Brain Connectivity and Inflammatory Markers During Short-Term Psychotherapy for Treatment-Resistant Depression

NCT07847242 | Completed

• 2 other identifiers: 2021AS03722022R1A2C1010195
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Some adults continue to experience depression despite treatment with antidepressant medicines. This study aimed to explore relationships between depression symptoms, brain function, and blood markers of inflammation, and changes in these measures during a course of psychotherapy. Adults with treatment-resistant depression were assigned to receive 10 weekly sessions of individual short-term dynamic psychotherapy, a form of talking therapy, alongside their ongoing medication. Healthy adults served as a reference group and received no study treatment. Assessments were planned at the start of participation and at a 10-week follow-up. These included depression ratings, quality-of-life questionnaires, blood tests, and measurements of brain activity. The study aimed to compare initial measurements between participants with depression and healthy adults and to explore changes over time within each group.

Conditions

Depressive Disorder, Treatment-Resistant

Keywords

Short-Term Dynamic Psychotherapy; Psychodynamic Psychotherapy; Inflammatory Biomarkers; Functional Near-Infrared Spectroscopy; Functional Connectivity; Quality of Life

Outcome Measures

Primary Outcomes (8)

• Change from Baseline in 17-Item Hamilton Depression Rating Scale (HAM-D) Total Score

  Depressive symptom severity was assessed by the treating psychiatrist using the Korean version of the 17-item Hamilton Depression Rating Scale (K-HDRS). Total scores range from 0 to 52, with higher scores indicating more severe depressive symptoms. Change in total score was assessed between baseline and week 10.

  Baseline and week 10

• Change from Baseline in Mean Prefrontal Functional Connectivity (fNIRS)

  Resting-state functional connectivity was assessed from 5-minute recordings using a 48-channel prefrontal fNIRS system (NIRSIT). Pairwise Pearson correlations were calculated from preprocessed oxygenated hemoglobin time series, transformed using Fisher's r-to-z transformation, and summarized as mean connectivity across the recorded prefrontal network. Connectivity values are dimensionless. Change was assessed between baseline and week 10.

  Baseline and week 10

• Change from Baseline in the Area Under the Small-Worldness Curve Across Correlation Thresholds (fNIRS)

  Small-worldness of the prefrontal functional network was calculated from resting-state fNIRS oxygenated hemoglobin signals. Binary networks were constructed using Pearson correlation thresholds of 0.2, 0.3, 0.4, 0.5, and 0.6. Small-worldness was summarized as the area under the curve across these thresholds using trapezoidal integration. This measure is dimensionless. Change was assessed between baseline and week 10.

  Baseline and week 10

• Change from Baseline in the Area Under the Mean Clustering Coefficient Curve Across Correlation Thresholds (fNIRS)

  Mean clustering coefficient of the prefrontal functional network was calculated from resting-state fNIRS oxygenated hemoglobin signals. Binary networks were constructed using Pearson correlation thresholds of 0.2, 0.3, 0.4, 0.5, and 0.6. Mean clustering coefficient was summarized as the area under the curve across these thresholds using trapezoidal integration. This measure is dimensionless. Change was assessed between baseline and week 10.

  Baseline and week 10

• Change from Baseline in the Area Under the Local Efficiency Curve Across Correlation Thresholds (fNIRS)

  Local efficiency of the prefrontal functional network was calculated from resting-state fNIRS oxygenated hemoglobin signals. Binary networks were constructed using Pearson correlation thresholds of 0.2, 0.3, 0.4, 0.5, and 0.6. Local efficiency was summarized as the area under the curve across these thresholds using trapezoidal integration. This measure is dimensionless. Change was assessed between baseline and week 10.

  Baseline and week 10

• Change from Baseline in the Area Under the Global Efficiency Curve Across Correlation Thresholds (fNIRS)

  Global efficiency of the prefrontal functional network was calculated from resting-state fNIRS oxygenated hemoglobin signals. Binary networks were constructed using Pearson correlation thresholds of 0.2, 0.3, 0.4, 0.5, and 0.6. Global efficiency was summarized as the area under the curve across these thresholds using trapezoidal integration. This measure is dimensionless. Change was assessed between baseline and week 10.

  Baseline and week 10

• Change from Baseline in Resting-State Brain Functional Connectivity Assessed by fMRI

  Resting-state functional magnetic resonance imaging (fMRI) was used to assess brain functional connectivity. The outcome is change in functional connectivity from baseline to week 10.

  Baseline and week 10

• Brain Metabolite Concentrations Measured by Magnetic Resonance Spectroscopy (MRS)

  Brain metabolite concentrations were assessed using magnetic resonance spectroscopy (MRS). The protocol specified measurements at baseline and week 10.

  Baseline and week 10

Secondary Outcomes (10)

• Change from Baseline in the Sum of the Four World Health Organization Quality of Life Assessment Instrument-Brief Form (WHOQOL-BREF) Domain Scores

  Baseline and week 10

• Change from Baseline in Serum Interleukin-6 (IL-6) Concentration

  Baseline and week 10

• Change from Baseline in Serum Tumor Necrosis Factor-Alpha (TNF-alpha) Concentration

  Baseline and week 10

• Change from Baseline in C-Reactive Protein (CRP) Concentration

  Baseline and week 10

• Change from Baseline in Serum Brain-Derived Neurotrophic Factor (BDNF) Concentration

  Baseline and week 10

Study Arms (3)

Short-Term Dynamic Psychotherapy

EXPERIMENTAL

Fifteen participants with treatment-resistant depression were assigned to receive 10 weekly sessions of individual short-term dynamic psychotherapy alongside ongoing pharmacotherapy. Assessments were scheduled at baseline and week 10.

Behavioral: Short-Term Dynamic Psychotherapy

Healthy Reference Group

NO INTERVENTION

Sixteen healthy participants were enrolled as a reference group. They received no study treatment. Clinical and biological assessments were scheduled at baseline and week 10.

Mindfulness-Based Cognitive Therapy (Not Implemented)

EXPERIMENTAL

This arm was specified in the approved protocol to receive a 10-week course of group mindfulness-based cognitive therapy. The arm was not implemented. No participants were enrolled, and the intervention was not delivered.

Behavioral: Mindfulness-Based Cognitive Therapy

Interventions

Short-Term Dynamic Psychotherapy BEHAVIORAL

Individual short-term dynamic psychotherapy was provided once weekly over a planned 10-week course, in addition to ongoing pharmacotherapy.

Also known as: STDP

Short-Term Dynamic Psychotherapy

Mindfulness-Based Cognitive Therapy BEHAVIORAL

The protocol planned group mindfulness-based cognitive therapy comprising 10 weekly 50-minute sessions, to be delivered via Zoom or in person at the hospital. This intervention was not implemented, and no participants received it.

Also known as: MBCT

Mindfulness-Based Cognitive Therapy (Not Implemented)

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants:
• Aged 19 to 65 years.
• All four grandparents are Korean.
• Able to understand the study information and provide voluntary informed consent.
• Participants with treatment-resistant depression:
• Persistent depressive symptoms despite treatment with at least two antidepressants for at least 6 weeks.
• A 17-item Hamilton Depression Rating Scale (HAM-D) score of 17 or higher.
• A history of at least two major depressive episodes.
• First major depressive episode at age 14 years or older and before age 50 years.
• Healthy participants:
• \- No current or past psychiatric disorder.

You may not qualify if:

• History of bipolar disorder or psychosis.
• History of alcohol or other substance dependence predating the onset of depression.
• History of intellectual disability.
• A parent or grandparent who is not Korean.
• History of significant central nervous system disease, including traumatic brain injury, loss of consciousness, Parkinson's disease, epilepsy, Alzheimer's disease, or Huntington's disease.
• Current infection, infection within the preceding 3 months, or an immunocompromised state. Immunocompromised states include congenital immune impairment and acquired conditions associated with immunosuppressive treatment, previous or current chemotherapy, or human immunodeficiency virus (HIV) infection.
• Ongoing long-term use of oral corticosteroids or nonsteroidal anti-inflammatory drugs.
• Pregnancy or breastfeeding.
• Clinically significant suicide risk in the judgment of the treating psychiatrist or investigator.
• Thoughts or intent to harm others.
• Use of an unapproved drug within the preceding 30 days or current participation in a related clinical study.
• Clinically significant abnormal screening findings in the judgment of the principal investigator.
• An acute or chronic illness that makes participation unsuitable in the investigator's judgment.
• Likely inability to follow study procedures and requirements.
• Coronavirus disease 2019 (COVID-19) vaccination within the preceding month.

Sponsors & Collaborators

• Konyang University Hospital: collaborator
• National Research Foundation of Korea: collaborator
• Korea University Ansan Hospital: lead

Study Sites (1)

Korea University Ansan Hospital

Ansan, Gyeonggi-do, 15355, South Korea

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Mindfulness-Based Cognitive Therapy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Mindfulness; Cognitive Behavioral Therapy; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: The protocol specified three parallel groups: mindfulness-based cognitive therapy (MBCT), individual psychotherapy, and a healthy reference group. Planned random allocation between the psychotherapy groups was subsequently removed. In the study as conducted, 15 participants with treatment-resistant depression received short-term dynamic psychotherapy alongside ongoing pharmacotherapy, and 16 healthy participants received no study treatment. The planned MBCT arm was not implemented, and no participants were enrolled in that arm. Assessments were scheduled at baseline and week 10.

Study Record Dates

• First Submitted: September 22, 2026
• First Posted: September 29, 2026
• Study Start: February 15, 2022
• Primary Completion: August 26, 2023
• Study Completion: August 26, 2023
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data may be made available beginning after publication of the corresponding manuscript and for as long as the de-identified data are retained in accordance with applicable institutional and ethical requirements.
• Access Criteria: Researchers may request access by contacting the corresponding author, Sangho Shin, at sangho\ shin@kyuh.ac.kr. Data access is subject to institutional and ethical approval.

Locations

KR (1)