The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression

Song, Cai; Lin, Aihua; Bonaccorso, Stefania; Heide, Carine; Verkerk, Robert; Kenis, Günter; Bosmans, Eugène; Scharpé, Simon; Whelan, A.; Cosyns, Paul; Jongh, R. De; Maes, Michaël

doi:10.1016/s0165-0327(98)00025-1

Cited by 220 publications

(139 citation statements)

References 48 publications

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“…An in vitro study reports increased PGE 2 secretion from lymphocytes of depressed patients compared to healthy controls. 10 Increased PGE 2 in the saliva, the serum and the cerebrospinal fluid of depressed patients has previously been described. [11][12][13][14] According to the stimulating effect of PGE 2 on IL-6, most of the studies dealing with IL-6 report a marked increase of IL-6 in vitro production 15 or serum levels in depressed patients.…”

Section: Introductionmentioning

confidence: 86%

The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine

et al. 2006

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Signs of an inflammatory process, in particular increased pro-inflammatory cytokines and increased levels of prostaglandine E 2 (PGE 2 ), have repeatedly been described in major depression (MD). As cyclooxygenase-2 (COX-2) inhibitors inhibit the PGE 2 production and the production of pro-inflammatory cytokines, we performed a therapeutic trial with the COX-2 inhibitor celecoxib. In a prospective, double-blind, add-on study, 40 patients suffering from an acute depressive episode were randomly assigned to either reboxetine and celecoxib or to reboxetine plus placebo. After a wash-out period, 20 patients received 4-10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks. The treatment effect was calculated by analysis of variance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or reboxetine dose or plasma levels. Over 6 weeks, both groups of patients showed significant improvement in scores of the Hamilton Depression Scale. However, the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group. Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology. Moreover, the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder, although the exact mechanisms remain to become elucidated.

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Section: Introductionmentioning

confidence: 86%

The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine

et al. 2006

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“…89 As a product of activated monocytes and macrophages, IL-6 is one of the most frequently investigated immune parameters in MD. The majority of reports demonstrate a markedly higher in vitro IL-6 production, 80,94 or higher serum IL-6 levels in depressed patients 65,87,93,[99][100][101][102][103][104] as well as IL-6 mRNA expression in leukocytes. 98 The elevation of IL-6 seems to be especially profound in the morning.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

“…[134][135][136] In vitro studies likewise show an increased PGE 2 secretion from lymphocytes of depressed patients compared with healthy controls. 102 Twenty years ago, it was suggested that antidepressants inhibit PGE 2 . 137 A recent in vitro study has shown that both tricyclic antidepressants and selective serotonin inhibitors attenuated cytokine-induced PGE 2 and nitric oxide production by inflammatory cells from synovial tissue.…”

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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“…Most publications report a marked increase of in vitro IL-6 production (Maes et al 1993) or serum IL-6 levels in depressed patients (Maes et al 1995b(Maes et al , 1997aSluzewska et al 1995Sluzewska et al , 1996Berk et al 1997;Frommberger et al 1997;Song et al 1998). Most of these studies also report elevated plasma levels of acute phase proteins Á markers of the unspecific (innate) immune system.…”

Section: Interleukin-6mentioning

confidence: 99%

“…Increased concentrations of PGE 2 in saliva of depressed patients have been repeatedly described (Ohishi et al 1988;Nishino et al 1989). Moreover, in vitro studies show an increased PGE 2 secretion from lymphocytes of depressed patients compared to healthy controls (Song et al 1998).…”

Section: Interleukin-6mentioning

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

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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The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression

Cited by 220 publications

References 48 publications

The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine

The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine

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

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