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This study aimed to investigate whether 12-week moderate-intensity aerobic exercise has beneficial effects on oxidative stress markers in blood and on cognitive functions in patients who have methamphetamine dependence. Serum levels of oxidative stress markers, including total anti-oxidation capability, super oxide dismutase (SOD), catalase (CAT), and methane dicarboxylic aldehyde (MDA), were measured at baseline (all participants) and the 12-week follow-up (methamphetamine-dependent patients). Serum levels of CAT and MDA in methamphetamine-dependent patients ( n  = 68) were higher than those in healthy controls ( n  = 35) at baseline. Furthermore, the international shopping list (ISL) task scores of methamphetamine-dependent patients were significantly lower than those of the controls, indicating verbal memory deficits in methamphetamine-dependent patients. Although there were no significant interactions for all cognitive function scores, aerobic exercise improved the processing speed in methamphetamine-dependent patients. Of interest, aerobic exercise significantly attenuated a spontaneous increase in serum MDA levels in methamphetamine-dependent patients after 12-weeks of abstinence. In conclusion, this study showed that methamphetamine-dependent patients with verbal learning and memory deficits have higher serum levels of MDA, and that a 12-week aerobic exercise program may have beneficial effects on the processing speed as well as blood lipid peroxidation in methamphetamine-dependent patients. [ABSTRACT FROM AUTHOR]

Background and aims Chronic methamphetamine (MA) use is associated with cognitive impairment and psychopathological symptoms. This longitudinal study aims to examine the cognitive function of MA addicts during periods of abstinence. Methods Fifty-four MA dependent individuals and 58 healthy controls (HC) completed the psychological wellbeing scales and the CogState Battery that evaluated seven cognitive domains. During approximately 6-month abstinence, the subjects completed the CogState battery twice at the interval of 3 months. Results In the tasks of verbal memory, social emotional cognition, and spatial working memory, working memory, and problem solving the MA group performed worse than the HC group (P < 0.05). After 6-month abstinence, impaired verbal memory, social emotion, and problem solving were improved in the MA group (P < 0.01). Furthermore, the MA group showed lower scores in batteries of social adaptation ( t = 3.13, P = 0.002) and quality of life ( t = 3.70, P < 0.001) than the HC group, and 83.3% MA addicts displayed various psychiatric symptoms before study entry. Conclusions Chronic MA addicts exhibited impairment of some CogState battery domains and poor psychological wellbeing, and that some of these subdomains were recoverable on abstinence. Therefore, improved cognitive function should be considered an important component in the treatment of MA dependence. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) can effectively reduce cravings in methamphetamine use disorder (MUD). However, a considerable group still fails to respond. Cognitive and emotional disturbance, as well as impulsive features, are widespread in patients with MUD and might mediate the treatment response of rTMS. The purpose of this study is to figure out whether these variables can help predicting patients' responses to rTMS treatment. Ninety-seven patients with severe MUD and thirty-one gender- and age-matched healthy subjects were included. Patients were randomized to receive 20 sessions of real or sham rTMS. Intermittent theta burst protocols (iTBS) or sham iTBS were applied every weekday over the DLPFC for 20 daily sessions. Both groups received regular treatment. Craving induced by drug-related cue was measured before and after stimulation. Cognition was evaluated by using the CogState Battery. Baseline characteristics were collected through the Addiction Severity Index, Patient Health Questionnaire-9, General Anxiety Disorder Scale-7, and Barrett Impulsivity Scale-11. Results showed that patients with MUD have worse spatial working memory, problem-solving ability, as well as depression and anxiety symptoms compared with healthy controls. Cognition and emotion differed between responders (craving decrease ≥60%) and non-responders in real rTMS group but not in the sham group. Better cognitive and emotional functions means that patients have higher possibility for better response to real rTMS treatment. This study suggests that cognitive, emotional and impulsive features could be used to predict the prospective treatment responses of rTMS in patients with MUD. [ABSTRACT FROM AUTHOR]

• iTBS reduced cue-induced craving in patients with severe methamphetamine use disorder. • iTBS improved cognitive function in patients with severe methamphetamine use disorder. • iTBS improved sleep quality in patients with severe methamphetamine use disorder. Methamphetamine is the most commonly used illicit drug in China. We previously demonstrated that 10 Hz rTMS over the DLPFC reduces craving in methamphetamine users. Here, we applied intermittent theta burst stimulation (iTBS), a new form of rTMS, in a large sample at four clinical centers. 126 participants (age 31.64 ± 6.33; 106 men) with severe methamphetamine use disorder according to DSM-5 were randomized to receive either iTBS or sham over the DLPFC for four weeks (20 daily sessions, 900 pulses per day). Cue-induced craving and cognitive function were assessed before and after rTMS intervention. Relapse was followed up by urine test after discharge from the rehabilitation center. iTBS significantly reduced craving and improved cognition and sleep quality. This study suggests that rTMS may be a useful and safe treatment option for methamphetamine use disorder, warranting future large scale trials. [ABSTRACT FROM AUTHOR]

Methamphetamine is one of the most commonly used drugs around the world, leading to serious public health and psychiatric problems. Due to the lackness of objective laboratory evaluation indicators, the molecular mechanisms of methamphetamine dependence still remain unclear. Previous evidence demonstrated that repetitive transcranial magnetic stimulation (rTMS) may be useful in treating drug addiction. The aim of this study was to identify and validate plasma metabolomics biomarkers in patients with methamphetamine use disorder before and after rTMS intervention. An untargeted gas chromatography–time-of-flight mass spectrometry (GC-TOFMS) based metabolomics approach was applied to characterize the metabolic profile of forty methamphetamine dependent subjects and thirty-eight healthy controls in peripheral blood mononuclear cells (PBMCs). Patients were randomized to receive either rTMS or sham over the DLPFC for four weeks (20 daily sessions, 900 pulses per day). Cognitive function were assessed before and after rTMS intervention. Eight PBMC metabolites responsible for distinguishing real rTMS from sham treatment were identified. These metabolites were mainly involved in energy metabolism and oxidative stress. Compared with baseline, the expression of three metabolites was reversed after rTMS intervention: alpha-tocopherol, glyceric acid and fumaric acid. Changes of the alpha-tocopherol were associated with cognitive function improvement following rTMS. These findings suggest that energy metabolism and oxidative stress system may be associated with the effect of rTMS on cognitive function in methamphetamine dependence, and warrant further investigation. [ABSTRACT FROM AUTHOR]

Accumulated studies in substance use disorders indicated that the mesocorticolimbic reward circuit and executive control circuit played interactive roles in the cue-reactivity and gamma oscillatory in the cortex, as well as autonomic nervous activity was associated with it. This study aimed to explore the mechanism of processing drug-related cues. Sixty methamphetamine users were recruited and exposed to the drug-related virtual reality (VR) environments. Self-reported craving was assessed and skin conductance level (SCL) and heart rate variability were used to measure the autonomic nervous reactivity. With source estimation, gamma current density was used to measure the activity of medial prefrontal cortex/orbitofrontal cortex (MPFC/OFC) and dorsolateral prefrontal cortex (DLPFC) which are responsible for the mesocorticolimbic reward circuit and the executive control circuit. The VR drug-related cue induced an increased craving and SCL compared with the neutral condition. Gamma activity in MPFC/OFC and right DLPFC were decreased after cue exposure and predicted the SCL changes. However, no association was found between self-reported craving and electrophysiological response. Cue-reactivity in cortex and ANS, as well as their association, were observed in this study. Cue-induced electrophysiological responses were related to gamma activity in the mesocorticolimbic reward circuit and the executive control circuit. [ABSTRACT FROM AUTHOR]

Background Previous studies have demonstrated brain gray matter reduction in methamphetamine (MA) users; however, little is known about longitudinal brain structural alternations during abstinence. Method Brain volumes were compared among 30 MA-dependent patients (average 6.3 years of drug use) at 6 months' abstinence and 27 drug-naïve controls by voxel-based morphometry. A longitudinal analysis of MA subjects was performed from 6 to 12 months' abstinence, and multiple regression analyses were performed between drug use patterns and gray matter volumes (GMV) at 6 months' abstinence. Results Compared with drug-naïve subjects, subjects with 6 months' abstinent of MA showed significantly lower GMV in the precentral gyrus, caudate head, fusiform gyrus, and cerebellum. Compared to 6 months' abstinence, GMV was greater in the cerebellum and lower in the cingulate gyrus at 12 months' abstinence. Accumulated years of MA use negatively correlated with GMV in the right superior frontal gyrus, the right superior temporal cortex, and the right caudate nucleus (significant at the whole brain level, p < 0.001; FWE cluster-corrected p < 0.05). Conclusion The present study suggested that heavy MA users' GMV could show dynamic alterations in different brain regions at different time lengths of abstinence. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation and modulation electrophysiological technique, it can change cortical excitability of target brain region, modulate neuron plasticity and brain connections. Previous researches indicated that rTMS could reduce cue-induced craving in drug addiction.Objective: In this study, we employed real and sham rTMS of the left dorsolateral prefrontal cortex (DLPFC) to test whether it could reduce cue-induced craving for methamphetamine (MA) and influence cognitive function in a randomised clinical trial.Methods: Thirty MA-addicted patients were randomized to receive 5 sessions of 8min sham or 10Hz rTMS to the left DLPFC. Subjects rated their craving at baseline, after exposed to MA-associated cues and after rTMS sessions.Results: Real rTMS over the left DLPFC reduced craving significantly after 5 sessions of rTMS as compared to sham stimulation. Furthermore, real rTMS improved verbal learning and memory and social cognition in MA-addicted patients.Conclusions: The present study suggests that 10Hz rTMS of the left DLPFC may reduce craving and have no negative effects on cognitive function in MA-addicted patients, supporting the safety of rTMS in treating MA addiction. [ABSTRACT FROM AUTHOR]

Amphetamine-type stimulants are the second most commonly abused illicit drug worldwide, with no effective medical treatments currently available. Previous studies have demonstrated that high frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) reduced cue-induced craving in patients with methamphetamine dependence. However, the neuroplastic mechanism underlying rTMS intervention in methamphetamine users remains to be elucidated. Sixty participants (40 males) with severe methamphetamine use disorder according to DSM-5 were randomized to receive either intermittent theta burst protocols (iTBS) (short bursts of 50 Hz rTMS repeated at a rate in the theta range (5 Hz), 2-sec on, 8-sec off for 5 min; 900 pulses) or sham rTMS over the DLPFC over four weeks (20 daily sessions). Resting state functional connectivity magnetic resonance imaging was acquired before and after rTMS intervention. Participants received drug related cue exposure and rated their craving before and after stimulation. Seed-based functional connectivity analysis was performed to probe rTMS-induced neuroplastic reorganization of brain functional networks. Results showed that twenty daily rTMS sessions decreased craving, increased functional connectivity between left DLPFC and inferior parietal lobule, and decreased functional connectivity between insula and inferior parietal lobule, medial temporal lobe and precuneus. Moreover, the increase of functional connectivity between DLPFC and inferior parietal lobule correlated with craving reduction. This study suggests that neuroplastic changes of frontoparietal functional connectivity contributes to craving reduction, shedding light on the therapeutic effect of rTMS on methamphetamine use disorder. This article is part of the special issue on Stress, Addiction and Plasticity. • rTMS reduce methamphetamine craving by neuroplastic mechanism. • Resting state functional connectivity reflects synchroplasticity in brain regions. • Changes of frontoparietal functional connectivity contribute to craving reduction. • Targeting DLPFC and insula provides potential solution to reduce craving. [ABSTRACT FROM AUTHOR]

• We genotyped six SNPs on five miRNA in 400 methamphetamin induced psychosis patients and 488 controls. • Rs10760371 within miR-181a showed marginal differences between cases and controls. • The expression of five miRNA was observed in 55 cases and 57 controls and an eQTL analysis was measured. • MiR-181a, miR-15b, miR-let-7e and miRlet-7d associated with MA induced psychosis. • No positive association with MA induced psychosis was found for eQTL analysis. Methamphetamine (MA) is an addictive psychostimulant substance that mainly leads to schizophrenia-like psychotic symptoms. The expression of miRNAs in brain plays an important role in neurological disorders and may affect by genetic variant(s) in the target site (MiRSNPs). In this study, we investigated whether polymorphisms in miRNAs are associated with MA disorder with psychosis. We carried out a case-control association study in 400 MA users with psychotic characters and 448 controls. Six MiRSNPs with predicted functional relevance miRNAs (miR-181b, miR-181a, miR-15b, miR-let-7e and miRlet-7d) were selected for genotyping. Allele and genotype frequencies were compared between MA users and healthy individuals. The expression of five miRNAs were measured by quantitative real-time RT-PCR in 55 cases and 57 controls. We also explored an expression Quantitative Trait Loci (eQTL) analysis based on the miRNAs expression and SNP genotype. The SNP rs10760371 within miR-181a was nominally associated with MA disorder (P = 0.046). For rs1099308, rs10760371 and rs10993081 in strong linkage disequilibrium (LD), no significant association had been detected from haplotype analysis. Discrepancy had been found between MA users and healthy individuals (P < 0.01) in terms of the expression of miR-181a, miR-15b, miR-let-7e and miR-let-7d. and no noticeable difference had been found from the eQTL analysis. Our findings suggest that rs10760371 within miR-181a may relate to the development of MA dependence with psychosis. The miRNAs expression is unlikely to be regulated by the SNPs within it. [ABSTRACT FROM AUTHOR]