Does TMS Affect Neuroplasticity? The Role of Brain-derived Neurotrophic Factor and Neuronal Cell Adhesion Molecules - an Intensive Clinical Protocol Among Patients With Obsessive-compulsive Disorders

OCD

TMS, OCD, cTBS, BDNF, Neuroplasticity

Patients expressing interest in participating will undergo psychiatric assessment to verify the diagnosis of treatment-resistant obsessive-compulsive disorder (OCD), assess symptom severity, and exclude TMS contraindications. The study involves a cycle of 35 continuous theta burst stimulations (cTBS) in the supplementary motor area (SMA) over 5 working days, with 7 stimulation sessions each day lasting 40 seconds. A 1-hour break between sessions will be observed, and each session will comprise 600 pulses at 90% of the motor threshold intensity. Biochemical analysis of blood serum from 40 patients will be conducted at three time points in an open-label study with active TMS stimulation: T0 - before starting stimulation T1 - after completing stimulation T2 - 1 month after completing stimulation Inclusion criteria: Diagnosis of depression or OCD according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) criteria, Hamilton Depression Rating Scale (HAM-D) score \> 16 points, or Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score \> 19 points; age 18-70 years. Exclusion criteria: Contraindications to TMS procedures, lack of informed consent, and documented persistent non-cooperation with treatment

Transcranial Magnetic Stimulation (TMS) is an accepted non-invasive method of neurostimulation. Evidence has demonstrated that TMS allows for the reduction of depression symptoms, and an increasing number of reports support its efficacy in reducing symptoms of obsessive-compulsive disorder (OCD). There is a limited body of clinical research available on the mechanisms of TMS action. Neuroplasticity refers to the capacity of neural tissue to form new connections for the purpose of reorganization and adaptation. Brain-Derived Neurotrophic Factor (BDNF) and Cell Adhesion Molecules (CAM) are markers of neuroplasticity. BDNF influences transmission in both excitatory and inhibitory synapses, enhancing neurotransmitter release in cholinergic and dopaminergic neurons. According to the neurotrophic hypothesis, stress may decrease BDNF levels. Serum BDNF concentrations are reduced in untreated patients with depression and normalized by antidepressant treatment. Neuronal CAMs are among the most prevalent proteins, playing a crucial role in synaptic plasticity. Various CAMs appear to interact with BDNF. In depression, both reduced BDNF levels and polysialylated (PSA) neuronal CAMs are observed. Conversely, the levels of Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intracellular Adhesion Molecule-1 (ICAM-1) in depression are inversely correlated with BDNF. To address this gap, the investiagators aimed to verify the hypothesis that TMS in OCD leads to symptom reduction by inducing neuroplasticity through: Comparing changes in BDNF and CAM protein concentrations after TMS stimulation in OCD patients before and after stimulation. Assessing the correlation between changes in BDNF and CAM concentrations and the reduction of psychopathological symptoms. Evaluating the predictive value of initial BDNF and CAM concentrations. Study assumptions and planned procedures: Patients expressing interest in participating will undergo psychiatric assessment to verify the diagnosis of treatment-resistant OCD, assess symptom severity, and exclude TMS contraindications. The study involves a cycle of 35 cTBS stimulations in the supplementary motor area (SMA) over 5 working days, with 7 TMS sessions each day lasting 40 seconds. A 1-hour break between sessions will be observed, and each session will comprise 600 pulses at 90% of the motor threshold intensity. Biochemical analysis of blood serum from 40 patients will be conducted at three time points in an open-label study with active TMS stimulation: T0 - before starting stimulation T1 - after completing stimulation T2 - 1 month after completing stimulation Inclusion criteria: Diagnosis of depression or OCD according to ICD-10 criteria, Hamilton Depression Rating Scale (HAM-D) score \> 16 points, or Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score \> 19 points; age 18-70 years. Exclusion criteria: Contraindications to TMS procedures, lack of informed consent, and documented persistent non-cooperation with treatment.

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