Post-traumatic stress disorder (PTSD) is a growing health problem whose neurobiology remains incompletely understood. Neuroimaging is useful in probing PTSD-related brain dysfunction, and techniques continue to evolve. Structural–functional coupling (SFC) offers a novel integrated perspective on PTSD neurobiology. We sought to define unique SFC alterations in PTSD and explore their associations with clinical symptoms, brain molecular architecture, and gene expression.

We studied 61 PTSD patients and 62 trauma-exposed non-PTSD controls (TENC) recruited from earthquake survivors. We compared SFC constructed from multimodal MRI data by an eigendecomposition method between the two groups. We explored the spatial correlation of SFC with molecular maps, used partial least squares (PLS) regression to associate them with Allen Human Brain Atlas gene data, and conducted enrichment analysis on the identified genes.

PTSD patients showed significant regional SFC alterations in multiple regions: lower SFC in PTSD versus TENC in the default mode network (DMN), frontoparietal network (FPN), dorsal attention network, sensorimotor network, visual network, and thalamus, and higher SFC in PTSD versus TENC in the DMN, FPN, and ventral attention network. Some changes were correlated with clinical symptom severity. In both groups, the spatial distribution of SFC was similarly correlated with molecular architectures. The second component of the PLS regression genes were linked to PTSD-specific SFC variations, enriched mainly in molecular functions and pathways related to synapses and neurotransmitter signaling.

This study yields new insights into PTSD pathophysiology by connecting macroscale SFC changes with their microscale molecular and transcriptional basis.