Metabolite Alternations in the Dopamine Circuit Associated with Methamphetamine-Related Psychotic Symptoms: A Proton Magnetic Resonance Spectroscopy Study

Chronic METH use results in neurodegenerative alternations in the human brain. The present study aimed to assess the long-term METH impact on brain metabolite concentrations in cases meeting the DSM-5 criteria regarding METH use.

We recruited 42 METH users meeting the DSM-5 criteria and 21 healthy controls. Psychotic signs were measured using the Positive and Negative Syndrome Scale (PANSS).Proton magnetic resonance spectroscopy (1HMRS) evaluating Myo-inositol (Ml), Choline (Cho), Glutamine plus Glutamate (Glx), N-acetyl aspartate (NAA), and Creatine (Cre) were obtained in the dopaminergic pathway (Frontal Cortex, Substantia nigra, Ventral Tegmental Area (VTA), Nucleus Accumbens (NAc), Hippocampus, Striatum,) the subjects. All participants collected urine specimens for 24 hours to measure presence of specific metabolites including METH metabolite level, 5-Hydroxy indoleacetic acid metabolite (for serotonin level monitoring), and metanephrine metabolite (for dopamine level monitoring).

Dopamine and Serotonin increased in the METH group (P<0.001).METH caused an increase in the Cre (P<0.001) and a decline in the Glx (P<0.001), NAA (P= 0.008), and MI (P<0.001) metabolite concentrations of dopamine circuits in METH users in comparison with healthy subjects. We found no change in Cho metabolite concentration. Psychological data and the neurometabolite concentrations in the studied area of the brain were significantly correlated.

There is an association between METH use and active neurodegeneration in the dopamine circuit, and it causes serious mental illness. 1HMRS can detect patient’s deterioration and progression of disease as well as follow-up management in patients with METH use disorder.