Effects Of High And Low Frequency Repetitive Transcranial Magnetic Stimulation On Metabolic Indexes In Patients With Chronic Schizophrenia

Objective:To observe the effects of high-frequency and low-frequency repetitive transcranial magnetic stimulation（rTMS）on the related indexes of body weight,lipid metabolism,prolactin and estradiol in patients with chronic schizophrenia,so as to provide theoretical basis for clinical treatment of metabolic diseases.Meanwhile,the safety of different frequencies of rTMS stimulation in patients with chronic schizophrenia was compared.Methods:Patients with chronic schizophrenia who were hospitalized in Jiangcun Hospital of affiliated Brain Hospital of Guangzhou Medical University from June 2022 to January 2023 were randomly assigned to either the high-frequency stimulation group or the low-frequency stimulation group.Both groups received antipsychotic drugs,and the stimulation targets for both groups were the left dorsolateral prefrontal cortex（DLPFC）.In the high-frequency group,the stimulation frequency was 20 Hz,the duration was 20 seconds,and the interval was 20 seconds.The patients in the high-frequency group received a total of 2000 stimulation pulses per treatment,while in the low-frequency group,the stimulation frequency was 1 Hz,the duration was 45seconds,and the interval time was 4 seconds.The patients in the low-frequency group received a total of 675 stimulation pulses per treatment.Both groups received treatment once a day,5 days a week,for a total of 4 weeks.Before treatment（V0）,after 2 weeks of treatment（V1）,after 4 weeks of treatment（V2）,and after 4 weeks of treatment,the patients’weight,abdominal circumference and body mass index（BMI）were measured at the 8th week of treatment（V3）.At the same time,total cholesterol（TC）,triglyceride（TG）,low-density lipoprotein cholesterol（LDL-C）,prolactin（PRL）and estradiol（E2）of the patients were detected by V0,V2 and V3,and adverse reactions were recorded by pain rating index（PRI）after each treatment.After collecting all the data,the Epi Data3.1 software was used to input and collate the data,and the SPSS24.0 statistical software was used for data analysis.The measurement data were analyzed using either a t-test or a rank sum test,while the counting data were analyzed using a chi-square test.Repeated measures analysis of variance was used for data that met normal distribution,while generalized estimation equation（GEE）was used for data that did not meet normal distribution.A p-value of less than 0.05 was considered statistically significant.Results:A total of 82 patients with chronic schizophrenia were included in this study,and6 cases were removed during the follow-up period（2 cases in the high-frequency group and 4 cases in the low-frequency group）.There were no significant differences in demographic characteristics,disease characteristic variables（including course of disease,family history,PANSS scale score,major drug use）,body weight,BMI and metabolic indexes at baseline between the two groups（P>0.05）.The group-time interaction effect of body weight between the two groups was significant（χ2=9.490,P=0.023）,and the time-alone effect within the group showed that body weight in the high-frequency group increased with the extension of time（P<0.05）.However,pairwise comparison showed that the main effect was not significant（χ2=0.490,P=0.484）.The group-time interaction effect of BMI between the two groups was not significant（χ2=6.948,P=0.074）,and the time-in-group main effect showed that the BMI of patients in the high-frequency group increased with the extension of time（P<0.001）.However,pairwise comparison showed that the main effect was not significant（χ²=1.064,P=0.302）.The group-time interaction effect of PRL and E2 levels between the two groups was not significant(χ2_-PRL=0.758,P=0.685;χ2_-E2=1.373,P=0.503).The time main effect showed that:（1）the PRL of V3 in the high-frequency group decreased by152.13m IU/L compared to V0（P=0.047）,and that in the low-frequency group decreased by 255.37 m IU/L compared to V0（P=0.005）;（2）in the high-frequency group,E2 of V2 increased by 13.497 pmol/L compared to V0（P=0.633）,but decreased by 31.265 pmol/L compared to V3 and V2（P=0.005）.The time main effect,group-time interaction,and group main effect of abdominal circumference level(P_-group=0.743;P_-time=0.245;P_-interaction=0.680),TC(P_-group=0.051;P_-time=0.216;P_-interaction=0.122),TG(P_-group=0.431;P_-time=0.807;P_-interaction=0.958),and LDL-C(P_-group=0.425;P_-time=0.266;P_-interaction=0.548)were not statistically significant between the two groups.There was no statistically significant difference between the two groups in the types of antipsychotics that mainly affected metabolic indexes at V0（χ2=5.464,P=0.113）and V3（χ2=3.272,P=0.369）.There was no significant difference in the incidence of headache and dizziness between the two groups（χ2=3.200,P=0.074）.Conclusion:High and low frequency repetitive transcranial magnetic stimulation（rTMS）did not significantly reduce body weight,body mass index（BMI）,total cholesterol（TC）,triglycerides（TG）,low-density lipoprotein cholesterol（LDL-C）,or other metabolic indices in chronic schizophrenia patients who received long-term treatment with antipsychotic drugs.High frequency rTMS may increase levels of estradiol,a form of estrogen,but this effect may require continuous stimulation to be sustained.Both high-frequency and low-frequency rTMS can decrease prolactin levels in chronic schizophrenia patients who have received long-term treatment with antipsychotic medications,without increasing adverse reactions.