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Sensorimotor circuit connectivity as a candidate biomarker for responsiveness to sertraline in obsessive–compulsive disorder

Neuropsychopharmacology (2026)Cite this article

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Abstract

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.

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Fig. 1: Brain regions with significant FC differences among the nOCD, rOCD and HC groups based on ANOVA analysis.
Fig. 2: Bar plots for partial results of post hoc analyses of FC values between each pair group (nOCD group vs. rOCD group, nOCD group vs. HC, rOCD group vs. HC).
Fig. 3: Exploratory prediction of sertraline response in OCD patients.

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Data availability

Individual-level clinical and imaging data derive from an ongoing longitudinal study, and therefore they cannot be publicly shared until the cohort’s primary results are published. Derived measures and analysis code are available from the corresponding author upon reasonable request.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (82230045、82071518) and granted from the Shanghai Science and Technology Committee (25Y22800100). We acknowledge Dr. Michael William Simpson for useful discussions during the paper preparation.

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  1. These authors contributed equally: Tingyue Bai, Yang Wang.

Authors and Affiliations

  1. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China

    Tingyue Bai, Yang Wang, Hanyang Ruan, Gui Zhang, Jian Gao, Zifeng Zheng, Di Li, Qing Zhao, Huiqin Han, Qing Fan, Dongdong Shi & Zhen Wang

  2. Neuroimaging Centre (TUM-NIC), TUM Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Hanyang Ruan

  3. Shanghai Intelligent Psychological Evaluation and Intervention Engineering Technology Research Center, Shanghai, PR China

    Zhen Wang

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Contributions

Tingyue Bai: Writing – original draft, Writing – review & editing, Formal analysis, Investigation, Data curation; Yang Wang: Writing – review & editing, Conceptualization, Methodology, Validation; Hanyang Ruan: Writing – review & editing, Conceptualization, Methodology, Validation; Gui Zhang: Conceptualization; Jian Gao: Investigation; Zifeng Zheng: Investigation; Di Li: Investigation; Qing Zhao: Investigation; Huiqin Han: Resources; Qing Fan: Resources; Dongdong Shi: Resources; Zhen Wang: Supervision, Resources, Funding acquisition, Conceptualization.

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Correspondence to Zhen Wang.

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Bai, T., Wang, Y., Ruan, H. et al. Sensorimotor circuit connectivity as a candidate biomarker for responsiveness to sertraline in obsessive–compulsive disorder. Neuropsychopharmacol. (2026). https://doi.org/10.1038/s41386-026-02375-5

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