Neurostructural alterations, trait impulsivity, and genetic architecture in individuals with methamphetamine...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Methamphetamine use disorder (MUD) poses a global health challenge due to limited understanding of its neurobiology and lack of effective treatments.
• Investigating structural brain changes, impulsivity, and genetic factors is crucial for developing interventions for MUD.

Purpose of the Study:

• To explore structural brain alterations, specifically gray matter volume (GMV), in individuals with MUD.
• To examine the relationship between GMV, trait impulsivity, and genetic factors in MUD.
• To identify potential genetic biomarkers for MUD risk and treatment.

Main Methods:

• Structural magnetic resonance imaging (MRI) and whole-exome sequencing were performed on 142 male participants (91 MUD patients, 51 controls).
• Voxel-based morphometry (VBM) analyzed GMV differences, while mediation analysis explored the role of motor impulsivity (MI).
• Gene- and gene set-based burden tests, GO, KEGG, and gene-environment interaction analyses identified associated genes and pathways.

Main Results:

• MUD patients showed significantly reduced left thalamus GMV, negatively correlated with MI.
• MI mediated the link between thalamic GMV, duration of use, and MUD severity.
• 72 genes and pathways (Cytidine Analogs Cytotoxicity, Muscle Structure Development, Nuclear Speck) were linked to thalamic volume; cytoskeletal and ciliary functions were implicated.

Conclusions:

• The thalamus is a key structural area linking impulse control to METH-induced neurotoxicity.
• Genetic variants influencing thalamic volume may serve as biomarkers for MUD risk stratification.
• Understanding cytoskeletal dynamics and ciliary function is vital for personalized MUD interventions.