Neurocognitive function profiles in Chinese patients with melancholic vs. non-melancholic major depressive disorder

The study aimed to investigate the neurocognitive characteristics of Chinese patients with melancholic depression (MEL) versus non-melancholic depression (NMEL). Data were derived from a multicenter, multiphase prospective study conducted across nine top-tier hospitals in six provinces of China. A total of 287 healthy controls (HCs), 643 patients with major depressive disorder (MDD) were included. Melancholic traits were assessed using the Chinese version of the Mini-International Neuropsychiatric Interview (MINI). Cognitive function, encompassing processing speed, attention, verbal learning, visual learning, and executive function, was evaluated in both HCs and MDD patients. Among all MDD patients, 457 (71.07%) were classified as MEL. Both MEL and NMEL subgroups exhibited multi-domain cognitive impairment compared with HCs, including processing speed, attention, verbal learning, visual learning, and executive function (all P < 0.05). After Bonferroni correction, MEL patients showed significantly poorer performance on processing speed (Auditory Verbal Fluency, AVF) compared with NMEL patients (corrected P = 0.011). In contrast, no significant differences were observed between MEL and NMEL patients for executive function (Stroop Color-Word Test, SCWT, corrected P = 0.671) or any other cognitive domains (attention, verbal learning, visual learning). Multiple linear regression analysis confirmed that melancholic features were independently associated with poorer performance on both AVF test (B = -2.807, SE = 1.098, t = -2.556, P = 0.011, 95% CI = -4.964, -0.651) and SCWT (B = -2.360, SE = 1.039, t = -2.272, P = 0.023, 95% CI = -4.400, -0.320), after adjusting for potential confounders. Both MEL and NMEL patients demonstrate multi-domain cognitive impairment, with more severe deficits in the MEL group. Melancholic features were a robust independent predictor of processing speed (AVF), whereas their association with executive function (SCWT) was only present in regression models and not significant after Bonferroni correction. These findings highlight the importance of cognitive assessment, especially for processing speed, in MEL patients. ClinicalTrials.gov identifier: NCT02023567; registration date: 15 December 2013.