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The interaction between kynurenine pathway, suicidal ideation and augmentation therapy with minocycline in patients with treatment-resistant depression

Nettis, Maria Antonietta ; Lombardo, Giulia ; Hastings, Caitlin ; Zajkowska, Zuzanna ; Mariani, Nicole ; Nikkheslat, Naghmeh ; Sforzini, Luca ; Worrell, Courtney ; Begum, Amina ; Brown, Mollie ; Cleare, Anthony J ; Young, Allan H ; Pariante, Carmine M ; Mondelli, Valeria

Journal of psychopharmacology (Oxford), 2023-06, Vol.37 (6), p.531-538 [Periódico revisado por pares]

London, England: SAGE Publications

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Título:
The interaction between kynurenine pathway, suicidal ideation and augmentation therapy with minocycline in patients with treatment-resistant depression
Autor: Nettis, Maria Antonietta ; Lombardo, Giulia ; Hastings, Caitlin ; Zajkowska, Zuzanna ; Mariani, Nicole ; Nikkheslat, Naghmeh ; Sforzini, Luca ; Worrell, Courtney ; Begum, Amina ; Brown, Mollie ; Cleare, Anthony J ; Young, Allan H ; Pariante, Carmine M ; Mondelli, Valeria
Assuntos: Adjuvant therapy ; Antidepressants ; Antidepressive Agents - therapeutic use ; C-Reactive Protein ; Clinical trials ; Depression - drug therapy ; Humans ; Inflammation ; Interleukin 10 ; Kynurenine - metabolism ; Mental depression ; Metabolites ; Minocycline ; Minocycline - pharmacology ; Minocycline - therapeutic use ; Neurotoxicity ; Original Papers ; Placebos ; Quinolinic acid ; Suicidal Ideation ; Suicides & suicide attempts ; Tryptophan ; Tryptophan - metabolism
É parte de: Journal of psychopharmacology (Oxford), 2023-06, Vol.37 (6), p.531-538
Notas: ObjectType-Article-1
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Descrição: 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.
Editor: London, England: SAGE Publications
Idioma: Inglês

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The interaction between kynurenine pathway, suicidal ideation and augmentation therapy with minocycline in patients with treatment-resistant depression

Nettis, Maria Antonietta ; Lombardo, Giulia ; Hastings, Caitlin ; Zajkowska, Zuzanna ; Mariani, Nicole ; Nikkheslat, Naghmeh ; Sforzini, Luca ; Worrell, Courtney ; Begum, Amina ; Brown, Mollie ; Cleare, Anthony J ; Young, Allan H ; Pariante, Carmine M ; Mondelli, Valeria

London, England: SAGE Publications

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