Immune and hormonal activity in adults suffering from depression

Nunes, Sandra; Reiche, Edna Maria Vissoci; Morimoto, Helena Kaminami; Matsuo, Tiemi; Itano, Eiko Nakagawa; Xavier, Ely Caetano; Yamashita, Chinami; Vieira, Valdeli; Menoli, Adriana V.; Silva, S.S.; Costa, Fernando B. Da; Reiche, F.; Silva, F.L.V.; Kaminami, Mari Sumigawa

doi:10.1590/s0100-879x2002000500011

Cited by 72 publications

(45 citation statements)

References 31 publications

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“…62,63 Activation of the immune system in MD The characteristics of the immune activation in MD include increased numbers of circulating lymphocytes and phagocytic cells, upregulated serum levels of parameters indicating activated immune cells (for example, soluble IL-2 receptor), higher serum concentrations of positive acute phase proteins (APP), coupled with reduced levels of negative APP, as well as an increased release of proinflammatory cytokines, such as IL-1, IL-2, TNF-a and IL-6 through activated macrophages and IFN-g through activated T cells. [64][65][66][67][68][69][70] Increased numbers of peripheral mononuclear cells have been described by different groups of researchers. [71][72][73] According to these findings, an increased secretion of neopterin has been described by several Immune-mediated alteration of serotonin and glutamate N Müller and MJ Schwarz groups of researchers.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

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

2007

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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 ...

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Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

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

2007

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“…211 Dysregulated activity of the immune system in depression, with increased proinflammatory activity, has repeatedly been demonstrated. [212][213][214][215][216] In addition, inflammatory diseases are typically associated with depressed mood. 217,218 Administration of proinflammatory cytokines (e.g.…”

Section: Stressmentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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“…Activated monocytes or macrophages from these patients ex vivo produce increased levels of IL-1, IL-6, TNF and prostaglandin E 2 (PGE 2 ). Activated T cells from depressed individuals ex vivo have been shown to produce increased levels of IFN [33][34][35][36][37][38][39][40]. Increased serum levels of IFN as well in increased INF-/IL-4 and INF-/transforming growth factor (TGF)-ratio are found.…”

Section: Systemic Th1-dominated Cytokine Re-sponse In Depressed Indivmentioning

confidence: 99%

Depression has a Strong Relationship to Alterations in the Immune, Endocrine and Neural System

Hestad¹,

Aukrust²,

Tønseth³

et al. 2009

CPSR

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Epidemiological findings indicate a connection between depressive symptoms and changes in status of the immune system in depressed patients. This raises the possibility of causative connections. Theories on mechanisms for interactions between immune and affective systems -directly and via endocrine system -are evolving. Such hypothesized causative connections are supported by several findings. First, in depressed patients changes in the status of the immune system in vivo and ex vivo are seen. Also, depressive symptoms are seen in patients with altered immune status (physiologically, pathologically or chemically induced). Knowledge in this field may have implications regarding psychiatric follow up of physically ill people suffering from diseases caused by an altered immune system (long lasting infections, autoimmune diseases, hypersensitivity disorders) as well as disorders for which treatment and prognoses depends on the immune system (infections, cancer). Similarly, medical treatment of depressed patients may be adjusted by more specific knowledge about the interaction between neuroimmunology and depression. Important findings and the present knowledge and theories are reviewed.

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Immune and hormonal activity in adults suffering from depression

Cited by 72 publications

References 31 publications

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

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

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Depression has a Strong Relationship to Alterations in the Immune, Endocrine and Neural System

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