Elevated serum homocysteine levels and cognitive impairment in methamphetamine use disorder: the impact of attention deficit hyperactivity disorder comorbidity

Introduction
The aim of this study was to investigate the relationship between serum homocysteine levels and cognitive functions in individuals diagnosed with methamphetamine use disorder (MUD), especially in the presence of comorbid attention deficit hyperactivity disorder (ADHD).

Material and methods
Forty-four male patients diagnosed with MUD according to DSM-5 diagnostic criteria and 45 healthy male individuals were included in the study. Serum homocysteine, vitamin B12, and folate levels were measured.

Results
Homocysteine levels were significantly higher (p < 0.001) in the MUD group. A negative correlation was found between homocysteine levels and MoCA scores in the MUD group (r = –0.464, p = 0.002), and a positive correlation was found between duration of METH use and homocysteine levels (r = 0.424, p = 0.004). Homocysteine levels were significantly higher in MUD patients with comorbid ADHD (p < 0.001). No significant differences were found between the groups in terms of vitamin B12 and folate levels.

Conclusions
High homocysteine levels in patients with MUD are associated with cognitive dysfunction. This association is more pronounced in individuals with comorbid ADHD. This increase, which is particularly evident in patients with comorbid ADHD, points to a distinct neurobiological phenotype requiring targeted treatment approaches. Homocysteine may be a potential biomarker and targetable therapeutic area in cognitive impairments related to MUD.