Abstract
Cognitive dysfunction is common but heterogeneous in patients with Major depressive disorder (MDD). This study aimed to validate MDD subtypes based on IQ trajectories and to elucidate their cognitive and multimodal neuroimaging characteristics. Premorbid IQ was estimated using a validated Wechsler Adult Intelligence Scale-based algorithm and compared to current IQ to classify patients. Neuropsychological assessments were conducted, and multimodal neuroimaging analyses included measurements of gray matter volume and low-frequency fluctuation amplitude. A total of 164 MDD patients with preserved IQ (PIQ), 67 MDD patients with deteriorated IQ (DIQ), and 353 healthy controls (HCs) participated in the study. The DIQ group exhibited poorer performance on logical memory and executive function tasks compared to the PIQ group. Patients with IQ decline exhibited greater cognitive impairment. Neuroimaging results revealed reduced gray matter volume and increased amplitude of low-frequency fluctuations, with distinct patterns observed between PIQ and DIQ groups. Using K-nearest neighbors (KNNs), we achieved an accuracy of 0.6442 and an area under the curve of 0.8023 for predicting cognitive changes. These findings confirm the cognitive heterogeneity in depression, highlighting the potential for personalized treatment strategies.