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

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

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18-60

SponsorIstanbul University - Cerrahpasa

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

Disqualifiers

Primary neurological disorders (e.g., dementia or traumatic brain injury).

Schizophrenia or other psychotic disorders.

Bipolar disorder diagnosis,

Intracranial space-occupying lesions.

Trial population

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

Trial design

Design model

Case-control

Time perspective

Prospective

Treatments tested in this trial

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.

Treatment groups

62 Participants

are divided into 2 treatment groups

Group A: Patients between 18 and 60 years of age diagnosed with Treatment Resistant Major Depressive Disorder1 intervention

Group B: Healthy control0 interventions

Trial outcomes

Primary outcomes

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.

Time frame

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.

Time frame

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).

Time frame

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).

Time frame

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

Correlation between baseline neuroinflammatory biomarkers and treatment response

Correlation coefficients between baseline concentrations of neuroinflammatory biomarkers and change in Hamilton Depression Rating Scale scores following ECT will be calculated.

Time frame

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

Correlation coefficients between baseline concentrations of neuroinflammatory biomarkers and change in Montgomery-Asberg Depression Rating Scale scores following ECT will be calculated.

Time frame

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

Correlation coefficients between changes in neuroinflammatory biomarker concentrations and changes in EEG microstate parameters (duration, occurrence, coverage, and transition probabilities) following ECT will be calculated.

Time frame

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

Neutrophil-to-Lymphocyte Ratio (NLR) will be calculated from complete blood count parameters and expressed as ratios.

Time frame

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

Other outcomes

Clinical Cognitive Assessment

Cognitive function will be assessed using the Mini-Mental State Examination before ECT initiation and at 2 and 8 weeks after the cessation of ECT sessions. The scale is a clinician-administered cognitive assessment with a total score ranging from 0 to 30, with higher scores indicating better cognitive function. Changes in the total scores from baseline will be evaluated following ECT.

Time frame

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

Sponsors and contacts

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Istanbul University - Cerrahpasa

Lead sponsor

Source ClinicalTrials.gov

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