Multimodal Biomarkers and Precision TMS for Postpartum Depression

Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age18-45
SponsorUniversity of Macau

About this trial

The purpose of this study is to identify multimodal biological markers associated with postpartum depression (PPD) and to evaluate the effectiveness of precision brain stimulation treatment. PPD is a common mental health condition after childbirth that can affect maternal well-being and early child development. Current identification of PPD relies largely on clinical assessments and screening questionnaires, which may not fully capture underlying biological changes. This study uses brain activity, cardiac signals, blood-based biomarkers, interoceptive assessments, and clinical measures to characterize multimodal biological profiles associated with PPD and treatment response.

The main questions it aims to answer are:

* What multimodal biological differences exist between women with diagnosed PPD and healthy comparison groups, including postpartum and non-postpartum controls? * Which biological or psychological markers can predict whether a patient will respond well to repetitive transcranial magnetic stimulation (rTMS) treatment? * Can a clinical model be created to help doctors choose the best treatment based on these markers? The study focuses on characterizing multimodal biological differences in women with diagnosed PPD and examining clinical response profiles following rTMS treatment, rather than predicting the onset of PPD in the general population.

Participants will:

* Undergo electroencephalography (EEG) using a 128-channel cap to measure neural activity. * Have electrocardiography (ECG) recorded to analyze heart rate variability and autonomic function. * Provide blood samples to measure inflammatory cytokines, endocrine levels, and metabolic markers. * Complete Interoceptive Assessments (tasks to measure awareness of internal body signals) and clinical psychological surveys. * Complete follow-up assessments via online surveys and scheduled visits at 2 weeks, 1 month, and 3 months postpartum.

Participants in the PPD group will:

* Receive 4 weeks of high-precision, robot-guided rTMS treatment (20 sessions total). * Undergo pre-intervention multimodal assessments, including EEG, ECG, blood biomarkers, and interoceptive tasks, to identify potential predictors of clinical response to rTMS treatment.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Biological female, aged 18-45 years.

For HR-PPD and LR-PPD groups: Pregnant women in the third trimester (≥ 32 weeks gestation) with a singleton pregnancy.

For HR-PPD group: Beck Depression Inventory (BDI) score ≥ 14 during the third trimester.

For LR-PPD group: BDI score < 14 during the third trimester, with no history of depression.

Disqualifiers

Multiple pregnancies, preterm labor, or severe pregnancy complications (e.g., pre-eclampsia, gestational diabetes with complications).

Life-threatening emergencies during delivery (e.g., amniotic fluid embolism, major hemorrhage).

Cognitive impairment or language barriers that hinder cooperation with assessments.

History of major psychiatric disorders (e.g., schizophrenia, bipolar disorder).

Trial design

Design model

Parallel

Treatments tested in this trial

  • Repetitive Transcranial Magnetic Stimulation (rTMS)

    Device

    Participants diagnosed with postpartum depression will receive a standardized repetitive transcranial magnetic stimulation (rTMS) intervention targeting the left dorsolateral prefrontal cortex (DLPFC). Treatment will be administered by trained clinicians using a neuronavigation-assisted rTMS system. Resting motor threshold (RMT) will be determined prior to treatment, and coil positioning will be guided by a robotic navigation system with a localization error of less than 1 mm. Stimulation will be delivered at 10 Hz and 120% of the individual resting motor threshold. Each train will last 4 seconds with an inter-train interval of 26 seconds, for a total of 3,000 pulses per session. Participants will receive 20 treatment sessions over 4 weeks (5 sessions per week).

Treatment groups

290 Participants
are divided into 3 treatment groups
Group A: Patients with PPDExperimental treatment 1 intervention
Group B: Woman in late pregnancyNo intervention 0 interventions
Group C: Healthy Non-Parturient Control (HC)No intervention 0 interventions

Trial outcomes

Primary outcomes

1

Postpartum depressive symptom severity measured by the Edinburgh Postnatal Depression Scale (EPDS)

The EPDS total score ranges from 0 to 30, with higher scores indicating greater postpartum depressive symptom severity. Scores of 10 or above indicate elevated depressive symptoms, while scores of 13 or above are commonly used as a threshold for probable postpartum depression. The EPDS will serve as the primary measure of postpartum depressive symptom severity and risk identification. EPDS scores will be tracked longitudinally from late pregnancy through 3 months postpartum to characterize symptom development and identify high-risk individuals.

Time frame
T0 (Baseline, third trimester of pregnancy); T1 (2 weeks postpartum remote follow-up); T2 (1 month postpartum remote follow-up); T3 (3 months postpartum remote follow-up); Pre-rTMS treatment
2

Self-reported depressive symptom severity measured by the Beck Depression Inventory-II (BDI-II)

The BDI-II will be used to assess self-reported depressive symptom severity. The BDI-II total score ranges from 0 to 63, with higher scores indicating more severe depressive symptoms. Scores of 0-13 indicate minimal depression, 14-19 mild depression, 20-28 moderate depression, and 29-63 severe depression.

Time frame
T0 (Baseline, third trimester of pregnancy); T1 (2 weeks postpartum remote follow-up); T2 (1 month postpartum remote follow-up); T3 (3 months postpartum remote follow-up); Pre-rTMS treatment
3

Depression severity measured by the 17-item Hamilton Depression Rating Scale (HAMD-17)

The HAMD-17 total score ranges from 0 to 52, with higher scores indicating greater depression severity. Scores of 0-7 are generally considered normal, 8-16 mild depression, 17-23 moderate depression, and ≥24 severe depression.

Time frame
T0 (Baseline, third trimester of pregnancy); T1 (2 weeks postpartum remote follow-up); T2 (1 month postpartum remote follow-up); T3 (3 months postpartum remote follow-up); Pre-rTMS treatment
4

Quality of life measured by the WHO Quality of Life Instrument-Short Form (WHOQOL-BREF)

The WHOQOL-BREF is a 26-item self-report questionnaire used to assess quality of life across four distinct domains: Physical Health (7 items), Psychological Health (6 items), Social Relationships (3 items), and Environment (8 items). Each item is rated on a 5-point Likert scale. Raw domain scores are mathematically transformed to a linear 0 to 100 scale for each domain according to the official WHO guidelines. Scores range from 0 to 100, where higher scores represent a better perceived quality of life in that specific domain.

Time frame
T0 (Baseline, third trimester of pregnancy); T1 (2 weeks postpartum remote follow-up); T2 (1 month postpartum remote follow-up); T3 (3 months postpartum remote follow-up); Pre-rTMS treatment

Secondary outcomes

1

Area Under the Receiver Operating Characteristic Curve for Prediction of rTMS Treatment Response

The area under the receiver operating characteristic curve (AUC) will be used to evaluate the ability of the multimodal machine-learning model to discriminate between participants with and without a prespecified clinical response to repetitive transcranial magnetic stimulation (rTMS). AUC values range from 0.5 to 1.0, with higher values indicating better discrimination.

Time frame
After completion of 20 rTMS sessions (4 weeks)
2

F1-Score of the Multimodal Model for Prediction of rTMS Treatment Response

The F1-score will be used to evaluate the balance between precision and sensitivity of the multimodal machine-learning model in classifying participants with and without a prespecified clinical response to repetitive transcranial magnetic stimulation (rTMS). The F1-score ranges from 0 to 1, with higher values indicating better classification performance.

Time frame
After completion of 20 rTMS sessions (4 weeks)
3

Clinical Response to Robot-Guided rTMS Treatment

Clinical response to robot-guided repetitive Transcranial Magnetic Stimulation (rTMS) will be evaluated by changes in depression symptom severity measured using clinician-rated and self-reported depression scales before and after treatment. Treatment response will be defined based on percentage reduction in depressive symptoms and categorical responder status where applicable.

Time frame
Before initiation of rTMS treatment and after completion of 20 rTMS sessions (4 weeks)
4

Association Between Baseline Multimodal Biomarkers and rTMS Treatment Response

Baseline multimodal biomarkers, including EEG features, autonomic indices, peripheral inflammatory and endocrine markers, and interoceptive measures, will be examined as potential predictors of individual variability in clinical response following rTMS treatment.

Time frame
Before initiation of rTMS treatment and after completion of 20 rTMS sessions (4 weeks)

Other outcomes

1

Fertility Intentions

A structured self-report questionnaire will be used to assess subjective fertility intention and future fertility aspirations. Lower scores or negative responses reflect a reduced intention or aspiration for future fertility. This exploratory measure will be correlated with perinatal depressive symptoms, interoceptive awareness, and quality of life scores to explore how physiological and psychological stress during the transition to motherhood influences future fertility decisions.

Time frame
T1 (2 weeks postpartum remote follow-up); T2 (1 month postpartum remote follow-up)
2

Subjective Experiences and Perceptions of the Traditional Postpartum Ritual ("Sitting-the-Month")

Participants' subjective experiences, cultural compliance, and perceived psychological stress related to the traditional Chinese postpartum confinement ritual ("sitting-the-month") will be evaluated using a structured self-report questionnaire. Scores will capture dimensions of perceived emotional support versus behavioral restriction and interpersonal friction within the family.

Time frame
T1 (2 weeks postpartum remote follow-up); T2 (1 month postpartum remote follow-up)

Sponsors and contacts

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University of Macau

Lead sponsor

Kiang Wu Hospital

Collaborator

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