Behavioral regulation in methamphetamine abusers: An fMRI study

To examine whether overlapping cognitive deficits exist in currently drug-abstinent chronic methamphetamine (MA) abusers and schizophrenia (SZ) patients. Both SZ and chronic MA abuse are associated with frontostriatal disruption as well as deficits in cognitive control, such as selective attention. To identify overlapping cognitive profiles, we compared performance of the 2 groups on the Stroop attention task. Data were analyzed from 69 MA abusers who had been MA-abstinent for differing periods of time and from 23 SZ patients and 38 non-substance-abusing controls. The MA abusers in early abstinence displayed more Stroop interference than the SZ patients (P=0.004), long-term abstinent MA abusers (P=0.009), and controls (P=0.002). In the MA abusers, the magnitude of Stroop interference correlated positively with longer drug use (P=0.01) and negatively with longer drug abstinence (P=0.04). No correlations were found between psychotic symptoms and task performance. On this task of attentional selection, only the MA abusers in early stages of abstinence showed performance deficits compared with controls. More research is needed to further elucidate overlapping patterns between MA abuse and SZ.

Although there is some evidence that methamphetamine (MA) abuse may play a causative role in the development of schizophrenia, studies directly linking these 2 are rare. In our study, the effect of MA abuse on the development of schizophrenia was investigated in 15 MA abusers who are offspring of patients with schizophrenia and 15 siblings of MA abusers without a history of drug abuse. Cognitive deficits and resting-state brain function were evaluated in all participants. Correlations between cognitive deficits and schizophrenia development were investigated. Significantly more cognitive impairments were observed in MA abusers, compared with their siblings without a history of drug use. Significant abnormalities in regional homogeneity (ReHo) signals were observed in resting brain in MA abusers. Decreased ReHo was found to be distributed over the bilateral cingulate gyrus, right Brodmann area 24, and bilateral anterior cingulate cortex. Seven MA abusers were diagnosed with schizophrenia, while 1 control sibling was diagnosed with schizophrenia during the 5-year follow-up. The cognitive scores correlated with the development of schizophrenia in MA abusers. Our study provides direct evidence for the causative role of MA use in the etiology of schizophrenia and highlights the role of MA-induced brain abnormalities in cognitive deficiency and development of schizophrenia.

Relationship between N-acetyl-aspartate in gray and white matter of abstinent methamphetamine abusers and their history of drug abuse: A proton magnetic resonance spectroscopy study

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

Objective To investigate the decision making deficit of former methamphetamine (MA) users following a long period of withdrawal. Methods Twenty-four MA dependent individuals who had been withdrawal for longer than six months and 24 healthy controls were recruited to undertake an Iowa gambling task (IGT) assessment in order to evaluate decision making function. Correlation analysis was done to investigate the relationship between IGT, impulsivity (Barratt Impulsivity Scale-11) and drug use characteristics. Results There was no difference in net IGT scores between MA group and controls((-10.75±24.32) vs (-5.96±14.45)). Differential performances appeared when facing different benefit-loss conditions. When facing pure-gain cards, controls and MA abstainers changed their card in the same frequency((50.92±25.04)% vs (48.67±24.92)%), but when facing net losses, MA abstainers((71.46±24.09)%) changed their card less often than controls(87.96±20.34)%)(F(1, 46)=6.57, P=0.01). The BIS score negatively correlated with the card change ratio under the net-loss condition (r=-0.43, P=0.04) and the pure-gain condition (r=-0.47, P=0.02). Conclusion The study confirm the hypothesis that MA dependent individuals show some deficits in their decision making. These individuals seem to utilize a risky decision making pattern and tolerate high risk. The high tolerance to risk might be associated with impulsivity. Key words: Methamphetamine; Lowa gambling task; Addiction; Decision making; Impulsivity

To describe the thermal injuries related to methamphetamine (METH) production, characterize patients' courses, and compare patients with matched controls and to the previously published series. Trauma registry data from January 2001 to November 2005 was retrospectively reviewed. METH patients were compared with other burn patients of similar age and total body surface area burn size for toxicology, injury extent, therapies, hospital course, outcomes, and hospital charges. The METH group was compared with the other published series of METH-related burn patients. Twenty-nine patients (86.2% male) had METH-related burns. METH and control groups were similar in age, gender, predicted resuscitation fluid volume, and total body surface area. Mortality, mean length of stay, surgical procedures, and mean hospital charges did not differ significantly between the groups. Endotracheal intubation was required more frequently in METH patients (55.2% vs. 24.1%, p = 0.020). METH patients mean resuscitation volume was greater than controls (9,638 mL vs. 6,633 mL, p = 0.011), but neither group exceeded the volume predicted by the Parkland formula. More METH patients had inhalation injury (41.4% vs. 13.8%, p = 0.019). A METH patient was more likely to have a complication than his matched control (p = 0.049), and pneumonia was more frequent in the METH group (p = 0.005). Private insurance was less common in METH patients (10.3% vs. 58.6%, p < 0.001). METH patients suffer more frequent inhalation injuries, need greater initial fluid resuscitation volume, require endotracheal intubation more frequently, and are more likely to have complications than matched controls. This does not translate to greater mortality, longer length of stay, more surgical procedures, or significantly greater hospital charges. Few METH patients hold private insurance.

Previous research indicates a complex link between methamphetamine (METH) and driving performance. Acute dosing with amphetamines has improved driving-related performance in some laboratory studies, while epidemiological studies suggest an association between METH use, impaired driving, and accident culpability. Current METH users were compared to a control group of nonusers on driving simulator performance. Groups were matched for age, gender, and driving experience. Subjects were assessed for current drug use, drug dependence, and drug levels in saliva/blood as well as personality variables, sleepiness, and driving performance. METH users, most of whom met the criteria for METH dependence, were significantly more likely to speed and to weave from side to side when driving. They also left less distance between their vehicle and oncoming vehicles when making a right-hand turn. This risky driving was not associated with current blood levels of METH or its principal metabolite, amphetamine, which varied widely within the METH group. Other drugs were detected (principally low levels of THC or MDMA) in some METH users, but at levels that were unlikely to impair driving performance. There were higher levels of impulsivity and antisocial personality disorder in the METH-using cohort. These findings confirm indications from epidemiological studies of an association between METH use and impaired driving ability and provide a platform for future research to further explore the factors contributing to increased accident risk in this population.

Clinical relevance Considering the significant relationship between methamphetamine abuse and some anterior segment indices, methamphetamine abuse should be considered in differential diagnosis especially in the case of angle closure glaucoma. Background To investigate the effect of inhaled methamphetamine (meth) and crystal methamphetamine (crystal meth) on the quantitative indices of the cornea and anterior chamber using pentacam and anterior segment optical coherence tomography. Methods In this cross-sectional study, the participants were (crystal) meth addicts living in Zahedan. The participants were transported to the examination site to undergo imaging and optometric tests. Pentacam and anterior segment optical coherence tomography imaging were then conducted so as to evaluate corneal and anterior chamber quantitative indices. Results A total of 42 (crystal) meth addicts and 42 healthy subjects with matching age and gender were examined. Out of 42 subjects in the case group, 6 were female and 36 were male (mean age: 35.7 ± 8.6 years). The mean dose of drug used was 0.0074 ± 0.0034 g, and the mean duration of drug use was 6.9 ± 2.6 years (5–12 years). Based on the images of both devices, corneal curvature was significantly steeper in both meridians of anterior and posterior surfaces compared to the control group (p = 0.01). Among the anterior chamber parameters, the anterior chamber depth and volume were lower in the cases than the controls (p < 0.01). However, the lens rise was higher in addicts than controls (p = 0.01). Conclusion Quantitative changes in corneal and anterior segment indices including dilated pupils, shallower anterior chamber depth and higher lens rise in addicted cases compared to the control group may precipitate the risk of closed-angle in these individuals.

Impaired cognitive and behavioral control has often been observed in people who use methamphetamine (MA). However, a comprehensive understanding of the neural substrates underlying these impairments is still lacking. The goal of the present study was to study the neural correlates of impaired cognitive control in individuals with MA dependence according to DSM-IV criteria. Eighteen individuals with MA dependence and 21 healthy controls were investigated using Stroop task, fMRI, and an impulsivity questionnaire. Overall, patients were found to have significantly poorer accuracy on the Stroop task and higher self-rated impulsivity. Comparing brain activations during the task, decreased activation in the dorsolateral prefrontal cortex (DLPFC), anterior midcingulate cortex (aMCC), and dorsal striatum was observed in individuals with MA dependence, compared to healthy controls. Altered fMRI signal in DLPFC and aMCC significantly correlated with impaired behavioral task performance in individuals with MA dependence. Furthermore, significantly lower and pronounced brain activations in the MA group were additionally detected in several sensory cortical regions, i.e., in the visual, auditory, and somatosensory cortices. The results of the current study provide evidence for the negative impact of chronic crystal meth consumption on the proper functioning of the fronto-cingulate and striatal brain regions, presumably underlying the often-observed deficits in executive functions in individuals with MA use disorder. As a new finding, we also revealed abnormal activation in several sensory brain regions, suggesting the negative effect of MA use on the proper neural activity of these regions. This blunted activation could be the cause of the observed deficits in executive functions and the associated altered brain activation in higher-level brain networks.

Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron.

Background: The medial prefrontal cortex (mPFC) contains various neurotransmitter systems and plays an important role in drug use. Broad body of literature on how methamphetamine (MA) affects the structure and metabolism in the animal's mPFC is emerging, while the effects on metabolites of mPFC among human is still unclear. In this study, proton magnetic resonance spectroscopy (1H MRS) was used to measure metabolites of mPFC in methamphetamine dependent subjects.Methods: Sixty-one subjects with a history of MA dependence (fulfiled the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria) and 65 drug-naïve control subjects (age19–45) completed 1H MRS scans using 3.0T Siemens MRI scanner. Single voxel spectra were acquired from the mPFC bilaterally using a point resolved spectroscopy sequence (PRESS). The 1H MRS data were automatically fit with linear combination model for quantification of metabolite levels of n-acetyl-aspartate (NAA), myo-inositol (mI), glycerophosphocholine plus phosphocholine(GPC+PC), phosphocreatine plus creatine (PCr+Cr), and glutamate (Glu). Metabolite levels were reported as ratios to PCr+Cr.Results: The MA group showed a significant reduction in NAA/PCr+Cr ratio and elevation in Glu/PCr+Cr ratio and mI/PCr+Cr ratio, compared with healthy control. No significant correlation was found between metabolite ratios and MA use variables.Conclusions: MA use is associated with a significant increased Glu/PCr+Cr ratio, mI/PCr+Cr ratio and reduced NAA/PCr+Cr ratio in the mPFC of MA dependence subjects. These findings suggest that Glu may play a key role in MA induced neurotoxicity.

Effect of chronic methamphetamine injection on levels of BDNF mRNA and its CpG island methylation in prefrontal cortex of rats.

Different doses of methamphetamine alter long-term potentiation, level of BDNF and neuronal apoptosis in the hippocampus of reinstated rats.

Methamphetamine (METH) addiction and its induced mental disorders have become a severe worldwide problem. A candidate Chinese herbal medicine (CCHM) in our lab had therapeutic effects on METH-induced locomotor sensitization, however, its chemical and pharmacological profiles remain to be elucidated. The current study aimed to investigate the effect of CCHM on conditioned place preference (CPP) induced by METH and screen the main active ingredients and key targets by using network pharmacology and molecular docking methods. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Gene ontology (GO) analysis and protein-protein interaction (PPI) network were performed to discover the potential mechanisms. Results showed that CCHM could significantly inhibit METH-induced CPP behaviors in mice. A total of 123 components and 43 targets were screened. According to the network pharmacology analysis, ten hub targets including D(2) dopamine receptor (DRD2) and 5-hydroxytryptamine receptor 3A (HTR3A) were screened. GO analysis and KEGG enrichment indicated that mechanisms of CCHM treatment of METH addiction were related to multiple pathways such as dopaminergic synapse and serotoninergic synapse. Western blot results showed that the protein expressions of DRD2 in nucleus accumbens and prefrontal cortex were significantly decreased in METH group, while the protein expressions of HTR3A were significantly increased. These changes caused by METH could be prevented by CCHM pretreatment. The results of molecular docking displayed that the five active ingredients such as (S)-Scoulerine, Hyndarin, and Beta-Sitosterol had good affinities with DRD2 and HTR3A. In conclusion, this study constructed the CCHM’s pharmacologic network for treating METH addiction based on the method of network analysis and experimental verification, and analyzed its major active ingredients and potential targets, indicating a new direction for further revealing its mechanisms of effect on METH addiction.

Methamphetamine abuse has continued to increase in the United States since the late 1980s with its use spreading from the West Coast to areas across the country. Methamphetamine use in pregnancy endangers the health of the woman and increases the risk of low birth weight and small for gestational age babies and such use may increase the risk of neurodevelopmental problems in children. All pregnant women should be asked about their drug and alcohol use. Urine toxicology screening may be useful in detecting methamphetamine and other substance abuse during pregnancy, but this screening should only be done with maternal consent after counseling regarding the potential ramifications of a positive test result. Women reporting continuing use of methamphetamine in pregnancy should be referred for treatment and followed up with serial ultrasound examinations to assess fetal growth.