Lower synaptic density associated with gaming disorder: an ¹⁸F-SynVesT-1 PET imaging study

Background: Internet gaming disorder (IGD) is an ideal model to study the mechanisms underlying synaptic deficits in addiction as it eliminates the confounding effects of substance use. Synaptic loss and deficits are hypothesised to underlie the enduring maladaptive behaviours and impaired cognitive function that contribute to IGD.

Aims: This study aimed to determine whether subjects with IGD have lower synaptic density than control subjects and the relationship between synaptic density and IGD severity.

Methods: Eighteen unmedicated subjects diagnosed with current IGD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and 16 demographically matched healthy controls (HCs) participated in the study and underwent ¹⁸F-labelled difluoro-analogue of UCB-J (¹⁸F-SynVesT-1) positron emission tomography scans to assess the density of synaptic vesicle glycoprotein 2A (SV2A). The Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA), Barratt Impulsiveness Scale Version 11 (BIS-11), Stroop Colour-Word Test (SCWT), stop-signal paradigms and N-back tasks were administered to all subjects.

Results: Patients with IGD had significantly higher scores on the IGDS9-SF, HAMD, HAMA and BIS-11 than HCs. HCs performed better on the two-back and SCWT tests as well as in terms of stop-signal reaction times (SSRTs) in the stop-signal paradigms than patients with IGD. Lower uptake was found in the bilateral putamen, right pregenual anterior cingulate cortex and Rolandic operculum of patients with IGD compared with HCs. Furthermore, in the IGD group, IGDS9-SF scores and daily gaming hours were negatively correlated with the standardised uptake value ratios of ¹⁸F-SynVesT-1 in the bilateral putamen. Longer SSRTs were significantly associated with lower SV2A density in the right pregenual anterior cingulate cortex and right Rolandic operculum.

Conclusions: The in vivo results in this study suggest that lower synaptic density contributes to the severity and impairments in inhibitory control of IGD. These findings may provide further incentive to evaluate interventions that restore synaptic transmission and plasticity to treat IGD.