Biomarkers of systemic inflammation and depression and fatigue in moderate clinically stable COPD

<p>Abstract</p> <p>Introduction</p> <p>COPD is an inflammatory disease with major co-morbidities. It has recently been suggested that depression may be the result of systemic inflammation. We aimed to explore the association between systemic inflammation and symptoms of depression and fatigue in patients with mainly moderate and clinically stable COPD using a range of inflammatory biomarkers, 2 depression and 2 fatigue scales.</p> <p>Method</p> <p>We assessed 120 patients with moderate COPD (FEV₁% 52, men 62%, age 66). Depression was assessed using the BASDEC and CES-D scales. Fatigue was assessed using the Manchester COPD-fatigue scale (MCFS) and the Borg scale before and after 6MWT. We measured systemic TNF-α, CRP, TNF-α-R1, TNF-α-R2 and IL-6.</p> <p>Results</p> <p>A multivariate linear model of all biomarkers showed that TNF-α only had a positive correlation with BASDEC depression score (p = 0.007). TNF-α remained positively correlated with depression (p = 0.024) after further adjusting for TNF-α-R1, TNF-α-R2, 6MWD, FEV₁%, and pack-years. Even after adding the MCFS score, body mass and body composition to the model TNF-α was still associated with the BASDEC score (p = 0.044). Furthermore, patients with higher TNF-α level (> 3 pg/ml, n = 7) had higher mean CES-D depression score than the rest of the sample (p = 0.03). Borg fatigue score at baseline were weakly correlated with TNF-α and CRP, and with TNF-α only after 6MWT. Patients with higher TNF-α had more fatigue after 6MWD (p = 0.054).</p> <p>Conclusion</p> <p>This study indicates a possible association between TNF-α and two frequent and major co-morbidities in COPD; i.e., depression and fatigue.</p

Interleukin-1beta Promoter (−31T/C and −511C/T) Polymorphisms in Major Recurrent Depression

To elucidate a genetic predisposition to major depressive disorder, we investigated two polymorphisms (−31T/C and −511C/T) in the interleukin-1beta promoter region in patients who suffered from major recurrent depression. The aim of the current work was to compare alleles and genotype layout between patients with major recurrent depression and healthy people. We would like to indicate such combination of genotypes which corresponds with major recurrent depression. Correlations between genotypes for analyzed polymorphisms and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset were investigated as well. The study group consisted of 94 patients diagnosed with major recurrent depression. The control group included 206 healthy individuals. Both groups involved representatives of Caucasian population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. A specific haplotype, composed of the C allele at −31 and the T allele at −511, has a tendency to have a statistically significant difference (p = 0.064) between patients and control group. Correspondence analysis revealed that genotype T/T at −31 and genotype C/C at −511 are associated with major recurrent depression. No association was found between genotypes for studied polymorphic sites and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset

Cytokine Production by Leukocytes of Military Personnel with Depressive Symptoms after Deployment to a Combat-Zone: A Prospective, Longitudinal Study

Major depressive disorder (MDD) is frequently diagnosed in military personnel returning from deployment. Literature suggests that MDD is associated with a pro-inflammatory state. To the best of our knowledge, no prospective, longitudinal studies on the association between development of depressive symptomatology and cytokine production by peripheral blood leukocytes have been published. The aim of this study was to investigate whether the presence of depressive symptomatology six months after military deployment is associated with the capacity to produce cytokines, as assessed before and after deployment. 1023 military personnel were included before deployment. Depressive symptoms and LPS- and T-cell mitogen-induced production of 16 cytokines and chemokines in whole blood cultures were measured before (T0), 1 (T1), and 6 (T2) months after return from deployment. Exploratory structural equation modeling (ESEM) was used for data reduction into cytokine patterns. Multiple group latent growth modeling was used to investigate differences in the longitudinal course of cytokine production between individuals with (n = 68) and without (n = 665) depressive symptoms at T2. Individuals with depressive symptoms after deployment showed higher T-cell cytokine production before deployment. Moreover, pre-deployment T-cell cytokine production significantly predicted the presence of depressive symptomatology 6 months after return. There was an increase in T-cell cytokine production over time, but this increase was significantly smaller in individuals developing depressive symptoms. T-cell chemokine and LPS-induced innate cytokine production decreased over time and were not associated with depressive symptoms. These results indicate that increased T-cell mitogen-induced cytokine production before deployment may be a vulnerability factor for development of depressive symptomatology in response to deployment to a combat-zone. In addition, deployment to a combat-zone affects the capacity of T-cells and monocytes to produce cytokines and chemokines until at least 6 months after return

Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed

Research review: the role of cytokines in depression in adolescents: a systematic review

Background: While cytokines have been implicated in the pathophysiology of depression in adults, the potential role in younger age groups such as adolescents is less clear. This article therefore reviews the literature (a) to explore the relationship between cytokines and depression in adolescents, and (b) to examine how cytokines may be related to adolescent depression in the context of other neurobiological theories of depression. Method: A systematic review of the scientific literature on the subject was conducted in February 2013, searching the Web of Knowledge, PubMed (Medline), PsycInfo and Cochrane electronic databases. Results: Eighteen studies were identified measuring both depression or depressive symptoms and cytokines or immune markers in adolescents. Adolescents with depression show age-specific characteristics of the immune and inflammatory system, specifically in NK cell activity and in pro-inflammatory cytokines (such as IL-1 beta and TNF-alpha). In addition, the role of cytokines in adolescent depression is influenced by neurodevelopment, hormonal changes, stress and trauma. Conclusions: There may be differences in the neurobiology of adolescent major depressive disorder (MDD) compared with adult MDD. Increased understanding of the role of cytokines in adolescent MDD may lead to improved outcomes in the treatment of adolescent depression

A magic pill? A qualitative analysis of patients' views on the role of antidepressant therapy in inflammatory bowel disease (IBD)

Background: Studies with healthy volunteers have demonstrated that antidepressants can improve immunoregulatory activity and thus they may have a potential to positively impact the disease course in inflammatory bowel disease (IBD), a chronic and incurable condition. However, patients’ views on the role of antidepressants in the management of their IBD are unknown. Thus, this study aimed to explore patients’ experiences and opinions regarding the effect of antidepressants on IBD course before possibly undertaking future treatment trials with antidepressants. Methods: Semi-structured in-depth interviews with open-ended questions were conducted with a randomly selected sample of IBD patients recruited at the Australian public hospital IBD clinic and currently receiving antidepressants. A qualitative content analysis was undertaken to summarise patients’ responses. A Visual Analogue Scale was used to provide a quantitative assessment of patients’ experiences with antidepressants. Results: Overall, 15 IBD sufferers currently on antidepressants (nine females, six males) were interviewed. All 15 reported a positive response to antidepressants reporting they improved their quality of life, with minimal sideeffects. Five patients (33.3%) felt the antidepressant had specifically improved their IBD course. Three patients noted how they believed the reduction in feelings of stress mediated the positive influence of the antidepressant on IBD course. Ten patients (66.7%) felt the antidepressants had not specifically influenced their IBD. Nine patients (60.0%) had a generally positive attitude towards antidepressants, four patients (26.7%) were ambivalent, and two patients (13.3%) held a negative view towards antidepressants. Twelve patients (80.0%) stated that they would be willing to participate in clinical trials. Conclusions: Antidepressants seem to be well tolerated by IBD patients. One third of patients reported an observable improvement of their IBD under the influence of this treatment. The positive attitude towards antidepressants in these participants may make the conduct of clinical trials to further assess for any specific role on IBD course feasible. However, due to a small sample size, a qualitative nature of this study and in light of the results of studies on other populations indicating reluctance to taking antidepressants at least in some patients, these results should be interpreted with caution until confirmed in quantitative studies.Antonina A Mikocka-Walus, Andrea L Gordon, Benjamin J Stewart and Jane M Andrew