Connectome gradient dysfunction in earthquake-induced posttraumatic stress disorder and its association with gene expression and neurotransmitter profiles.

BACKGROUND: Posttraumatic stress disorder (PTSD) exhibits disrupted functional organization of brain networks involving sensory and association cortices. Connectome studies reveal a principal unimodal-to-transmodal gradient in the brain functional network that supports the spectrum from sensation to cognition. However, the disruption of the connectome gradient in PTSD and its associated transcriptional and neurotransmitter patterns remains poorly understood. METHODS: Using resting-state functional magnetic resonance imaging data from a cohort of 86 non-comorbid adult patients with PTSD caused by an earthquake and 86 trauma-exposed non-PTSD (TENP) controls who experienced the same disaster, we examined PTSD-related changes in the principal connectome gradient, their links to symptom severity and sex/age interactions, and brain-wide associations between gradient changes and microscale transcriptomic and neurotransmitter maps and macroscale cognitive function. RESULTS: Compared with TENP controls, PTSD exhibited global topographic abnormalities in the principal unimodal-to-transmodal gradient, and focal aberrance mainly in the unimodal (visual network) and transmodal systems (limbic, ventral attention, and frontoparietal networks). Sex had no significant effects, while gradient decrease in the subcortical network is more prominent in adolescents with PTSD than adults. The PTSD-related gradients colocalized with brain-wide gene expression enriched in mitochondria and DNA/RNA metabolic process and corresponded with the distribution of dopamine, opioid, noradrenaline, and cholinergic neurotransmitter systems. CONCLUSIONS: These findings highlight the dysfunctional connectome hierarchy in PTSD and its association with transcriptomic and molecular profiles, suggesting that early traumatization may more significantly impact the development of subcortical network. This work provides insight into the neurobiological basis of PTSD and indicates potential biomarkers for prediction and prevention.