Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Nettis MA

PROVIDER: S-EPMC10291376 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Nettis Maria Antonietta MA Lombardo Giulia G Hastings Caitlin C Zajkowska Zuzanna Z Mariani Nicole N Nikkheslat Naghmeh N Sforzini Luca L Worrell Courtney C Begum Amina A Brown Mollie M Cleare Anthony J AJ Young Allan H AH Pariante Carmine M CM Mondelli Valeria V

Journal of psychopharmacology (Oxford, England) 20230515 6

<h4>Background and aims</h4>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.<h4>Methods</h4>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 (< ...[more]

PMID: 37183855

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Project description:Therapeutic seizures may work for treatment-resistant depression (TRD) by producing neuroplasticity. We evaluated whether magnetic seizure therapy (MST) produces changes in suicidal ideation and neuroplasticity as indexed through transcranial magnetic stimulation and electroencephalography (TMS-EEG) of the dorsolateral prefrontal cortex (DLPFC). Twenty-three patients with TRD were treated with MST. Changes in suicidal ideation was assessed through the Scale for Suicidal Ideation (SSI). Before and after the treatment course, neuroplasticity in excitatory and inhibitory circuits was assessed with TMS-EEG measures of cortical-evoked activity (CEA) and long-interval cortical inhibition (LICI) from the left DLPFC, and the left motor cortex as a control condition. As in our previous report, the relationship between TMS-EEG measures and suicidal ideation was examined with the SSI. Results show that 44.4% of patients experienced resolution of suicidal ideation. Based on DLPFC assessment, MST produced significant CEA increase over the frontal central electrodes (cluster p < 0.05), but did not change LICI on a group level. MST also reduced the SSI scores (p < 0.005) and the amount of reduction correlated with the decrease in LICI over the right frontal central electrodes (cluster p < 0.05; rho = 0.73 for Cz). LICI change identified patients who were resolved of suicidal ideation with 90% sensitivity and 88% specificity (AUC = 0.9, p = 0.004). There was no significant finding with motor cortex assessment. Overall, MST produced significant rates of resolution of suicidal ideation. MST also produced neuroplasticity in the frontal cortex, likely through long-term potentiation (LTP)-like mechanisms. The largest reduction in suicidal ideation was demonstrated in patients showing concomitant decreases in cortical inhibition-a mechanism linked to enhanced LTP-like plasticity. These findings provide insights into the mechanisms through which patients experience resolution of suicidal ideation following seizure treatments in depression.

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Dataset Information

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

Background and aims

Methods

Results

Conclusion

Publications

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

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