Effects Of Transcranial Magnetic Stimulation On Alcohol Use Disorder And Biomarker Research

Part 1:Effect of Tanscranial Magnetic Stimulation on Drinking Behavior and Mental Health of Alcohol Use DisorderObjective:Excessive alcohol consumption is one of the main causes of preventable deaths worldwide,with approximately three million deaths caused by alcohol every year.Alcohol use disorder(AUD)is one of the most common neuropsychiatric disorders globally.It is caused by complex interactions between genetic and environmental factors.It may physiologically and psychologically affect patients and lead to significant damage to their psychosocial function,resulting in great social and economic burden.Transcranial magnetic stimulation(TMS)technology can induce long-term changes in brain function by altering cortical excitability,regulating neurotransmitters,and remodeling neurons and other brain pathways,thus reducing the desire for addictive substances and ultimately reducing the recurrence rate.TMS is considered a promising non-invasive brain stimulation technique for the treatment of alcohol abuse.Recently,important progress has been made in the research and application of TMS in the field of mental health.In this study,changes in alcohol consumption,craving,and mental health before and after treatment with TMS were assessed.Methods:Participants with AUD were randomly assigned to receive one of the two treatments(active or sham TMS).All participants received 10 daily active or sham TMS sessions over the left dorsolateral prefrontal cortex(LDLPFC)for two weeks,with follow-up visits at baseline and immediately after the completion of the treatments.The average number of heavy drinking days(HDDs)per week,visual analogue scale(VAS)scores,and the mental health component scores(MCSs)of the Medical Outcomes Study 36-Item Short Form Health Survey were used to assess the efficacy of TMS.SPSS statistical software(version 22.0;IBM,Armonk,NY,United States)was used for statistical analyses.HDDs per week,VAS scores,and MCS scores before and after treatment were compared between the two groups.The correlation and potential significance of drinking patterns and mental health with other clinical results were also evaluated.Results:At the end of treatment,the average number of HDDs per week in both groups decreased from baseline,especially in the active TMS group(p<0.01),and slightly decreased in the sham TMS group(p=0.04).The decrease in the active TMS group was significantly greater than that in the sham TMS group(p<0.01).The VAS score in the active TMS group was significantly lower than that at baseline(p<0.01);there was no significant change in the sham TMS group(p>0.05).The VAS score reduction in the active TMS group was significantly greater than that in the sham TMS group(p<0.01).The active TMS group showed significantly better improvement in MCS scores than the sham TMS group(p=0.005),and the active TMS group showed more significant improvements in the social function scale(p=0.007)and mental health scale scores(p=0.001).There was no significant improvement in vitality or role-emotional scales in either group;therefore,there was no significant difference between scores at the end of the study and baseline(p>0.05).Furthermore,decreases in alcohol consumption levels were positively associated with decreased VAS but not MCS scores.There was no significant correlation between baseline MCS score and percentage of HDDs or alcohol craving in AUD patients,and the total MCS score was negatively associated with the percentage of HDDs at the end of treatment but had no significant correlation with alcohol craving.Conclusion:TMS of the LDLPFC is safe,well tolerated,and can reduce alcohol consumption and craving in patients with AUD in a short time.Additionally,it has positive influences on neuropsychology and social-functioning.TMS of the LDLPFC is an effective treatment for alcohol abusers with mental health problems.Part 2:Neurofilament Light Chain Protein as a Biomarker for Monitoring the Efficacy of Transcranial Magnetic Stimulation on Alcohol Use DisorderObjective:Alcohol use disorder(AUD)is highly prevalent and damaging and causes heavy burden on individuals,families and society.Long-term heavy alcohol drinking can have serious adverse effects on brain structure and function.A large number of scientific studies have shown that long-term alcohol consumption can lead to structural and functional brain disorders.Common structural changes include brain white matter lesions and gray matter and white matter atrophy with groove widening and ventricle enlargement.Some previous studies found that the risk level of alcohol-induced brain damage cannot be determined based on factors such as the amount of alcohol intake.Recent studies have demonstrated that axonal damage or degeneration in CNS diseases causes elevated neurofilament light chain(NfL)concentrations in the CSF and blood;therefore,NfL is considered a potential biomarker of neuronal axonal cell damage.Detection of NfL levels could provide a more sensitive and accurate assessment of the degree of axonal damage in the white matter,where no apparent abnormalities are found.In this study,we explored the possibility of using NfL as a dynamic observation indicator of early-stage alcoholic brain injury by measuring its serum concentration before and after transcranial magnetic stimulation(TMS)intervention and noting any changes in the levels before and after TMS treatment.Methods:A double-blind,randomized control method was used in this experiment.The experimental group received 10 daily sessions of active TMS of the left dorsolateral prefrontal cortex(LDLPFC)for two weeks,and the control group received sham TMS.Follow-up was performed before and 10 weeks after the end of treatment,including the assessment of the average number of heavy drinking days(HDDs)per week,visual analogue scale(VAS)scores for alcohol craving,and mental component summary(MCS)scores for mental health.The serum NfL levels were measured 10 weeks after the end of the intervention.Serum NfL concentrations were measured using single-molecule array techniques,and all tests were performed by laboratory technicians who were blinded to the clinical data.Statistical analysis was performed by SPSS(version 22.0;IBM,Armonk,NY,United States)for intra-and between-group comparisons of serum NfL levels before and after treatment between both groups and to explore the correlation of serum NfL changes with changes in the mean number of HDDs per week,VAS scores,and MCS scores.Results:Ten weeks after the intervention,the serum NfL level was significantly lower than that at baseline(p<0.01),and the serum NfL level in the sham group was also slightly lower than that at baseline(p=0.02).The decrease in serum NfL level was significantly greater in the TMS group than in the sham group(p<0.01).Changes in serum NfL concentration were positively associated with mean HDDs(r=0.743,p<0.001)and changes in VAS score(r=0.740,p<0.001)10 weeks after treatment but negatively correlated with the change in MCS score(r=0.567,p<0.001).Conclusions:Decrease in serum NfL concentration was greater in the TMS group than in the sham group.Serum NfL concentration changes were positively correlated with changes in average number of HDDs and alcohol craving and negatively correlated with changes in mental health scores.The repair process of brain injury occurs simultaneously with decreased craving and improved mental health.NfL serves as an early serological indicator of changes in the degree of axonal injury induced by alcohol.