Investigations of the cellular immunity during depression and the free interval: evidence for an immune activation in affective psychosis

Müller, Norbert; Hofschuster, E.; Ackenheil, Manfred; Mempel, W; Eckstein, Reinhold

doi:10.1016/0278-5846(93)90055-w

Cited by 97 publications

(35 citation statements)

References 38 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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“…Early studies showed an increase of T-helper cells (CD4 ' cells) and an increased CD4 ' /CD8 ' ratio in depressive disorders (Syvalähti et al 1985;Maes et al 1992;Mü ller et al 1993). Further investigations of the cellular components of the immune system focussed on monocytes and macrophages.…”

Section: Immune Cellsmentioning

confidence: 99%

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

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227

126

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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.

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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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Investigations of the cellular immunity during depression and the free interval: evidence for an immune activation in affective psychosis

Cited by 97 publications

References 38 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

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

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

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