The impact of electroconvulsive therapy on the tryptophan–kynurenine metabolic pathway

Gülöksüz, Sinan; Arts, Baer; Walter, S; Drukker, Marjan; Rodríguez, Lucía Aja; Myint, Aye-Mu; Schwarz, Markus J.; Ponds, Rudolf; Os, Jim van; Kenis, Günter; Rutten, Bart P. F.

doi:10.1016/j.bbi.2015.02.029

Cited by 51 publications

(45 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, neither KynA/3HK nor KynA/QA levels were significantly different across groups. Although inflammation and kynurenine metabolism have been implicated in the pathophysiology of depression, there have been negative studies [47, 48, 55], and these biological processes are believed to contribute to depression in a subset rather than the entirety of patients [56]. Notwithstanding, sleep disturbance was significantly associated with hs-CRP and KynA/QA in this study, which suggests that kynurenine metabolism might be more robustly associated with a subtype of depression characterized by prominent sleep disturbances.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, several cross-sectional studies have reported that patients with depressive spectrum disorders, including major depression [42, 43], bipolar depression [44], and suicidality [45, 46], display a decrease in KynA and/or an increase in 3HK or QA in blood [42–44] and CSF [45, 46]. Further, electroconvulsive therapy was demonstrated to significantly reduce QA [43] and increase KynA as well as KynA/3HK [47] in patients with depression. However, it should be noted that there have also been more nuanced or negative findings regarding the role of the kynurenine pathway in depression pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sleep disturbance and kynurenine metabolism in depression

Cho

Savitz

Dantzer

et al. 2017

Journal of Psychosomatic Research

View full text Add to dashboard Cite

Objective Although the interrelationships between sleep disturbance, inflammation, and depression have been found, molecular mechanisms that link these conditions are largely unknown. Kynurenine metabolism is hypothesized to be a key mechanism that links inflammation and depression. Inflammation activates the kynurenine pathway, leading to increases in 3-hydroxykynurenine (3HK) and quinolinic acid (QA), potentially neurotoxic metabolites, and decreases in kynurenic acid (KynA), a potentially neuroprotective compound. This relative neurotoxic shift in the balance of kynurenine metabolites has been associated with depression, but never been examined regarding sleep disturbance. We tested the association between sleep disturbance and this relative neurotoxic shift in 68 currently depressed, 26 previously depressed, and 66 never depressed subjects. Methods Sleep disturbance was assessed using the Pittsburgh Sleep Quality Index. Serum concentrations of kynurenine metabolites were measured using high performance liquid chromatography. Putative neuroprotective indices reflecting the relative activity of neuroprotective and neurotoxic kynurenine metabolites were calculated as KynA/QA and KynA/3HK (primary outcomes). Results Sleep disturbance was associated with reduced KynA/QA in the currently depressed group only (unadjusted beta −0.43, p<0.001). This association remained significant even after controlling for age, sex, analysis batch, body-mass index, and depressive symptoms in currently depressed subjects (adjusted beta −0.30, p=0.02). There was no significant association between sleep disturbance and KynA/3HK in any of the groups. Sleep disturbance was associated with increased C-reactive protein in currently depressed subjects only (unadjusted beta 0.38, p=0.007; adjusted beta 0.33, p=0.02). Conclusion These data support the hypothesis that altered kynurenine metabolism may molecularly link sleep disturbance and depression.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sleep disturbance and kynurenine metabolism in depression

Cho

Savitz

Dantzer

et al. 2017

Journal of Psychosomatic Research

View full text Add to dashboard Cite

show abstract

“…Another metabolite of kynurenine, kynurenic acid, is considered to have neuroprotective properties (Haroon et al, 2012;Myint & Kim, 2003). It has been suggested that in patients with depression, activation of IDO could turn the kynurenine pathway toward the generation of neurotoxic metabolites (Guloksuz et al, 2015). ECT was recently reported to increase the levels of kynurenic acid, referring to the fact that ECT can alter the balance of the kynurenine pathway toward a neuroprotective course (Schwieler et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Low tumor necrosis factor‐α levels predict symptom reduction during electroconvulsive therapy in major depressive disorder

et al. 2018

View full text Add to dashboard Cite

ObjectiveChanges in the tumor necrosis factor‐α (TNFα) have been associated with major depressive disorder (MDD). Findings concerning the effects of electroconvulsive therapy (ECT) on the TNFα level have been contradictory. The aim was to examine the immediate and long‐term changes in the TNFα level and their associations with symptom reduction in patients with MDD during ECT.MethodThe study included 30 patients with MDD. Their TNFα levels were measured at baseline and 2 and 4 hr after the first, fifth and last ECT session. Depressive symptoms were assessed with the Montgomery‐Asberg Depression Rating Scale (MADRS).ResultsThe TNFα level decreased from baseline to the 2‐ and 4‐hr measurements. There was a correlation between the first ECT session TNFα levels and the relative symptom reduction according to the MADRS score after the ECT series. Both the first (baseline) ECT and 4‐hr TNFα levels were lower in responders than in nonresponders.Conclusion ECT consistently induced a decrease in the TNFα level after each studied session. A low TNFα level at the first ECT appeared to predict a symptom reduction. These findings suggest that TNFα might have a role in the pathogenesis in MDD and in the mechanism of action of ECT.

show abstract

“…Electroconvulsive therapy (ECT) has been used as a treatment for mental disorder since the 1930s [1] because of its effectiveness and the fast action in several psychiatric disorders such as bipolar disorder, major depression, and schizophrenia accompanied by catatonia, extreme depression, mania, and other affective components [2, 3]. Nevertheless, views on ECT vary; some researchers consider that it is probably ineffective and certainly causes brain damage, while others think it is completely safe and the most effective treatment available in psychiatry [4].…”

Section: Introductionmentioning

confidence: 99%

Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

Limoa

Hashioka

Miyaoka

et al. 2016

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundAlthough electroconvulsive therapy (ECT) is regarded as one of the efficient treatments for intractable psychiatric disorders, the mechanism of therapeutic action remains unclear. Recently, many studies indicate that ECT affects the immune-related cells, such as microglia, astrocytes, and lymphocytes. Moreover, microglial activation and astrocytic activation have been implicated in the postmortem brains of schizophrenia patients. We previously demonstrated that Gunn rats showed schizophrenia-like behavior and microglial activation in their brains. The present study examined the effects of electroconvulsive shock (ECS), an animal counterpart of ECT, on schizophrenia-like behavior, microgliosis, and astrogliosis in the brain of Gunn rats.MethodsThe rats were divided into four groups, i.e., Wistar sham, Wistar ECS, Gunn sham, and Gunn ECS. ECS groups received ECS once daily for six consecutive days. Subsequently, prepulse inhibition (PPI) test was performed, and immunohistochemistry analysis was carried out to determine the activation degree of microglia and astrocytes in the hippocampus by using anti-CD11b and anti-glial fibrillary acidic protein (GFAP) antibody, respectively.ResultsWe found PPI deficit in Gunn rats compared to Wistar rats, and it was significantly improved by ECS. Immunohistochemistry analysis revealed that immunoreactivity of CD11b and GFAP was significantly increased in Gunn rats compared to Wistar rats. ECS significantly attenuated the immunoreactivity of both CD11b and GFAP in Gunn rats.ConclusionsECS ameliorated schizophrenia-like behavior of Gunn rats and attenuated microgliosis and astrogliosis in the hippocampus of Gunn rats. Accordingly, therapeutic effects of ECT may be exerted, at least in part, by inhibition of glial activation. These results may provide crucial information to elucidate the role of activated glia in the pathogenesis of schizophrenia and to determine whether future therapeutic interventions should attempt to up-regulate or down-regulate glial functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0688-2) contains supplementary material, which is available to authorized users.

show abstract

The impact of electroconvulsive therapy on the tryptophan–kynurenine metabolic pathway

Cited by 51 publications

References 32 publications

Sleep disturbance and kynurenine metabolism in depression

Sleep disturbance and kynurenine metabolism in depression

Low tumor necrosis factor‐α levels predict symptom reduction during electroconvulsive therapy in major depressive disorder

Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

Contact Info

Product

Resources

About