Regional and network-level resting state functional connectivity markers of pharmacological treatment resistance in obsessive-compulsive disorder

Treatment resistance in obsessive-compulsive disorder (OCD) is common, with 40-60% of patients failing to respond to pharmacotherapy. Identifying functional differences between responders and non-responders may guide alternative treatment strategies. We investigated resting-state brain differences between selective serotonin reuptake inhibitor (SSRI) responders and non-responders and compared them with healthy controls (HC). 3T MRI scans were acquired from 80 participants with OCD and 50 HCs. Structural and 5-minute resting-state data were processed using the CONN toolbox. Regions showing group differences in amplitude of low-frequency fluctuation (ALFF) were identified for seed-based connectivity analysis. ANCOVA revealed significant ALFF differences among groups in the anterior middle temporal gyrus (R-aMTG) and temporal pole (R-TP). SSRI responders showed reductions in seed-to-voxel connectivity than non-responders between these regions and the left superior and inferior occipital cortices, left superior parietal lobule, and left temporo-occipital middle temporal gyrus. Responders also showed reductions in connectivity with the left superior parietal lobule compared with HCs. Across the OCD group, Y-BOCS scores positively correlated with ALFF in the R-aMTG (p=0.008) and R-TP (p=0.044). Altered temporal cortical activity and connectivity with posterior regions were associated with SSRI treatment response, supporting a role for temporal-posterior cortical networks in OCD treatment response.