Heavy Methamphetamine Use Research Articles

Independent and combined effects of methamphetamine use disorders and APOEε4 allele on cognitive performance and brain morphometry.

Prior studies showed that methamphetamine (METH) users had greater than normal age-related brain atrophy; whether having the apolipoprotein E (APOE)-ε4 allele may be a contributory factor has not been evaluated. We aimed to determine the independent and combined effects of chronic heavy METH use and having at least one copy of the APOE-ε4 allele (APOE-ε4+) on brain morphometry and cognition, especially in relation to aging. We compared brain morphometry and cognitive performance in 77 individuals with chronic heavy METH use (26 APOE-ε4+, 51 APOE-ε4-) and 226 Non-METH users (66 APOE-ε4+, 160 APOE-ε4-), using a 2 × 2 design (two-way analysis of co-variance). Vertex-wise cortical volumes, thickness and seven subcortical volumes, were automatically measured using FreeSurfer. Linear regression between regional brain measures, and cognitive scores that showed group differences were evaluated. Group differences in age-related decline in brain and cognitive measures were also explored. Regardless of APOE-ε4 genotype, METH users had lower Motor Z-scores (P = 0.005), thinner right lateral-orbitofrontal cortices (P < 0.001), smaller left pars-triangularis gyrus volumes (P = 0.004), but larger pallida, hippocampi and amygdalae (P = 0.004-0.006) than nonusers. Across groups, APOE-ε4+ METH users had the smallest volumes of superior frontal cortical gyri bilaterally, and of the smallest volume in left rostral-middle frontal gyri (all P-values <0.001). Smaller right superior-frontal gyrus predicted poorer motor function only in APOE-ε4+ participants (interaction-P < 0.001). Cortical volumes and thickness declined with age similarly across all participants; however, APOE-ε4-carriers showed thinner right inferior parietal cortices than noncarriers at younger age (interaction-P < 0.001). Chronic heavy use and having at least one copy of the APOE-ε4 allele may have synergistic effects on brain atrophy, particularly in frontal cortices, which may contribute to their poorer cognitive function. However, the enlarged subcortical volumes in METH users replicated prior studies, and are likely due to METH-mediated neuroinflammation.

Maybe It's Not the Meth: Considering Biopsychosocial Contributors to Cognitive Impairment in Methamphetamine Polydrug Use.

ObjectiveIn considering the cognitive harms of methamphetamine (MA) use, there is currently a limited appreciation of the profile of pre-existing, comorbid, or modifiable risk factors for cognitive impairment in individuals with MA-polydrug use who present to clinical services. This is in contrast to the well-recognized evidence in alcohol use groups. The aim of this study was to investigate the biopsychosocial and neuropsychological profiles of MA-polysubstance using individuals reporting cognitive impairment in comparison to an alcohol-using group.MethodsA retrospective file audit was undertaken of individuals who presented for assessment to a specialist addiction neuropsychology service and reported either more than 1 year of heavy MA use as part of a polydrug use history (n = 40) or having only used alcohol (n = 27). Clinical histories including demographic, medical, mental health, substance use, and neuropsychological assessment results were extracted from medical records. Between group comparisons were conducted to explore differences in the MA-polydrug vs. the alcohol group.ResultsIndividuals in the MA-polydrug group were significantly younger, commenced substance use at an earlier age, were more likely to have an offending history, and experienced an overdose than those in the alcohol group. No differences in comorbid neurodevelopmental, psychiatric or acquired brain injury diagnoses were observed between groups. For neuropsychological functioning, significant group differences were observed in overall IQ, semantic verbal fluency, and psychomotor tracking, where individuals in the alcohol group performed significantly worse.ConclusionsNeuropsychological profiles were largely equivalent between groups across cognitive domains, with minor differences in favor of the MA-polydrug group. Relative to the general population, cognitive functioning was reduced for both groups across a range of domains. High rates of comorbid mental health concerns were common across both groups, however, individuals in the MA-polydrug group presented with a higher risk of overall harm from substance use at a significantly younger age which is a unique concern for this group. These findings highlight the importance of considering the biopsychosocial factors, such as age of first use, emotional distress, indirect substance related harms including overdose and blood born virus infection that may be relevant to experiences of cognitive difficulty in MA-polydrug users.

Methamphetamine (MA) Use Induces Specific Changes in LINE-1 Partial Methylation Patterns, Which Are Associated with MA-Induced Paranoia: a Multivariate and Neuronal Network Study.

The use of psychoactive substances, including methamphetamine (MA) may cause changes in DNA methylation. The aim of this study was to examine the effects of MA use on long interspersed element-1 (LINE-1) methylation patterns in association with MA-induced paranoia. This study recruited 123 normal controls and 974 MA users, 302 with and 672 without MA-induced paranoia. The Semi-Structured Assessment for Drug Dependence and Alcoholism was used to assess demographic and substance use variables. Patterns of LINE-1 methylation were assessed in peripheral blood mononuclear cells and a combined bisulfite restriction analysis (COBRA) was used to estimate overall LINE-1 methylation (mC) while COBRA classified LINE-alleles into four patterns based on the methylation status of two CpG dinucleotides on each strand from 5' to 3', namely two methylated (mCmC) and two unmethylated (uCuC) CpGs and two types of partially methylated loci (mCuC that is 5'm with 3'u and uCmC that is 5'u with 3'm CpGs). MA users showed higher % mCuC and % mCuC + uCmC levels than controls. Use of solvents and opioids, but not cannabis and alcohol dependence, significantly lowered % uCmC levels, while current smoking significantly increased % uCuC levels. MA-induced paranoia was strongly associated with changes in LINE-1 partial methylation patterns (lowered % uCmC), heavy MA use, lower age at onset of MA use, and alcohol dependence. Women who took contraceptives showed significantly lower LINE-1 % mC and % mCmC and higher % uCuC levels than women without contraceptive use and men. The results show that MA-induced changes in LINE-1 partial methylation patterns are associated with MA-induced paranoia and could explain in part the pathophysiology of this type of psychosis. It is argued that MA-induced neuro-oxidative pathways may have altered LINE-1 partial methylation patterns, which in turn may regulate neuro-oxidative and immune pathways, which may increase risk to develop MA-induced paranoia.

Methamphetamine-associated difficulties in cognitive control allocation may normalize after prolonged abstinence

Chronic heavy methamphetamine use likely causes dopaminergic neurotoxicity, which is commonly thought to result in cognitive control deficits. Both of these alterations may persist even after the use is discontinued, but tend to (partly) improve with increasing duration of abstinence. While several studies have demonstrated that the reinstatement of comparatively normal dopaminergic signaling may take months, if not years, the amelioration of cognitive deficits has predominantly been investigated in much shorter intervals of several weeks to less than half a year. Against this background, we set out to investigate the effects on prolonged abstinence in n = 27 abstinent former methamphetamine users in a cross-sectional design using behavioral and neurophysiological measures of cognitive control.Our behavioral results suggest that former users struggled to identify and adapt to different degrees of cognitive control requirements, which made their behavioral performance less expedient than that of healthy controls. On the neurophysiological level, this was reflected by reduced modulations of the N2-N450 amplitude in response to high vs. low cognitive control requirements. Yet, those effects could only be observed in methamphetamine users who had been abstinent for a relatively short time (mean 9.9; max. 18 months), but not in former users who had been abstinent two years or longer.While this finding alone does not allow for causal inferences, it suggests that the amelioration of control deficits may take longer than what is commonly investigated (1–6 months). Hence, some of the statements about permanent/irreversible dopamine-dependent executive dysfunctions in former methamphetamine users should be interpreted with caution.

N-Acetyl and Glutamatergic Neurometabolites in Perisylvian Brain Regions of Methamphetamine Users.

BackgroundMethamphetamine induces neuronal N-acetyl-aspartate synthesis in preclinical studies. In a preliminary human proton magnetic resonance spectroscopic imaging investigation, we also observed that N-acetyl-aspartate+N-acetyl-aspartyl-glutamate in right inferior frontal cortex correlated with years of heavy methamphetamine abuse. In the same brain region, glutamate+glutamine is lower in methamphetamine users than in controls and is negatively correlated with depression. N-acetyl and glutamatergic neurochemistries therefore merit further investigation in methamphetamine abuse and the associated mood symptoms.MethodsMagnetic resonance spectroscopic imaging was used to measure N-acetyl-aspartate+N-acetyl-aspartyl-glutamate and glutamate+glutamine in bilateral inferior frontal cortex and insula, a neighboring perisylvian region affected by methamphetamine, of 45 abstinent methamphetamine-dependent and 45 healthy control participants. Regional neurometabolite levels were tested for group differences and associations with duration of heavy methamphetamine use, depressive symptoms, and state anxiety.ResultsIn right inferior frontal cortex, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate correlated with years of heavy methamphetamine use (r = +0.45); glutamate+glutamine was lower in methamphetamine users than in controls (9.3%) and correlated negatively with depressive symptoms (r = -0.44). In left insula, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate was 9.1% higher in methamphetamine users than controls. In right insula, glutamate+glutamine was 12.3% lower in methamphetamine users than controls and correlated negatively with depressive symptoms (r = -0.51) and state anxiety (r = -0.47).ConclusionsThe inferior frontal cortex and insula show methamphetamine-related abnormalities, consistent with prior observations of increased cortical N-acetyl-aspartate in methamphetamine-exposed animal models and associations between cortical glutamate and mood in human methamphetamine users.

Clinical and Autopsy Characteristics of Fatal Methamphetamine Toxicity in Australia.

Characteristics of death attributed solely to methamphetamine toxicity (MT, n = 93) by forensic pathologists were examined and compared to cases of multiple drug toxicity (MDT, n = 634). The mean age of MT cases was 36.7 years, and 86.0% were male. Strenuous activity was reported in 12.9%. The most common witness observations were: collapse (60.3%), difficulty in breathing (36.2%), and hyperthermia (27.6%). MT cases had higher blood methamphetamine (0.54 vs. 0.11 mg/L) and amphetamine (0.04 vs. 0.02 mg/L) concentrations and lower likelihoods for opioids (12.5% vs. 80.9%), hypnosedatives (27.3 vs. 60.7%), antidepressants (14.8 vs. 29.8%), and antipsychotics (9.1 vs. 19.7%). MT cases had significantly heavier hearts than MDT cases (423.4 vs. 385.8 g) and were more likely to have cardiomegaly (37.1 vs. 20.4%) and replacement fibrosis (25.7 vs. 14.5%). The clinical picture was of a sudden cardiac event in a middle-aged man with a high methamphetamine concentration. Cardiovascular signs of heavy methamphetamine use are frequently seen.

Gender differences in the effect of tobacco use on brain phosphocreatine levels in methamphetamine-dependent subjects

Background: A high prevalence of tobacco smoking has been observed in methamphetamine users, but there have been no in vivo brain neurochemistry studies addressing gender effects of tobacco smoking in methamphetamine users. Methamphetamine addiction is associated with increased risk of depression and anxiety in females. There is increasing evidence that selective analogues of nicotine, a principal active component of tobacco smoking, may ease depression and improve cognitive performance in animals and humans. Objectives: To investigate the effects of tobacco smoking and gender on brain phosphocreatine (PCr) levels, a marker of brain energy metabolism reported to be reduced in methamphetamine-dependent subjects. Methods: Thirty female and 27 male methamphetamine-dependent subjects were evaluated with phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to measure PCr levels within the pregenual anterior cingulate, which has been implicated in methamphetamine neurotoxicity. Results: Analysis of covariance revealed that there were statistically significant slope (PCr versus lifetime amount of tobacco smoking) differences between female and male methamphetamine-dependent subjects (p = 0.03). In females, there was also a statistically significant interaction between lifetime amounts of tobacco smoking and methamphetamine in regard to PCr levels (p = 0.01), which suggests that tobacco smoking may have a more significant positive impact on brain PCr levels in heavy, as opposed to light to moderate, methamphetamine-dependent females. Conclusion: These results indicate that tobacco smoking has gender-specific effects in terms of increased anterior cingulate high energy PCr levels in methamphetamine-dependent subjects. Cigarette smoking in methamphetamine-dependent women, particularly those with heavy methamphetamine use, may have a potentially protective effect upon neuronal metabolism.

The risk and associated factors of methamphetamine psychosis in methamphetamine-dependent patients in Malaysia

ObjectiveThe objective of this study was to determine the risk of lifetime and current methamphetamine-induced psychosis in patients with methamphetamine dependence. The association between psychiatric co-morbidity and methamphetamine-induced psychosis was also studied. MethodsThis was a cross-sectional study conducted concurrently at a teaching hospital and a drug rehabilitation center in Malaysia. Patients with the diagnosis of methamphetamine based on DSM-IV were interviewed using the Mini International Neuropsychiatric Interview (M.I.N.I.) for methamphetamine-induced psychosis and other Axis I psychiatric disorders. The information on sociodemographic background and drug use history was obtained from interview or medical records. ResultsOf 292 subjects, 47.9% of the subjects had a past history of psychotic symptoms and 13.0% of the patients were having current psychotic symptoms. Co-morbid major depressive disorder (OR=7.18, 95 CI=2.612–19.708), bipolar disorder (OR=13.807, 95 CI=5.194–36.706), antisocial personality disorder (OR=12.619, 95 CI=6.702–23.759) and heavy methamphetamine uses were significantly associated with lifetime methamphetamine-induced psychosis after adjusted for other factors. Major depressive disorder (OR=2.870, CI=1.154–7.142) and antisocial personality disorder (OR=3.299, 95 CI=1.375–7.914) were the only factors associated with current psychosis. ConclusionThere was a high risk of psychosis in patients with methamphetamine dependence. It was associated with co-morbid affective disorder, antisocial personality, and heavy methamphetamine use. It is recommended that all cases of methamphetamine dependence should be screened for psychotic symptoms.

Major depression among methamphetamine users entering drug treatment programs

To determine the prevalence of major depression among people entering treatment for methamphetamine use. The study was a cross-sectional survey involving 41specialised drug and alcohol treatment agencies in Brisbane and Sydney. Services provided by these agencies included residential rehabilitation, detoxification and counselling. Participants were 400people entering treatment for methamphetamine use who were recruited from participating treatment agencies between January 2006and November 2007. Participants underwent a structured, face-to-face, 1.5-hour interview. Assessment instruments included the Composite International Diagnostic Interview and the Short Form 12. Diagnosis of a major depressive episode in the year prior to the study. The prevalence of major depression in the year prior to the study was 40% (95% CI, 35%-44%). A noteworthy post-hoc observation was that a further 44% of participants met the symptom criteria for major depression but were excluded from a diagnosis because their symptoms were better accounted for by psychoactive substance use. Both major depression and these latter cases of "substance-induced depression" were associated with severe symptoms of depression, high levels of disability and suicidal ideation. Most people entering treatment programs for methamphetamine use have levels of depression that require clinical management. Making a diagnosis of major depression in the context of heavy methamphetamine use is problematic because of substance-induced symptoms of depression.

Prenatal methamphetamine use and neonatal neurobehavioral outcome

Background Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How prenatal MA exposure affects neonatal neurobehavior is unknown. Objective To examine the neurobehavioral effects of prenatal MA exposure. Design The Infant Development, Environment and Lifestyle (IDEAL) study screened 13,808 subjects and 1632 were eligible and consented. 166 ( n = 74 exposed) were enrolled in a longitudinal follow-up. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life. Analyses conducted on NNNS summary scores included exposure group effects, heavy MA use effects, association with frequency of use by trimester, and dose–response relationships with amphetamine metabolites. Results After adjusting for covariates, exposure to MA was associated with increased physiological stress. Heavy MA use was related to lower arousal, more lethargy, and increased physiological stress. First trimester MA use was related to elevated stress abstinence. Third trimester use was related to poorer quality of movement. Higher level of amphetamine metabolites in meconium was associated with increased CNS stress. Conclusions Prenatal MA exposure was associated with neurobehavioral patterns of decreased arousal, increased stress, and poor quality of movement. The dose–response relationships may represent neurotoxic effects from MA.