Sara L. Simon

Structural Abnormalities in the Brains of Human Subjects Who Use Methamphetamine

We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.

Validation of the alcohol, smoking and substance involvement screening test (ASSIST)

AIM The concurrent, construct and discriminative validity of the World Health Organizations Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were examined in a multi-site international study. PARTICIPANTS One thousand and 47 participants, recruited from drug treatment (n = 350) and primary health care (PHC) settings (n = 697), were administered a battery of instruments. MEASUREMENTS Measures included the ASSIST; the Addiction Severity Index-Lite (ASI-Lite); the Severity of Dependence Scale (SDS); the MINI International Neuropsychiatric Interview (MINI-Plus); the Rating of Injection Site Condition (RISC); the Drug Abuse Screening Test (DAST); the Alcohol Use Disorders Identification Test (AUDIT); the Revised Fagerstrom Tolerance Questionnaire (RTQ); and the Maudsley Addiction Profile (MAP). FINDINGS Concurrent validity was demonstrated by significant correlations between ASSIST scores and scores from the ASI-Lite (r = 0.76-0.88), SDS (r = 0.59), AUDIT (r = 0.82) and RTQ (r = 0.78); and significantly greater ASSIST scores for those with MINI-Plus diagnoses of abuse or dependence (P < 0.001). Construct validity was established by significant correlations between ASSIST scores and measures of risk factors for the development of drug and alcohol problems (r = 0.48-0.76). Discriminative validity was established by the capacity of the ASSIST to discriminate between substance use, abuse and dependence. Receiver operating characteristic (ROC) analysis was used to establish cut-off scores with suitable specificities (50-96%) and sensitivities (54-97%) for most substances. CONCLUSIONS The findings demonstrated that the ASSIST is a valid screening test for identifying psychoactive substance use in individuals who use a number of substances and have varying degrees of substance use.

Cognitive Impairment in Individuals Currently Using Methamphetamine

Although there are increasing reports of methamphetamine use, studies examining the cognitive consequences of methamphetamine have not been performed on a population currently using the drug. To characterize this population, 65 people currently using MA regularly and 65 non-users were given a battery of cognitive tests. The battery included recall, recognition, Digit Symbol, Trail Making A & B, Stroop, Wisconsin Card Sort, backward digit span, and the FAS test of verbal fluency. The methamphetamine users were significantly more impaired on recall tasks, digit symbol, Stroop color words, and Trail Making B, but scores fell within the normal ranges on the other measures.

Cognitive performance of current methamphetamine and cocaine abusers.

Abstract Forty currently using methamphetamine (MA) abusers. 40 currently using cocaine (COC) abusers, and 80 comparison participants who did not use psychostimulants received a cognitive battery and questionnaires covering medical history and stimulant use patterns. Forty comparison participants were matched to the 40 MA users on age. education, ethnicity, and gender. The other 40 comparison participants were matched to the cocaine users on the same variables. This design was chosen because there were significant differences in age and ethnicity between COC and MA users that precluded a direct comparison between the groups. The COC group was older and predominantly African American compared to the predominantly Caucasian MA group. When compared to their matched non-using control groups, both MA and COC abusers were impaired on cognitive measures, but the type and degree of impairments were somewhat different.

A Randomized Controlled Trial of a Brief Intervention for Illicit Drugs Linked to the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) in clients recruited from primary health care settings in four countries

AIMS This study evaluated the effectiveness of a brief intervention (BI) for illicit drugs (cannabis, cocaine, amphetamine-type stimulants and opioids) linked to the World Health Organization (WHO) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The ASSIST screens for problem or risky use of 10 psychoactive substances, producing a score for each substance that falls into either a low-, moderate- or high-risk category. DESIGN Prospective, randomized controlled trial in which participants were either assigned to a 3-month waiting-list control condition or received brief motivational counselling lasting an average of 13.8 minutes for the drug receiving the highest ASSIST score. SETTING Primary health-care settings in four countries: Australia, Brazil, India and the United States. PARTICIPANTS A total of 731 males and females scoring within the moderate-risk range of the ASSIST for cannabis, cocaine, amphetamine-type stimulants or opioids. MEASUREMENTS ASSIST-specific substance involvement scores for cannabis, stimulants or opioids and ASSIST total illicit substance involvement score at baseline and 3 months post-randomization. FINDINGS Omnibus analyses indicated that those receiving the BI had significantly reduced scores for all measures, compared with control participants. Country-specific analyses showed that, with the exception of the site in the United States, BI participants had significantly lower ASSIST total illicit substance involvement scores at follow-up compared with the control participants. The sites in India and Brazil demonstrated a very strong brief intervention effect for cannabis scores (P < 0.005 for both sites), as did the sites in Australia (P < 0.005) and Brazil (P < 0.01) for stimulant scores and the Indian site for opioid scores (P < 0.01). CONCLUSIONS The Alcohol, Smoking and Substance Involvement Screening Test-linked brief intervention aimed at reducing illicit substance use and related risks is effective, at least in the short term, and the effect generalizes across countries.

Brain Activity in Cigarette Smokers Performing a Working Memory Task: Effect of Smoking Abstinence

BACKGROUND When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. METHODS We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (< or = 1.5 hours abstinence) and abstinence (> or = 14 hours abstinence) conditions. RESULTS Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels. CONCLUSIONS We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety.

Cerebral Metabolic Dysfunction and Impaired Vigilance in Recently Abstinent Methamphetamine Abusers

BACKGROUND Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. METHODS We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology. RESULTS Methamphetamine users had higher error rates than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. CONCLUSIONS Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.

A Comparison of Patterns of Methamphetamine and Cocaine Use

Abstract Typical use patterns of methamphetamine (MA) users were examined using self-report measures from 120 MA and 63 cocaine users. Twenty (14 MA and 6 cocaine) of the participants also took part in structured interviews designed to provide more specific descriptions of their drug use. The typical MA user uses more than 20 days a month. Use is evenly spaced throughout the day, and although the amount of drug used per day is not different, MA users use fewer times per day than do cocaine users. Fewer of the cocaine users are continuous users, and they use in the evening rather than the daytime. The cocaine pattern of fewer days of use, evening use, and more frequent doses per day fits a picture of recreational use, whereas the all-day-most-days methamphetamine pattern does not.

Cognitive deficits among methamphetamine users with attention deficit hyperactivity disorder symptomatology

Abstract Understanding the association between attention deficit hyperactivity disorder (ADHD) and substance abuse, specifically methamphetamine (MA) abuse, is challenging, partly because little is known about the specific constellation of cognitive impairments produced by MA. The present investigation serves to address this relationship by comparing the cognitive performance of MA abusers with ADHD symptomatology (n = 28) and MA abusers without ADHD symptomatology (n = 41) on tests of attention, memory and general intellectual functioning, executive functioning, problem solving, verbal fluency, and abstract thinking. Both MA samples had deficiencies in measures of memory and learning function, psychomotor speed and abstract thinking when compared to a control group (n = 40). Additional deficits were noted on tasks involving executive functioning, attention, and general intellectual functioning in MA abusers with ADHD symptomatology. The preliminary data suggests that executive function deficits and some of the symptoms associated with long-term MA use may be due to the fact that a large proportion of MA addicts had ADHD symptomatology as children.

Effect of Cigarette Smoking on Prefrontal Cortical Function in Nondeprived Smokers Performing the Stroop Task

Some reports indicate that cigarette smoking can help smokers focus attention, even when they have not abstained from smoking for a substantial period of time (eg, >1 h). Understanding the mechanisms by which smoking affects attention may help in designing smoking cessation treatments. Thirteen nonsmokers and nine smokers participated in two tests of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). During fMRI, the participants performed the Stroop Task. There was a 15-min break between the two tests. During the break, each smoker smoked one cigarette. For smokers, the first test began 45–60 min after the last cigarette of ad libitum smoking. The differences in BOLD signal changes between Stroop conditions (ie, incongruent minus congruent) showed a group × test interaction in the right precentral sulcus, including the putative human frontal eye field (FEF). Smokers, but not nonsmokers, showed greater changes (relative to rest) in BOLD signal in the incongruent than in the congruent condition in the first fMRI test but not in the second. Even after brief abstinence from smoking, therefore, smokers exhibit compromised functional efficiency in the right FEF and adjacent precentral sulcus in a test of selective attention; and smoking ameliorates this condition.