The effect of electroconvulsive therapy (ECT) on serum tryptophan metabolites

Abstract

Background: Prior studies suggest that activation of the tryptophan catabolism via the kynurenine pathway by proinflammatory cytokines may be involved in the pathophysiology of depression. Electroconvulsive therapy (ECT) is an effective treatment for major depression (MD) with immunomodulation as one of the proposed modes of action. Objective: The aim of this study was to investigate serum concentrations of tryptophan and kynurenine pathway metabolites in MD patients and healthy controls, and to explore the effect of ECT on components of the kynurenine pathway. Methods: The study included 27 moderately to severely depressed patients referred to ECT. Blood samples were collected prior to treatment and after the completed ECT-series. Baseline samples were also collected from 14 healthy, age-and sex-matched controls. Serum concentrations of tryptophan, kynurenine, 3-hydroxykynurenine (HK), kynurenic acid (KA), xanthurenic acid (XA), anthranilic acid (AA), 3-hydroxyanthranilic acid (HAA), quinolinic acid (QA), picolinic acid (Pic), pyridoxal 5 0 -phosphat (PLP), riboflavin, neopterin and cotinine were measured. Results: Patients with MD had lower levels of neuroprotective kynurenine-pathway metabolites (KA, XA and Pic) and lower metabolite ratios (KA/Kyn and KA/QA) reflecting reduced neuroprotection compared to controls. The concentration of the inflammatory marker neopterin was increased after ECT, along with Pic and the redox active and immunosuppressive metabolite HAA. Conclusion:In this pilot study, we found increased concentrations of inflammatory marker neopterin and putative neuroprotective kynurenine metabolites HAA and Pic in MD patients after ECT. Further research in larger cohorts is required to conclude whether ECT exerts its therapeutic effects via changes in the kynurenine pathway.

Elevated body weight modulates subcortical volume change and associated clinical response following electroconvulsive therapy

“…42 Furthermore, preliminary evidence suggests that ECT might interfere with serum concentrations of kynurenine pathway metabolites. 43 Future ECT research should explore whether these mechanisms might explain the pattern of results observed in the present work.…”

The tryptophan catabolite or kynurenine pathway in a major depressive episode with melancholia, psychotic features and suicidal behaviors; a systematic review and meta-analysis

“…Moreover, in the plasma of suicidal MDD patients, QA levels were either significantly decreased (Achtyes, Keaton et al 2020) or unaltered (Brundin, Sellgren et al 2016). No significant changes in QA levels were found in depressed patients with psychotic features or melancholia (Dahl, Andreassen et al 2015, Aarsland, Leskauskaite et al 2019). In the current study, we did not find any difference between peripheral and central QA levels or between patients with melancholia, psychotic features, and suicidal behavior, but, overall, there was a significant increase.…”

“…We employed MESH terms and keywords (all shown in ESF, Table 1) to perform the initial search process, including inspection of 10861 articles. Based on our exclusion criteria 35 studies were selected as eligible in our systematic review and meta-analysis (Cowen, Parry-Billings et al 1989, Anderson, Parry-Billings et al 1990, Maes, Jacobs et al 1990, Price, Charney et al 1991, Quintana 1992, Maes, Meltzer et al 1993, Møller 1993, Maes, De Backer et al 1995, Maes, Wauters et al 1996, Song, Lin et al 1998, Hoekstra, Fekkes et al 2006, Miller, Llenos et al 2006, Myint, Kim et al 2007, Myint, Kim et al 2007, Gabbay, Klein et al 2010, Steiner, Walter et al 2011, Sublette, Galfalvy et al 2011, Erhardt, Lim et al 2013, Bay-Richter, Linderholm et al 2015, Bradley, Case et al 2015, Busse, Busse et al 2015, Dahl, Andreassen et al 2015, Savitz, Drevets et al 2015, Brundin, Sellgren et al 2016, Clark, Pocivavsek et al 2016, Zhou, Zheng et al 2018, Aarsland, Leskauskaite et al 2019, Pompili, Lionetto et al 2019, Sellgren, Gracias et al 2019, Achtyes, Keaton et al 2020, Ryan, Allers et al 2020, van den Ameele, van Nuijs et al 2020, Milaneschi, Allers et al 2021, Trepci, Sellgren et al 2021).…”

Blood plasma B vitamins in depression and the therapeutic response to electroconvulsive therapy

“…1 ; Majewski et al., 2016 ; Ueland et al., 2017 ). Notably, we and others have recently shown concentrations of tryptophan and kynurenine pathway metabolites, including XA, HAA, KYNA, and AA, to be reduced in patients with depression ( Aarsland et al., 2019 ; Arnone et al., 2018 ; Ogyu et al., 2018 ; Ryan et al., 2020 ). Many studies have also shown links between inflammation and depression ( Chamberlain et al., 2019 ; Enache et al., 2019 ; Hiles et al., 2012 ; Howren et al., 2009 ; Lamers et al., 2019 ; Mikkelsen et al., 2017 ; Valkanova et al., 2013 ), which may be linked to vitamin B status since both human and animal studies have shown that B vitamin concentrations are related to immune cell activity and inflammatory mediator concentrations, e.g., C-reactive protein (CRP), interleukin-6 (IL-6) (see Mikkelsen et al., 2017 ; Ueland et al., 2017 ).…”