Linking macro-scale structural-functional networks to micro-scale neurotransmitter architectures in first-episode, drug-naïve OCD.

We investigated the multimodal neuroimaging alterations and their neurochemical underpinnings in obsessive-compulsive disorder (OCD). Structural and resting-state functional MRI (rs-fMRI) data were collected from 61 first-episode, medication-naïve patients with OCD and 59 healthy controls (HCs). Parallel independent component analysis (p-ICA) was used to integrate gray matter volume (GMV) and amplitude of low-frequency fluctuations (ALFF) maps, identifying coupled structural-functional networks. Furthermore, we utilized the JuSpace toolbox to examine the spatial correlations between the multimodal network alterations and normative neurotransmitter maps. We identified a significantly coupled structural-functional component pair (GMV_IC4 and ALFF_IC5) that reliably distinguished patients with OCD from HCs. The structurally significant component primarily involved corticolimbic and striatal regions, including the hippocampus parahippocampal gyrus, basal ganglia, amygdala, temporal cortex, occipital cortex, prefrontal cortex, insula, and anterior and posterior cingulate cortices. The functionally significant component was mainly centered in sensorimotor and higher-order cognitive networks, particularly the dorsolateral prefrontal cortex, parietal cortex, sensorimotor cortex, including the precentral and postcentral gyri, and the supplementary motor area. Spatially, these macroscale network alterations showed significant spatial correspondence with normative PET/SPECT-derived neurotransmitter maps. Alterations in ALFF_IC5 were significantly associated with serotonin receptor subtypes 1B (5-HT1B) and 2 A (5-HT2A), the dopamine transporter (DAT), fluorodopa (FDOPA), the gamma-aminobutyric acid type A receptor (GABAa), the serotonin transporter (SERT), and metabotropic glutamate receptor 5 (mGluR5). Changes in GMV_IC4 were significantly associated with 5-HT1A, dopamine D1 receptor (D1), DAT, FDOPA, mu-opioid receptor (MU), and SERT. These findings provide novel insights into the multiscale neurochemical context of OCD-related structural and functional imaging alterations.