Vulnerability Markers for Depression

The Hong Kong Polytechnic University166 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

166

Conditions

Major Depressive Disorder Remission Major Depressive Disorder Healthy

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Oxyhemoglobin (HbO) change compared to baseline

Primary imaging outcome measure: iTBS-induced HbO change in the bilater prefrontal cortex during and after stimulation.

Time frame: During and within 3 minutes post TBS-fNIRS measurement.

Verbal fluency task induced-oxyhemoglobin (HbO) change compared to baseline

Primary imaging outcome measure: cognitive task-induced HbO change in the bilateral prefrontal cortex.

Time frame: During the 60 seconds word-generation blocks.