Acupoints are the stimulus points and reactive points for acupuncture to treat the diseases. Therefore, this study is designed to detect the biological specificity of acupoints in healthy participants and major depressive disorder (MDD) participants by using multiple objective assessment tools. And then acupoints that are statistically different between the two groups will be defined as strong reaction points, and other acupoints without statistically different will be defined as weak response points. In addition, this clinical trial will be conducted to explore whether the efficacy of stimulating strong reaction acupoints is more effective than weak reaction points, thereby confirming the specificity of the acupoint.

Part 1: This study will include 40 patients with MDD and 40 healthy control participants. Infrared thermography (IRT), laser doppler flowmetry (LDF), functional near-infrared spectroscopy (FNIS), and digital pressure pain gauge (PPG), respectively, will be adopted to assess 4 kinds of biological specificity of MDD related acupoints, namely, the thermal transport specificity, the microcirculatory specificity, the metabolic specificity, and the pain sensitivity specificity. Based on the results of this study, we will select acupoints with statistical differences between the two groups as the strong reaction acupoints and the remaining acupoints as the weak reaction acupoints.

Part 2: A total of 120 participants with MDD who meet the inclusion criteria will be included in the study. All participants will receive basic treatment of selective serotonin reuptake inhibitors (SSRIs) antidepressants. They will be randomly divided into the acupuncture (strong reaction acupoints) group, acupuncture (weak reaction acupoints) group, and sham acupuncture group. We will evaluate the therapeutic effect and safety of acupuncture for MDD, furthermore, to demonstrate whether stimulating strong reaction acupoints has more advantages in the treatment of MDD than weak reaction acupoints.

Inclusion Criteria:

1. Inclusion criteria for health volunteers:

   • Healthy volunteers who could provide a recent depression screening report, and confirm they have not any cardiovascular, respiratory, digestive, urinary, hematological, endocrine, or neurological disease;
   • 12 ≤ age ≤60 years, male or female;
   • Participants have clear consciousness and could communicate with others normally;
   • Participants could understand the full study protocol and have high adherence. Written informed consent is signed by themselves or their lineal kin (for minor participants, their guardian should sign the informed consent form for them).

2. Inclusion criteria for MDD:

   • Patients should meet the diagnostic criteria of the International Classification of Diseases 10th Edition (ICD-10) diagnostic criteria for depression and are evaluated as moderate or severe MDD according to the severity of depression;
   • 12 ≤ age ≤60, male or female;
   • Participants have clear consciousness and could communicate with others normally;
   • Participants could understand the full study protocol and have high adherence. Written informed consent is signed by themselves or their lineal kin (for minor participants, their guardian should sign the informed consent form for them).

Exclusion Criteria:

1. Exclusion criteria of health volunteers:

   • Participants with serious primary diseases of cardiovascular diseases, liver diseases, kidney diseases, urinary diseases, and hematological diseases;
   • Participants have a mental illness, alcohol dependence, or a history of drug abuse;
   • Pregnant or lactating participants;
   • Participants are participating in other trials.

2. Exclusion criteria for MDD:

   • Participants with serious primary diseases of cardiovascular, respiratory, digestive, urinary, hematological, endocrine, neurological disease, and other serious primary diseases, and the disease cannot be effectively controlled clinically;
   • Major depressive disorders caused by organic mental disorders, schizophrenia, bipolar disorder, psychoactive substances, and non-addictive substances;
   • Participants with suicidal tendencies;
   • Pregnant or lactating participants;
   • Participants taking other antidepressants that were not SSRIs or the pharmacological effects of such antidepressants have not been cleared;
   • Participants with intellectual disabilities who cannot cooperate with the questionnaire survey;
   • Participants with bleeding tendency, skin disease, allergic constitution, and allergic to adhesive tape;
   • The skin at the test site of participants has scars, hyperpigmentation, red and swollen;
   • Participants are participating in other trials.