The Relationship of EEG Microstate Parameters and Neuroinflammatory Biomarkers With Treatment Response in Patients With Treatment-Resistant Major Depressive Disorder Receiving Electroconvulsive Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Clinical Response and Remission Assessed by the Montgomery-Åsberg Depression Rating Scale
研究概览
简要总结
This study aims to investigate the neurophysiological and inflammatory changes associated with electroconvulsive therapy (ECT) in patients diagnosed with Major Depressive Disorder who are resistant to at least two antidepressant treatments, using microstate analysis derived from resting-state electroencephalography (EEG) recordings. Within this scope, EEG recordings obtained before and after ECT will be compared to determine the relationships between changes in microstate parameters and inflammatory marker levels, clinical variables, and psychometric scale scores reflecting clinical improvement.
Peripheral blood samples collected from the same patient group will be analyzed for complete blood count parameters as well as levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), soluble glycoprotein 130 (sgp-130), soluble interleukin-6 receptor (sIL-6R), interferon gamma-induced protein 10 kDa (IP-10), and C-reactive protein (CRP). In addition, inflammatory indices, including the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR), will be calculated. The association between baseline levels of these biomarkers and treatment response will be evaluated. Moreover, changes in biomarker levels following ECT will be statistically examined in relation to clinical scale scores and EEG microstate parameters.
Although microstate analysis and inflammatory biomarkers have each been extensively investigated in psychiatric disorders, studies evaluating these two biomarkers together, particularly with the inclusion of healthy control participants, remain limited. In this regard, the present study aims to evaluate the effects of ECT on patients with treatment-resistant depression using objective neurophysiological indicators, to contribute to the understanding of the pathophysiology of depression at the level of brain networks, and to provide a scientific basis for the development of personalized treatment approaches in the future.
详细描述
Treatment-resistant depression (TRD) is defined as the failure to achieve an adequate clinical response to at least two antidepressant medications administered at appropriate doses and durations in individuals diagnosed with Major Depressive Disorder (MDD). TRD is associated with an increased risk of suicide, impaired social functioning, higher rates of hospitalization, and substantial economic burden. For this patient population, in whom conventional pharmacotherapy and psychotherapy often fail to provide sufficient benefit, electroconvulsive therapy (ECT) remains one of the most effective treatment options available. However, the mechanisms underlying the therapeutic effects of ECT have not been fully elucidated, and numerous biological, neurochemical, and structural hypotheses have been proposed.
Electroencephalography (EEG) is a non-invasive neurophysiological method capable of measuring the brain's electrical activity with high temporal resolution. Microstate analysis of EEG data focuses on brief periods of stable scalp topographies that are thought to represent transient states of large-scale neural networks. Each microstate is considered a temporary representation of a specific neural network, and parameters such as duration, occurrence, coverage, and transition probabilities provide valuable information about the brain's functional organization and dynamic stability. Although EEG-based studies investigating the effects of ECT on neuroplasticity, neurotransmitter systems, hippocampal volume, functional connectivity, and electrophysiological dynamics have gained increasing attention in recent years, research specifically focusing on microstate analysis remains limited. Existing studies are often characterized by small sample sizes, heterogeneity in treatment parameters, and potential confounding effects on microstate measures, highlighting the need for more comprehensive and controlled investigations in this field.
Accordingly, the present study aims to investigate the neurophysiological changes induced by ECT in individuals diagnosed with treatment-resistant depression through resting-state EEG microstate analysis. EEG recordings obtained before and after ECT will be compared to evaluate whether significant changes occur in microstate parameters, including duration, occurrence, coverage, and transition probabilities. Furthermore, the relationships between changes in microstate parameters and psychometric scale scores reflecting clinical improvement, together with other clinical variables, will be examined. Thus, not only the neurophysiological effects of ECT but also their associations with clinical outcomes will be comprehensively evaluated.
Another objective of the study is to investigate whether baseline EEG microstate characteristics may serve as potential biomarkers capable of predicting clinical response to ECT. By identifying neurophysiological indicators associated with favorable treatment outcomes, the study aims to advance predictive models for individualized treatment planning.
Through these aspects, the study seeks to evaluate the effects of ECT on patients with treatment-resistant depression using objective neurophysiological indicators, to contribute to the understanding of the pathophysiology of depression at the level of brain networks, and to provide a scientific basis for future personalized treatment approaches.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patient Group
- •Age 18-60 years
- •Diagnosis of Major Depressive Disorder, current major depressive episode, according to DSM-5 criteria.
- •Clinical indication for electroconvulsive therapy (ECT).
- •Ability to provide written informed consent.
- •Willingness to participate in the study.
- •Healthy Control Group:
- •Age ≥55 years.
- •No current psychiatric disorder.
- •No known neurological disorder.
- •Good general physical health.
- •No current use of medications known to affect EEG activity or inflammatory biomarkers significantly.
- •Ability to provide written informed consent.
- •Willingness to participate in the study.
排除标准
- •Primary neurological disorders (e.g., dementia or traumatic brain injury).
- •Schizophrenia or other psychotic disorders.
- •Bipolar disorder diagnosis,
- •Intracranial space-occupying lesions.
- •Increased intracranial pressure.
- •Myocardial infarction within the previous 3 months.
- •Cerebrovascular disease within the previous month.
- •Unstable cerebral aneurysm.
- •Pheochromocytoma.
- •Electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the previous month.
- •Cognitive impairment severe enough to prevent adequate cooperation during EEG recording.
- •Current alcohol or substance use disorder.
- •Active infectious disease.
- •Autoimmune or chronic inflammatory disorders.
- •Current use of systemic corticosteroids, immunosuppressive agents, or other medications known to affect inflammatory biomarkers significantly.
研究组 & 干预措施
Patients between 18 and 60 years of age diagnosed with Treatment Resistant Major Depressive Disorder
干预措施: Electroconvulsive Therapy (Device)
Healthy control
The healthy control group will consist of age- and sex-matched volunteers between 18 and 60 years of age who do not use any medication that may significantly influence EEG activity or inflammatory biomarkers, and who do not have a current neurological or psychiatric disorder. Healthy controls will also provide written informed consent before participation. EEG recordings will be obtained once and will serve as reference data for normal brain activity.
结局指标
主要结局
Clinical Response and Remission Assessed by the Montgomery-Åsberg Depression Rating Scale
时间窗: These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.
Before ECT initiation and 2 and 8 weeks after the cessation of ECT sessions, depressive symptom severity will be assessed using the Montgomery-Åsberg Depression Rating Scale. Montgomery-Åsberg Depression Rating Scale total score ranges from 0 to 60, with higher scores indicating greater severity of depressive symptoms. Change in total score from baseline will be assessed following electroconvulsive therapy (ECT).Clinical response will be defined as a ≥50% reduction in MADRS total score from baseline. Remission will be defined as a MADRS total score ≤7.
Clinical Response Assessed by Hamilton Depression Rating Scale
时间窗: These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.
Before ECT initiation and 2 and 8 weeks after the cessation of ECT sessions, depressive symptom severity will be assessed using the Hamilton Depression Rating Scale. The total score of scale ranges from 0 to 52, with higher scores indicating greater severity of depressive symptoms. Change in Hamilton Depression Rating Scale total score from baseline will be assessed following electroconvulsive therapy (ECT).Clinical response will be defined as a ≥50% reduction in total score from baseline. Remission will be defined as a total score ≤7.
EEG Microstate Duration
时间窗: These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.
Participants will be instructed to remain relaxed, quiet, and motionless during EEG recording. EEG acquisition will consist of 5 minutes with eyes open followed by 5 minutes with eyes closed. Raw EEG data will undergo preprocessing, including artifact removal, band-pass filtering, and re-referencing. Microstate analysis will be performed using MICROSTATELAB v2.1, an EEGLAB extension. Four canonical microstate classes (A, B, C, and D) will be identified. For each microstate class, duration will be calculated as the mean time for which the microstate remains stable following its onset and will be reported in milliseconds (ms).
EEG Microstate Occurrence
时间窗: These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.
Participants will be instructed to remain relaxed, quiet, and motionless during EEG recording. EEG acquisition will consist of 5 minutes with eyes open followed by 5 minutes with eyes closed. Raw EEG data will undergo preprocessing, including artifact removal, band-pass filtering, and re-referencing. Microstate analysis will be performed using MICROSTATELAB v2.1, an EEGLAB extension. Four canonical microstate classes (A, B, C, and D) will be identified. For each microstate class, occurrence will be calculated as the mean number of times the microstate occurs per second and will be reported in Hertz (Hz).
EEG Microstate Coverage
时间窗: These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.
Participants will be instructed to remain relaxed, quiet, and motionless during EEG recording. EEG acquisition will consist of 5 minutes with eyes open followed by 5 minutes with eyes closed. Raw EEG data will undergo preprocessing, including artifact removal, band-pass filtering, and re-referencing. Microstate analysis will be performed using MICROSTATELAB v2.1, an EEGLAB extension. Four canonical microstate classes (A, B, C, and D) will be identified. For each microstate class, coverage will be calculated as the percentage of the total EEG recording time occupied by that microstate class and will be reported as a percentage (%).
EEG Microstate Transition Probability
时间窗: These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.
Participants will be instructed to remain relaxed, quiet, and motionless during EEG recording. EEG acquisition will consist of 5 minutes with eyes open followed by 5 minutes with eyes closed. Raw EEG data will undergo preprocessing, including artifact removal, band-pass filtering, and re-referencing. Microstate analysis will be performed using MICROSTATELAB v2.1, an EEGLAB extension. Four canonical microstate classes (A, B, C, and D) will be identified. For each pair of microstate classes, transition probability will be calculated as the proportion of transitions from a given microstate class to a specific subsequent microstate class relative to all transitions originating from that microstate class. Transition probability will be reported as a proportion ranging from 0 to 1.
次要结局
- Correlation between baseline neuroinflammatory biomarkers and treatment response(These assessments will be repeated at three time points: within 1 week before ECT starts, 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Correlation between changes in neuroinflammatory biomarkers and EEG microstate parameters(These assessments will be repeated at three time points: within one week before ECT starts, 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Inflammatory indices derived from complete blood count(These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Inflammatory indices derived from complete blood count(These assessments will be repeated within 1 week before ECT starts, and at 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Inflammatory indices derived from complete blood count(These assessments will be repeated within 1 week before ECT starts, at 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Clinical Response Assessed by Clinical Global Impression- Severity(These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Clinical Response Assessed by Beck Scale for Suicidal Ideation(These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Clinical Response Assessed by Hamilton Anxiety Scale(These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Clinical Response Assessed by Beck Anxiety Scale(These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Clinical Response Assessed by Beck Depression Inventory(These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Clinical Response Assessed by Center for Epidemiologic Studies Depression Scale(These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Concentration of peripheral neuroinflammatory biomarkers(These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.)
研究者
Zeynep Ozge Dagoglu Sarac
Psychiatry Department Trainee Doctor
Istanbul University - Cerrahpasa