This observational cohort study (n=130) will assess neurobiological changes in adults with major depressive disorder (MDD) and high suicidal risk during rapid antidepressant treatment, with a focus on suicidal tendency and the mechanisms of fast-acting antidepressant effects. Participants will be followed across electroconvulsive therapy (ECT), esketamine nasal spray, or conventional antidepressant treatment paths, with the main outcome being change in Hamilton Depression Rating Scale (HAMD-17) total score from baseline to follow-up. The study will collect data at three time points: baseline, 24 hours after the first treatment, and at remission 4–6 weeks later, with overall treatment follow-up to 8 weeks. It will compare a cohort of 70 patients receiving ECT, 30 receiving esketamine, and 30 receiving conventional medication, while also integrating clinical scales such as the C-SSRS and QIDS-SR16 with multimodal measures including whole genome sequencing, single-cell sequencing, proteomics, metabolomics, DNA methylomics, gut metagenomics, fMRI, DTI, and 32-channel resting-state EEG. Eligible participants are adults aged 18–65 years with DSM-5 MDD and suicidal ideation.
This study focuses on the neurobiological changes in MDD patients with high suicidal risk during rapid antidepressant treatments, such as Esketamine and Electroconvulsive Therapy (ECT). Core ObjectivesEstablish a standardized longitudinal cohort for high-risk suicidal populations to ensure high-quality data for clinical transformation. Investigate the biological mechanisms of rapid-acting interventions by analyzing changes in brain function and molecular pathways. Develop predictive biomarkers to identify treatment responders early, thereby reducing ineffective trial-and-error treatments and lowering suicide risk. Methodology \& Data CollectionThe study integrates multi-dimensional data across three critical time points: T0 (Baseline), T1 (Acute Phase/24h post-first treatment), and T2 (Remission Phase/4-6 weeks). Sample Cohort: A total of 130 participants (70 ECT, 30 Esketamine, 30 conventional medication). Multimodal Data Integration:Clinical Phenotyping: Standardized scales including HAMD-17 (Primary Indicator), C-SSRS (Suicide Assessment), and QIDS-SR16. Biological Omics: Whole Genome Sequencing (WGS), single-cell sequencing, proteomics, metabolomics, DNA methylomics, and gut metagenomics. Neuroimaging \& Physiology: Functional MRI (fMRI), Diffusion Tensor Imaging (DTI), and 32-channel resting-state EEG. SignificanceBy capturing dynamic "treatment-response" trajectories, the project aims to move beyond descriptive symptoms to a system biology-based diagnosis. The findings are expected to provide scientific evidence for individualized intervention strategies and improve the efficiency of care for patients with treatment-resistant depression and acute suicidal ideation.