Title:The General Neurocognitive Decline in Patients with Methamphetamine Use and Transient Methamphetamine-induced Psychosis is Primarily Determined by Oxidative and AGE-RAGE Stress
Volume: 24
Issue: 20
Author(s): Michael Maes*, Mazin Fadhil Altufaili, Amer Fadhil Alhaideri, Shatha Rouf Moustafa, Kristina Stoyanova, Mengqi Niu, Bo Zhou, Jing Li and Hussein Kadhem Al-Hakeim
Affiliation:
- Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University
of Electronic Science and Technology of China, Chengdu 610072, China
- Key Laboratory of Psychosomatic Medicine,
Chinese Academy of Medical Sciences, Chengdu, 610072, China
- Department of Psychiatry, Faculty of Medicine,
Chulalongkorn University, Bangkok, Thailand
- Cognitive Impairment and Dementia Research Unit, Faculty of
Medicine, Chulalongkorn University, Bangkok, Thailand
- Cognitive Fitness and Biopsychological Technology Research
Unit, Faculty of Medicine Chulalongkorn University, Bangkok, 10330, Thailand
- Department of Psychiatry,
Medical University of Plovdiv, Plovdiv, Bulgaria
- Research Institute, Medical University of Plovdiv, Plovdiv, Bulgaria
- Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
- Research and Innovation
Program for the Development of MU - PLOVDIV-(SRIPD-MUP), Creation of a Network of Research Higher Schools,
National Plan for Recovery and Sustainability, European Union - NextGenerationEU
Keywords:
Pathophysiology , Schizophrenia, Oxidative and nitrosative stress, Antioxidants, Biomarkers, Neurocognition.
Abstract:
Background: Chronic Methamphetamine (MA) usage is linked to oxidative and AGE
(advanced glycation end products) - RAGE (receptors for AGEs) stress, changes in magnesium,
calcium, and copper, increased psychotic symptoms, and neurocognitive deficits. Nevertheless, it
is still unclear whether these biological pathways mediate the latter impairments.
Objective: This study aimed to investigate the relationships between neurocognition, the aforementioned
biomarkers, and psychotic symptoms.
Methods: We recruited 67 participants, namely 40 patients diagnosed with MA-substance use and
27 healthy controls, and assessed the Brief Assessment of Cognition in Schizophrenia (BACS),
symptoms of psychosis, excitation, and formal thought disorders, oxidative toxicity (computed as
the sum of myeloperoxidase (MPO), oxidized high-density lipoprotein (HDL), oxidized low-DL,
and malondialdehyde), antioxidant defenses (catalase, glutathione peroxidase, total antioxidant capacity,
zinc, and HDL), and increased AGEs and RAGEs.
Results: We were able to extract one validated latent vector from the Mini-Mental State Examination
score and the BACS test results (including executive functions, verbal fluency, and attention),
labeled general cognitive decline (G-CoDe). We found that 76.1% of the variance in the G-CoDe
was explained by increased oxidative toxicity, lowered antioxidant defenses, number of psychotic
episodes, and MA dose. In patients with MA use, MPO was significantly associated with the GCoDe.
Conclusion: The use of MA induced mild cognitive impairments through MA-induced activation
of detrimental outcome pathways, including oxidative and AGE-RAGE stress, and suppression of
protective antioxidant pathways. Increased MPO, oxidative, and AGE-RAGE stress are new drug
targets to prevent neurocognitive deficits and psychosis due to MA use.
