Cytokine profiles in women with different subtypes of major depressive disorder

Marques-Deak, Andrea; Neto, Francisco Lotufo; Dominguez, Wagner Vasques; Solis, Ana Cristina de Oliveira; Kurcgant, Daniela; Sato, Fábio Pinato; Ross, Jerilyn; Prado, E B A

doi:10.1016/j.jpsychires.2005.11.003

Cited by 101 publications

(74 citation statements)

References 38 publications

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“…A considerable number of studies showed elevated serum levels of TNF-a 70,86,[89][90][91][92][93] and IL-1b [94][95][96] in depressed patients, whereas only few investigators reported unchanged levels of these cytokines. 97 A study on elevated mRNA levels of TNF-a in peripheral mononuclear cells of depressed patients confirms the majority of findings on elevated serum levels. 98 Levels of IL-1b are also elevated in cerebrospinal fluid (CSF), whereas TNF-a levels are not altered in CSF of depressed patients.…”

Section: The Inflammatory Hypothesis Of Depressionsupporting

confidence: 59%

“…106 Contradictory results are very few indicating reduced, 107 or not altered, serum IL-6 levels. 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.…”

Section: The Inflammatory Hypothesis Of Depressionmentioning

confidence: 99%

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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 Depressionsupporting

confidence: 59%

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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“…1 Although the contributions of immune mediators to the pathophysiology and treatment of psychiatric disorders may be traced back to over 80 years with the work of Nobel laureate Julius Wagner-Jauregg, 3 evidence from clinical and basic research have recently supported a role for dysregulation of the immune system in MDD. 4 Both acute stress and MDD are states of hyperarousal, in which a sustained focus on the threatening stimulus, fear-related behaviors and stereotyped states of cognition and affect are matched with indices of physiological hyperarousal, such as activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic activation, and inhibition of counterproductive neurovegetative functions during life-threatening situations. 5,6 Depression-like symptoms have been associated with activation of the HPA axis, sympathetic nervous system and inflammatory response characterized by hypercortisolaemia, 7 increased central corticotropin-releasing hormone (CRH) [8][9][10] and norepineprhine 11,12 functions, increased numbers of peripheral leukocytes, positive acute phase proteins and proinflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response

et al. 2008

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There are clinical parallels between the nature and course of depressive symptoms in major depressive disorder (MDD) and those of inflammatory disorders. However, the characterization of a possible immune system dysregulation in MDD has been challenging. Emerging data support the role of T-cell dysfunction. Here we report the association of MDD and antidepressant response to genes important in the modulation of the hypothalamic-pituitaryadrenal axis and immune functions in Mexican Americans with major depression. Specifically, single nucleotide polymorphisms (SNPs) in two genes critical for T-cell function are associated with susceptibility to MDD: PSMB4 (proteasome b4 subunit), important for antigen processing, and TBX21 (T bet), critical for differentiation. Our analyses revealed a significant combined allele dose-effect: individuals who had one, two and three risk alleles were 2.3, 3.2 and 9.8 times more likely to have the diagnosis of MDD, respectively. We found associations of several SNPs and antidepressant response; those genes support the role of T cell (CD3E, PRKCH, PSMD9 and STAT3) and hypothalamic-pituitary-adrenal axis (UCN3) functions in treatment response. We also describe in MDD increased levels of CXCL10/IP-10, which decreased in response to antidepressants. This further suggests predominance of type 1 T-cell activity in MDD. T-cell function variations that we describe here may account for 47.8% of the attributable risk in Mexican Americans with moderate MDD. Immune function genes are highly variable; therefore, different genes might be implicated in distinct population groups.

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“…It has been established that proinflammatory cytokines induce not only symptoms of sickness, but also true major depressive disorders [2][3][4][5]. However, conflicting results have also been described [3,6]. Although the role of cytokines in depressive disorders is complex and requires to be clarified, a hypothesis regarding the pathophysiology of depression has been debated in the literature [7].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous measurement of 23 plasma cytokines in late-life depression

et al. 2009

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According to the cytokine hypothesis of depression, cytokines play key roles in the behavioral, neuroendocrinal, and neurochemical features of depression. In this study, we used a bioplex assay to simultaneously measure the levels of 23 plasma cytokines in 18 patients with late-life depression and 38 normal controls, and these levels were compared between the two groups. The plasma interleukin-1alpha (IL-1a) levels were found to be significantly different between the two groups. After adjusting for age, gender, low-density lipoprotein cholesterol, and triglyceride, the plasma IL-1a levels were significantly higher in the patients with late-life depression than in the normal control subjects. Thus, this study provides preliminary evidence that plasma IL-1a may play important roles in the pathogenesis of late-life depression.

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Cytokine profiles in women with different subtypes of major depressive disorder

Cited by 101 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

Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response

Simultaneous measurement of 23 plasma cytokines in late-life depression

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