Molecular Signatures of TMS Response in Treatment-Resistant Depression

Inclusion Criteria: * 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. * Routine pre-TMS laboratory tests reveal no abnormalities that may significantly affect treatment response, including: * Normal thyroid hormone profile * No significant vitamin deficiencies * No markedly elevated inflammatory markers * No history or current evidence of hearing loss on clinical evaluation; if present, evaluation by an otolaryngologist will be obtained. * Age 18 years and older. * Ability to provide written informed consent. Exclusion Criteria: * 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). * Abnormal thyroid hormone levels in pre-TMS laboratory testing. * Significantly elevated inflammation markers (e.g., CRP) in pre-TMS bloodwork. * Vitamin deficiencies associated with cognitive impairment (e.g., B12, folate) in pre-TMS labs. * Electrolyte imbalances on pre-TMS blood testing. * History of psychotic disorder or bipolar I/II disorder. * History of substance-induced psychosis or bipolar disorder. * Current or past substance use disorder (including alcohol, stimulants, or illicit drugs), unless abstinent from substances (excluding alcohol) for a minimum of 12 months. * Voluntary discontinuation of TMS during the treatment course. * Any serious adverse event or unexpected clinical condition during treatment that necessitates discontinuation of TMS.