Genetic and molecular factors associated with changes in structural-functional coupling in medication-free...

Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder. While existing studies have revealed abnormalities in brain structure and function associated with OCD, there is a paucity of research integrating these two aspects, and the transcriptional patterns underlying these abnormalities remain unclear. This study is a multiscale, exploratory investigation designed to generate hypotheses rather than to test causal mechanisms. We aimed to investigate aberrations in brain structure-function coupling (SFC) in OCD patients and, by integrating gene expression profiles and neurotransmitter maps, to explore the potential molecular and genetic bases of these changes. We recruited 100 medication-free OCD patients and 90 healthy controls, and employed multimodal imaging techniques to systematically analyze abnormalities in static SFC in OCD patients. Subsequently, we conducted transcriptomic analysis to identify genes associated with SFC abnormalities and performed spatial correlation analysis with neurotransmitter atlases to investigate potential links between SFC dysregulation and transcriptional patterns. Our findings demonstrated that OCD patients exhibit significant SFC abnormalities in the right temporoparietal junction (rTPJ). These SFC abnormalities are significantly associated with 2,421 gene expression profiles and the serotonin neurotransmitter system. Gene enrichment analysis revealed that these aberrant genes are primarily involved in key biological processes, such as brain development, synaptic signaling, cell projection development, and regulation of neuronal processes. By integrating multimodal imaging, transcriptomic, and neurotransmitter data, this study provides multiscale evidence for the potential molecular basis of SFC abnormalities in the rTPJ of OCD patients, offering preliminary insights into a possible pathological pathway of OCD.