Intervention Effect of High Definition Transcranial Alternating Current Stimulation (HD-tACS) on Depressive Disorder

Study Overview
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Brief Summary
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To investigate the intervention effect of high definition transcranial alternating current stimulation (HD-tACS) on suicidal ideation in patients with depressive disorder and its underlying neural mechanism by magnetic resonance imaging (MRI) and electroencephalography (EEG).

Detailed Description
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Forty patients with depressive disorder diagnosed by DSM-5 were recruited from the Anhui Mental Health Center and the first affiliated Hospital of Anhui Medical University. All participants underwent a structured interview and routine laboratory examination before and after receiving high definition transcranial alternating current stimulation (HD-tACS) treatment after meeting the inclusion criteria and obtaining informed consent. Each participant will complete the clinical evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG), and HD-tACS treatment conducted by trained researchers at the Anhui Mental Health Center. All the participants were randomized (1:1) to receive an active HD-tACS or sham HD-tACS treatment protocol. tACS: the central electrode was placed over F3 with return electrodes placed at Fp1, Fz, F7 and C3. Fourteen 2-mA sessions (ramp-up and ramp-down periods of 15 and 15 seconds, respectively) were applied for 30 minutes per session, twice daily over 7 consecutive days, and the stimulus frequency was set as individual alpha frequency (IAF). Sham HD-tACS was delivered using the same protocol and current intensity, but the period of active stimulation was only during the ramp-up and ramp-down periods of 15 and 15 seconds. Before and after the treatments, the patients received a battery measure of neuropsychological tests, resting EEG, and MRI scans in multimodalities. The neuropsychological assessment included HAMD, MADRS, BDI, HAMA, BSS, C-SSRS, PHQ15, RRS, TEPS, PVAQ, MoCA, Stroop Test, VFT, DST, and AVLT. Multimodal MRI includes 3D-T1, rs-fMRI, and DTI. The symptoms of the patients were followed up one and two months after the end of treatments.

Official Title
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Intervention Effect of High Definition Transcranial Alternating Current Stimulation (HD-tACS) on Depressive Disorder

Conditions
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Transcranial Alternating Current Stimulation, Depressive Disorder

Intervention / Treatment
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* Device: High definition transcranial alternating current stimulation
* Device: sham high definition transcranial alternating current stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: the patients were diagnosed by more than 2 psychiatrists and met the diagnostic criteria of DSM-5 for depression, and HAMD>17, BSS>6, PHQ-15>5. the age ranged from 18 to 65 years old, and the length of education was more than 5 years. the visual acuity or corrected visual acuity is normal, right-handed, can cooperate with the completion of various experimental tests. Exclusion Criteria: accompanied by severe somatic diseases, such as severe heart, liver, renal insufficiency and so on. accompanied by other neurological diseases, such as stroke, epilepsy and so on. pregnant and lactating women. accompanied by other mental disorders, such as drug abuse, schizophrenia, schizophrenic affective

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: real stimulation<br>The central electrode was placed over F3, with return electrodes at Fp1, Fz, F7 and C3. Fourteen 2-mA sessions (ramp-up and ramp-down periods of 15 and 15 seconds, respectively) were applied for 30 minutes per session, twice daily over 7 consecutive days, and the stimulus frequency was set as IAF. | Device: High definition transcranial alternating current stimulation<br>* tACS is described as a non-invasive form of brain stimulation that uses a low-intensity, alternating current applied directly to the head through scalp electrodes.<br>|
| Sham Comparator: sham stimulation<br>In the sham condition, tACS was delivered only during the ramp-up and ramp-down periods (15 and 15 s); no current was delivered during the 30-minute intervention. Participants will receive sham tACS twice daily for two weeks. | Device: sham high definition transcranial alternating current stimulation<br>* In the sham condition, tACS was delivered only during the ramp-up and ramp-down periods (15s and 15s); no current was delivered during the 30-minute intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Depression Rating Scale (HAMD) Score | The HAMD is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. | baseline and immediately after the intervention | 
| Change in Beck Scale for Suicide Ideation (BSS) Score | The BSS is a 19-item scale to measure the severity of suicidal ideation, where each item is rated on a scale from 0 to 2. The BSS total score ranges from 0 to 38 with lower scores indicating less suicidal ideation. | baseline and immediately after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score | The MADRS is a 10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60, with lower scores indicating less depressive symptoms. | baseline and immediately after the intervention | 
| Change in Beck Depression Inventory (BDI) Score | The BDI is a 13-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 3. The BDI total score ranges from 0 to 39, with lower scores indicating less depressive symptoms. | baseline and immediately after the intervention | 
| Change in Hamilton Anxiety Scale (HAMA) Score | The HAMA is a 14-item scale to measure the severity of anxiety symptoms, where each item is rated on a scale from 0 to 4. The HAMA total score ranges from 0 to 56, with lower scores indicating less anxiety symptoms. | baseline and immediately after the intervention | 
| Change in the Patient Health Questionnaire-15 (PHQ-15) scale | The PHQ-15 is a 15-item scale to measure the severity of somatic symptoms, where each item is rated on a scale from 0 to 2. The PHQ-15 total score ranges from 0 to 30, with lower scores indicating less somatic symptoms. | baseline and immediately after the intervention | 
| Change in Montreal Cognitive Assessment (MoCA) Score | We adopted a localized version of MoCA in line with the Chinese cultural background. It includes 11 inspection items in 8 cognitive fields. With a total score of 30 or more than 26, it is normal. Anyone who has been educated for less than 12 years will need to add one point to his final score. A higher score indicates a better outcome. | baseline and immediately after the intervention | 
| Change in Auditory Verbal Learning Test (AVLT) Score | We adopted a localized version of AVLT in line with the Chinese cultural background. It includes a 5-trial presentation of a 15-word list (List A), a single presentation of an interference list (List B)(Trial 6), two post-interference recall trials (one immediate - Trial 7, one delayed - Trial 8) and recognition of the target words in the orthographic modality with distractors (Trial 9). Scoring includes the percent score of the mean of Trial 1 through 5, Trial 7, Trial 8 and Trial 9. A higher score indicates a better outcome. | baseline and immediately after the intervention | 
| EEG Measure of Frontal Alpha Asymmetry (FFA) Oscillations | EEG recordings were obtained from each subject based on 64 electrode locations of the International 10-20 system (sampling frequency 1000Hz). The change in FFA (8-13 Hz electrical activity) over time was measured. | baseline and immediately after the intervention | 
| MRI measures of functional connectivity (FC) | the functional connectivity between stimulated target and the whole brain areas; the global and regional activity measures. | baseline and immediately after the intervention |