Augmentation of Interpersonal Psychotherapy With High-Definition Transcranial Direct Current Stimulation for Adolescent Depression

Augmentation of Interpersonal Psychotherapy With High-Definition Transcranial Direct Current Stimulation for Adolescent Depression

Effects of Augmentation of Interpersonal Psychotherapy With High-Definition Transcranial Direct Current Stimulation for Adolescent Depression: A Randomized Clinical Trial

Depression is among the most prevalent psychiatric disorders, with an upward trend in its manifestation in younger individuals. In contrast to adult depression, adolescent depression often presents with longer attack durations, higher recurrence rates, chronicity, and elevated disability rates. At present, treatment options for adolescent depression encompass pharmacological, physical, and psychological therapies. However, current evidence suggests that no antidepressant medication is entirely safe for youths, with only fluoxetine and escitalopram being FDA-approved for treating adolescent depression. Given the weight of interpersonal stressors faced by teenagers, the NICE guidelines recommend interpersonal therapy(IPT) as a first-line treatment. A 2020 meta-analysis in the Journal of the American Academy of Child and Adolescent Psychiatry reported that interpersonal therapy exhibited significantly greater improvements in depression symptoms than cognitive behavioral therapy(CBT), although psychotherapeutic effects were modest, achieving a remission rate of 60%. These results underscore the need for further research to enhance interpersonal therapy's effectiveness in treating adolescent depression. High-Definition Transcranial Direct Current Stimulation (HD-tDCS）is a highly secure non-invasive brain stimulation technique that produces sustained effects even after stimulation has discontinued, rendering it particularly valuable for therapeutic interventions. The proposed study aims to augment a single IPT treatment with HD-tDCS stimulation for adolescent depression. By enhancing the excitability of the cerebral cortex, HD-tDCS could potentially enhance IPT's therapeutic efficacy in treating adolescent depression while facilitating further investigation of its underlying neural circuit mechanisms.

Assessment of depressive symptoms. Score<8: normal; >20: mild or moderate depression; >35: severe depression.

Assessment of depressive symptoms. Score<8: normal; >20: mild or moderate depression; >35: severe depression.

Assessment of depressive symptoms. Score<8: normal; >20: mild or moderate depression; >35: severe depression.

Assessment of depressive symptoms. Score<8: normal; >20: mild or moderate depression; >35: severe depression.

Assessment of depressive symptoms. Score<40: normal; 40~60: mild or moderate depression; >60: severe depression.

Assessment of depressive symptoms. Score<40: normal; 40~60: mild or moderate depression; >60: severe depression.

Assessment of depressive symptoms. Score<40: normal; 40~60: mild or moderate depression; >60: severe depression.

Assessment of depressive symptoms. Score<40: normal; 40~60: mild or moderate depression; >60: severe depression.

Score<7:No anxiety; Score≥7:Possibly anxious; Score≥14:Definitely anxious; Score≥21:Definitely significantly anxious; Score≥29:Possibly severely anxious.

Score<7:No anxiety; Score≥7:Possibly anxious; Score≥14:Definitely anxious; Score≥21:Definitely significantly anxious; Score≥29:Possibly severely anxious.

Score<7:No anxiety; Score≥7:Possibly anxious; Score≥14:Definitely anxious; Score≥21:Definitely significantly anxious; Score≥29:Possibly severely anxious.

Score<7:No anxiety; Score≥7:Possibly anxious; Score≥14:Definitely anxious; Score≥21:Definitely significantly anxious; Score≥29:Possibly severely anxious.

Assessment of suicidal ideation. The test taker first completes the initial five questions. If the responses to both the fourth and fifth items are "no," it is considered that there is no suicidal ideation, and the questionnaire concludes. Suicidal risk is evaluated based on items six to nineteen of the scale, which assess the likelihood of actual suicidal behavior among individuals with suicidal ideation. The calculation formula for the total score is [(sum of scores for items six to nineteen) - 9) / 33] * 100, resulting in a score ranging from 0 to 100. A higher score indicates a greater risk of suicide.

Assessment of suicidal ideation. The test taker first completes the initial five questions. If the responses to both the fourth and fifth items are "no," it is considered that there is no suicidal ideation, and the questionnaire concludes. Suicidal risk is evaluated based on items six to nineteen of the scale, which assess the likelihood of actual suicidal behavior among individuals with suicidal ideation. The calculation formula for the total score is [(sum of scores for items six to nineteen) - 9) / 33] * 100, resulting in a score ranging from 0 to 100. A higher score indicates a greater risk of suicide.

Assessment of suicidal ideation. The test taker first completes the initial five questions. If the responses to both the fourth and fifth items are "no," it is considered that there is no suicidal ideation, and the questionnaire concludes. Suicidal risk is evaluated based on items six to nineteen of the scale, which assess the likelihood of actual suicidal behavior among individuals with suicidal ideation. The calculation formula for the total score is [(sum of scores for items six to nineteen) - 9) / 33] * 100, resulting in a score ranging from 0 to 100. A higher score indicates a greater risk of suicide.

Assessment of suicidal ideation. The test taker first completes the initial five questions. If the responses to both the fourth and fifth items are "no," it is considered that there is no suicidal ideation, and the questionnaire concludes. Suicidal risk is evaluated based on items six to nineteen of the scale, which assess the likelihood of actual suicidal behavior among individuals with suicidal ideation. The calculation formula for the total score is [(sum of scores for items six to nineteen) - 9) / 33] * 100, resulting in a score ranging from 0 to 100. A higher score indicates a greater risk of suicide.

A total of 14 items, each with a score of 1 to 4, will be used to calculate the total score. The higher the score The higher the score, the more severe the pleasure deficit

A total of 14 items, each with a score of 1 to 4, will be used to calculate the total score. The higher the score The higher the score, the more severe the pleasure deficit

A total of 14 items, each with a score of 1 to 4, will be used to calculate the total score. The higher the score The higher the score, the more severe the pleasure deficit

A total of 14 items, each with a score of 1 to 4, will be used to calculate the total score. The higher the score The higher the score, the more severe the pleasure deficit

A score of 0-8 indicates that interpersonal relationship is good, a score of 9-14 indicates that there is a certain degree of interpersonal relationship distress, and a score of 15-28 indicates that interpersonal relationship distress is more serious, that is, the lower the score of the comprehensive diagnostic scale of interpersonal relationship, the better the interpersonal relationship.

A score of 0-8 indicates that interpersonal relationship is good, a score of 9-14 indicates that there is a certain degree of interpersonal relationship distress, and a score of 15-28 indicates that interpersonal relationship distress is more serious, that is, the lower the score of the comprehensive diagnostic scale of interpersonal relationship, the better the interpersonal relationship.

A score of 0-8 indicates that interpersonal relationship is good, a score of 9-14 indicates that there is a certain degree of interpersonal relationship distress, and a score of 15-28 indicates that interpersonal relationship distress is more serious, that is, the lower the score of the comprehensive diagnostic scale of interpersonal relationship, the better the interpersonal relationship.

A score of 0-8 indicates that interpersonal relationship is good, a score of 9-14 indicates that there is a certain degree of interpersonal relationship distress, and a score of 15-28 indicates that interpersonal relationship distress is more serious, that is, the lower the score of the comprehensive diagnostic scale of interpersonal relationship, the better the interpersonal relationship.

A total of 10 items were scored at 7 points. The higher the score, the higher the frequency of using emotion regulation strategies.

A total of 10 items were scored at 7 points. The higher the score, the higher the frequency of using emotion regulation strategies.

A total of 10 items were scored at 7 points. The higher the score, the higher the frequency of using emotion regulation strategies.

A total of 10 items were scored at 7 points. The higher the score, the higher the frequency of using emotion regulation strategies.

It consists of 3 factors, difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT), which are called F1, F2, and F3 factors, containing 20 items, each scored within a 5-point scale (1: completely disagree to 5: completely agree), 20-100 points, the higher the score, the more pronounced the dysfunction in describing feelings.

It consists of 3 factors, difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT), which are called F1, F2, and F3 factors, containing 20 items, each scored within a 5-point scale (1: completely disagree to 5: completely agree), 20-100 points, the higher the score, the more pronounced the dysfunction in describing feelings.

It consists of 3 factors, difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT), which are called F1, F2, and F3 factors, containing 20 items, each scored within a 5-point scale (1: completely disagree to 5: completely agree), 20-100 points, the higher the score, the more pronounced the dysfunction in describing feelings.

It consists of 3 factors, difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT), which are called F1, F2, and F3 factors, containing 20 items, each scored within a 5-point scale (1: completely disagree to 5: completely agree), 20-100 points, the higher the score, the more pronounced the dysfunction in describing feelings.

Assesses the degree of agreement or disagreement with narratives about reflective functioning, with higher scores representing higher levels of reflective functioning.

Assesses the degree of agreement or disagreement with narratives about reflective functioning, with higher scores representing higher levels of reflective functioning.

Assesses the degree of agreement or disagreement with narratives about reflective functioning, with higher scores representing higher levels of reflective functioning.

Assesses the degree of agreement or disagreement with narratives about reflective functioning, with higher scores representing higher levels of reflective functioning.

Detection of serum IL-6 levels using flow cytometry. The normal value is 0-5.30 pg/ml. There is a goodcorrelation between depression and elevated serum IL-6 levels.

Detection of serum IL-6 levels using flow cytometry. The normal value is 0-5.30 pg/ml. There is a goodcorrelation between depression and elevated serum IL-6 levels.

Reflecting brain function. It will be used for analysing Left-right asymmetry of forehead Alpha wave energy，mapping the brainnetworks.

Reflecting brain function. It will be used for analysing Left-right asymmetry of forehead Alpha wave energy，mapping the brainnetworks.

Reflecting cortical excitability. N15, P30, N45, P55, N100, P180 and N280 components were evoked during single-pulse TMS stimulation of motor cortex (M1). Early components of TEPs (N15-P30) reflect cortical excitatory activity, while other components (N45-N100) are associated with cortical inhibitory activity.

Reflecting cortical excitability. N15, P30, N45, P55, N100, P180 and N280 components were evoked during single-pulse TMS stimulation of motor cortex (M1). Early components of TEPs (N15-P30) reflect cortical excitatory activity, while other components (N45-N100) are associated with cortical inhibitory activity.

THINC-it（https://progress.im/en/）is the first tool to assess cognitive functioning in MDD using both subjective and objective tests and is available as a free download for use on tablets, smartphones or computers. The tool's four objective test sections use recognized cognitive paradigms to assess subjects' performance in the key cognitive domains of attention, working memory, and executive function. The Choice Reaction Time (CRT) focuses on attention and executive function, the 1-Back Memory Task (1-Back) examines memory, attention/concentration, and executive function, the Digit Symbol Substitution Test (DSST) examines processing speed, attention, and executive function, and the Test of Connectivity B (TMT-B) assesses executive function. The 5-item Cognitive Impairment Questionnaire (PDQ⁃5⁃D) is the subjective component of the instrument and can be used to assess patients' performance in attention/concentration, planning/organization, retrospection, and prospective memory.

THINC-it（https://progress.im/en/）is the first tool to assess cognitive functioning in MDD using both subjective and objective tests and is available as a free download for use on tablets, smartphones or computers. The tool's four objective test sections use recognized cognitive paradigms to assess subjects' performance in the key cognitive domains of attention, working memory, and executive function. The Choice Reaction Time (CRT) focuses on attention and executive function, the 1-Back Memory Task (1-Back) examines memory, attention/concentration, and executive function, the Digit Symbol Substitution Test (DSST) examines processing speed, attention, and executive function, and the Test of Connectivity B (TMT-B) assesses executive function. The 5-item Cognitive Impairment Questionnaire (PDQ⁃5⁃D) is the subjective component of the instrument and can be used to assess patients' performance in attention/concentration, planning/organization, retrospection, and prospective memory.

The participants are instructed to watch the animations，while EEG data is recorded. Event-related Mu-wave will be used for evaluating social interaction ability.

The participants are instructed to watch the animations，while EEG data is recorded. Event-related Mu-wave will be used for evaluating social interaction ability.

Inclusion Criteria: Sign a written informed consent form, willing to participate in the study and accept treatment (patients under 18 years of age need to obtain the consent of their parents or legal guardians); Age between 12 and 18 years; Right-handed; Han ethnicity; Meet the DSM-5 diagnostic criteria for depression; HAMD-24≥20; Understand written language and able to complete questionnaires; First-episode depression patients who have never received any treatment or relapse depression patients, have not taken any psychotropic drugs in the past 2 weeks, have not received systematic psychological or physical therapy. Exclusion Criteria: Exclusion criteria for tDCS: (1) Patients with metal implants in the body; those with metal implants such as titanium or magnetic devices (including aneurysm clips); (2) Patients with implanted devices such as cardiac pacemakers, deep brain stimulators (DBS); (3) Patients with intracranial hypertension, skull defects, or tumors; (4) Patients with unstable vital signs such as severe cardiac or somatic diseases; (5) Patients in the acute phase of cerebrovascular diseases; (6) Patients with adverse reactions to electrical stimulation; (7) Patients with pain sensitivity, injury, or inflammation in the stimulation area. Exclusion criteria for MRI; Patients with severe neurological, cardiac, liver, kidney, endocrine, and blood system diseases, or any other condition that may interfere with the study evaluation; Patients with organic mental disorders and mental retardation; Patients with alcohol or drug dependence; Patients with a high risk of suicide.