This study will apply a comprehensive tools that integrates neuroimaging, psychological evaluation, and sleep monitoring through 18F-MPPF PET/MR, neuropsychological tests, and polysomnography (PSG) to explore the neurobiological mechanisms underlying transcranial alternating current stimulation (tACS) for depressive disorders, mainly focusing on the serotonergic system revealed by Serotonin-1A (5-HT1A) receptor.

5-HT1A receptor appears to be significantly involved in the effectiveness of electroconvulsive therapy (ECT). Like alternating current in ECT, tACS also applies alternating current to intervene in neuropsychiatric disorders. We previously found that tACS with large current, such as 15 mA, via the forehead and bilateral mastoids can improve depressive symptoms. However, the underlying mechanism of 15 mA tACS in depression remains unclear. We propose a scientific hypothesis that 15 mA tACS may increase hippocampal 5- HT1A receptors, then to reduce depression in depressive patients. Meanwhile, 15 mA tACS may increase the whole-brain functional connectivity with the hippocampus as the seed point. This study will utilize a multimodal data through 18F-MPPF PET/MR, including MPPF metabolism, resting-state fMRI, DTI, and 3D-T1 structural images. By observing the alterations of 5-HT1A receptor and the functional network between MDD patients and healthy controls, and between the pre- and post-tACS intervention in MDD patients, our aims to explore the effect of tACS on the serotonergic system in depression.

Inclusive Criteria:

1. 18 to 65 years old, Chinese, male or female.
2. Non-psychotic major depressive disorder according to DSM-IV.
3. HAMD-17 total score ≥ 17 at the baseline.
4. Currently experiencing an acute episode.
5. No history of prior treatment with psychotropic medications.
6. Understanding of all aspects of the research protocol and the ability to provide informed consent.

Exclusion Criteria for patients:

1. Unable to do PET/MR examinations.
2. Have secondary insomnia disorders, anxiety disorders, or depressive disorders caused by physical illnesses.
3. Severe or unstable organic diseases.
4. Pregnant or lactating women or those planning a pregnancy in the near future.
5. Alcohol or substance dependence or abuse within the past year.
6. Received electroconvulsive therapy or transcranial magnetic stimulation in the month preceding enrollment.
7. Skin damage at the electrode placement site or those allergic to electrode gel or adhesives.
8. Participated in any other clinical trials within the month before baseline.
9. Any inappropriate conditions considered by the study group.

Inclusion Criteria for healthy volunteers

1. To undergo PET/MR examinations.
2. Be matched with the patient group regarding age, sex, and educational level.

Exclusion Criteria for healthy volunteers:

1. Those who are enrolled in other clinical studies.
2. The inappropriate conditions considered by the study group.