A tablet-based attentional cognitive bias modification intervention for positive emotion processing in major depressive disorder: a single-blind randomised controlled two-centre trial

Background Patients with Major Depressive Disorder (MDD) exhibit biased information processing. This study investigates the clinical and neural efficacy of a cognitive bias modification (CBM) training in patients and healthy control (HCS), fostering processing of positive emotion stimuli. Methods In a single-blind randomised controlled trial (DRKS00029756), MDD outpatients and HCS, aged 18–60 years, were randomised to positivity training (PT) or control training (CT). Randomisation was carried out by study assistants, blinding researchers. Participants underwent 10 tablet-based dot-probe sessions over 14 days. PT implicitly redirected attention toward positive stimuli to improve depressive symptoms. Primary outcome was pre and post-training EEG-derived Early Posterior Negativity (EPN), investigating neural sensitivity towards positive stimuli. Secondary clinical outcomes included changes in depression symptoms. Findings From February 2023 to October 2024, 240 participants were included (119 MDD; 121 HCS). 62 MDD and 61 HCS underwent PT; 57 MDD and 60 HCS received CT. In MDD, EPN to positive high arousal stimuli revealed an interaction between time (pre/post) and training (PT/CT), F(1,97) = 5.017, p < 0.028, η 2 = 0.049. The between-treatment difference was 1.65 μV, 95% CI [0.19, 3.11]. EPN amplitudes shifted towards negativity in PT and positivity in CT. Depression symptom decreased from pre to post and from pre to follow-up. With respect to adverse events, one patient in the control training was regularly admitted to hospital. Interpretation CBM positivity training was associated with neural changes in MDD, supporting its potential to target pre-attentive positive emotion processing. Further EEG follow-up and higher stimulus contrasts in the training conditions may clarify clinical relevance.