Neural, neurotransmitter, and molecular signatures of gray matter volume alterations in digital addiction

Digital addiction (DA), involving compulsive use of social media, gaming, and smartphones, is increasingly viewed as a behavioral addiction with neurobiological underpinnings. However, neuroimaging findings remain heterogeneous, and underlying neurotransmitter and molecular mechanisms are unclear. This study aimed to identify consistent gray matter volume (GMV) alterations in DA and explore their neurotransmitter and transcriptomic correlates.

A voxel-based morphometry (VBM) meta-analysis using seed-based d mapping (SDM) was performed to determine GMV alterations in DA compared to controls. Spatial correlations between GMV changes and normative neurotransmitter maps were assessed using Juspace. Transcriptomic decoding was conducted via partial least squares regression (PLSR) using the Allen Human Brain Atlas, followed by gene enrichment and cell-type analyses.

The meta-analysis revealed GMV reductions in the bilateral anterior cingulate cortex (ACC), left middle frontal gyrus (MFG), and left medial orbitofrontal cortex (mOFC). These regions corresponded spatially with serotonergic and GABAergic systems. Transcriptomic analysis identified 534 genes associated with GMV changes, enriched for synaptic function and ion channel activity, primarily expressed in excitatory and inhibitory neurons.

This multiscale integrative analysis links DA-related GMV alterations to specific neurotransmitter systems and gene expression profiles. The findings provide convergent evidence for the involvement of serotonergic, inhibitory, and reward-related neurobiological systems, and may contribute to a more comprehensive neurobiological understanding of DA within the I-PACE framework.