Changes in Serum miRNA and BDNF Levels in Bipolar II Depression Treated by Theta-burst Stimulation: A Randomized Sham-controlled Exploratory Study

In this 2-year prospective, randomized, and controlled study, the investigators plan to recruit a total of 60 patients with BD-II depression. According to a random distribution table, the participants will be randomly divided into the two subgroups, respectively: the real iTBS group (n=30) and the sham iTBS group (n=30). Patients with BD-II depression between 20 and 65 years old will be recruited in 2 years. Patients will be evaluated by research psychiatrists after a thorough medical and neurological workup. The Chinese Version of Modified Schedule of Affective Disorder and Schizophrenia-Life Time (SADS-L) will be conducted for confirmation of the diagnosis. Although DSM-IV-TR criteria require a minimum duration of 4 days of hypomania, current epidemiologic data suggest that a 2-day duration is more prevalent in community samples; therefore, the investigators will use the 2-day minimum for hypomania in the diagnosis of BD-II. Eligible participants, aged 20-65, need to have a DSM-IV-TR diagnosis of BD-II. HDRS and YMRS will be used to evaluate severity of mood symptoms. Only patients in depressive state (HDRS≧18) will be recruited. Inclusion criteria are those with diagnosis of BD-II either first-onset or with previous episodes. Exclusion criteria are (i) any DSM-IV-TR Axis I diagnosis, including organic mental disorders, substance use disorder, and other major and minor mental illnesses other than BD-II, (ii) any significant medical illness, (iii) any neurological disorders, and (iv) any poorly controlled physical illness that might influence the interview and study results; (v) any form of metal implants; (iv) any history of seizures, or medications known to lower seizure threshold; (vii) history of exposure to rTMS or electroconvulsive therapy.

During the course of the follow-up, all patients will receive open-label quetiapine adjusted individually according to the clinical response and side effects in the first two weeks and will be maintained till the end of the trial, with the final dose ranging from 200 to 700 mg/d. Concomitant benzodiazepine medication (lorazepam < 4 mg) may be used for insomnia during the study. No other antidepressants, mood stabilizers, first or second-generation antipsychotics will be allowed during the study.

Twenty milliliters of whole blood will be withdrawn from the antecubital vein of each participant and prepared as serum for the purpose of total RNA extraction and for level of BDNF analysis.

The patients will be followed for 12 weeks and blood samples (20cc whole blood) and clinical symptoms will be examined at week0, the end of week 2, 6 and week 12.

Clinical severity will be assessed by the HDRS and YMRS and Clinical ratings will be performed by research psychiatrists who are trained and experienced in the rating scales. Assessments will be performed after recruitment, week 0 and on the end of week 2, 6, and 12. RNA extraction Serum will be isolated from the whole blood and stored at -80°C immediately.