Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis

Haack, Monika; Hinze-Selch, D.; Fenzel, T.; Kraus, Thomas; Kühn, Martin; Schuld, Andreas; Pollmächer, Thomas

doi:10.1016/s0022-3956(99)00021-7

Cited by 314 publications

(160 citation statements)

References 90 publications

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“…Hepcidin prohormone, a recently discovered hepatic peptide that regulates intestinal iron absorption, 53,54 was found unaffected by the high-dose EPO treatment as was the inflammatory cytokine IL-6, which had previously been found to be elevated in schizophrenia 55 (Table 6). Both hepcidin and IL-6 did not differ significantly between groups and were always within the normal range (according to the manufacturers).…”

Section: Resultsmentioning

confidence: 97%

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin

et al. 2006

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Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a doubleblind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N = 39) with defined cognitive deficit (X1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N = 20) or placebo (N = 19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) -perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

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Section: Resultsmentioning

confidence: 97%

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin

et al. 2006

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“…97,108,109 The potential influence of possibly interfering variables, such as age, smoking, gender, recent infections and prior medication (including insufficient washout period) to IL-6 release and concentration must be considered. 110 An agerelated increase of IL-6 serum values was reported in patients with MD, 111 but also elderly depressed patients exhibit higher IL-6 serum levels compared with control persons of comparable age. 92 In contrast, CSF levels of IL-6 and soluble IL-6 receptor were found to be markedly reduced in geriatric patients suffering from depression.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 91%

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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“…An age-related increase of IL-6 serum values was reported in patients with major depression (Ershler et al 1993). From a methodological point of view, the potential influence of possibly interfering variables such as smoking, gender, recent infections and prior medication on IL-6 release and concentration must be considered (Haack et al 1999).…”

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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Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis

Cited by 314 publications

References 90 publications

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin

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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