The Relationship Between EEG Microstate Parameters, Neuroinflammatory Biomarkers and Treatment Response in Older Patients With Major Depressive Disorder or Bipolar Disorder Undergoing 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 older age patients diagnosed with Major Depressive Episode, Major Depression, and Bipolar Disorder, 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, in the older age population remain limited. In this regard, the present study aims to evaluate the effects of ECT on older age patients using objective neurophysiological indicators, contribute to the understanding of the pathophysiology of depression at the level of brain networks, and provide a scientific basis for the development of personalised treatment approaches in the future.
详细描述
Major Depressive Disorder (MDD) and Major Depressive Episodes are leading causes of disability worldwide because of the substantial functional impairment they cause in affected individuals as well as their considerable socioeconomic burden. Late-life depression is associated with physical disability, worsening of coexisting medical illnesses, institutionalization, and increased mortality. The primary goals of treatment are to achieve complete remission, restore psychosocial functioning and quality of life, and prevent relapse and recurrence. All patients diagnosed with depression should receive appropriate psychoeducation, followed by antidepressant pharmacotherapy and/or psychotherapy through a shared decision-making process involving both the clinician and the patient.
Electroconvulsive therapy (ECT) is currently regarded as one of the most effective treatment modalities for Major Depressive Episode. Among elderly patients with severe major depressive episode, with or without psychotic features, particularly those presenting with active suicidal ideation, inadequate response to pharmacotherapy and/or psychotherapy, or intolerance to pharmacological treatment, ECT provides rapid clinical improvement with remission rates approaching 80%, making it one of the most effective biological treatment options currently available. Despite its well-established clinical efficacy, the mechanisms underlying ECT's therapeutic effects remain incompletely elucidated, and several biological, neurochemical, and structural hypotheses have been proposed.
Electroencephalography (EEG) is a non-invasive neurophysiological technique that measures fluctuations in the electrical activity generated by neuronal populations with excellent temporal resolution. Brief periods of stable scalp topographies lasting approximately 80-120 milliseconds are referred to as EEG microstates. These microstates are considered the electrophysiological correlates of transient large-scale functional brain networks. Parameters such as microstate duration, frequency of occurrence, coverage, and transition probability 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 attracted increasing attention in recent years, studies specifically focusing on EEG microstate analysis remain limited, especially in the older age population. Existing investigations are generally characterized by relatively small sample sizes, heterogeneity in treatment protocols, and methodological differences that may influence microstate measurements, emphasizing the need for larger and better-controlled studies.
As the search for reliable predictors of treatment response has intensified, increasing evidence suggests that abnormalities in immune regulation contribute to the pathophysiology of both unipolar and bipolar depression, highlighting the immune system as a promising source of biological markers. In particular, accumulating evidence indicates that pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP), as well as anti-inflammatory cytokines such as interleukin-2 (IL-2) and interleukin-10 (IL-10), are involved in the pathophysiology of depression and may influence response to antidepressant treatment and electroconvulsive therapy (8-10). Furthermore, a recent meta-analysis demonstrated significantly higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values in patients with depression compared with healthy controls. However, studies evaluating NLR, PLR, and monocyte-to-lymphocyte ratio (MLR) as predictors of response to ECT remain scarce.
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
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patient Group
- •Age ≥55 years.
- •Diagnosis of Major Depressive Disorder or Bipolar 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.
- •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.
- •Uncontrolled autoimmune or chronic inflammatory disorders. Participants with stable disease who had received the same maintenance treatment within the previous 3 months were eligible for inclusion.
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 at 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 at 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 at 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 at 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 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 start and 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 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, 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 and 14+6 days and 8 weeks + 6 days after ECT cessation.)
- Correlation between baseline neuroinflammatory biomarkers and treatment response(These assessments will be repeated within 1 week before ECT starts and 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 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 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 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 Clinical Global Impression- Severity(These assessments will be repeated within 1 week before ECT start and 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 at 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