Molecular Signatures of TMS Response in Treatment-Resistant Depression

Summary

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.

Eligibility

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.

Conditions2

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