Predicting Illness Trajectories In Fully Remitted Major Depression Using Concurrent TBS/fNIRS

Not Applicable

Not yet recruiting

• Conditions: Major Depression in Remission; Healthy
• Interventions: Device: Theta-burst stimulation (TBS); Other: telephone interviews

• Registration Number: NCT05579015
• Lead Sponsor: The Hong Kong Polytechnic University

Brief Summary

Major depressive disorder (MDD) is the world's leading cause of disability according to the World Health Organization. MDD is highly recurrent, even if clinical remission is reached after successful treatment. In fact, the enormous burden of disability, mortality and financial costs is due to the recurrent and chronic nature of MDD. The reliable prediction of the recurrence of major depressive episodes (MDEs) based on a prognostic model that is informed by biological, neurophysiological or neuroimaging data would be valuable and lifesaving for many. However, such models are still lacking.

Several lines of evidence point to abnormal prefrontal control over limbic emotion processing areas in MDD owing to diminished prefrontal excitability that seems to persist during MDD remission (rMDD). Prefrontal excitability in rMDD may thus be a trait marker of MDD and may potentially be indicative of disease recurrence. Yet, research investigating the potential utility of prefrontal excitability for predicting the recurrence of MDEs is lacking. Cortical excitability can be investigated using transcranial magnetic stimulation (TMS); however, human studies have mostly probed cortical excitability of the motor cortex, a brain region not considered to be central in the neuropathology of MDD. Hence, knowledge of the effect of TMS on prefrontal excitability is limited. Moreover, whether immediate prefrontal modulation by TMS can predict the recurrence of MDEs in fully remitted MDD patients remains to be investigated. Thus, there is a need for research that aims to quantify the direct and immediate aftereffects of TMS on prefrontal function. Most importantly, with regard to precision medicine, there is a need for research that explores the utility of immediate prefrontal reactivity to TMS for predicting MDE recurrence. Here, the investigators propose a research program that will exploit the combination of functional near-infrared spectroscopy (fNIRS) with brain stimulation. Concurrent theta-burst stimulation (TBS)/fNIRS measurements will allow us to systematically investigate stimulation-induced modulation of blood oxygenation as a proxy for induced brain activity changes (TBS is a modern form of patterned TMS). The findings from this study will (1) elucidate the immediate effects of excitatory and inhibitory brain stimulation on prefrontal activity in rMDD and controls and (2) validate the potential utility of stimulation-induced brain modulation for the prediction of MDE recurrence.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-14
• Study First Submitted QC: 2022-10-12
• Study First Posted: 2022-10-13
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-07
• Last Update Posted: 2023-03-08
• Study Start: 2024-01
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

• 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;
• at least two previous MDEs within the last 10 years;
• no or stable (≥4 weeks) psychopharmacological medication.

Exclusion Criteria

• severe internal diseases;
• neurological disorders or a history of severe head injuries;
• current psychiatric comorbidities, including addiction;
• pregnancy;
• 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. Potential participants taking antidepressants will be included if there has been no recent change to either dosage or medication (within 4 weeks).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rMDD group	telephone interviews	Participants with remitted MDD who will receive concurrent TBS/fNIRS with iTBS and followed by cTBS after one hour. This group will also receive follow-up telephone interviews every 3 months for 2 years to monitor major depressive episode recurrence.
Healthy control group	Theta-burst stimulation (TBS)	Healthy participants who will receive TBS/fNIRS with iTBS and followed by cTBS after one hour. No follow-up interviews will be conducted for this group.
rMDD group	Theta-burst stimulation (TBS)	Participants with remitted MDD who will receive concurrent TBS/fNIRS with iTBS and followed by cTBS after one hour. This group will also receive follow-up telephone interviews every 3 months for 2 years to monitor major depressive episode recurrence.

Primary Outcome Measures

Name	Time	Method
Oxyhemoglobin (HbO) change compared to baseline	During and within 3 minutes post TBS-fNIRS measurement.	Primary imaging outcome measure: TBS-induced HbO change in the dorsolateral prefrontal cortex (DLPFC) during and after stimulation.
Recurrence of a major depressive episode	Up to 2 years.	Primary clinical outcome measure: recurrence of a major depressive episode (based on MINI and PhQ-9 ≥ 5).

Secondary Outcome Measures

Name	Time	Method
Hemoglobin (Hb) change compared to baseline	During and within 3 minutes post TBS-fNIRS measurement	Secondary Imaging Outcome Measure: TBS-induced Hemoglobin (Hb) change in the dorsolateral prefrontal cortex (DLPFC) during and after stimulation