This is an assessor-blinded, randomized, MAS-controlled trial. A total of 148 adolescents aged 15-22 years experiencing mild to moderate anxiety or depressive symptoms will be recruited. They will be randomly assigned to DCEAS+BA (n = 74) and MAS (n = 74) for 2 sessions per week for 8 weeks, followed by a 4-week post-treatment observation period. A post-intervention visit will be held at week 12. The primary outcome will be assessed using the Chinese version of the Beck Anxiety Inventory (BAI-C). The secondary outcomes include the Beck Depression Inventory II (C-BDI-II) for depression, the Zung Self-Rating Anxiety Scale (SAS) and the Zung Self-Rating Depression Scale (SDS) as additional assessments for anxiety and depression, the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, and the World Health Organization Quality of Life-Brief (WHOQOL-BREF) (HK version) for the general quality of life. Assessment will be carried out every 4 weeks till week 12, while saliva will be collected at baseline and at the end of the 8 weeks. Salivary oxytocin and cortisol will be analyzed. A generalized linear mixed-effect model will be applied to compare treatment outcomes over time in the two groups and linear regression will be conducted to examine intercorrelations among clinical improvement and changes in biomarker levels. Subgroup analysis will be conducted to identify specific effects of DCEAS+BA.

Psychological distress refers to a state of emotional suffering characterized by symptom(s) including anxiety, depression, and stress, and is often accompanied by somatic symptoms such as insomnia, headache, and lack of energy. As subclinical symptoms or clinical diagnoses, anxiety and depression are often core symptoms in psychological distress. They are highly comorbid and are often accompanied by physical and sleep problems. Psychological distress is particularly prevalent in adolescents and can be a precursor or features of various psychiatric disorders. One epidemiological study conducted in Hong Kong local university students has revealed that approximately 70% of students complained of some degree of depression and 54% of anxiety; nearly 9% had moderately severe to severe depressive symptoms and 6% had severe anxiety. Two most recent large-scale surveys respectively conducted in Hong Kong and China further revealed about 17% of children and youths probably had a mental problem. This has become more severe during and post COVID-19 pandemic. However, psychiatric disorders of youths are often underdiagnosed and vastly undertreated, because the condition of most young patients is mild and they may fear drugs' side effects which sometimes are a greater risk than the disease itself. This has led to particularly low acceptability for medication interventions in adolescents. The development of novel non-pharmacological treatment strategies for youth is therefore greatly desired.

A large body of evidence well confirms the benefits and effectiveness of acupuncture in the treatment of depression, anxiety, and various related disorders. Recently, we further developed a novel acupuncture mode called 'dense cranial electroacupuncture stimulation plus body acupuncture (DCEAS+BA)', where "dense" represents the use of many acupoints mainly located on the forehead. DCEAS is a novel nerve stimulation that is established based on neuroanatomical rationales, i.e., electrical stimulation is conducted on many forehead acupoints that are innervated by the first branch of the trigeminal nerve. We have demonstrated the effectiveness of DCEAS in the treatment of major depression, post-stroke cognitive impairment, insomnia, obsessive-compulsive disorder (OCD), and chemotherapy-induced cognitive impairment. Previous studies also have revealed that transcutaneous trigeminal nerve stimulation is effective in reducing depression, anxiety, attention-deficit/hyperactivity disorder (ADHD) and epilepsy. Compared to adults, adolescents are more sensitive to peripheral nerve stimulation, producing robust neuromodulatory effects. These have led to the hypothesis that DCEAS+BA may have particular effects in alleviating adolescents' psychological distress.

Saliva collection is highly acceptable for children and adolescents. Salivary oxytocin and cortisol are the two most compelling biomarkers for screenings, diagnoses, and predicting treatment outcomes in children and adolescents with psychiatric disorders. Children and adolescents with social disorder and emotional distress had significantly lower levels of salivary oxytocin and higher cortisol levels. Electroacupuncture and acupuncture suppressed salivary cortisol levels while anxiety symptoms were alleviated. The oxytocin system plays an important role in the therapeutic mechanisms of acupuncture in the treatment of pain disorders and autism. These studies suggest that salivary oxytocin and cortisol could serve as valid biomarkers for predicting the treatment outcomes of acupuncture.

Over the past years, we have completed a series of clinical trials evaluating the efficacy of acupuncture, with particular DCEAS+BA in patients with cognitive impairment, depression, and insomnia. However, our previous studies of DCEAS mainly focused on the general population with psychiatric disorders and aged subjects with stroke, and only estimated clinical efficacy, but did not explore associations with specific biomarker profiles. In particular, it is not yet validated in young subjects with psychological distress.

There have been several lines of evidence suggesting that younger subjects with psychiatric disorders could achieve earlier responses and may be more efficacious for nerve and brain stimulation compared to older adults. There also exists an age difference in the analgesic effects of electroacupuncture between adult and juvenile rats. On the other hand, meta-analysis and recent trials suggested that acupuncture and electroacupuncture may have more benefits in treating anxiety disorders and insomnia, and produce comparable efficacy in improving anxiety disorders as compared to anxiolytics. This has led to the anticipation that youths with psychological distress could achieve better outcomes on DCEAS+BA compared to other subpopulations. Therefore, we further propose this trial to examine the efficacy of DCEAS+BA and its associations with salivary oxytocin and cortisol in adolescents with psychological distress. As youths with psychiatric disorders are vastly undertreated, are often reluctant and even decline to take the medications due to fear of the drugs' side effects, the validation of the efficacy of DCEAS+BA provides an effective and acceptable option for this special subpopulation. The exploration of the associations with biomarkers will help us gain more insights into the mechanisms of DCEAS.

Inclusion Criteria:

Subjects will be eligible for this study if they:

1. are experiencing anxiety as evidenced by a BAI-C score of at least 8 (no symptoms = 0-7; mild = 8-15; moderate = 16-25; severe = 26-63), and/or a C-BDI-II score of at least 14 (no symptoms = 0-13, mild = 14-19; moderate = 20-28; severe = 29-63);
2. have symptoms that have persistent for more than 3 months;
3. are able to provide informed consent for participation, and complete treatments and questionnaires as scheduled; and
4. have no suicidal ideation, as evidenced by "no" answers or a score of <3 for all questionnaires of the Columbia-Suicide Severity Rating Scale (C-SSRS).

Exclusion Criteria:

Subjects will be excluded if they:

1. have unstable systemic medical conditions that may limit their participation in the study, for example, severe liver, cardiovascular, or kidney impairment; gastrointestinal or endocrine dysfunction; malignancy; autoimmune disease; acute infectious disease; or any conditions with unstable vital signs or require intensive hospitalization;
2. have bipolar or psychotic disorder (e.g. schizophrenia);
3. have a history of brain injury or surgery;
4. have alcohol abuse or substance abuse;
5. are pregnant or in lactation, or intend to conceive;
6. have heart pacemaker or other metal devices implanted in the body;
7. have concurrent or use of drug treatment for anxiety/depression in the previous 6 months;
8. have treatment with acupuncture or brain stimulation in the previous 6 months;
9. have a history of epilepsy;
10. have a condition of bleeding tendency, or coagulopathy, or currently receiving anti-coagulant treatment; or
11. involved in other interventional clinical studies in the last 3 months or any relevant condition potentially interfering with study evaluation.