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Inflammation and neuronal plasticity: a link between childhood trauma and depression pathogenesis.

Cattaneo A, Macchi F, Plazzotta G, Veronica B, Bocchio-Chiavetto L, Riva MA, Pariante CM - Front Cell Neurosci (2015)

Bottom Line: However, it is still not clear whether inflammation represents a cause or whether other factors related to depression result in these immunological effects.Indeed, early life stressful events can cause, possibly through epigenetic changes that persist over time, up to adulthood.Moreover, we will discuss the role of epigenetics in inducing alterations in inflammation-immune systems as well as dysfunction in neuronal plasticity, thus contributing to the long-lasting negative effects of stressful life events early in life and the consequent enhanced risk for depression.

View Article: PubMed Central - PubMed

Affiliation: Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, King's College London London, UK ; IRCCS Centro S Giovanni di Dio, Fatebenefratelli Brescia, Italy.

ABSTRACT
During the past two decades, there has been increasing interest in understanding and characterizing the role of inflammation in major depressive disorder (MDD). Indeed, several are the evidences linking alterations in the inflammatory system to Major Depression, including the presence of elevated levels of pro-inflammatory cytokines, together with other mediators of inflammation. However, it is still not clear whether inflammation represents a cause or whether other factors related to depression result in these immunological effects. Regardless, exposure to early life stressful events, which represent a vulnerability factor for the development of psychiatric disorders, act through the modulation of inflammatory responses, but also of neuroplastic mechanisms over the entire life span. Indeed, early life stressful events can cause, possibly through epigenetic changes that persist over time, up to adulthood. Such alterations may concur to increase the vulnerability to develop psychopathologies. In this review we will discuss the role of inflammation and neuronal plasticity as relevant processes underlying depression development. Moreover, we will discuss the role of epigenetics in inducing alterations in inflammation-immune systems as well as dysfunction in neuronal plasticity, thus contributing to the long-lasting negative effects of stressful life events early in life and the consequent enhanced risk for depression. Finally we will provide an overview on the potential role of inflammatory system to aid diagnosis, predict treatment response, enhance treatment matching, and prevent the onset or relapse of Major Depression.

No MeSH data available.


Related in: MedlinePlus

Schematic rappresentation of the direct and indirect effect of stress on inflammation and neuroplasticity related processes. Stress induces directly an immediate release of glucocorticoids and pro-inflammatory cytokines (IL-1β, IL-6, CRP, TNF-α, INF-α); in turn incresead levels of glucocorticoids act on the brain by altering the CRH-ACTH signaling and, in turn, negatively affecting neurogenesis as well as the production of neurotrophic factors, including Brain Derived neurotrophic Factor (BDNF). Similarly, proinflammatory cytokines can negatively affect brain functioning and neurotrophins production and release. Stress can also work indirectly by activating epigenetic mechanisms (methylation, deacetylation, miRNAs), which may act on the same target stress related genes i.e., glucocorticid receptors, cytokines and BDNF. Red arrows indicate a suppressive effect, green arrows a stimulating effect.
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Figure 1: Schematic rappresentation of the direct and indirect effect of stress on inflammation and neuroplasticity related processes. Stress induces directly an immediate release of glucocorticoids and pro-inflammatory cytokines (IL-1β, IL-6, CRP, TNF-α, INF-α); in turn incresead levels of glucocorticoids act on the brain by altering the CRH-ACTH signaling and, in turn, negatively affecting neurogenesis as well as the production of neurotrophic factors, including Brain Derived neurotrophic Factor (BDNF). Similarly, proinflammatory cytokines can negatively affect brain functioning and neurotrophins production and release. Stress can also work indirectly by activating epigenetic mechanisms (methylation, deacetylation, miRNAs), which may act on the same target stress related genes i.e., glucocorticid receptors, cytokines and BDNF. Red arrows indicate a suppressive effect, green arrows a stimulating effect.

Mentions: There are several mechanisms by which cytokines can access the brain, influence central neuronal functions and cause behavioral changes known as “sickness behavior”, a coordinated set of psychological and physiological modifications that develop during the course of an infection (Dantzer, 2004) and that resemble depressive symptoms. One pathway may involve macrophage-like cells located in the circumventricular organs and the choroid plexus, which detect and respond to circulating pathogen-associated molecular patterns by producing pro-inflammatory cytokines; these cytokines can then cross the Blood Brain Barrier (BBB) and affect neuronal function and microglia activation. Another mechanism by which cytokines can reach the brain is via binding with their specific transporters, which are located on the BBB. Moreover, microglia cells in the brain produce cytokines receptors and thus amplify the inflammatory signals (Besedovsky and del Rey, 1996; Capuron and Miller, 2004). Once in the brain, cytokines can affect brain function in a variety of ways, including the modulation of neurotransmitter metabolism and neurotoxic mechanisms. As an example, cytokines induce the enzyme Indoleamine 2,3 Dioxygenase (IDO), which breaks down the serotonin precursor tryptophan into kynurenine that, once converted into quinolinic acid, may lead to neurotoxicity through the activation of the glutamatergic system (Myint and Kim, 2014). Cytokines have also been shown to decrease the neurotrophic support and to reduce neurogenesis in several brain areas, particularly in the hippocampus (Hashmi et al., 2013; Williamson and Bilbo, 2013). This may eventually contribute to the reduction of neuronal plasticity that represents a core feature of depression-related dysfunction (see below). Furthermore, as we have also represented in Figure 1, cytokines can increase the levels of stress hormones, including corticotrophin releasing hormone (CRH), adreno-corticotrophin hormone (ACTH) and cortisol, which have been reported to be elevated in patients with depression (Besedovsky and del Rey, 1996; Pariante and Miller, 2001) and may therefore participate to HPA dysfunction (Miller et al., 2009).


Inflammation and neuronal plasticity: a link between childhood trauma and depression pathogenesis.

Cattaneo A, Macchi F, Plazzotta G, Veronica B, Bocchio-Chiavetto L, Riva MA, Pariante CM - Front Cell Neurosci (2015)

Schematic rappresentation of the direct and indirect effect of stress on inflammation and neuroplasticity related processes. Stress induces directly an immediate release of glucocorticoids and pro-inflammatory cytokines (IL-1β, IL-6, CRP, TNF-α, INF-α); in turn incresead levels of glucocorticoids act on the brain by altering the CRH-ACTH signaling and, in turn, negatively affecting neurogenesis as well as the production of neurotrophic factors, including Brain Derived neurotrophic Factor (BDNF). Similarly, proinflammatory cytokines can negatively affect brain functioning and neurotrophins production and release. Stress can also work indirectly by activating epigenetic mechanisms (methylation, deacetylation, miRNAs), which may act on the same target stress related genes i.e., glucocorticid receptors, cytokines and BDNF. Red arrows indicate a suppressive effect, green arrows a stimulating effect.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4379909&req=5

Figure 1: Schematic rappresentation of the direct and indirect effect of stress on inflammation and neuroplasticity related processes. Stress induces directly an immediate release of glucocorticoids and pro-inflammatory cytokines (IL-1β, IL-6, CRP, TNF-α, INF-α); in turn incresead levels of glucocorticoids act on the brain by altering the CRH-ACTH signaling and, in turn, negatively affecting neurogenesis as well as the production of neurotrophic factors, including Brain Derived neurotrophic Factor (BDNF). Similarly, proinflammatory cytokines can negatively affect brain functioning and neurotrophins production and release. Stress can also work indirectly by activating epigenetic mechanisms (methylation, deacetylation, miRNAs), which may act on the same target stress related genes i.e., glucocorticid receptors, cytokines and BDNF. Red arrows indicate a suppressive effect, green arrows a stimulating effect.
Mentions: There are several mechanisms by which cytokines can access the brain, influence central neuronal functions and cause behavioral changes known as “sickness behavior”, a coordinated set of psychological and physiological modifications that develop during the course of an infection (Dantzer, 2004) and that resemble depressive symptoms. One pathway may involve macrophage-like cells located in the circumventricular organs and the choroid plexus, which detect and respond to circulating pathogen-associated molecular patterns by producing pro-inflammatory cytokines; these cytokines can then cross the Blood Brain Barrier (BBB) and affect neuronal function and microglia activation. Another mechanism by which cytokines can reach the brain is via binding with their specific transporters, which are located on the BBB. Moreover, microglia cells in the brain produce cytokines receptors and thus amplify the inflammatory signals (Besedovsky and del Rey, 1996; Capuron and Miller, 2004). Once in the brain, cytokines can affect brain function in a variety of ways, including the modulation of neurotransmitter metabolism and neurotoxic mechanisms. As an example, cytokines induce the enzyme Indoleamine 2,3 Dioxygenase (IDO), which breaks down the serotonin precursor tryptophan into kynurenine that, once converted into quinolinic acid, may lead to neurotoxicity through the activation of the glutamatergic system (Myint and Kim, 2014). Cytokines have also been shown to decrease the neurotrophic support and to reduce neurogenesis in several brain areas, particularly in the hippocampus (Hashmi et al., 2013; Williamson and Bilbo, 2013). This may eventually contribute to the reduction of neuronal plasticity that represents a core feature of depression-related dysfunction (see below). Furthermore, as we have also represented in Figure 1, cytokines can increase the levels of stress hormones, including corticotrophin releasing hormone (CRH), adreno-corticotrophin hormone (ACTH) and cortisol, which have been reported to be elevated in patients with depression (Besedovsky and del Rey, 1996; Pariante and Miller, 2001) and may therefore participate to HPA dysfunction (Miller et al., 2009).

Bottom Line: However, it is still not clear whether inflammation represents a cause or whether other factors related to depression result in these immunological effects.Indeed, early life stressful events can cause, possibly through epigenetic changes that persist over time, up to adulthood.Moreover, we will discuss the role of epigenetics in inducing alterations in inflammation-immune systems as well as dysfunction in neuronal plasticity, thus contributing to the long-lasting negative effects of stressful life events early in life and the consequent enhanced risk for depression.

View Article: PubMed Central - PubMed

Affiliation: Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, King's College London London, UK ; IRCCS Centro S Giovanni di Dio, Fatebenefratelli Brescia, Italy.

ABSTRACT
During the past two decades, there has been increasing interest in understanding and characterizing the role of inflammation in major depressive disorder (MDD). Indeed, several are the evidences linking alterations in the inflammatory system to Major Depression, including the presence of elevated levels of pro-inflammatory cytokines, together with other mediators of inflammation. However, it is still not clear whether inflammation represents a cause or whether other factors related to depression result in these immunological effects. Regardless, exposure to early life stressful events, which represent a vulnerability factor for the development of psychiatric disorders, act through the modulation of inflammatory responses, but also of neuroplastic mechanisms over the entire life span. Indeed, early life stressful events can cause, possibly through epigenetic changes that persist over time, up to adulthood. Such alterations may concur to increase the vulnerability to develop psychopathologies. In this review we will discuss the role of inflammation and neuronal plasticity as relevant processes underlying depression development. Moreover, we will discuss the role of epigenetics in inducing alterations in inflammation-immune systems as well as dysfunction in neuronal plasticity, thus contributing to the long-lasting negative effects of stressful life events early in life and the consequent enhanced risk for depression. Finally we will provide an overview on the potential role of inflammatory system to aid diagnosis, predict treatment response, enhance treatment matching, and prevent the onset or relapse of Major Depression.

No MeSH data available.


Related in: MedlinePlus