Decoding the striatum of drug-naive patients with obsessive-compulsive disorder: a transcriptome and longitudinal functional magnetic resonance imaging study

The striatum's role in obsessive-compulsive disorder (OCD) pathology is recognized. However, the specific contributions of individual striatal subregions (SSs) to OCD pathology are underexplored. We recruited 49 drug-naive OCD patients and 53 healthy controls, conducting clinical assessments and resting-state functional magnetic resonance imaging (rs-fMRI) scans pre- and post-4-week paroxetine treatment. Inter-group comparisons were conducted to investigate baseline and treatment-related changes in the patients' striatum using several fMRI metrics, including amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality (DC). Furthermore, these metrics, along with functional connectivity (FC), and effective connectivity (EC) of SSs, were analyzed. Associations between gene expression patterns and altered information flow patterns in SSs were examined, where information flow was measured using EC, followed by enrichment analysis of relevant genes. While no significant alterations were observed in the patients' striata in whole-brain statistical analyses, significant changes in DC, FC, and EC were identified in SSs pre- and post-treatment. In particular, the EC analysis unveiled an enhanced top-down control and diminished bottom-up regulation in drug-naive OCD patients. Following treatment, bottom-up EC improved, along with an improvement in clinical symptoms. Additionally, information flow alteration-related genes were enriched in various biological processes and pathways. They substantially overlapped between bidirectional information flows among SSs and the rest of brain and between information flows among homotopical SSs and the rest of brain. This study highlights the diverse contributions of each striatal subregion to OCD pathology. Paroxetine may alleviate OCD symptoms by enhancing bottom-up regulation, specifically the normalization of aberrant connectivity. Furthermore, integrating transcriptomic and rs-fMRI findings offer novel insights into the biological substrates underlying the altered EC of SSs in OCD patients.