Subtyping OCD based on individual symptom networks: subtype-specific neural dynamics and morphometric similarity linked to molecular profiles
摘要
Obsessive-compulsive disorder (OCD) is clinically heterogeneous, posing challenges for diagnosis and treatment. Individual symptom network–based subtyping could provide the framework for characterizing this heterogeneity. This study developed an individualized symptom network (ISN)-based subtyping framework, leveraging a healthy control dataset (n = 3227) to model the normative symptom network. Based on the prominence of obsessive-compulsive (OC) symptoms within ISN (Expected Influence within ISN, EIISN), three OCD subtypes were identified in the discovery cohort (n = 238). Subtype 1 (39.50%) characterized by checking/obsessing, subtype 2 (6.30%) by ordering/washing and subtype 3 (54.20%) by hoarding, validated in another dataset (n = 79), the follow-up data from the discovery cohort (n = 109) and a subsample of the discovery cohort assessed using other OC symptom scale (n = 83). Nuroimaging analysis revealed distinct brain dynamics and morphometric similarity: subtype 1 exhibited more frequent transitions from the activated visual to frontoparietal control networks and higher morphometric similarity within the default mode network (DMN) compared to subtype 3. Subtype 2 exhibited increased regional intrinsic activity in the inferior frontal gyrus (opercular part) and the postcentral gyrus, with the lowest transitions from the activated somatomotor to the ventral attention networks. Subtype 1 also exhibited significantly higher morphometric similarity within the DMN and its connections to the dorsal/ventral attention networks compared to subtypes 2 and 3. Moreover, these neural features are associated with symptoms. Neurotransmitter-related subtype-specific dynamics to GABAa and μ-opioid, while transcriptomic analyses associated subtype-specific morphometric similarity with IL-1β and TNF-α. Together, biologically grounded 3 OCD subtypes based on EIISN exhibit replicability across time, samples and assessment scales and offer an individual framework for decoding OCD heterogeneity.