Immune activation in non-treated suicidal major depression

Mendlovic, Shlomo; Mozes, Edna; Eilat, Eran; Doron, Adiel; Lereya, Joseph; Zakuth, V.; Spirer, Z

doi:10.1016/s0165-2478(98)00145-x

Cited by 61 publications

(41 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, in contrast, it has previously been reported that higher amounts of IFN-γ were produced in lymphocytes of patients with major depression than in healthy controls [36]. Additionally, higher plasma levels of IFN-γ in depressed patients [10] and suicidal major depression patients [37] have been described. A possible mechanism contributing to the differences is that our data were collected from a mouse model, and the data reflected dynamic changes in Th1-related cytokines during the development of CUMS, but not fully formed depression.…”

Section: Discussionmentioning

confidence: 99%

Imbalance between Th17 and Treg Cells May Play an Important Role in the Development of Chronic Unpredictable Mild Stress-Induced Depression in Mice

Hong¹,

Zheng

Ding³

et al. 2012

Neuroimmunomodulation

View full text Add to dashboard Cite

Background: Recent data suggest that major depression is potentially associated with dysregulated cytokine production. However, the roles of T helper (Th) cells and their subsets in the development of depression still remain to be determined. The present study assessed changes in Th cell subsets and cytokines during the development of depression in a mouse model. Methods: Chronic unpredictable mild stress (CUMS) was used to simulate depression behavior in mice. The open field test, sucrose preference, and ingestion were used as evaluative indicators of depressive behavior. During the CUMS protocol, on days 3, 7, 14, and 21, we assessed behavioral changes, cytokine levels in serum or stimulated (CD3/CD28) cell culture medium, and mRNA expression (ELISA, RT-PCR), regulatory T (Treg) and Th17 subsets in spleen (ex vivo, flow cytometry, RT-PCR), and CD3/rIL-23-stimulated Th17 cell proliferation (MTT assay). Results: The results showed that in the depression model mice, IL-4 mRNA expression and serum levels increased on day 7, while no detectable change was observed in IFN-γ. Notably, a reduced proportion of Th17 cells with decreased proliferation capacity was observed at later stages, in parallel with a decline in serum IL-23 levels. In contrast, an increased Treg cell proportion and increased Foxp3 mRNA expression were observed in the mid-stages. Correlation analysis showed that the proportion of Tregs was correlated negatively with sucrose preference, while the proliferation of Th17 cells was notably correlated positively with sucrose preference. Also, an increased TGF-β level was detected in serum and was believed to be a key factor responsible for the imbalance between Th17 and Treg cells. Furthermore, the sucrose preference in TGF-β type I receptor blockade mice increased considerably, compared with CUMS mice. Conclusion: These results indicate that in CUMS-induced depression, behavioral changes may closely correlate with the imbalance between Th17 and Treg cell subsets, and TGF-β may be a key regulatory cytokine.

show abstract

Section: Discussionmentioning

confidence: 99%

Imbalance between Th17 and Treg Cells May Play an Important Role in the Development of Chronic Unpredictable Mild Stress-Induced Depression in Mice

Hong¹,

Zheng

Ding³

et al. 2012

Neuroimmunomodulation

View full text Add to dashboard Cite

show abstract

“…Mendlovic et al (1999) discriminated between suicidal and non-suicidal major depression patients in a small study. They found distinct associations between suicidality and type-1 immune response on the one hand and a predominance of type-2 immune parameters in non-suicidal patients on the other hand (Mendlovic et al 1999).…”

Section: Interleukin-2mentioning

confidence: 91%

Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markers in Depression

Mößner

Mikova

Koutsilieri

et al. 2007

The World Journal of Biological Psychiatry

227

126

View full text Add to dashboard Cite

Biological markers for depression are of great interest to aid in elucidating the causes of major depression. We assess currently available biological markers to query their validity for aiding in the diagnosis of major depression. We specifically focus on neurotrophic factors, serotonergic markers, biochemical markers, immunological markers, neuroimaging, neurophysiological findings, and neuropsychological markers. We delineate the most robust biological markers of major depression. These include decreased platelet imipramine binding, decreased 5-HT1A receptor expression, increase of soluble interleukin-2 receptor and interleukin-6 in serum, decreased brain-derived neurotrophic factor in serum, hypocholesterolemia, low blood folate levels, and impaired suppression of the dexamethasone suppression test. To date, however, none of these markers are sufficiently specific to contribute to the diagnosis of major depression. Thus, with regard to new diagnostic manuals such as DSM-V and ICD-11 which are currently assessing whether biological markers may be included in diagnostic criteria, no biological markers for major depression are currently available for inclusion in the diagnostic criteria.

show abstract

“…In a small study, distinct associations between suicidality and type 1 immune response and a predominance of type 2 immune parameters in non-suicidal patients were observed. 115 An epidemiological study also hypothezized that high IL-2 levels are associated with suicidality. 116 One study showed increased levels of serum sIL-2R in medication-free suicide attempters irrespective of the psychiatric diagnosis, 117 and treatment with high-dose IL-2 has been associated with suicide in a case report.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

2007

View full text Add to dashboard Cite

Beside the well-known deficiency in serotonergic neurotransmission as pathophysiological correlate of major depression (MD), recent evidence points to a pivotal role of increased glutamate receptor activation as well. However, cause and interaction of these neurotransmitter alterations are not understood. In this review, we present a hypothesis integrating current concepts of neurotransmission and hypothalamus-pituitary-adrenal (HPA) axis dysregulation with findings on immunological alterations and alterations in brain morphology in MD. An immune activation including increased production of proinflammatory cytokines has repeatedly been described in MD. Proinflammatory cytokines such as interleukin-2, interferon-c, or tumor necrosis factor-a activate the tryptophan-and serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Depressive states during inflammatory somatic disorders are also associated with increased proinflammatory cytokines and increased consumption of tryptophan via activation of IDO. An enhanced consumption of serotonin and its precursor tryptophan through IDO activation could well explain the reduced availability of serotonergic neurotransmission in MD. An increased activation of IDO and its subsequent enzyme kynurenine monooxygenase by proinflammatory cytokines, moreover, leads to an enhanced production of quinolinic acid, a strong agonist of the glutamatergic N-methyl-D-aspartate receptor. In inflammatory states of the central nervous system, IDO is mainly activated in microglial cells, which preferentially metabolize tryptophan to the NMDA receptor agonist quinolinic acid, whereas astrocytes -counteracting this metabolism due to the lack of an enzyme of this metabolism -have been observed to be reduced in MD. Therefore the type 1/type 2 immune response imbalance, associated with an astrocyte/microglia imbalance, leads to serotonergic deficiency and glutamatergic overproduction. Astrocytes are further strongly involved in re-uptake and metabolic conversion of glutamate. The reduced number of astrocytes could contribute to both, a diminished counterregulation of IDO activity in microglia and an altered glutamatergic neurotransmission. Further search for antidepressant agents should take into account anti-inflammatory drugs, for example, cyclooxygenase-2 inhibitors, might exert antidepressant effects by acting on serotonergic deficiency, glutamatergic hyperfunction and antagonizing neurotoxic effects of quinolinic acid. Molecular Psychiatry (2007) 12, 988-1000; doi:10.1038/sj.mp.4002006; published online 24 April 2007 Keywords: major depression; psychoneuroimmunology; IDO; glutamate; immune system; serotonin Glutamate in depressionGlutamatergic neurotransmission is involved in depression and interacts with the serotonergic and noradrenergic systems The common therapeutic mechanism of antidepressant drugs is the enhancement of serotonergic and/or noradrenergic neurotransmission. On the basis of this pharmacological profile of antidepressant drugs, neurochemical research on major depression ...

show abstract

Immune activation in non-treated suicidal major depression

Cited by 61 publications

References 13 publications

Imbalance between Th17 and Treg Cells May Play an Important Role in the Development of Chronic Unpredictable Mild Stress-Induced Depression in Mice

Imbalance between Th17 and Treg Cells May Play an Important Role in the Development of Chronic Unpredictable Mild Stress-Induced Depression in Mice

Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markers in Depression

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

Contact Info

Product

Resources

About