Biomarkers Identified for Methamphetamine-Induced Psychosis in Whole-Genome Expression Profiling Study

Abstract

Methamphetamine stimulates the central nervous system and affects several pathways in different organs. Methamphetamine use disorder changes behavioral characteristics, which in some cases, includes psychotic symptoms. Mechanisms of psychosis in meth-induced psychosis and its similarities and differences with psychosis in individuals with schizophrenia are not clear. The present study aimed to shed light on molecular mechanisms which were affected in methamphetamine-induced psychosis by using whole-genome expressions profiling in the postmortem prefrontal cortex (PFC) and live subjects’ blood along with clinical evaluation. The study was included chronic persons with methamphetamine use disorder without psychoses, chronic persons with methamphetamine use disorder with Meth-induced psychosis, schizophrenic patients, and non-psychiatric subjects. Each group was included 15 postmortem PFC tissue and 750 live subjects. RNA extracted and cDNA has been synthesized. Genome expression profiling was conducted by using the Affymetrix GeneChip Human Genome U133 plus 2.0 Array Platform and confirmed by qPCR. Clinical and demographic data were obtained from the subjects. Clinical assessements performed by PANSS and BPRS test in live subjects. Results indicate several genes expression changes in persons with methamphetamine use disorders, Meth-induced psychosis, and schizophrenic patients. Alteration of number of gene ontologies and pathways associated to immune system and mitochondria were common only in methamphetamine induced psychosis and schizophrenia. Some altered genes related to serotonergic synapse and metabolic pathways, changed only in Meth-induced psychotic patients. Also, several correlations were found between positive, negative and general psychiatric symptoms with the gene expression alterations in Meth-induced psychosis. Results suggest that there are hundreds of genes wich play role in meth-induced psychosis that has similarities and differences with genes involved in psychosis in schizophrenia. Findings could suggest new potential biomarkers for meth-psychoses as well as an extension of our knowledge about the molecular mechanisms of a very complicated mental situation wich called psychosis. Trial Registration: Registration number: GR34661. Funding: The study was funded neuroimaging genetic laboratory of Arvin gene Company and Islamic Azad university. Declaration of Interest: The authors declare that they have nothing to disclose. Ethical Approval: Study levels and the consent form were approved by the central ethical committee of Islamic Azad University based on Helsinki declaration obligations.