Neurofunctional gradients and molecular signatures underlying problematic smartphone use: A connectomic, psychological, and transcriptomic study.

Problematic smartphone use (PSU) is an emerging behavioral concern linked to impaired cognitive control and heightened social sensitivity, with fear of missing out (FoMO) increasingly recognized as a core psychological driver. However, the neurobiological mechanisms underlying PSU remain unclear. In this study, we investigated the neural architecture of PSU by integrating functional connectome gradient mapping, psychological mediation, and transcriptomic annotation. PSU severity was associated with altered principal gradients of functional connectivity, including increased connectivity gradients in the frontal pole and angular gyrus, and decreased connectivity gradients in the superior parietal lobule. Inter-subject representational similarity analyses further revealed that PSU-related gradient alterations were distributed across the default mode, frontoparietal, dorsal and ventral attention, sensorimotor, and visual networks. Mediation analyses demonstrated that FoMO significantly mediated the association between gradient 1 alterations in the bilateral superior parietal lobule and PSU severity. Transcriptomic analysis identified 1273 genes spatially aligned with the neural gradients, enriched for synaptic and glial functions, with distinct developmental expression profiles. Notably, hub genes such as BDNF, SYN1, and MRPS11 pointed to neuroplasticity and developmental mechanisms. Together, these findings provide a multilevel framework for understanding PSU, bridging neural gradients, molecular architecture, and psychological vulnerability.