Metabolic alterations in the anterior cingulate cortex and related cognitive deficits in late adolescent methamphetamine users

Abstract

The adolescent brain, with ongoing prefrontal maturation, may be more vulnerable to drug use-related neurotoxic changes as compared to the adult brain. We investigated whether the use of methamphetamine (MA), a highly addictive psychostimulant, during adolescence affect metabolic and cognitive functions of the anterior cingulate cortex (ACC). In adolescent MA users (n = 44) and healthy adolescents (n = 53), the levels of N-acetyl aspartate (NAA), a neuronal marker, were examined in the ACC using proton magnetic resonance spectroscopy. The Stroop color-word task was used to assess Stroop interference, which may reflect cognitive functions of behavior monitoring and response selection that are mediated by the ACC. Adolescent MA users had lower NAA levels in the ACC (t = -2.88, P = 0.005) and relatively higher interference scores (t = 2.03, P = 0.045) than healthy adolescents. Moreover, there were significant relationships between lower NAA levels in the ACC and worse interference scores in adolescent MA users (r = -0.61, P < 0.001). Interestingly, early onset of MA use, as compared to late onset, was related to both lower NAA levels in the ACC (t = -2.24, P = 0.03) as well as lower performance on interference measure of the Stroop color-word task (t = 2.25, P = 0.03). The current findings suggest that metabolic dysfunction in the ACC and its related cognitive impairment may play an important role in adolescent-onset addiction, particularly during early adolescence.

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

“…Among studies that reported group differences, higher myo- inositol levels were most reliably observed in the frontal cortex [124, 190-197]. Among studies that did not report a difference, methamphetamine/MDMA subjects tended to use less frequently than those reporting group differences [198, 201, 202, 204, 207]. …”

Cognition and Related Neural Findings on Methamphetamine Use Disorder: Insights and Treatment Implications From Schizophrenia Research

“…The Stroop task, which measures the ability to suppress irrelevant information, is one of the most commonly used tests of inhibitory control in neuropsychiatric patients. Chronic meth use is associated with poorer performance in the Stroop task in adolescents (35,37,65) and adults with meth use disorder (23,26,34,40,41,45,. Effects in adolescents suggest that reduced inhibitory control may be a predisposing factor to developing meth use disorder.…”

“…N-acetylaspartate levels correlate with poorer attention and inhibition in adult (68) and adolescent (37) meth users, and people with schizophrenia (150)(151)(152). Interestingly, reduced N-acetylaspartate in ACC is more dramatic with early onset of meth use (37), and reduced ACC levels of N-acetylaspartate are present at the early stages of schizophrenia (149), and in highrisk offspring of schizophrenia patients (152).…”

Increased Absolute Glutamate Concentrations and Glutamate-to-Creatine Ratios in Patients With Methamphetamine Use Disorders

“…Nonetheless, findings regarding metabolite concentrations in the brains of MA users remain inconsistent. In a 1H-MRS study of 29 patients with MA addiction and 45 healthy controls, Crocker et al discovered that patients of the MA group exhibited decreased levels of glutamate ( 49 , 50 ). In contrast to our findings, one previous study involving 44 adolescent MA users and 53 healthy adolescents reported that NAA levels were lower in the anterior cingulate cortex of teenagers in the MA group.…”