Vulnerability Markers for Depression
June 25, 2025 updated by: Dr Georg Kranz, The Hong Kong Polytechnic University
Vulnerability Markers for Depression: a Concurrent TMS-fNIRS Study
The current study is a pilot for the GRF project entitled "Predicting illness trajectories in fully remitted major depression using concurrent TBS/fNIRS".
The project aims to determine whether immediate prefrontal excitability modulated by intermittent theta-burst stimulation (iTBS) is altered in remitted major depressive disorder (rMDD) and therefore classifies as a potential trait marker to predict the incidence of recurrence.
In the present cross-sectional study, we will recruit four clusters of population, including patients diagnosed with rMDD, currently depressed patients with varying numbers of episodes, healthy subjects, and never-depressed healthy subjects with elevated risk for MDD (defined as having a first-degree relative with a history of depression), to investigate the relationship between the number of prior episodes, cognitive function, and TBS-induced instantaneous brain activity change in the presumed neuropathological prefrontal cortex (PFC).
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Observational
Enrollment (Actual)
166
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Hong Kong, Hong Kong
- The Hong Kong Polytechnic University
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Yes
Sampling Method
Non-Probability Sample
Study Population
Four clusters of the population will be recruited, including patients diagnosed with rMDD, currently depressed patients with varying numbers of episodes, healthy subjects, and never-depressed healthy subjects with elevated risk for MDD (defined as having a first-degree relative with a history of depression)
Description
Inclusion Criteria:
- rMDD patients: (a) aged 18 to 65; (b) a clinical diagnosis of recurrent depressive disorder by an experienced psychiatrist but currently in full remission (ICD 11, 6A71.7) according to results of the Mini International Neuropsychiatric Interview (MINI) and the Patient Health Questionnaire (PHQ-9), with a score ≤ 4; (c) at least two previous MDEs within the last 10 years; (d) no or stable (≥4 weeks) psychopharmacological medication.
Current MDD patients: (a) aged 18 to 65; (b) a clinical diagnosis of current unipolar depressive disorder by an experienced psychiatrist according to DSM-IV; (c) no or stable (≥4 weeks) psychopharmacological medication.
HCs: (a) aged 18 to 65 and (b) healthiness based on history and psychiatric assessment.
never-depressed HCs with elevated risk for MDD (HR-HCs): (a) aged 18 to 65, (b) healthiness based on history and psychiatric assessment and (c) with a family history of psychiatric illnesses.
Exclusion Criteria:
- rMDD patients: (a) severe internal diseases; (b) neurological disorders or a history of severe head injuries; (c) current psychiatric comorbidities, including addiction; (d) pregnancy; (e) common fNIRS and TMS exclusion criteria, such as a history of brain surgery, head injury, cardiac pacemaker, deep brain stimulation, intracranial metallic particles, history of seizures, and antiepileptics and benzodiazepines corresponding to a dose of >1 mg lorazepam/d.
MDD patients: (a) severe internal diseases; (b) neurological disorders or a history of severe head injuries; (c) Axis-I disorders and history of alcohol or substance abuse or past co-morbid axis-I disorders being the likely primary cause of the depressive syndrome within the past 6 months; (d) pregnancy; (e) common fNIRS and TMS exclusion criteria, such as a history of brain surgery, head injury, cardiac pacemaker, deep brain stimulation, intracranial metallic particles, history of seizures, and antiepileptics and benzodiazepines corresponding to a dose of >1 mg lorazepam/d.
HCs: (a) medical history of a major systemic illness or a neurological or psychiatric disorder; (b) psychiatric disorders in their first-degree relatives; (c) pregnancy; and (d) common fNIRS and TMS exclusion criteria as stated above.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
rMDD patients
Participants are required to visit the lab twice.
In the first visit, participants will first perform a verbal fluency task during which the brain activity will be recorded by fNIRS.
Then participants complete a cognitive test called Raven's Advanced Progressive matrices (~ 40 min).
In the second visit, participants will receive concurrent iTBS/fNIRS.
|
TBS comprises 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz).
iTBS consists of 2-second trains with an inter-train interval of 8 seconds.
The investigators will repeat the trains (30 pulses; 10 bursts) 20 times to reach a total number of 600 pulses (3x10x20).
Concurrent iTBS/fNIRS stimulation will be applied over the left DLPFC at an intensity of 90% resting motor threshold (RMT).
This corresponds to ~110% of the active motor threshold.
Stimulation at 90% RMT will also ensure compliance, reduce sensory discomfort and minimize dropout rates.
Still, scalp discomfort will be recorded directly after the stimulation.
The stimulation site over the DLPFC will be determined using the international 10-20 system and correspond to the F3 label.
Other Names:
|
|
MDD patients
Participants are required to visit the lab twice.
In the first visit, participants will first perform a verbal fluency task during which the brain activity will be recorded by fNIRS.
Then participants complete a cognitive test called Raven's Advanced Progressive matrices (~ 40 min).
In the second visit, participants will receive concurrent iTBS/fNIRS.
|
TBS comprises 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz).
iTBS consists of 2-second trains with an inter-train interval of 8 seconds.
The investigators will repeat the trains (30 pulses; 10 bursts) 20 times to reach a total number of 600 pulses (3x10x20).
Concurrent iTBS/fNIRS stimulation will be applied over the left DLPFC at an intensity of 90% resting motor threshold (RMT).
This corresponds to ~110% of the active motor threshold.
Stimulation at 90% RMT will also ensure compliance, reduce sensory discomfort and minimize dropout rates.
Still, scalp discomfort will be recorded directly after the stimulation.
The stimulation site over the DLPFC will be determined using the international 10-20 system and correspond to the F3 label.
Other Names:
|
|
Health Controls
Participants are required to visit the lab twice.
In the first visit, participants will first perform a verbal fluency task during which the brain activity will be recorded by fNIRS.
Then participants complete a cognitive test called Raven's Advanced Progressive matrices (~ 40 min).
In the second visit, participants will receive concurrent iTBS/fNIRS.
|
TBS comprises 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz).
iTBS consists of 2-second trains with an inter-train interval of 8 seconds.
The investigators will repeat the trains (30 pulses; 10 bursts) 20 times to reach a total number of 600 pulses (3x10x20).
Concurrent iTBS/fNIRS stimulation will be applied over the left DLPFC at an intensity of 90% resting motor threshold (RMT).
This corresponds to ~110% of the active motor threshold.
Stimulation at 90% RMT will also ensure compliance, reduce sensory discomfort and minimize dropout rates.
Still, scalp discomfort will be recorded directly after the stimulation.
The stimulation site over the DLPFC will be determined using the international 10-20 system and correspond to the F3 label.
Other Names:
|
|
High Risk-HCs
Participants are required to visit the lab twice.
In the first visit, participants will first perform a verbal fluency task during which the brain activity will be recorded by fNIRS.
Then participants complete a cognitive test called Raven's Advanced Progressive matrices (~ 40 min).
In the second visit, participants will receive concurrent iTBS/fNIRS.
|
TBS comprises 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz).
iTBS consists of 2-second trains with an inter-train interval of 8 seconds.
The investigators will repeat the trains (30 pulses; 10 bursts) 20 times to reach a total number of 600 pulses (3x10x20).
Concurrent iTBS/fNIRS stimulation will be applied over the left DLPFC at an intensity of 90% resting motor threshold (RMT).
This corresponds to ~110% of the active motor threshold.
Stimulation at 90% RMT will also ensure compliance, reduce sensory discomfort and minimize dropout rates.
Still, scalp discomfort will be recorded directly after the stimulation.
The stimulation site over the DLPFC will be determined using the international 10-20 system and correspond to the F3 label.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Oxyhemoglobin (HbO) change compared to baseline
Time Frame: During and within 3 minutes post TBS-fNIRS measurement.
|
Primary imaging outcome measure: iTBS-induced HbO change in the bilater prefrontal cortex during and after stimulation.
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During and within 3 minutes post TBS-fNIRS measurement.
|
|
Verbal fluency task induced-oxyhemoglobin (HbO) change compared to baseline
Time Frame: During the 60 seconds word-generation blocks.
|
Primary imaging outcome measure: cognitive task-induced HbO change in the bilateral prefrontal cortex.
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During the 60 seconds word-generation blocks.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Georg S Kranz, PhD, The Hong Kong Polytechnic University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 8, 2023
Primary Completion (Actual)
December 18, 2024
Study Completion (Actual)
April 1, 2025
Study Registration Dates
First Submitted
April 24, 2024
First Submitted That Met QC Criteria
May 2, 2024
First Posted (Actual)
May 7, 2024
Study Record Updates
Last Update Posted (Actual)
June 29, 2025
Last Update Submitted That Met QC Criteria
June 25, 2025
Last Verified
December 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HSEARS20230705001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
PD may be shared upon request
IPD Sharing Time Frame
Upon request
IPD Sharing Access Criteria
Upon request
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
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