Objectives: (1) To assess the therapeutic effects of tDCS on improving depressive symptoms in young individuals with Major Depressive Disorder (MDD), relative to sham stimulation ; and (2) to evaluate the tolerability, and feasibility of tDCS in young individuals with Major Depressive Disorder, to explore the feasibility for a scale-up study.

Hypothesis: 1) we hypothesize the tDCS stimulation of the dorsolateral prefrontal cortex (dLPFC) will reduce symptoms of depression more than sham stimulation, demonstrated by significant difference in change of Hamilton Depression Rating Scale (HDRS) and 2) tDCS active stimulation of the dLPFC will be tolerable and feasible among patients with MDD, as demonstrated by minimal adverse effects measured in the Adverse Events Questionnaire, adherence (with reasons of drop out), their motivation and enjoyment to participate in the study .

The incidence of probable depression during the fifth peak of COVID-19 was 24.6%, within the HK population, with the youths having experienced a disproportionately higher rate. A recent epidemiology survey conducted in HK revealed the 12-month prevalence of suicidal ideation among young individuals above secondary school age to be an alarming 8.4%. While guidelines and RCTs support the use of medication and psychotherapy as a standalone or combination treatments for major depressive disorder (MDD) in youths, a large proportion do not respond to either medication or psychotherapy. There is therefore an unmet need for new, effective treatment options for depression that can be tolerated by young individuals. Transcranial direct current simulation (tDCS) has its acute-effect is physiological change that reduces the threshold of membrane polarisation and increased the synaptic excitability. A handful of studies suggested that anodal stimulation of the dorsal lateral prefrontal cortex (DLPFC) is effective in reducing depressive symptoms in adults, however, whether similar effects applies to youth remains unknown. tDCS is portable, relatively inexpensive, and easy to use, proving to be very safe and tolerable for young individuals with minimal and temporary side effects.

Inclusion Criteria:

• Diagnosed with major depressive disorder (MDD) according to the Structured Clinical Interview for DSM-5, Clinical Version (SCID-DSM-5, CV)
• Scored ≥ 14 (i.e., at least mild to moderate depression on the 17-item Hamilton Depression Rating Scale (HDRS) at screening and at baseline;
• Right handedness;
• Stable dosage of antidepressants or other treatments for depression in recent 4 weeks; and
• Can read and write Chinese.

Exclusion Criteria:

• History of significant head trauma, neurological disorders (e.g., epilepsy), seizures;
• First degree relative with epilepsy;
• Concomitant unstable medical conditions; major neurological conditions;
• Comorbid disorders listed in the DSM-V, e.g., schizophrenia, substance use disorder, mental retardation, etc.;
• Pregnancy, lactating women, or women planning pregnancy;
• Device or metal clips on or inside the skull, cardiac pacemaker;
• Inability to provide informed consent.

At the beginning of the stimulations sessions, participants receiving both the active and sham stimulation would experience a ramp-up in current from 0 to 2 mA, then the current would ramp down to 0 mA for participants receiving sham stimulation.

Participants were told that they may experience sensations such as tingling, headache, or mild burning during the first 30 - 60 seconds of the stimulation session but that they may subside afterwards as they got used to it. In other words, participants would not be able to tell if diminishing of side effects were due to habituation (active tDCS) or ramping down of current (sham tDCS).

Moreover, the stimulation mode of the tDCS device was pre-set by a the principal investigator, who was not involved in the stimulation delivery or outcome measurements, both of which were conducted by a research assistant who was blinded to the stimulation mode.