Plasma levels of adiponectin and tumor necrosis factor-alpha in patients with remitted major depression receiving long-term maintenance antidepressant therapy

Narita, Kosuke; Murata, Tetsuhito; Takahashi, Tetsuya; Kosaka, Hirotaka; Omata, Naoto; Wada, Yuji

doi:10.1016/j.pnpbp.2006.03.030

Cited by 75 publications

(50 citation statements)

References 26 publications

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“…Markedly reduced TNF-a serum levels were found in remitted depressed patients after chronic antidepressant therapy for at least half a year. 199 However, there are again some conflicting results, showing no effect of certain antidepressants on serum levels of different cytokines. 65,100 Regarding the relationship between IL-6 and PGE 2 as mentioned above, an inhibiting action of antidepressants on PGE 2 would be expected.…”

Section: Antidepressant Pharmacotherapymentioning

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: Antidepressant Pharmacotherapymentioning

confidence: 99%

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

2007

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“…Emerging clinical evidence suggests an association between circulating adiponectin levels and depression but with inconsistent results, perhaps as a result of small sample sizes, sex differences, and age ranges covered in these studies (22)(23)(24)(25)(26). Questions remain to be answered as to whether adiponectin plays a role in the pathophysiology of depression and whether adiponectin modulates depressive behaviors.…”

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confidence: 99%

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Liu¹,

Guo²,

Zhang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

154

162

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Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte-derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, "anhedonia," and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressantlike behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.

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“…Clinical studies have reported lower levels of plasma adiponectin in patients with depression (17), which could be increased after antidepressant treatments (18). A recent study has also shown that adiponectin deficiency increases depressive symptoms in mice, whereas reintroduction of adiponectin exerts antidepressant effects (19).…”

mentioning

confidence: 99%

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin

Yau

Li²,

Hoo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

257

239

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Adiponectin (ADN) is an adipocyte-secreted protein with insulinsensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the bloodbrain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exerciseinduced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.adiponectin | adiponectin receptor | physical exercise | hippocampal neurogenesis | depression-like behavior

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Plasma levels of adiponectin and tumor necrosis factor-alpha in patients with remitted major depression receiving long-term maintenance antidepressant therapy

Cited by 75 publications

References 26 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

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin

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