Blog
About

34
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      The role of inflammation in depression: from evolutionary imperative to modern treatment target

      ,

      Nature Reviews Immunology

      Springer Science and Business Media LLC

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.

          Related collections

          Most cited references 78

          • Record: found
          • Abstract: found
          • Article: not found

          A neurotrophic model for stress-related mood disorders.

          There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotrophic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions.

            Although the fact that genetic predisposition and environmental exposures interact to shape development and function of the human brain and, ultimately, the risk of psychiatric disorders has drawn wide interest, the corresponding molecular mechanisms have not yet been elucidated. We found that a functional polymorphism altering chromatin interaction between the transcription start site and long-range enhancers in the FK506 binding protein 5 (FKBP5) gene, an important regulator of the stress hormone system, increased the risk of developing stress-related psychiatric disorders in adulthood by allele-specific, childhood trauma-dependent DNA demethylation in functional glucocorticoid response elements of FKBP5. This demethylation was linked to increased stress-dependent gene transcription followed by a long-term dysregulation of the stress hormone system and a global effect on the function of immune cells and brain areas associated with stress regulation. This identification of molecular mechanisms of genotype-directed long-term environmental reactivity will be useful for designing more effective treatment strategies for stress-related disorders.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Why rejection hurts: a common neural alarm system for physical and social pain.

              Numerous languages characterize 'social pain', the feelings resulting from social estrangement, with words typically reserved for describing physical pain ('broken heart', 'broken bones') and perhaps for good reason. It has been suggested that, in mammalian species, the social-attachment system borrowed the computations of the pain system to prevent the potentially harmful consequences of social separation. Mounting evidence from the animal lesion and human neuroimaging literatures suggests that physical and social pain overlap in their underlying neural circuitry and computational processes. We review evidence suggesting that the anterior cingulate cortex plays a key role in the physical-social pain overlap. We also suggest that the physical-social pain circuitry might share components of a broader neural alarm system.
                Bookmark

                Author and article information

                Journal
                Nature Reviews Immunology
                Nat Rev Immunol
                Springer Science and Business Media LLC
                1474-1733
                1474-1741
                January 2016
                December 29 2015
                January 2016
                : 16
                : 1
                : 22-34
                Article
                10.1038/nri.2015.5
                26711676
                © 2016

                Comments

                Comment on this article