Effect of repetitive transcranial magnetic stimulation on the kynurenine pathway in stroke patients

Abstract

Objective Repetitive transcranial magnetic stimulation (rTMS) improves depressive symptoms and motor function in stroke patients. While metabolic derangement of the kynurenine pathway has been reported in stroke patients, the effect of rTMS on this pathway remains unknown. This study was performed to investigate the effect of rTMS on serum levels of kynurenine and tryptophan in stroke patients. Methods Sixty-two stroke patients received rTMS in addition to intensive rehabilitation and 33 stroke patients received intensive rehabilitation alone for 14 days. The rTMS involved low-frequency stimulation (at 1 Hz) of the primary motor cortex on the unaffected side of the cerebrum. The depressive state of the patients was evaluated with the Beck Depression Inventory (BDI) before and after treatment. Motor function of the patients was evaluated with Fugl-Meyer Assessment (FMA). Serum levels of kynurenine and tryptophan levels were also measured before and after treatment. Results The serum tryptophan level decreased in the group receiving rTMS to the right brain and increased in the group receiving rTMS to the left brain. The serum kynurenine/tryptophan ratio was elevated in the group receiving rTMS to the right brain. The BDI indicated improvement of depressive symptoms in the rehabilitation alone group and the group receiving rTMS to the right brain plus rehabilitation. The FMA improved in all groups. Conclusions The effect of low-frequency rTMS on the kynurenine pathway may differ depending on whether it is applied to the right or left cerebral hemisphere.

Repetitive transcranial magnetic stimulation in the treatment of resistant depression: changes of specific neurotransmitter precursor amino acids

“…Laboratory parameters were not measured in a fasted state. As already argued in the foregoing study (Leblhuber et al 2019 ), the decrease of phenylalanine could possibly relate to changes in nutritional behavior of our patients studied, but concentrations of tryptophan—another essential amino acid—contrary to a recent series after hemispheric stimulation (Niimi et al 2020 ) did not change significantly.…”

Repetitive Transcranial Magnetic Stimulation of the Primary Motor Cortex beyond Motor Rehabilitation: A Review of the Current Evidence

“…This might explain, in part, the absence of clear efficacy of M1-rTMS as most patients had mild or no comorbid anxiety and depression, making it less likely to show a significant therapeutic effect. Intriguingly, however, two recent studies have investigated the effect of M1-rTMS in patients with stroke- and Parkinson’s disease-related depression and revealed antidepressant efficacy in these patients [ 148 , 165 ]. On the one hand, the mechanistic rationale behind the improvement in anxiety and depression following M1-rTMS might stem from its effect on the concomitant symptoms and consequently emotional improvement in mood and general behavior.…”

“…On the other hand, a recent meta-analysis combined with resting-state fMRI reported a positive correlation between M1 and depressive disorders-regions of interest (ROI), hence proposing M1 as a potential therapeutic target in depressive disorders [ 166 ]. In addition, M1-rTMS stimulation was found to alter the serum levels of kynurenine [ 165 , 167 ], a tryptophan metabolite and one culprit in the pathophysiology of depression [ 168 ]. Indeed, there have been preliminary reports of antidepressant efficacy of M1-rTMS in patients with Parkinson’s disease, stroke, and chronic pain.…”

“…On the other hand, in two non-shamcontrolled studies in stroke patients, a single session of 6 Hz primed- low frequency (1 Hz) rTMS at the contralesional M1 hand region significantly improved the depression scores for 5 days after stimulation [ 172 ]. While delivering 2 sessions/day for 22 total sessions of low-frequency rTMS at the contralesional M1 hand region and combined with motor rehabilitation showed a significant antidepressant efficacy and increased the serum kynurenine/tryptophan ratio by the end of the study [ 165 ]. Interestingly, these results were only noticeable when the low-frequency rTMS was applied to the right, but not the left, M1 cortex [ 165 ].…”

“…While delivering 2 sessions/day for 22 total sessions of low-frequency rTMS at the contralesional M1 hand region and combined with motor rehabilitation showed a significant antidepressant efficacy and increased the serum kynurenine/tryptophan ratio by the end of the study [ 165 ]. Interestingly, these results were only noticeable when the low-frequency rTMS was applied to the right, but not the left, M1 cortex [ 165 ]. Noteworthy, the laterality of the antidepressant efficacy of rTMS has already been established based on the frequency of stimulation over right vs. left DLPFC [ 173 ].…”