Effects Of Intermittent Theta Burst Stimulation On Suicidal Ideation And Executive Function In Adolescent Depression With Suicide Attempt

The lifetime prevalence of adolescent depression is estimated to be 14% to20%.Depressed teenagers are six times more likely to make suicide attempts as compared to non-depressed youth,with those who attempt suicide having a higher risk of suicide than the general population.Studies have shown that executive dysfunction plays a major role in the suicidal behavior of these adolescents.However,while existing data suggest psychotherapy and pharmacotherapy are not effective,thus it is very important to develop effective alternative or complementary treatments for depression in adolescents with suicide attempts.In recent years,intermittent theta burst stimulation（i TBS）,a novel TMS modality based on neuromodulation,has been widely used in the treatment of depression in adults.However,there are not any reports on the use of i TBS protocol to improve suicidal ideation as well as executive function in adolescents with depression.Therefore,in this study,we aim to explore a safe and effective TMS model suitable for adolescent depression to provide empirical support for the ensuing clinical treatment.The contents mainly include the following two studies:In the first study.Objectives: The aim of this exploratory study was to investigate the effect of i TBS on suicidal ideation as well as clinical core symptoms in adolescent depression.Methods: Forty-five adolescent depressed patients（mean=17.2years,SD=2.25,range=13-23）with concomitant suicide attempts were recruited in an inpatient hospital ward.All participants were randomly divided into 2 groups and received conventional antidepressant medication,the i TBS group received a once-a-day,10-day i TBS intervention,while the control group received sham-stimulation.Suicidal ideation and core clinical symptoms were assessed before and after the intervention.Measures of suicidal ideation included the Chinese version of Beck scale for suicide ideation（BSI-CV）,and measures of clinical core symptoms included the SelfRating Scale for Depression（SDS）and the 24 item Hamilton Depression Scale（HAMD-24）.Results: After 2 weeks of intervention,the BSI-CV total score,HAMD-24 total score,and SDS standard score were significantly reduced in the i TBS group（p<0.05）,and there was a significant difference in the reduction rate of BSI-CV total score and HAMD-24 total score compared with the control group（p<0.05）.Conclusions: The i TBS intervention on the left DLPFC was able to rapidly improve suicidal ideation and depressive symptoms in adolescent depression with suicide attempts within two weeks.In the second study.Objectives: To explore the effects of i TBS on executive function in adolescent depression with suicide attempts based on the first study and to further explore the mediating effect of executive function in improving suicidal ideation in patients.Methods: Inhibition,refreshing and switching of executive function were measured before and after the intervention.Executive function measures included the EPrime behavioral experiment（Stroop,1-back,2-back,and More-odd shifting tasks）and the Adolescent Executive Function Self-Rating Scale.Results: After 2 weeks of intervention,the i TBS group had better correct rates and reaction times on the Stroop,2-back,and More-Odd shifting tasks than the control group（p<0.05）;scores on each subdimension of the Adolescent Executive Functioning Self-Rating Scale decreased significantly（p<0.05）;The subfunctions of executive function could predict the decrease of suicidal ideation,and the switching and refreshing functions play a major mediating role in i TBS intervention to improve suicidal ideation in adolescent depression with suicide attempts.Conclusion: i TBS intervention which was consistent with endogenous theta-γ coupling oscillations in the human brain could improve executive function in adolescents with depression,and i TBS intervention may indirectly contribute to the reduction of suicidal ideation by improving switching and refreshing functions.This study is a randomized controlled,single-blind clinical trial demonstrating that i TBS,stimulated in the left dorsolateral prefrontal lobe,is a safe,effective,and welltolerated pharmacological supplementation therapy for the treatment of adolescent depression.A future randomized double-blind controlled trial with a large sample is recommended for validation and replication.