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Updates on immune system dysregulation in major depressive disorder
13th Psychoimmunology Expert Meeting March 3–6, 2016 / Neurology, psychiatry and brain research 22 (2016) 1–25
glial cells are reported in fronto-limbic brain regions in major depression and bipolar illness. In order to find common traits of microglia across different psychiatric disorders, we here compare microglia phenotypes between three different models of psychiatric endophenotypes (schizophrenia, autism, depression) using density measures and activation markers in different brain regions correlated with gene expression profiles utilized by RNAseq and behavior. We here propose that microglia undergo a possible reprogramming early in life, followed by a state of activation similar to a proinflammatory phenotype that finally can cumulate in a state of cellular senescence. While the stages of microglia activation are similar, the kinetic of this process is different depending on the animal model and thus most possibly also in patients. Treatment could be adapted according to the microglia phenotype (dormant, pro-inflammatory, senescence).
25
Ma-Li Wong
Clinical and pre-clinical data support a role for immune system dysregulation in major depressive disorder (MDD) and chronic stress. Dysregulation of the T-cell arm of the immune system has supported the role of immunomediators in depression. Cytokineproducing T cells Th1 and Th2 regulate the immune response to pathogens; these two main cell lineages differentiate from naı¨ve CD4+ T lymphocytes and have distinct cytokine profiles. Th1 patterns are related to increased inflammation and autoimmune conditions, and the production of IFN-g, TNF-a or IL-1; conversely, Th2 patterns are related to allergic responses and asthma, and the production of IL-6, IL-10 or IL-13. Our data support the notion that there is an imbalance of Th1/Th2 ratio in MDD, with a predominance of Th1 activation. However, different MDD subtypes may exhibit divergent immune profiles; decreased Th1 activation has been described in melancholic depressed patients with marked HPA axis activation, while non-melancholic and post-partum depression patients show increased inflammation features. Furthermore, antidepressants have immunoregulatory effects reducing Th1 cytokines production and promoting a shift towards Th2 patterns. We will discuss recent data from our lab that implicate a role for the inflammasome signalling in stress- and depressive-like behaviours, through the modulation of the relationship between stress and microbiota composition.
South Australian Health and Medical Research Institute/Flinders University, Adelaide, Australia
http://dx.doi.org/10.1016/j.npbr.2015.12.061
http://dx.doi.org/10.1016/j.npbr.2015.12.060 Updates on immune system dysregulation in major depressive disorder
glial cells are reported in fronto-limbic brain regions in major depression and bipolar illness. In order to find common traits of microglia across different psychiatric disorders, we here compare microglia phenotypes between three different models of psychiatric endophenotypes (schizophrenia, autism, depression) using density measures and activation markers in different brain regions correlated with gene expression profiles utilized by RNAseq and behavior. We here propose that microglia undergo a possible reprogramming early in life, followed by a state of activation similar to a proinflammatory phenotype that finally can cumulate in a state of cellular senescence. While the stages of microglia activation are similar, the kinetic of this process is different depending on the animal model and thus most possibly also in patients. Treatment could be adapted according to the microglia phenotype (dormant, pro-inflammatory, senescence).
25
Ma-Li Wong
Clinical and pre-clinical data support a role for immune system dysregulation in major depressive disorder (MDD) and chronic stress. Dysregulation of the T-cell arm of the immune system has supported the role of immunomediators in depression. Cytokineproducing T cells Th1 and Th2 regulate the immune response to pathogens; these two main cell lineages differentiate from naı¨ve CD4+ T lymphocytes and have distinct cytokine profiles. Th1 patterns are related to increased inflammation and autoimmune conditions, and the production of IFN-g, TNF-a or IL-1; conversely, Th2 patterns are related to allergic responses and asthma, and the production of IL-6, IL-10 or IL-13. Our data support the notion that there is an imbalance of Th1/Th2 ratio in MDD, with a predominance of Th1 activation. However, different MDD subtypes may exhibit divergent immune profiles; decreased Th1 activation has been described in melancholic depressed patients with marked HPA axis activation, while non-melancholic and post-partum depression patients show increased inflammation features. Furthermore, antidepressants have immunoregulatory effects reducing Th1 cytokines production and promoting a shift towards Th2 patterns. We will discuss recent data from our lab that implicate a role for the inflammasome signalling in stress- and depressive-like behaviours, through the modulation of the relationship between stress and microbiota composition.
South Australian Health and Medical Research Institute/Flinders University, Adelaide, Australia
http://dx.doi.org/10.1016/j.npbr.2015.12.061
http://dx.doi.org/10.1016/j.npbr.2015.12.060 Updates on immune system dysregulation in major depressive disorder