Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder.
ABSTRACT Over the last 15 years, an increasing body of evidence has suggested a causal relationship between depression and the immunological activation and hypersecretion of pro-inflammatory cytokines, such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha (TNF-alpha). However, little is known about the probable relationship of serum TNF-alpha with major depressive disorder (MDD).
To assess whether serum TNF-alpha levels could be associated with the clinical course of MDD.
TNF-alpha and C-reactive protein (CRP) serum concentrations, erythrocyte sedimentation rate, and leukocyte count were measured in 26 MDD patients and in 17 controls. The measurements were repeated following 6 weeks of antidepressant treatment with selective serotonin re-uptake inhibitors. Psychopathological improvement and the severity of depression were evaluated with the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI).
On admission, serum TNF-alpha and leukocyte count were significantly higher in MDD patients compared to controls ( P<0.001 and P=0.005, respectively). With the antidepressant treatment, both HAMD and BDI scores decreased significantly (P<0.001 for both). Comparison of pre- and post-treatment measurements revealed that TNF-alpha, CRP, and leukocyte count decreased to levels comparable with those of the control subjects ( P<0.001, P=0.01, and P=0.01, respectively).
The results emphasized that some immunological parameters, such as CRP, leukocyte count and TNF-alpha, are significantly involved in the clinical course and treatment response in MDD. TNF-alpha in particular could be considered as a potential state marker in MDD.
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ABSTRACT: Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d = 0.54, p < 0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d = 0.47, p < 0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d = 0.40, p = 0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d = −0.05, p = 0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression.Brain Behavior and Immunity 06/2015; 20. DOI:10.1016/j.bbi.2015.06.001 · 6.13 Impact Factor
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ABSTRACT: The complex bidirectional communication between the central nervous system and the peripheral immune system is of possible relevance for both normal brain functions and the development of psychiatric disorders. The aim of this investigation was to study central expression of inflammatory markers in a genetic rat model of depression (the Flinders Sensitive line (FSL) and its control, the Flinders Resistant line (FRL)). A peripheral immune activation was induced by lipopolysaccharide (LPS) in order to investigate possible differences in immune reactions between the two rat lines. To confirm behavioural differences between the rat lines the forced swim test was performed, a test to assess depressive-like behaviour. Expression of candidate inflammatory genes was measured in amygdala, hippocampus, hypothalamus, prefrontal cortex and striatum using quantitative real time PCR. Our results show, for the first time, significantly lower central expression of the glial-specific protein S100B and complement factor C3 in several brain regions of the FSL rats compared to controls, both at baseline and after peripheral immune stimulation. No significant differences in immune responses to LPS were observed between the rats lines. Both S100B and C3 have been suggested to be of relevance for brain development and plasticity as well as brain disorders. These proteins may be of importance for the behavioural differences between the FSL and FRL rats, and this model may be useful in studies exploring the influence of the immune system on brain functions.Behavioural Brain Research 09/2014; 281. DOI:10.1016/j.bbr.2014.09.025 · 3.39 Impact Factor
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ABSTRACT: There is burgeoning interest in the ability to detect inflammatory markers in response to stress within naturally occurring social contexts and/or across multiple time points per day within individuals. Salivary collection is a less invasive process than current methods of blood collection and enables intensive naturalistic methodologies, such as those involving extensive repeated measures per day over time. Yet the reliability and validity of saliva-based to blood-based inflammatory biomarkers in response to stress remains unclear. We review and synthesize the published studies that have examined salivary markers of inflammation following exposure to an acute laboratory stressor. Results from each study are reviewed by analyte (IL-1β, TNF-α, IL-6, IL-2, IL-4, IL-10, IL-12, CRP) and stress type (social-cognitive and exercise-physical), after which methodological issues and limitations are addressed. Although the literature is limited, several inflammatory markers (including IL-1β, TNF-α, and IL-6) have been reliably determined from saliva and have increased significantly in response to stress across multiple studies, with effect sizes ranging from very small to very large. Although CRP from saliva has been associated with CRP in circulating blood more consistently than other biomarkers have been associated with their counterparts in blood, evidence demonstrating it reliably responds to acute stress is absent. Although the current literature is presently too limited to allow broad assertion that inflammatory biomarkers determined from saliva are valuable for examining acute stress responses, this review suggests that specific targets may be valid and highlights specific areas of need for future research.Brain Behavior and Immunity 09/2014; 44. DOI:10.1016/j.bbi.2014.08.008 · 6.13 Impact Factor