Affective symptoms are associated with markers of inflammation and immune activation in bipolar disorders but not in schizophrenia
ABSTRACT Elevated levels of inflammation are reported in bipolar disorders (BP), but how this relates to affective symptoms is unclear. We aimed to determine if immune markers that consistently have been reported elevated in BP were associated with depressive and manic symptoms, and if this was specific for BP.
From a catchment area, 112 BP patients were included together with 153 schizophrenia (SCZ) patients and 239 healthy controls. Depression and mania were assessed and the patients were grouped into depressed, neutral, and elevated mood. We measured the immune markers tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), high sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG) and von Willebrand factor (vWf) which have been found increased in severe mental disorders.
In BP all inflammatory markers were lowest in depressed state, with significant group differences after control for confounders with respect to TNF-R1 (p = 0.04), IL-1Ra (p = 0.02), OPG (p = 0.004) and IL-6 (p = 0.005). STNF-R1 was positively correlated with the item elevated mood (p = 0.02) whereas sad mood was negatively correlated with OPG (p = 0.0003), IL-1Ra (p = 0.001) and IL-6 (p = 0.006). Compared to controls the neutral mood group had significantly higher levels of OPG (p = 0.0003) and IL-6 (p = 0.005), and the elevated mood group had higher levels of TNF-R1 (p = 0.000005) and vWf (p = 0.002). There were no significant associations between affective states orsymptoms in SCZ.
The current associations between inflammatory markers and affective symptomatology in BP and not SCZ suggest that immune related mechanisms are associated with core psychopathology of BP.
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ABSTRACT: Increased cytokine production possibly due to oxidative stress has repeatedly been shown to play a pivotal role in the pathophysiology of epilepsy and bipolar disorder. Recent in vitro and animal studies of valproic acid (VPA) report antioxidative and anti-inflammatory properties, and suppression of interleukin (IL)-6 and tumor necrosis factor (TNF)- α . We tested the effect of drugs with antiepileptic or mood stabilizer properties, namely, primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), VPA, oxcarbazepine (OXC), topiramate (TPM), phenobarbital (PB), and lithium on the production of the following cytokines in vitro: interleukin (IL)-1 β , IL-2, IL-4, IL-6, IL-17, IL-22, and TNF- α . We performed a whole blood assay with stimulated blood of 14 healthy female subjects. Anti-human CD3 monoclonal antibody OKT3, combined with 5C3 antibody against CD40, was used as stimulant. We found a significant reduction of IL-1 and IL-2 levels with all tested drugs other than lithium in the CD3/5C3-stimulated blood; VPA led to a decrease in IL-1 β , IL-2, IL-4, IL-6, IL-17, and TNF- α production, which substantiates and adds knowledge to current hypotheses on VPA's anti-inflammatory properties.Oxidative Medicine and Cellular Longevity 03/2014; 2014:806162. DOI:10.1155/2014/806162 · 3.36 Impact Factor
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ABSTRACT: ObjectiveTNF system (TNF and its soluble receptors sTNFR1 and 2) has been investigated as a potential molecular target in bipolar disorder. The aim of the study was to compare plasma levels of these receptors in unmedicated bipolar depressed patients compared with healthy controls, and to evaluate the effects of a 6-week lithium treatment on sTNFR1 and sTNFR2 levels.Methods The study enrolled 29 patients with unmedicated bipolar disorder in a major depressive episode and 27 matched controls. Patients had blood collected at baseline and after 6 weeks of lithium treatment. The concentration of sTNFRs was measured by ELISA.ResultssTNFR1 and sTNFR2 levels were significantly increased in bipolar depression in comparison with healthy subjects. Lithium treatment did not significantly change sTNFR1 and sTNFR2 levels from baseline to endpoint. There was no correlation between improvement in depressive symptoms and the change in sTNFR1 or sTNFR1 levels.Conclusion These results reinforce the involvement of an activated immune response system in the pathophysiology of bipolar disorder, with no impact of lithium treatment on the related biomarkers. Copyright © 2014 John Wiley & Sons, Ltd.Human Psychopharmacology Clinical and Experimental 01/2015; 30(1). DOI:10.1002/hup.2450 · 1.85 Impact Factor
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ABSTRACT: Bipolar disorder (BD) is a chronic psychiatric illness of which the etiology remains unknown. Extensive research has provided some hypotheses for the pathophysiology of this disorder; however, there are no molecular tests available to help support the diagnosis obtained by self-report and behavioral observations. A major requirement is to identify potential biomarkers that could be used for early diagnosis in patients susceptible to the disease and for its treatment. The most recently published findings regarding alterations in BD were found to be related to oxidative stress, inflammatory and trophic factor deregulation, and also polymorphisms of genes that are associated with the development of BD. Many of these targets are potential biomarkers which could help to identify the BD subgroups and to advance treatment strategies, which would beneficiate the quality of life of these patients. Therefore, the main objective of this review is to examine the recent findings and critically evaluate their potential as biomarkers for BD.Current Psychiatry Reports 12/2014; 16(12):514. DOI:10.1007/s11920-014-0514-4 · 3.05 Impact Factor