Kynurenine pathway metabolites predict antianhedonic effects of electroconvulsive therapy in patients with treatment-resistant depression.

BACKGROUND

Electroconvulsive therapy (ECT) is a rapid and effective antianhedonic treatment for treatment-resistant depression (TRD). Whether this effect is related to kynurenine (KYN) pathway metabolites lacks evidence, so we examined if the changes in these metabolites can serve as potential biomarkers for the antianhedonic effects of ECT.

METHODS

In this single-arm clinical trial, sixty patients diagnosed with TRD received a series of eight ECT treatments and provided blood samples. Antianhedonic effects were measured by items 1 (apparent sadness), 2 (reported sadness), 6 (concentration difficulties), 7 (lassitude) and 8 (inability to feel) of the Montgomery-Åsberg Depression Rating Scale (MADRS). Serum tryptophan (TRP), KYN, kynurenic acid (KYNA) concentration, KYN/TRP ratio and KYNA/KYN ratio, were measured at baseline and after ECT sessions 2, 4, 6 and 8.

RESULTS

Anhedonia responders had higher TRP levels (after ECT session 8) and lower KYNA levels (after ECT sessions 4 and 6) than non-responders (all p's < 0.05). Anhedonia remitters had a lower KYNA/KYN ratio (after ECT sessions 2, 6) and lower KYN/TRP ratio (after ECT sessions 8) compared to non-remitters (all p's < 0.05). The reduction in anhedonia scores after ECT session 2 were related to the reduction of KYN levels from baseline to ECT session 2 (r = 0.3, p = 0.049). TRP, KYN levels and KYN/TRP ratios predicted antianhedonic efficacy for ECT (TRP: β = 1.6, p = 0.029; KYN: β = -2.4, p = 0.033; KYN/TRP ratio: β = 1.9, p = 0.027).

CONCLUSION

This preliminary study found that ECT treatment significantly improved anhedonia symptoms in TRD patients and this improvement was related to biomarker changes in the KYN pathway.