Transcranial Magnetic Stimulation (TMS) therapy is an approved and effective treatment option for treatment-resistant depression (TRD). This study aims to identify biomarkers that predict TMS treatment response in TRD, provide insights into the neurobiological mechanisms underlying TMS efficacy, and contribute to personalized treatment strategies. By establishing proteomic and metabolomic signatures, this research seeks to enhance clinical decision-making, reduce healthcare costs, and improve patient outcomes in TRD. The findings will align with the precision medicine movement in psychiatry, advancing biomarker-driven therapeutic approaches for treatment-resistant depression.
Diagnosis of Major Depressive Disorder (MDD) according to DSM-5-TR criteria.
Inadequate clinical response to at least two different antidepressants and/or anti-obsessive agents administered at therapeutic doses and durations.
Clinical symptoms not better explained by metabolic or organic medical conditions.
No epileptic activity detected on routine electroencephalography (EEG) prior to TMS initiation.
Any contraindication to TMS as identified in the standardized pre-TMS risk assessment form.
Presence of epileptic focus detected on pre-TMS EEG.
History of significant head trauma, loss of consciousness, or intracranial surgery.
Presence of metal implants or foreign bodies incompatible with TMS (e.g., aneurysm clips, surgical clamps, metallic fragments).
Single group
TMS
DeviceTranscranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique approved for the treatment of major depressive disorder (MDD), particularly in individuals with treatment-resistant depression (TRD). TMS targets the left dorsolateral prefrontal cortex (DLPFC), a brain region often underactive in depression, and modulates neural activity through magnetic pulses. This study aims to evaluate the effects of TMS on plasma proteomic and metabolomic profiles in patients with TRD. Participants will undergo 20 sessions of intermittent theta burst stimulation (iTBS) over four weeks. Blood samples will be collected before and after treatment to identify molecular changes associated with clinical response. Healthy controls will provide single-time-point blood samples for baseline comparison. Findings may support the development of biomarker-based strategies for personalized treatment in psychiatry.
Plasma Proteomic Profile Changes After TMS in Patients with Treatment-Resistant Depression
Assessment of differences in plasma proteomic profiles in treatment-resistant depression (TRD) patients before and after transcranial magnetic stimulation (TMS), using high-resolution liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Changes in protein expression will be used to identify potential biomarkers of treatment response.
Plasma Metabolomic Profile Changes After TMS in Patients with Treatment-Resistant Depression
Evaluation of global metabolomic changes in plasma of TRD patients pre- and post-TMS therapy. Analysis will be conducted via liquid chromatography-mass spectrometry with ion mobility separation (LC-TIMS-TOF-MS), enabling identification of differential metabolites associated with clinical outcomes.
Fold Change in Baseline Proteomic Markers Between Treatment Responders and Non-Responders
Differences in baseline proteomic markers between treatment responders and non-responders will be assessed using LC-MS/MS. Fold change values will be calculated to identify proteins with significant differential expression between the two groups.
Variable Importance in Projection Scores of Predictive Proteins
Variable Importance in Projection scores will be calculated using multivariate statistical analysis (e.g., PLS-DA) to rank the importance of baseline proteomic markers in distinguishing treatment responders from non-responders.
Change in Depression Severity Based on Hamilton Depression Rating Scale (HAM-D, 17-item)
Depression severity will be assessed using the 17-item clinician-administered HAM-D scale. Scores range from 0 to 34, with higher scores indicating more severe depressive symptoms. A clinical response is defined as a ≥50% reduction in HAM-D total score from baseline to post-treatment
Change in Depression Severity Based on Patient Health Questionnaire-9 (PHQ-9)
Depression severity will be self-assessed by participants using the PHQ-9 scale. Scores range from 0 to 27, with higher scores reflecting more severe symptoms. A clinical response is defined as a ≥50% reduction in PHQ-9 total score from baseline to post-treatment.
Change in Subjective Sleep Quality Measured by Pittsburgh Sleep Quality Index [Sleep Quality]
Subjective sleep quality will be assessed using the Pittsburgh Sleep Quality Index(PSQI) a self-reported questionnaire consisting of 24 items that evaluate sleep quality over the past month across seven domains (e.g., sleep latency, duration, disturbances). Total score range: 0 to 21. Minimum possible score: 0 (indicating good sleep quality). Maximum possible score: 21 (indicating poor sleep quality). Interpretation: Higher scores indicate worse sleep quality. Changes in PSQI total scores from baseline to the end of the 4-week treatment period will be analyzed.
Correlation Between Antidepressant Medication Use and Clinical Response to TMS Measured by Hamilton Depression Rating Scale-17
This outcome will assess the correlation between concurrent antidepressant medication use and clinical response to Transcranial Magnetic Stimulation (TMS). Medication data collected: Drug name, dosage, duration. Clinical outcome: Change in Hamilton Depression Rating Scale-17 (HAM-D17) total score from baseline to end of treatment. Statistical method: Pearson or Spearman correlation (based on data distribution). Unit of Measure (Antidepressant Use): Continuous (daily dose in mg), duration in weeks. Unit of Measure (TMS Response): Change in HAM-D17 total score
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