Clinical Implication Of Prefrontal ?-aminobutyric Acid And Glutamate Levels In Heroin Addicts Undergoing Methadone Maintenance Treatment Measured In Vivo With Proton Magnetic Resonance Spectroscopy

Objective:This study aimed to detect absolute concentration of GABA and Glu in the prefrontal cortex of prescription opioid dependents by ~1H magnetic resonance spectroscopy,and to explore the correlation among absolute concentration of GABA and Glu in the prefrontal cortex and neuropsychology.Material and Methods:Twenty-nine heroin dependent patients undergoing methadone maintenance treatment and 20 matched healthy controls participated in this study.According to the different duration of methadone maintenance treatment,subjects were divided into three groups:methadone maintenance treatment for 2 years(10 patients),methadone maintenance treatment for 4 years(9 patients)and methadone maintenance treatment for 6 years(10patients).The Barratt Impulsivity Scale(BIS-11)was used as a self-administered questionnaire to measure impulsiveness,and the montreal Cognitive Assessment Scale(MOCA)was utilized to evaluate patients'cognitive function and Depression Self-assessment Scale(SDS)was chosen to evaluate depressive symptoms,and the Self-Rating Anxiety Scale(SAS)was selected to evaluate anxiety symptoms.Scans were performed on Siemens MAGNETOM Skyra 3.0T MR scanner,equipped with a20-channel phased-array head and neck joint coil.All subjects wore earplugs to reduce the noise from MRI in the scanning process,while the subject was in the resting state.T1-weighted 3D high-resolution anatomical images of whole brain were acquired and used to locate the spectroscopic volumes of interest.Glu and GABA spectral data in the medial prefrontal cortex were acquired with Optimal TE and MEGA-PRESS editing sequence.For quality control,a phantom with a concentration of 50 mM Cr was measured before each MRS session using the standard study protocol.Post-processing of the MRS date was carried out using the jMRUI v5.0 software.A single factor variance analysis was used to compare the four groups of the absolute concentration of metabolites,and clinical characteristics,and between-group differences using the unpaired t-test for independent samples.Spearman correlation analysis was used to evaluate the correlation between the levels of metabolites in the ventromedial prefrontal cortex and clinical features in heroin addicts treated with methadone maintenance.Results:BIS-11 scores of patients treated with methadone for 2 years,4 years and 6 years were higher than healthy controls(P<0.001),and MOCA score was lower than that of healthy controls(P<0.001).SDS score of patients undergoing methadone treatment for 4years and 6years is higher than healthy control group(P<0.01&P<0.05),and SAS score of patients with methadone treatment for 2,4 years is higher than healthy control group(P<0.05&P<0.01).The group comparisons revealed significantly higher Glu concentrations in the vmPFC in heroin addicts undergoing MMT for 2,4,6 years relative to the controls(P<0.05&P<0.05&P<0.05),while significantly lower GABA concentrations in the vmPFC(P<0.001&P<0.05&P<0.01).The absolute concentration of GABA in the vmPFC of heroin addicts treated with methadone was negatively correlated with the absolute concentration of Glu,BIS-11,SDS and MOCA scores,and the absolute concentration of Glu was positively correlated with the scores of BIS-11,MOCA,and SDSConclusion:(1)Neuropsychological scores including impulsiveness,cognitive function,depression and anxiety were persistently abnormal in heroin addicts undergoing methadone maintenance treatment and did not increase with the prolonged treatment.(2)The levels of Glu and GABA in the prefrontal cortex of heroin addicts treated with methadone maintenance treatment were showed persistent abnormalities and did not aggravate with the duration of treatment.(3)The changes in neuropsychological scores including impulsiveness,cognitive function,depression and anxiety in heroin addicts undergoing methadone maintenance treatment were associated with abnormal prefrontal Glu and GABA levels.In consequence,the persisting abnormal Glu and GABA levels in prefrontal cortex may be one of the causes of neuropsychological changes induced by methadone.Therefore,how to prevent heroin addicts from abstinence symptoms and restrain their desires for heroin effectively,while reducing or eliminating neuropsychological changes that caused by methadone,which is a concern about addiction medicine should be payed attention to.How to maintain the dynamic balance of excitatory and inhibitory amino acids in brain may be one of the key-points in addiction treatment.Thus,methadone maintenance treatment is a double-edged sword for controlling opioid addiction.