10-24) or adolescence (PND30-44) [control: 12:12 light (150 lx)/dark (0 lx) cycle]. Behaviors were assessed during juvenile (PND 42-44) and adult (PND60) periods. Contrary to our hypothesis, juvenile mice that were exposed to dim LAN did not exhibit changes in anxiety- or depressive-like behaviors. By adulthood, adolescent LAN-exposed female mice showed a modest anxiety-like phenotype in one behavioral task but not another. Adolescent LAN exposure also induced depressive-like behavior in a forced swim task in adulthood in both male and female mice. Additionally, developmental LAN exacerbated the hippocampal cytokine response (IL-1β) following peripheral LPS in female, but not male mice. These results suggest female mice may be more susceptible to developmental LAN than male mice: LAN female mice had a modest anxiety-like phenotype in adulthood, and upon LPS challenge, higher hippocampal IL-1β expression. Taken together, developmental LAN exposure in mice promotes a modest increase in susceptibility to anxiety- and depressive-like symptoms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: As the fight against the COVID-19 epidemic continues, medical workers may have allostatic load., Objective: During the reopening of society, medical and nonmedical workers were compared in terms of allostatic load., Methods: An online study was performed; 3,590 Chinese subjects were analyzed. Socio-demographic variables, allostatic load, stress, abnormal illness behavior, global well-being, mental status, and social support were assessed., Results: There was no difference in allostatic load in medical workers compared to nonmedical workers (15.8 vs. 17.8%; p = 0.22). Multivariate conditional logistic regression revealed that anxiety (OR = 1.24; 95% CI 1.18-1.31; p < 0.01), depression (OR = 1.23; 95% CI 1.17-1.29; p < 0.01), somatization (OR = 1.20; 95% CI 1.14-1.25; p < 0.01), hostility (OR = 1.24; 95% CI 1.18-1.30; p < 0.01), and abnormal illness behavior (OR = 1.49; 95% CI 1.34-1.66; p < 0.01) were positively associated with allostatic load, while objective support (OR = 0.84; 95% CI 0.78-0.89; p < 0.01), subjective support (OR = 0.84; 95% CI 0.80-0.88; p < 0.01), utilization of support (OR = 0.80; 95% CI 0.72-0.88; p < 0.01), social support (OR = 0.90; 95% CI 0.87-0.93; p < 0.01), and global well-being (OR = 0.30; 95% CI 0.22-0.41; p < 0.01) were negatively associated., Conclusions: In the post-COVID-19 epidemic time, medical and nonmedical workers had similar allostatic load. Psychological distress and abnormal illness behavior were risk factors for it, while social support could relieve it., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: Early life stress (ELS) has been linked to health disparities across the human lifespan, particularly increased risk for depression and its recurrence. In this study we explore two plausible and competing pathways through which ELS may lead to depression via inflammation., Methods: Participants (ages 18-22; n = 41) completed the Early Trauma Inventory as a measure of ELS. Participants then completed consecutive daily diaries of mood and other sickness behavior for the 7 days prior to and 7 days after receiving the annual influenza vaccine. Circulating concentrations of plasma interleukin-6 (IL-6) were measured immediately before and 24 hr after vaccination., Results: ELS was not associated with the magnitude of change in IL-6 from pre- to post-vaccine, however, exposure to ELS moderated the association between change in IL-6 from pre- to post-vaccine and changes in both cognitive difficulty and depressed mood. Individuals exposed to greater ELS showed greater psychological sensitivity to increases in IL-6., Conclusions: Exposure to ELS may increase sensitivity to peripheral inflammation in the central nervous system. Future studies elaborating on the impact of ELS on the sensitivity of specific neural circuits and cells to inflammation are needed., (© 2019 Wiley Periodicals, Inc.)

Rationale: While the relationship between inflammation and depression is well-established, the molecular mechanisms mediating this relationship remain unclear. RNA sequencing analysis comparing brains of vehicle- and lipopolysaccharide-treated mice revealed LCN2 among the most dysregulated genes. As LCN2 is known to be an important regulator of the immune response to bacterial infection, we investigated its role in the behavioral response to lipopolysaccharide., Objective: To explore the role of LCN2 in modulating behavior following lipopolysaccharide administration using wild type (WT) and lcn2 -/- mice., Methods: Using a within-subjects design, mice were treated with 0.33 mg/kg liposaccharide (LPS) and vehicle. Primary outcome measures included body weight, food consumption, voluntary wheel running, sucrose preference, and the tail suspension test. To evaluate the inflammatory response, 1 week later, mice were re-administered either vehicle or LPS and terminated at 6 h., Results: While lcn2 -/- mice had increased baseline food consumption and body weight, they showed a pattern of reduced food consumption and weight loss similar to WT mice in response to LPS. WT and lcn2 -/- mice both recovered voluntary activity on the fourth day following LPS. LPS induced equivalent reductions in sucrose preference and TST immobility in the WT and lcn2 -/- mice. Finally, there were no significant effects of genotype on inflammatory markers., Conclusions: Our data demonstrate that lcn2 is dispensable for sterile inflammation-induced sickness and depression-like behavior. Specifically, lcn2 -/- mice displayed sickness and immobility in the tail suspension test comparable to that of WT mice both in terms of intensity and duration.

The communication between the immune and central nervous system (CNS) is affected in many neurological disorders. Peripheral injections of the endotoxin lipopolysaccharide (LPS) are widely used to study this communication: an LPS challenge leads to a biphasic syndrome that starts with acute sickness and is followed by persistent brain inflammation and chronic behavioral alterations such as depressive-like symptoms. In vitro, the response to LPS treatment has been shown to involve enhanced expression of system x c - . This cystine-glutamate antiporter, with xCT as specific subunit, represents the main glial provider of extracellular glutamate in mouse hippocampus. Here we injected male xCT knockout and wildtype mice with a single intraperitoneal dose of 5 mg/kg LPS. LPS-injection increased hippocampal xCT expression but did not alter the mainly astroglial localization of the xCT protein. Peripheral and central inflammation (as defined by cytokine levels and morphological activation of microglia) as well as LPS-induced sickness and depressive-like behavior were significantly attenuated in xCT-deficient mice compared with wildtype mice. Our study is the first to demonstrate the involvement of system x c - in peripheral and central inflammation in vivo and the potential therapeutic relevance of its inhibition in brain disorders characterized by peripheral and central inflammation, such as depression., (© 2018 Wiley Periodicals, Inc.)

The serotonergic and immunological hypothesis of depression proposes that certain types of excessive stress distort the relationship between the activities of the innate immune and central nervous systems, so that the stress caused by an infection, or excessive psychological stress, activate toll-like receptors such as the TLR-4, the transcription factor NF-kB, the inflammasome NLRP3, as well as the secretion of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and other factors of the innate immune response, causing first, the general symptoms of the disease which appear with any infection, but also those characteristic of depressive illness such as dysphoria and anhedonia. The evidence indicates that, if the stimulus persists or recurs within 24 hours, the indole-2, 3-dioxygenase enzyme (IDO) of the kynurenine metabolic pathway, which increases the synthesis of quinolinic acid, is activated with an associated reduction of serotonin synthesis. Quinolinic acid activates NMDA receptors in the central nervous system and stimulates the secretion of interleukins IL-6 and 1L-1β, among others, promoting hyper-activity of the HPA axis and reinforcing a bias of the tryptophan metabolism to produce quinolinic acid, and interleukins by the innate immune system, further reducing the synthesis of serotonin and consolidating the depressive process. We discuss the evidence showing that this process can be initiated by either interleukin stimulated by an infection or some vaccines or excessive psychological stress that activates the HPA axis together with said innate immune response, causing a process of aseptic inflammation in the central nervous system.

The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To determine whether depressed or anxious patients experience greater affective change than mentally healthy individuals following influenza vaccination., Methods: Participants (n=112) completed the Positive and Negative Affect Schedule (PANAS) before influenza vaccination and 1-2days post-vaccination (M=32.3h). Pre- and post-vaccination PANAS scores were compared using two-tailed, paired-samples t-tests. Change in positive affect between participants with depression or anxiety and those without was compared using two-way ANOVA. Follow up positive affect was further examined using multiple linear regression., Results: Positive affect decreased following vaccination (M=2.18, 95% CI [1.07, 3.29], t(111)=3.89, p<0.001) for all participants and was more pronounced for those with anxiety or depression (F(1, 110)=7.51, p=0.009). Similarly, predicted follow up affect score was higher for those without a mental health conditions (β=3.67, 95% CI [1.18, 6.16], t(103)=2.92, p=0.004)., Conclusions: These data suggest that influenza vaccine has a greater effect on affect in patients with depression and anxiety than in mentally healthy individuals. This effect was focused on positive affect, suggesting that influenza vaccine induced inflammation may be best suited to examine alterations in positive affect and positive valence systems., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Depression is highly prevalent in the working population and is associated with significant loss of workdays; however, access to evidence-based treatment is limited., Objective: This study evaluated the effectiveness of a Web-based intervention in reducing mild to moderate depression and sickness absence., Methods: In an open-label randomized controlled trial, participants were recruited from a large-scale statutory health insurance and were assigned to two groups. The intervention group had access to a 12 week Web-based program consisting of structured interactive sessions and therapist support upon request. The wait-list control group had access to unguided Web-based psycho-education. Depressive symptoms were self-assessed at baseline, post-treatment, and follow-up (12 weeks after treatment) using the Patient Health Questionnaire (PHQ-9) and Beck Depression Inventory (BDI-II) as primary outcome measures. Data on sickness absence was retrieved from health insurance records. Intention-to-treat (ITT) analysis and per-protocol (PP) analysis were performed., Results: Of the 180 participants who were randomized, 88 completed the post-assessment (retention rate: 48.8%, 88/180). ITT analysis showed a significant between-group difference in depressive symptoms during post-treatment in favor of the intervention group, corresponding to a moderate effect size (PHQ-9: d=0.55, 95% CI 0.25-0.85, P<.001, and BDI-II: d=0.41, CI 0.11-0.70, P=.004). PP analysis partially supported this result, but showed a non-significant effect on one primary outcome (PHQ-9: d=0.61, 95% CI 0.15-1.07, P=.04, and BDI-II: d=0.25 95% CI -0.18 to 0.65, P=.37). Analysis of clinical significance using reliable change index revealed that significantly more participants who used the Web-based intervention (63%, 63/100) responded to the treatment versus the control group (33%, 27/80; P<.001). The number needed to treat (NNT) was 4.08. Within both groups, there was a reduction in work absence frequency (IG: -67.23%, P<.001, CG: -82.61%, P<.001), but no statistical difference in sickness absence between groups was found (P=.07)., Conclusions: The Web-based intervention was effective in reducing depressive symptoms among adults with sickness absence. As this trial achieved a lower power than calculated, its results should be replicated in a larger sample. Further validation of health insurance records as an outcome measure for eHealth trials is needed., Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 02446836; http://www.isrctn.com/ISRCTN02446836 (Archived by WebCite at http://www.webcitation.org/6jx4SObnw)., (©Till Beiwinkel, Tabea Eißing, Nils-Torge Telle, Elisabeth Siegmund-Schultze, Wulf Rössler. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 15.06.2017.)

Pramipexole (PPX), a dopamine D2/3 receptor preferring agonist, is currently in use for the treatment of Parkinson's disease symptoms and restless legs syndrome. Recently, anti-inflammatory properties of PPX have been shown in an autoimmune model of multiple sclerosis, and case reports indicate PPX ameliorates depressive symptoms. Since peripheral inflammation is known to induce depression-like behavior in rodents, we assessed the potential antidepressant effect of PPX in an inflammatory model of depression induced by LPS. Repeated (daily for 7days, 1mg/kg, i.p.), but not acute (1h before LPS) treatment with PPX abolished the depression-like behavior induced by LPS (0.1mg/kg, i.p.) in the forced swim test, and the anhedonic behavior in the splash test. Interestingly, PPX per se decreased interleukin 1β levels and reversed LPS-induced increase in its content in mice hippocampus⋅ Repeated PPX treatment also prevented the increase in hippocampal levels of the 3-nitrotyrosine protein adducts induced by LPS. Haloperidol (0.2mg/kg, i.p.) and sulpiride (50mg/kg, i.p.) were unable to prevent the antidepressant-like effect of PPX in LPS-treated mice. Altogether, these results suggest that the observed antidepressant-like effect of PPX in LPS-treated mice may be dependent on its anti-inflammatory properties and may not be related to dopamine D2 receptor activation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A psychosomatic approach to the basic screening of distress for patient care in hospitals and other health services is presented. The aims of this study were to verify association between: (1) medical illnesses and distress; (2) patients' needs and distress; (3) type of illness and patients' needs; (4) patients' needs and sense of coherence. One hundred and eighty-nine patients (78 F and 111 M, average age 65 years±8.43) were assessed by self-report questionnaires. We found that higher anxiety and/or depression levels were associated with urogenital (p=0.026), rheumatologic (p=0.006), oncological (p=0.011), neurological (p=0.026) and respiratory (p=0.013) illnesses. Higher distress scoring was associated with rheumatologic illnesses (p=0.024) and illnesses of the liver and digestive system (p=0.037) while a higher severity of distress was associated with oncological illnesses (p=0.011). Depression/anxiety were associated with the need to speak to a psychologist (p=0.050), to a spiritual advisor (p=0.009), to be more reassured by relatives (p=0.017), to feel less abandoned (p=0.036). Only low sense of coherence was associated with the need for greater dialogue with physicians (p=0.012), the need to participate less in treatment decisions (p=0.041), the need to feel less left to one's own devices (p=0.023). Several needs are associated with medical illnesses. In conclusion, these results indicate that early psychological screening could be important to avoid worse or chronic distress., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Substantial evidence demonstrates that inflammatory processes may underlie depression for a subset of patients, including work showing that healthy subjects exposed to an inflammatory challenge show increases in depressed mood and feelings of social disconnection. However, despite the fact that depression is two times as likely to occur in females than males, the vast majority of this work has been carried out in males. Thus, the objective of this study was to determine whether females (vs males) would show greater increases in proinflammatory cytokines, depressed mood, and social disconnection in response to an inflammatory challenge. One hundred and fifteen healthy participants (69 female) completed this double-blind, placebo-controlled, randomized clinical trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), depressed mood, and feelings of social disconnection were assessed hourly. Results showed that endotoxin (vs placebo) led to increases in proinflammatory cytokines (TNF-α, IL-6), depressed mood, and feelings of social disconnection. Females exposed to endotoxin showed greater increases in depressed mood and feelings of social disconnection. Furthermore, increases in TNF-α and IL-6 were correlated with increases in social disconnection for females but not for males. These sex differences in the relationships between inflammatory and socioemotional responses to an inflammatory challenge may be particularly important for understanding why females are two times as likely as males to develop depressive disorders.

Sickness behavior has been widely recognized as a symptom cluster that is associated with pro-inflammatory cytokine activation resulting from diverse conditions. The symptoms that comprise sickness behavior overlap substantially with major depressive disorder (MDD), which raises questions about the relationship between these two constructs, both of which occur frequently in patients with cancer. The construct of sickness behavior, while well-established in animal research, has rarely been applied to studies examining cytokines and depression in humans, perhaps because no reliable or validated measure of sickness behavior has been developed. We developed a version of a sickness behavior measure (the Sickness Behavior Inventory or SBI) and conducted a preliminary examination of its scale properties. Specifically, we hypothesized that a measure of sickness behavior would be significantly associated with five biomarkers of immune functioning (serum IL-6, TNF-α, IL-1b, IL-4, IL-10) in a human sample. The sample was comprised of four groups: individuals with pancreatic cancer and MDD (n = 16), individuals with pancreatic cancer and who did not have a diagnosis of MDD (n =2 6), individuals without cancer who had MDD (n = 7), and individuals who did not have cancer or MDD (n = 25). The SBI demonstrated moderate reliability (Cronbach's alpha = .66), and total scores were significantly correlated with IL-6 (rs = .26, p = .03), but not with other markers of immune functioning. Factor analysis supported a 3-factor model of sickness behavior with different associations between the three SBI factors and cytokines. These results highlight the need to further refine symptom measurement to better understand the relationships among immune functioning, cancer, depression, and sickness behavior., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: Several studies suggested an association between dysregulation of immune mediators and behavioural, neuroendocrine and neurochemical features of depression. Available data showed that cytokines affect the serotonin transporter (SERT) activity through p38 MAP kinase (MAPK)-dependent mechanisms in some cell lines and mice neurons (Zhu et al., Neuropsychopharmacology, 2006; 31:2121-31). The aim of this study was to investigate the interaction of Interleukin-1β (IL-1β) or p38 MAPK with SERT activity in rat brain and cell lines., Main Methods: Synaptosomes or cells were treated with IL-1β or the p38 MAPK activator anisomycin at different concentrations and end-points and the modulation of SERT activity as Km and Vmax was evaluated., Key Findings: Treatments with IL-1β or anisomycin did not affect serotonin uptake and p38 MAPK activation in rat synaptosomes, in contrast to reports in mice (Zhu et al., Neuropsychopharmacology, 2010; 35:2510-20). The same treatments activated p38 MAPK phosphorylation in HeLa cells used as positive controls. Similarly, no changes after anisomycin treatment could be detected in [(3)H]serotonin uptake rate in LLC-PK cells expressing human SERT, although phosphorylated p38 MAPK levels augmented significantly. Direct cytokine release in brain was induced by intracerebroventricular administration of bacterial lipopolysaccaride. Although pro-inflammatory cytokines, such as IL-1ß, IL6, and Tumor Necrosis Factor α, showed significant increases in brain cortex, modulation of SERT activity in term of Km and Vmax was not detected., Significance: These results imply that the stimulation of serotonin uptake by cytokines may not be a unique and fundamental mechanism in the pathology of depression induced by altered immune response., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In this study we characterised the ability of the viral mimetic poly I:C to induce a neuroinflammatory response and induce symptoms of depression and anxiety in rats. Furthermore, the ability of poly I:C to deplete central tryptophan and serotonin via induction of indolamine 2,3 dioxygenase (IDO), and also the ability of poly I:C to impact upon expression of the neurotrophin BDNF and its receptor TrkB were examined as potential mechanisms to link inflammation to depression. Poly I:C induced a neuroinflammatory response characterised by increased expression of IL-1β, IL-6, TNF-α and CD11b in frontal cortex and hippocampus. In the first 24h following poly I:C administration rats displayed sickness behaviour characterised by reduced locomotor activity and weight gain. Anhedonia measured using the saccharin preference test was used as an indicator of depressive behaviour, and poly I:C induced depressive behaviour that persisted for up to 72h following administration. Anxiety was measured using the open field test and anxious behaviour was observed 24h following poly I:C, a time-point when sickness behaviour had resolved. These behavioural changes were accompanied by decreased expression of BDNF and TrkB in hippocampus and frontal cortex. In addition, poly I:C increased central IDO expression and increased concentrations of tryptophan, and its metabolite kynurenine. However this activation of the kynurenine pathway did not result in reduced central serotonin concentrations. These findings suggest that depressive and anxiety-like behaviours elicited by poly I:C are associated with a reduction in BDNF signalling, and activation of the kynurenine pathway, but not a reduction in serotonin., (Copyright © 2012 Elsevier Inc. All rights reserved.)

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers.

Insecure attachment has been hypothesized to be an important factor for understanding the experience of pain. Considering the Attachment-Diathesis Model of Chronic Pain developed by Meredith, Ownsworth, and Strong (2008), this cross-sectional study examines the relationship between attachment style, pain appraisal, and illness behavior. Two hundred healthy women recruited from community contexts completed a battery of self-report measures including the Short-form McGill Pain Questionnaire, Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale-20, Pain Vigilance and Awareness Questionnaire, Illness Attitude Scales, Beck Anxiety Inventory, Beck Depression Inventory, and the Experiences in Close Relationships Questionnaire-Revised. The results showed that attachment anxiety was significantly correlated with pain catastrophizing, pain-related fear, depression, and illness behavior. However, attachment anxiety and avoidance were not associated with pain intensity. Attachment anxiety moderated the relationship between pain catastrophizing and illness behavior, and between pain hypervigilance and illness behavior. Pain catastrophizing and pain-related fear partially mediated the effect of attachment anxiety on illness behavior. The findings highlight potential contributions of attachment style and pain appraisal for explaining illness behavior. This study supports earlier reports and suggests the usefulness of assessing attachment style for early identification of people who might exhibit a high risk of dysfunctional responses to pain. Our findings also suggest that increasing people's insight about their attachment style and modifying some associated dysfunctional responses may be important in the treatment of chronic pain., (© 2011 The Authors. Scandinavian Journal of Psychology © 2011 The Scandinavian Psychological Associations.)

The C57BL/6 mice were subjected to a chronic combined stress which resulted in the induction of a depressive-like state. The occurrence of a depressive-like state was defined by a decrease in sensitivity to the reward determined by the diminished preference of sweetened solutions over regular drinking water. Such decrease is generally considered as a sign of an unhedonic-like state: one of the key features of clinical depression. Applied here, the paradigm in mice allows unhedonia induction in a subpopulation of stressed animals (54% in the current study); remaining mice are regarded as resilient to stress-induced hedonic deficit. The resilient subgroup is taken, therefore, as a "functional control" for those effects of stress that are not accompanied by development of the stress-induced depressive-like state in mice. The analysis of the mRNA extracted from the hippocampi of stress-subjected and home-cage control mice enabled the assessment of gene expression level of over 13 000 genes. This study showed that unhedonic mice are characterized by an up-regulation of 278 and down-regulation of 174 genes related mostly to the CNS development and functions, inter-cellular interactions and signalling, neurological disorders, apoptosis and behavioural regulation. Resilient animals demonstrated up-regulation of 924 and down-regulation of only 29 genes that control formation of cell assemblies, molecular transport, CNS functioning, neurological disorders and various biochemical reactions. Thus, gene expression profiles in the hippocampus of susceptible vs resilient to stress-induced unhedonia inbred subgroups of animals are strictly distinct in both quantity and quality.

Although accumulating evidence supports a role for cytokines in the pathophysiology of depression, the cytokine hypothesis of depression is debatable. It has been suggested that neuroendocrine and immune systems acting in concert may have roles in the development and the maintenance of the disease. Glucocorticoid receptor (GR) is the key element which exerts both anti-inflammatory and cytokine-inhibiting effects. Whether functional changes of GR are involved in the pathophysiology of cytokine-induced depression remains elusive. In the present study, the effects of both acute and chronic GR blockade on depressive-like behaviour and cytokine production induced by lipopolysaccharides (LPS), cytokine inducer, were investigated in rats. Acute or chronic blockade of GR was achieved by a single administration or repeated administrations, respectively, of the GR antagonist RU486 (RU). Behavioural measurements, including saccharin preference, locomotor activity, and immobility time, were assessed. The serum levels of proinflammatory cytokines (TNFα, IL-1β, and IFNγ) were determined by ELISA. The results showed that LPS induced significant but transient depressive-like behaviour. Repeated, but not single, administration of RU significantly enhanced and prolonged LPS-induced depressive-like behaviour and an increase in the serum production of TNFα and IFNγ. These results indicate that the effective blockade of GR enhanced the depressive-like behaviour induced by cytokines. Findings from this study suggest that GR dysfunction may be an important contributing factor to the development of cytokine-related depression. These findings add to the growing evidence of mechanisms by which cytokines influence depression., (Copyright © 2011 Elsevier Inc. All rights reserved.)