Lower synaptic density and its association with cognitive dysfunction in patients with obsessive-compulsive disorder

Abstract

Background Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but in vivo research on this topic remains limited. Aims This study aimed to identify the synaptic density indicators in OCD and explore the relationship between cognitive dysfunction and synaptic density changes in OCD. Methods This study enrolled 28 drug-naive adults with OCD aged 18-40 years and 16 healthy controls (HCs). Three-dimensional T1-weighted structural magnetic resonance imaging and 18 F-SynVesT-1 positron emission tomography were conducted. Cognitive function was assessed using the Wisconsin Cart Sorting Test (WCST) in patients with OCD and HCs. Correlative analysis was performed to examine the association between synaptic density reduction and cognitive dysfunction. Results Compared with HCs, patients with OCD showed reduced synaptic density in regions of the cortico-striato-thalamo-cortical circuit such as the bilateral putamen, left caudate, left parahippocampal gyrus, left insula, left parahippocampal gyrus and left middle occipital lobe (voxel p<0.001, uncorrected, with cluster level above 50 contiguous voxels). The per cent conceptual-level responses of WCST were positively associated with the synaptic density reduction in the left middle occipital gyrus (R 2 =0.1690, p=0.030), left parahippocampal gyrus (R 2 =0.1464, p=0.045) and left putamen (R 2 =0.1967, p=0.018) in patients with OCD. Conclusions Adults with OCD demonstrated lower 18 F-labelled difluoro analogue of 18 F-SynVesT-1 compared with HCs, indicating potentially lower synaptic density. This is the first study to explore the synaptic density in patients with OCD and provides insights into potential biological targets for cognitive dysfunctions in OCD.