Functional Connectivity Of The Amygdala And The Antidepressant And Antisuicidal Effects Of Esketawiine Infusions In Adolescent Depression With Suicidal Ideation

Objective: Abnormal amygdala function is a core pathogenesis of depression,and studies have found that functional networks of the amygdala are altered in adult depressed patients after ketamine infusion,and that alterations are associated with the antidepressant efficacy of ketamine.However,whether esketamine infusion causes characteristic amygdala related network changes in adolescent depressed patients remains unclear.In this study,we aimed to explore the efficacy of esketamine on suicidal ideation and depressive symptoms in adolescent depressed patients with suicidal ideation,to search for amygdala related network changes associated with its treatment,and to seek for neuroimaging indicators that could predict the outcome of esketamine treatment.Methods: Using a randomized double-blind method,39 adolescent depressed patients with suicidal ideation were randomly assigned to receive 3 doses of esketamine(0.25 mg/kg)or midazolam(0.02 mg/kg).Sucidal ideation and depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale(MADRS)at baseline,days 2,4,6,12,and 19.Magnetic resonance imaging(MRI)scan would be perform at baseline,days 6 and day 12.Mixed structural model analysis was performed on MADRS scale data and MRI data for the midazolam and esketamine groups,respectively,to explore the therapeutic efficacy of esketamine and the characteristic amygdala functional network changes associated with it.39 healthy controls(HC)also underwent a single MRI scan as controls for amygdala resting state functional connectivity(RSFC)in adolescent depressed patients.Results: This study found that esketamine was effective for treating suicidal ideation in adolescent depressed patients with suicidal ideation,but did not find changes in amygdala RSFC associated with the grouping of esketamine and midazolam medications.In the esketamine subgroup analysis,we found that the RSFC from the left amygdala to the right middle frontal gyrus decreased in adolescent depressed patients with suicidal ideation after esketamine treatment,while this change was not associated with the rate of reduction in suicidal ideation and depressive symptoms.In addition,we found that RSFC from left amygdala to left orbital superior frontal gyrus in adolescent depressed patients with suicidal ideation in the esketamine group was predictive of antisuicidal efficacy at day 12;RSFC from the left amygdala to the right dorsolateral superior frontal gyrus as well as the right amygdala and right superior temporal gyrus could predict antidepressant efficacy at day 6;The combined RSFC of left amygdala and right middle occipital gyrus,right amygdala and right superior temporal gyrus,and right amygdala and left middle occipital gyrus could be associated with predicting antidepressant efficacy at day 12 as well as at day 19.Conclusions: Abnormal amygdala functional networks are present in adolescent depressed patients with suicidal ideation.Compared with midazolam,esketamine significantly reduces suicidal ideation in depressed adolescents with suicidal ideation and concomitantly modulates relevant circuits in the amygdala.While baseline amygdala RSFC has the potential to be a predictor of antisuicidal and antidepressant efficacy of esketamine in adolescent depressed patients with suicidal ideation.