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Perturbation of the Treatment-Resistant Depression (TRD) Connectome by Fast-Acting Therapies

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@data-hcp data-hcp released this 16 May 11:59
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Perturbation of the Treatment-Resistant Depression (TRD) Connectome by Fast-Acting Therapies

License

The FIB files are shared under the Creative Commons Attribution-ShareAlike 4.0 International License. If you use these data, please acknowledge the contribution of ACCESS resources: CIS200026 & MED230052.

Per the NDA agreement, I am not permitted to share raw MRI data. However, after consulting with the NDA program lead, I am authorized to share derived data, such as the FIB files. For access to other data, you can request it directly through NDA. Once you have the Data Use Agreement (DUA), feel free to share it with me, and I can provide you with a link to access the SRC files.

Project Overview

Depression affects a significant portion of the global population. Although treatable, approximately two-thirds of patients fail to respond to two or more standard pharmacotherapies, classifying them as having Treatment-Resistant Depression (TRD). These individuals face extremely low quality of life, significant social and occupational impairments, high healthcare costs, and elevated risk of suicide.

Despite extensive research implicating various brain networks, the underlying mechanisms of depression and successful treatment response remain unclear. This study leverages non-invasive MRI technologies and normative data from the Human Connectome Project (HCP, U54 MH091657) to investigate the brain connectome’s role in TRD and its treatment.

Study Objectives

  1. Longitudinal Analysis:

    • Determine whether changes in brain network connectivity predict and relate to responses to fast-acting therapeutic interventions, including:

      • Electroconvulsive Therapy (ECT, n = 60)
      • Serial Ketamine Infusion (n = 60)
      • Total Sleep Deprivation (TSD, n = 80)

  2. Cross-Sectional Analysis:

    • Explore how heterogeneity in clinical symptoms, behavioral profiles, sex, age, and diagnosis (e.g., unipolar vs. bipolar depression) contribute to structural and functional connectome differences across TRD populations.

Study Design and Data Collection

  • Participants:

    • 200 TRD patients clinically eligible for one of the three fast-acting interventions.
    • 140 controls (40 local, 100 from the HCP resource).

  • Data Collected Pre- and Post-Treatment:

    • Structural MRI
    • Functional MRI (resting-state)
    • Diffusion MRI
    • Arterial Spin Labeling (ASL) perfusion MRI to measure cerebral blood flow
    • Behavioral and cognitive assessments modeled after the HCP Lifespan protocol
    • Blood draws for peripheral gene function analysis

  • Behavioral Constructs of Interest:

    • Cognitive Control
    • Negativity Bias and Rumination
    • Reward Hypersensitivity

These behavioral functions are associated with critical brain regions, including the prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, and ventral striatum/pallidum, which are central to mood regulation, emotion, and reward processing.

Collection Investigator:

  • Katherine Narr

Significance

This study leverages the infrastructure and scientific advancements of the HCP to identify brain connectivity profiles that underlie treatment response in TRD, with the ultimate goal of enabling personalized medicine strategies for depression. Understanding these mechanisms could revolutionize treatment approaches for patients who do not respond to conventional therapies.

Would you like me to add a Funding and Publications section, or prepare this for a final document compilation?

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