Functional connectivity density alterations in obsessive-compulsive disorder are associated with neurotransmitter and genetic profiles

Obsessive-compulsive disorder (OCD) is characterized by disrupted brain network organization, yet the molecular basis underlying this dysconnectivity remains elusive. Here, we applied voxel-wise functional connectivity density (FCD) mapping to characterize brain network alterations across 145 patients with OCD and 168 healthy controls (HCs), while further evaluating its ability to support diagnostic classification and predict treatment response in OCD. Then, we examined the spatial correlations between FCD alterations, neurotransmitter distributions, and gene expression profiles. Relative to HCs, OCD patients showed increased FCD in the visual network and decreased FCD in the limbic and default mode networks. Support vector machine (SVM) and support vector regression (SVR) analyses demonstrated that FCD could efficiently discriminate OCD patients from HCs and predict treatment response. Additionally, the FCD alterations showed significant spatial correlations with four neurotransmitter distributions as well as gene expression patterns enriched in excitatory and inhibitory neurons, synaptic signaling, neuronal function, and cellular metabolism. By integrating neuroimaging, neurotransmitter profiles, and transcriptomics, this study reveals that aberrant FCD in OCD reflects both its clinical relevance and molecular basis, providing insights into the neurobiological mechanisms and potential targets for personalized intervention.