Multiple dimensions approach in polysubstance use: An ESEM analysis based on the RDoC framework

Substance use disorders (SUD) are associated with cognitive alterations, influenced by genetic, neurodevelopmental, and environmental factors, and frequently co-occur with emotional disorders, complicating treatment strategies. Employing the Research Domain Criteria (RDoC) framework and Exploratory Structural Equation Modeling (ESEM), this study investigated the direct and indirect relationships between drug abuse, neurocognitive performance, emotional indicators, and structural changes in brain regions implicated in emotional regulation and executive functions in SUD patients and healthy controls. High-resolution magnetic resonance imaging (MRI) scans were acquired from patients with SUD (n=50) and healthy controls (HC=50). Group differences were assessed using voxel-based morphometry (VBM) and regions of interest (ROIs). Participants were evaluated for substance use (ASSIST) and completed a battery of cognitive tasks and emotional tests. The SUD group exhibited higher levels of depression and anxiety, as well as cognitive deficits, compared to the control group. Additionally, the SUD group showed significantly lower gray matter volume (GMV) in cortical and limbic areas. However, the ESEM analysis indicated that limbic areas indirectly and negatively impacted ASSIST scores. Thus, we can conclude that structural impairments in limbic areas strongly influenced substance use patterns, even when reductions in cortical volume and impaired cognitive performance were also present.