Plasma nectin-4 levels are associated with changes in executive function in patients with methamphetamine use disorder undergoing treatment.

BACKGROUND

Executive dysfunction can influence the outcomes of methamphetamine use disorder (MAUD). Identifying which individuals experience substantial improvements in executive function after treatment for MAUD is important. Nectin-4, a cell adhesion molecule linked to addiction severity, may be associated with executive function in MAUD patients. This study aimed to compare the plasma levels of nectin-4, and executive function between MAUD patients and healthy controls (HCs) and to explore whether nectin-4 levels are associated with cognitive outcomes during treatment.

METHOD: MAUD patients and HCs were recruited, and their plasma nectin-4 levels and executive function were assessed. MAUD patients were followed for one year, and the WCST was readministered after one year of treatment. Multiple linear regressions and generalized estimating equations (GEEs) were used for analysis.

RESULTS

In total, 126 MAUD patients and 106 HCs were enrolled. The MAUD patients had significantly higher plasma nectin-4 levels (P < 0.001). Elevated nectin-4 levels were associated with poorer baseline WCST performance. The GEE analysis revealed that for MAUD patients, higher baseline nectin-4 levels were associated with greater total errors (P = 0.005), more perseverative errors (P < 0.001), fewer completed categories (P = 0.01), and lower conceptual scores (P = 0.004) on the WCST after one year of treatment.

CONCLUSION

Elevated nectin-4 levels in MAUD patients are linked to worse executive function and poorer post-treatment cognitive outcomes. Larger studies are needed to replicate the association between nectin-4 levels and executive function and to investigate the underlying mechanisms.