Repetitive transcranial magnetic stimulation (rTMS) therapy improves key biochemical markers in major depressive disorder (MDD) patients, indicating its effectiveness as an antidepressant treatment.
Highlights:
- Improved Antioxidant Levels: rTMS therapy significantly increased total antioxidant status (TAS), total thiol (TT), and native thiol (NT) levels in MDD patients compared to their levels before treatment.
- Reduced Oxidative Stress: The therapy notably decreased total oxidant status (TOS), oxidative stress index (OSI), and disulfide (DIS) levels, indicating reduced oxidative stress in patients post-treatment.
- Enhanced Neurotrophic Factors: Levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and allopregnanolone (ALLO) were significantly higher after rTMS therapy, promoting better brain health and function.
- Lowered Inflammatory Marker: S100 calcium-binding protein B (S100B) levels, which are associated with brain inflammation, were reduced following rTMS therapy.
- Potential Antidepressant Mechanism: The changes in these biochemical markers suggest that rTMS reduces oxidative stress, restores balance in the brain’s chemical environment, and supports neuroplasticity, contributing to its antidepressant effects.
Source: Translational Psychiatry (2024)
Repetitive Transcranial Magnetic Stimulation (rTMS) & Depression (Overview)
History of rTMS
Repetitive transcranial magnetic stimulation (rTMS) has its roots in the broader field of transcranial magnetic stimulation (TMS), which was first developed in the 1980s.
TMS emerged as a non-invasive method to stimulate the brain using electromagnetic fields.
The technique was initially used for diagnostic purposes to map brain function.
By the mid-1990s, rTMS, involving repeated sessions of TMS, was being explored as a therapeutic tool for neurological and psychiatric conditions, most notably for major depressive disorder (MDD).
In 2008, the FDA approved the use of rTMS for treatment-resistant depression, marking a significant milestone in its clinical application.
How rTMS Works
rTMS involves the use of a coil placed on the scalp that generates a rapidly changing magnetic field.
This magnetic field induces electrical currents in specific brain regions, most commonly the left dorsolateral prefrontal cortex (DLPFC), which is associated with mood regulation.
The repetitive nature of the stimulation modulates neuronal activity, enhancing or inhibiting neural circuits to achieve therapeutic effects.
Sessions typically last about 30-40 minutes and are administered daily over several weeks.
Mechanisms of rTMS
- Neuronal Activation: rTMS directly stimulates neurons, altering their firing patterns and enhancing synaptic plasticity. This helps in correcting abnormal neural activity associated with depression.
- Neurotrophic Effects: rTMS increases the levels of neurotrophic factors such as BDNF and GDNF, which support neuron growth and survival, thereby promoting neural health and plasticity.
- Reduction of Oxidative Stress: The therapy improves antioxidant defenses and reduces markers of oxidative stress, which are often elevated in depressed individuals.
- Regulation of Neuroactive Steroids: rTMS modulates levels of neuroactive steroids like allopregnanolone, which affect mood and anxiety through their action on neurotransmitter systems.
- Anti-inflammatory Effects: By reducing levels of inflammatory markers such as S100B, rTMS helps decrease brain inflammation, which is implicated in the pathophysiology of depression.
Efficacy of rTMS
Numerous clinical trials and meta-analyses have demonstrated the efficacy of rTMS in treating depression, particularly in patients who have not responded to traditional treatments like medications or psychotherapy.
Studies show that rTMS can lead to significant improvements in depressive symptoms, with some patients experiencing remission.
The therapy is generally well-tolerated, with the most common side effects being mild headaches and scalp discomfort.
Its non-invasive nature and minimal systemic side effects make rTMS an appealing option for many patients.
Main Findings: rTMS Changes Blood Biomarkers in Depression (2024)
1. Antioxidant Levels Improved
Total Antioxidant Status (TAS)
After undergoing rTMS therapy, patients showed a significant increase in their TAS levels.
This indicates that the therapy helped to bolster the body’s overall defense against oxidative stress, which is linked to depression.
Total Thiol (TT) & Native Thiol (NT) Levels
Both TT and NT, which are important antioxidants in the body, were significantly higher in patients post-rTMS.
This improvement suggests that the therapy helped restore a healthier balance of protective compounds in the brain.
2. Reduction in Oxidative Stress
Total Oxidant Status (TOS)
The study found that TOS, a measure of oxidative stress in the body, was significantly lower after rTMS therapy.
Lower TOS levels indicate reduced oxidative damage, which is beneficial for brain health.
Oxidative Stress Index (OSI) & Disulfide (DIS) Levels
Both OSI and DIS levels decreased notably following rTMS therapy.
This reduction highlights the therapy’s effectiveness in decreasing oxidative stress, which can contribute to the symptoms of depression.
3. Enhanced Neurotrophic Factors
Brain-Derived Neurotrophic Factor (BDNF)
BDNF levels, crucial for brain cell growth and maintenance, were significantly higher after rTMS therapy.
Increased BDNF is associated with better brain function and mood regulation.
Glial Cell Line-Derived Neurotrophic Factor (GDNF)
GDNF levels, important for the survival and maintenance of neurons, also increased significantly post-rTMS.
This suggests improved support for brain cell health.
Allopregnanolone (ALLO)
Levels of ALLO, a neuroactive steroid that influences mood, were higher after rTMS treatment.
Increased ALLO levels are linked to a reduction in depressive symptoms.
4. Decrease in Inflammatory Marker
S100 Calcium-Binding Protein B (S100B)
The study noted a significant decrease in S100B levels after rTMS therapy.
S100B is often elevated in cases of brain inflammation, so its reduction suggests a decrease in brain inflammation and potential improvement in brain health.
Study Details: TMS for Depression & Biomarker Changes (2024)
Participants
Total Participants: 51
- MDD Patients: 25 individuals diagnosed with Major Depressive Disorder (MDD).
- Healthy Volunteers: 26 individuals with no history of chronic diseases or psychiatric conditions.
Demographics: All participants were aged 18-45, and both groups had similar demographic characteristics to ensure comparability.
Methods
Design: Randomized case-control study.
Procedure:
- Blood Sample Collection: Blood samples were collected from all participants at 8:00 AM to ensure consistency. For female participants, samples were taken during the follicular phase of their menstrual cycle.
- rTMS Therapy Protocol: MDD patients received 20 sessions of repetitive transcranial magnetic stimulation (rTMS) over one month. Each session involved stimulation of the left dorsolateral prefrontal cortex (DLPFC) using a specific FDA-approved protocol (120% motor threshold, 10 Hz frequency, 4 seconds of stimulation, 26 seconds of rest).
Biochemical Analysis:
- Neurotrophic Factors: Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured using commercial kits.
- Oxidative Stress Parameters: Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were evaluated using the photometric method.
- Thiol-Disulfide Homeostasis: Total thiol (TT) and native thiol (NT) levels were measured, and disulfide (DIS) levels were calculated.
- Neuroactive Steroids: Allopregnanolone (ALLO) levels were assessed using ELISA kits.
Limitations
- Sample Size: The study had a relatively small sample size, limiting the generalizability of the findings.
- Single-Center Study: Conducted at a single medical center, which may limit the diversity of the participant pool.
- Peripheral Blood Samples: While useful, blood samples do not provide as comprehensive a picture as cerebrospinal fluid (CSF) samples, which more accurately reflect central nervous system conditions.
- Short-Term Assessment: The study focused on immediate post-treatment effects, with no long-term follow-up to assess the durability of the observed changes.
Conclusion: TMS in MDD & Effect on Biomarkers
This study highlights the promising effects of repetitive transcranial magnetic stimulation (rTMS) in treating major depressive disorder (MDD) by altering key blood biomarkers.
rTMS therapy significantly increased neurotrophic factors like BDNF and GDNF, which are vital for neural growth and repair, while reducing oxidative stress markers and inflammation-related proteins such as S100B.
These biochemical changes suggest that rTMS not only alleviates depressive symptoms but also enhances overall brain health.
The findings underscore the potential of rTMS to serve as a personalized treatment option, allowing clinicians to monitor and adjust therapy based on specific biomarker responses.
Additionally, the study opens avenues for further research into the use of rTMS for other neuropsychiatric conditions and its long-term benefits.
Overall, rTMS represents a valuable tool in the fight against depression, offering hope for improved outcomes and quality of life for patients.
References
- Study: Altered blood parameters in “major depression” patients receiving repetitive transcranial magnetic stimulation (rTMS) therapy: a randomized case-control study (2024)
- Authors: Beyza Nur Ozkan et al.
