iMORE+ Study: A Multi-Omics Cohort Study of Major Depressive Disorder

Official title

iMORE+ Study: An Enhanced Prospective Observational Cohort Study of Major Depressive Disorder Integrating Longitudinal Clinical Characterization and Multi-Omics Profiling

Overview

Major depressive disorder (MDD) is a common mental health condition characterized by substantial clinical heterogeneity and variability in treatment response. Current diagnosis and treatment selection for MDD mainly rely on clinical assessments, and reliable biological markers that can support diagnosis, predict antidepressant treatment response, guide personalized treatment, and improve understanding of disease mechanisms remain limited. The goal of this prospective observational cohort study is to develop and optimize multi-omics-based models for MDD diagnosis and antidepressant treatment response prediction using longitudinal clinical characteristics and biological data collected from an independent prospective cohort. The study also aims to evaluate the generalizability and predictive performance of existing multi-omics-based models in this independent cohort of participants aged 14-45 years. The main questions it aims to answer are: Can integrated clinical and multi-omics features identify biomarkers and develop predictive models for MDD diagnosis and antidepressant treatment response? Can existing multi-omics-based models for MDD diagnosis and treatment response prediction be replicated and validated in an independent prospective cohort? Participants with MDD and healthy controls will undergo standardized clinical assessments, longitudinal follow-up, and biological sample collection for multi-omics profiling. Clinical and multi-omics data will be integrated to identify biomarkers, develop and validate predictive models for MDD diagnosis, antidepressant treatment response, and long-term outcomes, and explore biological pathways and potential therapeutic targets associated with MDD. The study is expected to improve understanding of the biological heterogeneity of MDD and contribute to the development of objective approaches for diagnosis, treatment response prediction, personalized care, and future therapeutic discovery.

Primary outcome measures

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline to Week 8 [Time frame: Baseline to Week 8]

Secondary outcome measures (12)

• Antidepressant Treatment Response Rate Based on Montgomery-Åsberg Depression Rating Scale (MADRS) at Week 8 [Time frame: Baseline to Week 8]
• 17-item Hamilton Depression Rating Scale (HAMD-17)-Defined Treatment Response at Week 8 [Time frame: Baseline to Week 8]
• Montgomery-Åsberg Depression Rating Scale (MADRS)-Defined Antidepressant Treatment Remission at Week 8 [Time frame: Baseline to Week 8]
• 17-item Hamilton Depression Rating Scale (HAMD-17)-Defined Antidepressant Treatment Remission at Week 8 [Time frame: Baseline to Week 8]
• Change in Hamilton Anxiety Rating Scale (HAMA) Score From Baseline to Week 8 [Time frame: Baseline to Week 8]
• Change in Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) Score From Baseline to Week 8 [Time frame: Baseline to Week 8]
• Change in Clinical Global Impression-Severity (CGI-S) Score From Baseline to Week 8 [Time frame: Baseline to Week 8]
• Clinical Global Impression-Improvement (CGI-I) Score at Week 8 [Time frame: Baseline to Week 8]
• Number of Participants With Suicidal Ideation or Suicidal Behavior Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Week 8 [Time frame: Baseline to Week 8]
• Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score From Baseline to Week 8 [Time frame: Baseline to Week 8]
• Change in Sheehan Disability Scale (SDS) Score From Baseline to Week 8 [Time frame: Baseline to Week 8]
• Incidence of Depressive Relapse During 1-Year Follow-up [Time frame: Baseline to 1 year]

Eligibility criteria

Inclusion criteria

General criteria:

• Participants aged 14-45 years.
• Participants are able to understand the study procedures and provide written informed consent. For participants younger than 18 years, both the participant and their legal guardian must provide consent.

Major Depressive Disorder (MDD) cohort:

• Meet DSM-5 criteria for major depressive disorder (single or recurrent episode).
• Have a baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥24 and 17-item Hamilton Depression Rating Scale (HAMD-17) score ≥18.

Healthy Control (HC) cohort:

\- Healthy participants without a current or lifetime diagnosis of major psychiatric disorders.

Exclusion criteria

For all participants:

\- Severe or unstable medical conditions, pregnancy or breastfeeding, or other conditions considered unsuitable for study participation.

For the MDD cohort:

• Current or lifetime diagnosis of other major psychiatric disorders, including schizophrenia spectrum disorders, schizoaffective disorder, or bipolar disorder.
• Substance use disorder within 12 months prior to screening.
• Depression secondary to medical or neurological conditions.
• Regular antidepressant treatment within 2 weeks prior to enrollment.
• Electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation (VNS), or immunosuppressive therapy during the current depressive episode.
• Current active suicidal plan or recent suicidal behavior considered unsuitable for participation.

For the HC cohort:

• Current or lifetime diagnosis of any psychiatric disorder.
• Significant depressive, anxiety, manic, or psychotic symptoms.
• Previous treatment with antidepressants, antipsychotics, or mood stabilizers.
• Significant family history of major psychiatric disorders.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

China · 1 center

• Shanghai Mental Health Center — Shanghai

Identifiers

NCT: NCT07735143 · iMORE PLus-MDD-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗