The Multimodal MRI Study Of Efficacy And Mechanism Of Ketamine For Treatment-resistant Depression

Part I The MRS study of efficacy and mechanism of Ketamine for treatment-resistant depression Objective: Ketamine has obvious and rapid antidepressant effect and is also effective for treatment-resistant depression,but its antidepressant neural mechanism is still unclear.This study attempts to explore the antidepressant neural mechanism of ketamine and to provide objective imaging evidence for its efficacy.Methods: Magnetic resonance spectra of pregenual anterior cingulate cortex and anterior medial cingulate cortex were collected at 4 time points before(baseline),2 hours,24 hours and 7 days after the infusion of ketamine and placebo in 20 healthy controls and 20 patients with treatment-resistant depression using MRS.In comparison with healthy controls,we observed the abnormal cerebral biochemical and metabolic indexes of treatment-resistant depression and observe the change pattern of brain biochemical and metabolic indexes in patients with effective ketamine treatment at the above four time points.Results: 1.Compared to healthy controls,Cho/Cr and MI/Cr in the left pregenual anterior cingulate cortex of patients with treatment-resistant depression were significantly decreased(p<0.05),there was no statistical difference in NAA/Cr and Glx/Cr(p>0.05).There was no significant difference in Cho/Cr,MI/Cr,NAA/Cr and Glx/Cr of the right pregenual anterior cingulate cortex and the bilateral anterior medial cingulate cortex(p>0.05).2.The HAMD-17 score minus >50% was used as the effective standard and ketamine treatment was effective in 13 patients.However,no statistically significant changes in brain biochemical metabolites were detected in each brain region at each time point after ketamine infusion(p>0.05).Conclusions: 1.Patients with treatment-resistant depression have abnormal cell membrane synthesis or degradation and glial cell function in the left pregenual anterior cingulate cortex.The left pregenual anterior cingulate cortex can be used as the target area for the treatment of treatment-resistant depression.2.There are technical limitations in using the existing MRS technology to study the rapid antidepressant neural mechanism of ketamine.PartⅡ The rs-fMRI study of efficacy and mechanism of Ketamine for treatment-resistant depression Objective: We study the change pattern of resting brain function in patients with treatment-resistant depression before and after ketamine infusion in order to explore the therapeutic time window for the treatment-resistant depression of the ketamine,and attempt to explore the antidepressant neural mechanism of ketamine and to provide objective imaging evidence for its efficacy.Methods: ReHo and fALFF were used to analyze the differences in resting brain function between 20 treatment-resistant depression patients and 20 healthy controls,as well as the change patterns of resting brain function indicators in patients with effective treatment at baseline,2 hours,24 hours and 7 days after ketamine infusion.Results: 1.Compared to the healthy controls,the ReHo value of bilateral cingulate gyrus and the left subparietal lobule of treatment-resistant depression increased,while the ReHo value of the right posterior cerebellar lobe and the left insula decreased.The fALFF value of the left inferior temporal gyrus and middle temporal increased,while the fALFF of the right middle frontal decreased(p<0.001,cluster≥50).2.At 24 h after ketamine infusion,ReHo of the left cingulate gyrus and fALFF of the left medial temporal gyrus were reduced to normal in 13 patients with effective treatment(p<0.001,cluster≥50).3.No changes in functional brain areas which were abnormal at baseline were detected after 2 hours and 7 days of ketamine infusion(p>0.001).Conclusion: 1.Functional recovery of left cingulate gyrus and left middle temporal gyrus at 24 hours after ketamine infusion is one of the antidepressant neural mechanisms.2.Ketamine antidepressant effects that begin at 2 hours and last for a week may be achieved through other neural bases.Part Ⅲ The DKI study of efficacy and mechanism of Ketamine for treatment-resistant depression Objective: Diffusion kurtosis imaging(DKI)has higher sensitivity and specificity in the exploration of neurodevelopmental or pathological changes.In this study,we attempted to assess the ability of DKI in exploring white matter abnormalities in treatment-resistant depression and to explore the neural mechanism of ketamine as an antidepressant and provide objective imaging evidence for its efficacy using DKI.Methods: DKI data were collected from 20 healthy controls and 20 patients with treatment-resistant depression before and after the infusion of ketamine and placebo at 2 hours,24 hours and 7 days.Then we used voxel-based analysis to analyze the abnormal changes in the microstructure of white matter in patients and the microstructure change pattern of the white matter at 2 hours,24 hours and 7 days after ketamine infusion in patients who are treated effectively.Results: 1.Compare to healthy controls,we detected the diffusive indexes FA decreased,MD,AD,RD increased and the kurtosis indexes MK,AK and RK decreased in treatment-resistant depression(p<0.001,cluster≥50).2.Compared to the baseline,13 patients with effective ketamine treatment mainly showed increased FA value,decreased MD,AD and RD value,and increased kurtosis indexes MK,AK and RK in multiple brain regions(p<0.001,cluster≥50).3.Integrity of corpus callosum,internal and external capsule and radiated crown was restored after ketamine infusion.4.The microstructure of white matter began to improve at 2 hours after ketamine infusion,and was most obvious at 24 hours and decreased at 7 days.Conclusion: 1.DKI can sensitively detect abnormal changes in the white matter of treatment-resistant depression and the microstructural changes in the white matter of patients treated with ketamine.2.The microstructure recovery of corpus callosum,internal and external capsule and radiated crown after ketamine infusion may be one of the neural bases of ketamine antidepressants.3.DKI technology can provide objective imaging basis for the effective time window of ketamine.