Risk classification of internet gaming disorder based on neurobiological subtyping from impulsivity-linked...

Internet gaming disorder (IGD) often emerges in youth, yet early, brain-based risk stratification for IGD is scarce. Impulsivity is a central vulnerability factor for IGD that may provide informative biomarkers. Our primary objective was to identify high-risk IGD subgroup and derive biomarkers from impulsivity-anchored resting-state functional connectivity (RSFC).

In a cross-sectional sample (N = 770: 642 controls, 128 IGD), we derived RSFC features positively and negatively correlated with trait impulsivity to predict current IGD severity from positive-only, negative-only, and combined feature sets. In a 2-year longitudinal discovery cohort (N = 220) and an independent replication cohort (N = 65), we applied improved deep embedded clustering to baseline impulsivity-linked RSFC to identify subtypes, evaluated prospective IGD conversion in each subtype, examined subtype-specific RSFC signatures, and illuminated whether baseline impulsivity was associated with future risk of IGD through specific circuits.

Combining positively and negatively impulsivity-linked RSFC outperformed either alone in predicting current IGD severity (training r = 0.73, p < 0.0001; testing r = 0.27, p = 0.009; higher than two single-pattern models, p = 0.028 and p < 0.0001, respectively). Two subtypes emerged; the high-risk subtype showed greater 2-year IGD conversion (23.61% vs. 6.76%; χ² = 9.54, p = 0.002), replicated in an independent cohort (22.2% vs. 4.3%; χ² = 3.90, p = 0.048). High-risk individuals exhibited reduced orbitofrontal RSFC and increased occipital RSFC; the former was negatively and the latter positively associated with impulsivity. Baseline left orbitofrontal-left insula RSFC (c - c' = 0.032, 95% confidence interval (CI) 0.006-0.065) and right precentral-left lateral occipital RSFC (c - c' = 0.035, 95% CI 0.006-0.071) partially mediated the link between baseline impulsivity and IGD severity 2 years later.

Impulsivity-related RSFC identified a youth subtype at elevated risk for developing IGD. This high-risk subtype showed a higher future IGD conversion rate, greater subsequent increases in IGD severity, and a baseline orbitofrontal-occipital connectivity imbalance. These findings suggest that an orbitofrontal-occipital circuit imbalance may serve as a potential marker for identifying IGD risk in youth.