Cytokine-Associated Emotional and Cognitive Disturbances in Humans

Reichenberg, Abraham; Raz, Yael; Schuld, Andreas; Kraus, Thomas; Haack, Monika; Morag, Abraham; Pollmächer, Thomas

doi:10.1001/archpsyc.58.5.445

Cited by 1,207 publications

(811 citation statements)

References 51 publications

Supporting

Mentioning

753

Contrasting

Unclassified

Order By: Relevance

“…In addition, some treatment-induced physical symptoms (e.g. nausea) may either induce or be associated with altered mood state as part of the 'sickness response' [31]. Similarly, lower performance status was associated with increased levels of anxiety/depression.…”

Section: Discussionmentioning

confidence: 99%

Psychological distress and its correlates in ovarian cancer: a systematic review

2008

View full text Add to dashboard Cite

Objective: Ovarian cancer is often diagnosed at an advanced stage, and consequently high levels of distress are often experienced. It is necessary to understand the factors associated with psychological distress in order to guide interventions to target those factors. The purpose of this systematic review was therefore to identify correlates of psychological distress in ovarian cancer.Methods: Included studies had to be quantitative and empirical, with standardized measures of psychological distress (anxiety or depression), and to present results for ovarian cancer patients specifically. Standard systematic search methods were used. Information about design, ovarian cancer sample size, disease stage, time since diagnosis, measures of distress used and findings was extracted from each study. The studies were quality assessed using experimenterdefined criteria as good, average and poor quality. Strength of the evidence (strong, some, inconclusive) was based on the quality and consistency of findings.Results: Eighteen studies meeting the inclusion criteria were identified. There was strong evidence for a relationship between younger age, being diagnosed with more advanced disease, more physical symptoms and shorter time since diagnosis with increased levels of anxiety and/ or depression. Additional factors (e.g. immune) tested in a few studies also emerged as correlates of distress.Conclusions: Demographic, disease and quality of life factors correlated with distress. However, too few studies assessed possible psychological and immunological correlates, which could be potentially modified and should be assessed in future studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Psychological distress and its correlates in ovarian cancer: a systematic review

2008

View full text Add to dashboard Cite

show abstract

“…52 LPS, a potent activator of proinflammatory cytokines, was found to induce mild fever, anorexia, anxiety, depressed mood, and cognitive impairment. The levels of anxiety, depression and cognitive impairment were found to be related to the levels of circulating cytokines (see Table 1).…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

“…The levels of anxiety, depression and cognitive impairment were found to be related to the levels of circulating cytokines (see Table 1). 52,53 Side effects of cytokine therapies A depressive syndrome including suicidal ideations is a common side effect of cytokine administration, for example, IFN-a in the therapy of hepatitis C or malignant melanoma. [54][55][56][57][58] During these therapies, IDO is activated and the tryptophan metabolism increases.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

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

2007

View full text Add to dashboard Cite

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 ...

show abstract

“…Several studies in healthy volunteers have suggested that increased concentrations of IL-6, but also of TNF-a and IL-1 receptor antagonist (IL-1Ra) may cause depressed mood. [218][219][220] The increase of several proinflammatory cytokines appear to correlate with the severity of depressive symptom. 214,215,217,218,221 The 'cytokine theory of depression' implies that proinflammatory cytokines, acting as neuromodulators, represent the key factor in the (central) mediation of the behavioral, neuroendocrine and neurochemical features of depressive disorders.…”

Section: Stressmentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

View full text Add to dashboard Cite

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...

show abstract

Cytokine-Associated Emotional and Cognitive Disturbances in Humans

Abstract: In humans, a mild stimulation of the primary host defense has negative effects on emotional and memory functions, which are probably caused by cytokine release. Hence, cytokines represent a novel target for neuropsychopharmacological research.

Cited by 1,207 publications

References 51 publications

Psychological distress and its correlates in ovarian cancer: a systematic review

Psychological distress and its correlates in ovarian cancer: a systematic review

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

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Contact Info

Product

Resources

About