Abstract
OBJECTIVE: This study explored the gradient changes in structural similarity based on the cortical structure of patients with lifelong premature ejaculation (LPE) and further analyzed the characteristics of the associations between these changes and clinical phenotypes, gene expression profiles, and neurotransmitter distributions. MATERIALS AND METHODS: This study employed a novel method, morphological inverse divergence (MIND), to construct structural similarity gradients for 62 LPE patients and 53 healthy controls. Between-group comparisons were performed to examine the abnormalities in gradients among LPE patients. Partial least squares regression analysis explored the relationships between gene expression profiles and gradient changes, as well as neurotransmitter expression associations with these alterations. RESULTS: We found that both groups showed a classic unimodal-to-cross-modal transition along the principal gradient. In LPE patients, the principal gradient increased in the left visual cortex and right prefrontal regions but decreased in the right cingulate gyrus. The secondary gradient also decreased in the right somatosensory cortex and bilateral visual cortices. Notably, changes in these gradients in the right somatosensory and visual cortices were significantly negatively correlated with clinical phenotypes. Connectome-transcriptome analysis revealed that abnormal gradient patterns were linked to whole-brain gene expression profiles, with enriched genes in pathways related to hormone activity and other functions. Additionally, there was a spatial correlation between the gradients and neurotransmitter densities. CONCLUSION: We identified the biological pathways enriched in genes associated with the pathological process of LPE and characterized the distribution patterns of neurotransmitter receptors and transporters, thereby providing critical insights into the neuroimaging and neurobiological underpinnings of LPE. RELEVANCE STATEMENT: The MIND-based brain structural similarity gradient exhibits a pattern of segregation and integration. We analyzed the association between this structural gradient and the clinical phenotype of primary premature ejaculation, offering novel insights into the neuroimaging and neurobiological mechanisms underlying the disorder. KEY POINTS: We employed a novel approach, morphometric inverse divergence, to construct the brain structural similarity gradient. We provide evidence for abnormal structural similarity gradients in patients with LPE. We found an association between abnormal changes in gradients and clinical phenotypes, gene enrichment pathways, as well as neurotransmitter density.