Sensorimotor circuit connectivity as a candidate biomarker for responsiveness to sertraline in obsessive-compulsive...

Predicting selective serotonin reuptake inhibitor (SSRI) response in obsessive-compulsive disorder (OCD) remains a clinical challenge. Converging evidence implicated that the sensorimotor circuit is linked to OCD-related sensory phenomena and repetitive motor rituals, and it is densely innervated by serotonergic projections, making it a plausible substrate of SSRI effects. We therefore hypothesized that baseline functional connectivity (FC) of this circuit could serve as a candidate neural marker of SSRI treatment response. In this exploratory single-site resting-state fMRI study, 54 drug-naïve patients with OCD and 39 matched healthy controls (HCs) underwent scanning. Patients received sertraline for 12 weeks and were classified as responders (rOCD, n = 33) or non-responders (nOCD, n = 21) based on Yale-Brown Obsessive Compulsive Scale score reductions. Seed-based FC analysis of the sensorimotor circuit was conducted across the three groups. We observed that OCD patients exhibited abnormal FC primarily within the sensorimotor circuit and in its connections with the cerebellum. The rOCD group showed generally higher FC within the sensorimotor circuit than HCs, whereas the nOCD group showed lower FC values. Cerebellar regions with altered connectivity included areas involved in sensorimotor processing and higher-level functions. In prediction analyses, the connectivity between right thalamus and cerebellar Crus I region achieved an AUC of 0.854 for distinguishing responders from non-responders under leave-one-out cross-validation. Moreover, FC-based models showed better predictive performance than clinical models. These findings suggest that baseline sensorimotor-network FC may serve as a candidate biomarker of sertraline response in OCD, pending validation in large, independent samples.