Overview

Major depressive disorder (MDD) is a mood disorder characterized primarily by low mood, diminished interest, and reduced energy. Traditional views considered depression a non-degenerative condition; however, recent epidemiological studies have revealed its significant association with impaired social functioning. Data indicate that 59.3% of patients with depression experience social dysfunction of varying severity \[1\], particularly manifesting as difficulties in social interaction and relationship maintenance \[2\]. Therefore, investigating the mechanisms underlying social dysfunction is of great importance for promoting functional recovery in MDD, and dysfunction within the social reward system may represent a core factor, though the specific neural mechanisms remain unclear.

The ultimate goal of understanding the neural mechanisms underlying social reward impairment in depressed patients is to improve therapeutic outcomes. Temporal Interference (TI) stimulation, as a non-invasive deep brain stimulation technique, utilizes high-frequency current differentials to generate low-frequency amplitude-modulated electric fields, enabling precise targeting of deep brain regions. This study employs multimodal assessment methods-such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and specific cognitive-behavioral tasks-combined with TI stimulation to observe immediate changes in functional connectivity, neural activity, and related cognitive functions (e.g., decision-making, memory) across participant groups. The research aims to elucidate the roles of the parahippocampal gyrus, orbitofrontal cortex, and striatum in social reward impairment in depression, and to explore circuit-based intervention targets, thereby providing novel strategies for the recovery of social functioning in MDD.

Eligibility

Inclusion Criteria:

• 16-60 years old;
• Meeting with the criteria of major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5;
• Scored 20 or higher on the Hamilton's Depression Scale with 24 items (HAMD-24);
• With enough audio-visual ability and comprehensive ability to accomplish the visits;
• Be necessary and suitable to accept the treatment of antidepressants;
• Scored less than 14 on Hamilton's Anxiety Scale (HAMA) and scored less than 14 on the Hypomania Symptom Checklist-32 (HCL-32);
• With 2 or more atypical symptoms including significant weight gain or increase in appetite, hypersomnia, leaden paralysis, and a long-standing pattern of interpersonal rejection sensitivity that results in significant social or occupational impairment.

Exclusion Criteria:

• Severe medical or neurological problems;
• Previous mania or hypomania episodes;
• Female patients who are pregnant, planning to be pregnant or breastfeeding;
• Actively suicide ascertained by research psychiatrist or 3rd item of HAMD scored≥3(suicidality);
• Had ECT, MECT or rTMS in the past 6 months;
• Experienced severe personality disorder, mental retardation, anorexia/ bulimia nervosa.