Depression - Major Depressive Disorder, Treatment Resistant Depression
Conditions
Keywords
Major Depressive Disorder, Repetitive Transcranial Magnetic Stimulation, Retinal Ganglion Cells, ipRGCs, Treatment-resistant depression
Brief summary
This research explores the potential of retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs), as biomarkers for predicting response to transcranial magnetic stimulation (TMS) in treatment-resistant depression (TRD). We also aim to assess the impact of TMS treatment on RGCs and ipRGCs in TRD patients, investigating associations with clinical improvements and cognitive status. A clinical trial involving 44 patients with treatment-resistant depression (TRD) will be conducted. All participants will receive rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Data will be collected pre- and post-intervention, as well as at a 2-month follow-up, using multiple outcome measures, including the post-illumination pupil response (PIPR). The project seeks to confirm the effectiveness of TMS and the potential of RGCs/ipRGCs as predictors of treatment response, thereby facilitating the development of personalized treatment strategies for TRD patients undergoing rTMS therapy.
Interventions
DEVICERepetitive transcranial magnetic stimulation (rTMS)
Each participant's resting motor threshold (RMT) will be determined by visual observation in accordance with standard clinical practice. Intermittent theta-burst stimulation (iTBS) will be delivered over the left dorsolateral prefrontal cortex (DLPFC) using these parameters: stimulation intensity 120% RMT; bursts at 50 Hz; 2 s on and 8 s off; 600 pulses per session; total stimulation time approximately 3 minutes per session. Stimulation will be delivered using a MagPro X100 stimulator with MagOption, equipped with a B70 butterfly-shaped coil with static cooling (MagVenture, Denmark). Treatment will comprise 20 sessions, delivered once daily on weekdays.
Sponsors
Polytechnic Institute of Porto
Hospital de Sao Joao, Porto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of MDD, confirmed via the structured clinical interview; * TRD type; * Age between 18-65 years; * Visual acuity of 20/32 or better.
Exclusion criteria
* Prior rTMS treatment; * Contraindications for TMS; * Psychiatric disorders other than MDD; * Systemic diseases affecting the eyes (e.g., diabetes mellitus); * Ocular conditions; * Head injuries causing loss of consciousness; * Current or past alcohol/substance dependence within 6 months; * Neurodegenerative diseases; * Major neurological illnesses; * Use of medications affecting iris mechanics or the autonomic nervous system.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chromatic pupillometry | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To extract post-illumination pupil response (PIPR) derived from ipRGCs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Optical Coherence Tomography (OCT) | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To extract central retinal thickness and thicknesses of retina neuronal layers (GCL-IPL and RNFL) |
| Pattern Electroretinogram (PERG) | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To extract PERG N95 wave related to RGC function. |
| Contrast sensitivity test | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To measure contrast sensitivity |
| Montgomery-Åsberg Depression Rating Scale (MADRS) | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To evaluate treatment response. Scores range from 0 to 60, with higher scores indicating more severe depressive symptoms. |
| Maudsley Staging Depression | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To assess the level of treatment resistance in depression. Scores range from 3 to 15, with higher scores indicating greater treatment resistance. |
| California Verbal Learning Test-II (CVLT-II) | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To assess verbal learning and memory. Scores range from 0 to 80, with higher scores indicating better verbal learning and memory performance. |
| Reading Mind in Eyes Test (RMET) | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To assess social cognition and theory of mind through recognition of mental states from images of the eye region. Scores range from 0 to 36, with higher scores indicating better social cognitive performance. |
| Symbol Digit Modalities Test (SDMT) | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To assess information processing speed and attention. Scores range from 0 to 110, with higher scores indicating better cognitive processing speed performance. |
| Brief Visuospatial Memory Test-Revised (BVMT-R) | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To assess visuospatial learning and memory. Scores range from 0 to 36, with higher scores indicating better visuospatial memory performance. |
| WHODAS 12-item (Self-report) | Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention) | To assess disability and functional impairment in daily life. Scores range from 12 to 60, with higher scores indicating greater disability. |
Countries
Portugal
Contacts
CONTACTInês Duarte D Pais, MSc
CONTACTCatarina C Mateus, PhD
STUDY_DIRECTORCatarina C Mateus, PhD
Polytechnic Institute of Porto
Outcome results
None listed