Mood disorders, including mainly bipolar disorder (BD) and major depressive disorder (MDD), have become the primary health problem and one of the leading causes of functional disability in adolescents and young adults. In China, the incidence of mood disorders such as BD and MDD in adolescents and young adults has increased rapidly in recent years. Particularly, mood disorder patients currently experiencing major depressive episode are considered to be at high risk for suicide, and pharmacological treatment showed poor efficacy to such depressive patients. Mood disorders with major depressive episode have become one of the main threats to youth mental health in China. Therefore, it is of great significance to explore a series of early intervention strategies for adolescents and young adults with major depressive episode.

rTMS is a non-invasive brain stimulation treatment strategy with mild side effects. In 2008, rTMS was approved by the Food and Drug Administration (FDA) for the treatment of major depression. The selection of stimulation parameters often has a vital impact on the clinical efficacy of rTMS treatment. Several clinical trials have reported the efficacy and safety of rTMS on treatment resistant major depression. However, the evidence-based optimal targets and other stimulation parameters have not been clearly defined, which greatly limits the efficacy of rTMS in the treatment of major depressive episode. To date, there is no large randomized clinical trial (RCT) exploring an optimization of rTMS on adolescents and young adults with major depressive episode.

This study is a double-blind randomized controlled trial aiming at assessing the efficacy and safety of a novel personalized rTMS treatment protocol compared to sham stimulation for major depressive episode in adolescents and young adults with mood disorders. Participants will be assigned randomly (1:1) to the personalized rTMS group or the sham stimulation group. Participants in the rTMS group will be treated with 20 sessions (2 sessions per day) of personalized rTMS treatment, and participants in the sham stimulation group will receive the same scheme of rTMS treatment but with sham coil. The selection of stimulation parameters (stimulation site, frequency, number of pulses, number of sessions, train and inter-train duration) in both groups will be based on neuroimaging biomarkers extracted via machine learning method. Participants in both groups will maintain the stable drug regimen during the rTMS trial.

At baseline and after each 10 sessions of treatment, patients will receive the assessment of depressive symptom severity, cranial magnetic resonance imaging (MRI) scan and peripheral blood collection (about 15ml peripheral blood). Before and after 20 sessions of treatment, neurocognitive function test will be performed. The purposes of the present study are to: 1) evaluate the clinical response to the personalized rTMS treatment by comparing the change in depressive symptom and neurocognitive function over the course of rTMS trial. 2) further understand the possible biological mechanism underlying the efficacy of personalized rTMS treatment by analyzing alterations from multidimensional data of neuroimaging, plasma proteomics and metabolomics.