TY - JOUR
T1 - The interaction between kynurenine pathway, suicidal ideation and augmentation therapy with minocycline in patients with treatment-resistant depression
AU - Nettis, Maria Antonietta
AU - Lombardo, Giulia
AU - Hastings, Caitlin
AU - Zajkowska, Zuzanna
AU - Mariani, Nicole
AU - Nikkheslat, Naghmeh
AU - Sforzini, Luca
AU - Worrell, Courtney
AU - Begum, Amina
AU - Brown, Mollie
AU - Cleare, Anthony J
AU - Young, Allan H
AU - Pariante, Carmine M
AU - Mondelli, Valeria
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This research was funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Prof. Valeria Mondelli is also supported by MQ: Transforming Mental Health (grant: MQBF/1 and MQBF/4) and by the Medical Research Foundation (grant number MRF-160-0005-ELP-MONDE).
Funding Information:
We thank the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the National Institute for Health and Care Research NIHR/Wellcome Trust King’s Clinical Research Facility. All visits took place at the Clinical Research Facility of King’s College Hospital. The team of nurses has to be thanked for providing their valuable expertise to the study. The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This research was funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Prof. Valeria Mondelli is also supported by MQ: Transforming Mental Health (grant: MQBF/1 and MQBF/4) and by the Medical Research Foundation (grant number MRF-160-0005-ELP-MONDE).
Publisher Copyright:
© The Author(s) 2023.
PY - 2023/6
Y1 - 2023/6
N2 - Background and aims: We investigated kynurenine pathway (KP) metabolites levels and their association with suicidal ideation in patients with treatment-resistant depression (TRD) and elevated peripheral inflammation. The effect of antidepressant augmentation with minocycline on KP metabolites was tested. Methods: We analysed data from MINocycline in DEPression, a 4-week, randomized, placebo controlled (1:1) trial of minocycline added to antidepressant treatment in 39 TRD patients (n = 18 minocycline; n = 21 placebo) with C-reactive protein (CRP) ⩾1 mg/L. At baseline and at week 4, we collected data on suicidality (Beck Depression Inventory) and blood samples to measure inflammatory markers and KP metabolites. We tested (1) the association of KP metabolites ratios with inflammatory markers and suicidal ideation at baseline and (2) the role of suicidality and treatment (minocycline vs placebo) in affecting KP changes over time. Results: At baseline, kynurenine/tryptophan (KYN/TRP) ratio positively correlated with high-sensitivity CRP (Spearman’s ρ = 0.35, p = 0.02) and IL-10, (ρ = 0.41, p = 0.009); and tumour necrosis factor was positively correlated with quinolinic acid/3-hydroxykynurenine ratio (ρ = 0.55, p < 0.001). Moreover, participants with suicidal ideation showed higher levels of KYN/TRP (U = 143.000, p = 0.02) than those without suicidal ideation. There was no significant effect of minocycline on KP metabolites changes from baseline to week 4. However, in the minocycline group, the number of participants with suicidal thoughts decreased from 44.4% (8/18) to 22.2% (4/18). Conclusion: Increased KP neurotoxic metabolites are associated with elevated peripheral inflammation in depressed individuals, particularly in those with suicidal ideation. Targeting KP in this population could be a potential effective personalized approach. Whether this includes minocycline should be investigated in future larger trials.
AB - Background and aims: We investigated kynurenine pathway (KP) metabolites levels and their association with suicidal ideation in patients with treatment-resistant depression (TRD) and elevated peripheral inflammation. The effect of antidepressant augmentation with minocycline on KP metabolites was tested. Methods: We analysed data from MINocycline in DEPression, a 4-week, randomized, placebo controlled (1:1) trial of minocycline added to antidepressant treatment in 39 TRD patients (n = 18 minocycline; n = 21 placebo) with C-reactive protein (CRP) ⩾1 mg/L. At baseline and at week 4, we collected data on suicidality (Beck Depression Inventory) and blood samples to measure inflammatory markers and KP metabolites. We tested (1) the association of KP metabolites ratios with inflammatory markers and suicidal ideation at baseline and (2) the role of suicidality and treatment (minocycline vs placebo) in affecting KP changes over time. Results: At baseline, kynurenine/tryptophan (KYN/TRP) ratio positively correlated with high-sensitivity CRP (Spearman’s ρ = 0.35, p = 0.02) and IL-10, (ρ = 0.41, p = 0.009); and tumour necrosis factor was positively correlated with quinolinic acid/3-hydroxykynurenine ratio (ρ = 0.55, p < 0.001). Moreover, participants with suicidal ideation showed higher levels of KYN/TRP (U = 143.000, p = 0.02) than those without suicidal ideation. There was no significant effect of minocycline on KP metabolites changes from baseline to week 4. However, in the minocycline group, the number of participants with suicidal thoughts decreased from 44.4% (8/18) to 22.2% (4/18). Conclusion: Increased KP neurotoxic metabolites are associated with elevated peripheral inflammation in depressed individuals, particularly in those with suicidal ideation. Targeting KP in this population could be a potential effective personalized approach. Whether this includes minocycline should be investigated in future larger trials.
UR - http://www.scopus.com/inward/record.url?scp=85159370887&partnerID=8YFLogxK
U2 - 10.1177/02698811231173588
DO - 10.1177/02698811231173588
M3 - Article
C2 - 37183855
SN - 0269-8811
VL - 37
SP - 531
EP - 538
JO - Journal of psychopharmacology (Oxford, England)
JF - Journal of psychopharmacology (Oxford, England)
IS - 6
ER -
