MMP-9-BDNF pathway is implicated in cognitive impairment of male individuals with methamphetamine addiction during early withdrawal.

Cognitive impairment is often concomitant with current and abstinent methamphetamine (METH) misuse. However, the mechanism underlying the pathogenesis of cognitive impairment induced by METH remains unclear. As evidence indicates that brain-derived neurotrophic factor (BDNF) is associated with METH addiction, the present study aimed to investigate whether BDNF and the proteins regulating the BDNF signaling pathway might be implicated in the cognitive impairment of the METH abusers during early withdrawal. A total of 171 male subjects were recruited, including 85 METH abstainers and 86 healthy controls. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA) screening tool. The levels of serum proteins that regulate the BDNF signaling pathway were measured using enzyme-linked immunosorbent assay kits. 61.18% METH abstainers were determined to have cognitive impairment (MoCA＜26). The serum levels of mBDNF, proBDNF, and MMP-9, as well as the ratio of the mBDNF/proBDNF (M/P) were significantly decreased in the cognition-impaired METH abstainers than in the cognition-unimpaired METH abstainers. mBDNF, proBDNF, TrkB, MMP-9, MMP-9 activity, and M/P were significantly correlated with the MoCA score in the METH abstainers. The combination of mBDNF, TrkB, MMP-9, and MMP-9 activity demonstrated excellent diagnostic potential for cognitive impairment of METH abusers during early withdrawal (AUC = 0.978). The results provide the prospective evidence that the MMP-9-BDNF pathway may underlie the pathogenesis of cognitive impairment in METH abusers during early withdrawal.