Obsessive–Compulsive Disorder: Comorbidity, Biomarkers, Circuits, and Treatment Strategies
7 affiliations
- 1State Key Laboratory of Pharmaceutical Biotechnology, National Resource Center for Mutant Mice, Department of Anesthesiology, Nanjing Drum Tower Hospital, Institute for Brain Sciences Department of Physiology and AI Biology, School of Life Sciences Nanjing University Nanjing China
- 2Chemistry and Biomedicine Innovation Center (ChemBIC) ChemBioMed Interdisciplinary Research Center Nanjing University Nanjing China
- 3Department of Neurosurgery Jiangnan University Medical Center Wuxi China
- 4School of Biomedical Sciences The Chinese University of Hong Kong Hong Kong China
- 5Key Laboratory of Modern Acoustics (MOE) Department of Physics Collaborative Innovation Center of Advanced Microstructure Nanjing University Nanjing China
- 6Early Intervention Unit Department of Psychiatry The Affiliated Brain Hospital of Nanjing Medical University Nanjing China
- 7Department of Neuroscience City University of Hong Kong Hong Kong China
Abstract
Obsessive–compulsive disorder (OCD), characterized by intrusive thoughts and repetitive behaviors, frequently co‐occurs with anxiety disorders, contributing to greater diagnostic complexity, more severe symptoms, and poorer treatment outcomes. In this review, we consider OCD in the context of its comorbidity with anxiety and examine evidence that the two conditions may share genetic, neurochemical, and circuit‐level vulnerabilities. Particular attention is given to the cortico–striato‐thalamo–cortical, frontoparietal, and frontolimbic networks, which may interact to form a self‐reinforcing cycle in which anxiety intensifies OCD symptoms, while compulsive behaviors provide transient relief but may ultimately maintain pathological patterns of brain activity. We also discuss how these shared mechanisms may shape current and emerging treatment strategies, including pharmacological approaches targeting serotonergic, glutamatergic, dopaminergic, and histaminergic systems, cognitive–behavioral interventions, and neuromodulation techniques such as deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound. We further consider major depressive disorder and posttraumatic stress disorder as additional examples of psychiatric comorbidity, with overlapping neural substrates and clinical features. Taken together, these findings suggest that considering comorbidity alongside core OCD symptoms may improve our understanding of its pathophysiology, help identify clinically relevant biomarkers, and support individualized treatment, while providing a broader transdiagnostic perspective on psychiatric disorders.
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BibTeX
@article{zhang2026obsessivecompulsive,
title = {{Obsessive–Compulsive Disorder: Comorbidity, Biomarkers, Circuits, and Treatment Strategies}},
author = {Xiao‐Yang Zhang and Zi‐Hao Li and Li‐Ping Shen and Bing‐Qing Kong and Qi‐Peng Zhang and Ya Ke and Juan Tu and Fei Wang and Wing‐Ho Yung and Jing‐Ning Zhu},
journal = {MedComm},
year = {2026},
month = nov,
doi = {10.1002/mco2.71067},
url = {https://doi.org/10.1002/mco2.71067},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Obsessive–Compulsive Disorder: Comorbidity, Biomarkers, Circuits, and Treatment Strategies
AU - Xiao‐Yang Zhang
AU - Zi‐Hao Li
AU - Li‐Ping Shen
AU - Bing‐Qing Kong
AU - Qi‐Peng Zhang
AU - Ya Ke
AU - Juan Tu
AU - Fei Wang
AU - Wing‐Ho Yung
AU - Jing‐Ning Zhu
PY - 2026
DA - 2026/11/03
JO - MedComm
DO - 10.1002/mco2.71067
UR - https://doi.org/10.1002/mco2.71067
AB - Obsessive–compulsive disorder (OCD), characterized by intrusive thoughts and repetitive behaviors, frequently co‐occurs with anxiety disorders, contributing to greater diagnostic complexity, more severe symptoms, and poorer treatment outcomes. In this review, we consider OCD in the context of its comorbidity with anxiety and examine evidence that the two conditions may share genetic, neurochemical, and circuit‐level vulnerabilities. Particular attention is given to the cortico–striato‐thalamo–cortical, frontoparietal, and frontolimbic networks, which may interact to form a self‐reinforcing cycle in which anxiety intensifies OCD symptoms, while compulsive behaviors provide transient relief but may ultimately maintain pathological patterns of brain activity. We also discuss how these shared mechanisms may shape current and emerging treatment strategies, including pharmacological approaches targeting serotonergic, glutamatergic, dopaminergic, and histaminergic systems, cognitive–behavioral interventions, and neuromodulation techniques such as deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound. We further consider major depressive disorder and posttraumatic stress disorder as additional examples of psychiatric comorbidity, with overlapping neural substrates and clinical features. Taken together, these findings suggest that considering comorbidity alongside core OCD symptoms may improve our understanding of its pathophysiology, help identify clinically relevant biomarkers, and support individualized treatment, while providing a broader transdiagnostic perspective on psychiatric disorders.
SN - 2688-2663
ER -