EEG Microstate Parameters and Neuroinflammatory Biomarkers in Patients With Treatment-Resistant Major Depressive Disorder Receiving ECT

NCT07748091 | Recruiting FDA Device

• 2 other identifiers: CerrahpasaMEDE-24687260-604.01-1463071
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depression Severe; Major Depression With Comorbid Anxiety Symptoms; Major Depression With Panic Attacks; Major Depressive Disorder (MDD; Major Depression; Major Depression Moderate; Major Depression With Psychotic Features; Major Depressive Episode

Keywords

ECT; EEG; Treatment Resistant Depression; Difficult to Treat Depression; Microstate; Inflammatory biomarker; Major Depression; Major Depressive Episode

Outcome Measures

Primary Outcomes (6)

• Clinical Response and Remission Assessed by the Montgomery-Åsberg Depression Rating Scale

  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.

  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 Depression Rating Scale

  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.

  These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.

• EEG Microstate Duration

  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).

  These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.

• EEG Microstate Occurrence

  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).

  These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.

• EEG Microstate Coverage

  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 (%).

  These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.

• EEG Microstate Transition Probability

  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.

  These assessments will be repeated within 1 week before ECT starts and 14+6 days and 8 weeks + 6 days after ECT cessation.

Secondary Outcomes (15)

• 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 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.

Other Outcomes (1)

• Clinical Cognitive Assessment

  These assessments will be repeated within 1 week before ECT starts and at 14+6 days and 8 weeks + 6 days after ECT cessation.

Study Arms (2)

Patients between 18 and 60 years of age diagnosed with Treatment Resistant Major Depressive Disorder

Device: Electroconvulsive Therapy

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.

Interventions

Electroconvulsive Therapy DEVICE

ECT will be administered using the Thymatron System IV Integrated ECT Device under general anesthesia, in accordance with standard clinical protocols. Treatments will be delivered using bilateral electrode placement with brief-pulse square-wave stimulation, and if side effects are seen, right unilateral electrode placement will be applied. The duration of treatment, number of sessions, and stimulation parameters will be determined according to each patient's clinical condition.

Patients between 18 and 60 years of age diagnosed with Treatment Resistant Major Depressive Disorder

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients between 18 and 60 years of age diagnosed with Treatment-Resistant Major Depressive Disorder and suggested ECT sessions.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istanbul University - Cerrahpasa: lead

Study Sites (1)

İstanbul University- Cerrahpasa, Cerrahpasa Medicine Faculty, Psychiatry Department

Istanbul, Bakırköy, Turkey (Türkiye)

RECRUITING

Related Publications (4)

• Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry. 2007 Jan;52(1):46-54. doi: 10.1177/070674370705200108.

  PMID: 17444078 BACKGROUND

• Atluri S, Wong W, Moreno S, Blumberger DM, Daskalakis ZJ, Farzan F. Selective modulation of brain network dynamics by seizure therapy in treatment-resistant depression. Neuroimage Clin. 2018;20:1176-1190. doi: 10.1016/j.nicl.2018.10.015. Epub 2018 Oct 17.

  PMID: 30388600 BACKGROUND

• Brodbeck V, Kuhn A, von Wegner F, Morzelewski A, Tagliazucchi E, Borisov S, Michel CM, Laufs H. EEG microstates of wakefulness and NREM sleep. Neuroimage. 2012 Sep;62(3):2129-39. doi: 10.1016/j.neuroimage.2012.05.060. Epub 2012 May 30.

  PMID: 22658975 BACKGROUND

• Sackeim HA, Prudic J, Nobler MS, Fitzsimons L, Lisanby SH, Payne N, Berman RM, Brakemeier EL, Perera T, Devanand DP. Effects of pulse width and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. Brain Stimul. 2008 Apr;1(2):71-83. doi: 10.1016/j.brs.2008.03.001.

  PMID: 19756236 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

A total of 10 mL of venous blood will be collected from each participant. Blood samples will be divided into EDTA-containing tubes for complete blood count analyses and serum separator tubes for biochemical and inflammatory biomarker measurements.

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Alperen Kılıc

  Associate Professor

  STUDY DIRECTOR

• Burc Cagrı Poyraz, Professor

  Istanbul University - Cerrahpasa

  STUDY DIRECTOR

Central Study Contacts

Zeynep Özge Dagoglu Sarac, Dr

CONTACT

+905365942469; zod395@gmail.com

Yusuf Cicek, Dr

CONTACT

+905349624762; yusuf.cicek@iuc.edu.tr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatry Department Trainee Doctor

Study Record Dates

• First Submitted: July 5, 2026
• First Posted: August 5, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: August 5, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

TU (1)