The Relationship Between Inflammatory Markers in Peripheral Blood and Functional Brain Network in Patients With Treatment-Resistant Depression: Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Change from Baseline in 17-Item Hamilton Depression Rating Scale (HAM-D) Total Score
研究概览
简要总结
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.
详细描述
This was a single-center, prospective, nonrandomized interventional pilot study conducted at the Department of Psychiatry, Korea University Ansan Hospital, Republic of Korea.
The protocol initially planned a mindfulness-based cognitive therapy (MBCT) group, an individual psychotherapy group, and a healthy reference group. A protocol amendment removed the planned random allocation between the two psychotherapy groups because irregular recruitment could delay treatment while waiting to form MBCT groups. In the study as conducted, all enrolled participants with treatment-resistant depression were assigned to individual short-term dynamic psychotherapy alongside ongoing pharmacotherapy. No participants received MBCT. Healthy participants served as a reference group for clinical and biological measurements.
The broader protocol included clinical assessments, peripheral inflammatory and neurotrophic markers, and measures of brain function. Functional near-infrared spectroscopy was specified to examine prefrontal cortical activity and connectivity. Functional magnetic resonance imaging and magnetic resonance spectroscopy were used to examine resting-state brain networks and neurochemical measures. Additional planned procedures included stool collection for exploratory gut microbiome analyses and storage of peripheral blood mononuclear cells for laboratory research involving induced pluripotent stem cells.
研究设计
- 研究类型
- 干预性
- 分配方式
- 非随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 开放（无盲法）
入排标准
- 年龄范围
- 19 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 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.
排除标准
- 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 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.
- COVID-19 vaccination within the preceding month.
研究组 & 干预措施
Short-Term Dynamic Psychotherapy
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.
干预措施: Short-Term Dynamic Psychotherapy (Behavioral)
Healthy Reference Group
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)
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.
干预措施: Mindfulness-Based Cognitive Therapy (Behavioral)
结局指标
主要结局
Change from Baseline in 17-Item Hamilton Depression Rating Scale (HAM-D) Total Score
时间窗: Baseline and week 10
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.
Change from Baseline in Mean Prefrontal Functional Connectivity (fNIRS)
时间窗: Baseline and week 10
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.
Change from Baseline in the Area Under the Small-Worldness Curve Across Correlation Thresholds (fNIRS)
时间窗: Baseline and week 10
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.
Change from Baseline in the Area Under the Mean Clustering Coefficient Curve Across Correlation Thresholds (fNIRS)
时间窗: Baseline and week 10
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.
Change from Baseline in the Area Under the Local Efficiency Curve Across Correlation Thresholds (fNIRS)
时间窗: Baseline and week 10
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.
Change from Baseline in the Area Under the Global Efficiency Curve Across Correlation Thresholds (fNIRS)
时间窗: Baseline and week 10
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.
Change from Baseline in Resting-State Brain Functional Connectivity Assessed by fMRI
时间窗: Baseline and week 10
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.
Brain Metabolite Concentrations Measured by Magnetic Resonance Spectroscopy (MRS)
时间窗: Baseline and week 10
Brain metabolite concentrations were assessed using magnetic resonance spectroscopy (MRS). The protocol specified measurements at baseline and week 10.
次要结局
- Change from Baseline in Serum Interleukin-1 Beta (IL-1beta) Concentration(Baseline and week 10)
- Change from Baseline in the Sum of the Four 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)
- Change from Baseline in Serum Interleukin-10 (IL-10) Concentration(Baseline and week 10)
- Change from Baseline in Erythrocyte Sedimentation Rate (ESR)(Baseline and week 10)
- Five Facet Mindfulness Questionnaire (FFMQ) Mean Item Score(Baseline and week 10)
- Relative Abundance of Gut Microbial Taxa(Baseline and week 10)
研究者
研究点 (1)
标识符
- NCT 编号
- NCT07847242
- 其他研究编号
- 2021AS0372, 2022R1A2C1010195
日期
- 首次提交
- (8天前)
- 首次发布
- (昨天)
- 主要完成日期
- (3年前)
- 研究完成日期
- (3年前)
- 最近核实
- (29天前)
- 最近更新
- (昨天)
监管与共享
- FDA 监管药物
- 否
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 否
De-identified individual participant data underlying the manuscript findings on depressive symptoms, quality of life, and blood biomarkers may be made available upon reasonable request, subject to institutional and ethical approval.