Multi-level pathways linking personality and mood to problematic smartphone use: A behavioral and neuroimaging study.

Problematic smartphone use (PSU) is shaped by personality traits and emotional states, yet its neural and molecular underpinnings remain unclear. Guided by the I-PACE model, we combined behavioral assessment, task-based fMRI, and whole-brain transcriptomics to investigate how dispositional greed (DGS) and depressive symptoms (BDI) contribute to PSU. Participants from middle school and university cohorts completed PSU, DGS, and BDI measures and performed a Face-Matching task during fMRI. Behaviorally, higher DGS was directly associated with greater PSU, with BDI partially mediating this link. Neuroimaging revealed altered activation patterns in visual, emotional, and cognitive control networks related to PSU. Mediation analyses identified pathways in which BDI → lingual/occipital pole → PSU and DGS → BDI → occipital regions → PSU explained the behavioral associations, highlighting visual processing circuits as key intermediaries. Integration of PSU-related brain activation maps with transcriptomic data identified 447 significantly correlated genes (188 positive, 259 negative). Gene Ontology enrichment showed nuclear transcriptional regulation for the positive set, linked via GAMBA to the visual network and high cerebral metabolic rate of oxygen. The negative set was enriched in mitochondrial and metabolic functions, mapped to limbic networks with low CMRO2 and structural vulnerability patterns in major psychiatric disorders. Overall, DGS and BDI increase PSU vulnerability through emotion-reactivity and cognitive-control deficits mediated by visual network activity, underpinned by distinct gene expression profiles. This multi-level framework offers mechanistic insights into PSU and supports precision-targeted interventions.