Changes in cerebral glucose metabolism during early abstinence from chronic methamphetamine abuse

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90024-1759, USA.
Molecular Psychiatry (Impact Factor: 14.5). 11/2007; 13(9):897-908. DOI: 10.1038/
Source: PubMed


Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. A total of 10 methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence. A total of 12 healthy control subjects were tested at corresponding times. Global glucose metabolism increased between tests (P=0.01), more in methamphetamine-dependent (10.9%, P=0.02) than control subjects (1.9%, NS). Glucose metabolism did not change in subcortical regions of methamphetamine-dependent subjects, but increased in neocortex, with maximal increase (>20%) in parietal regions. Changes in reaction time and self-reports of negative affect varied more in methamphetamine-dependent than in control subjects, and correlated both with the increase in parietal glucose metabolism, and decrease in relative activity (after scaling to the global mean) in some regions. A robust relationship between change in self-reports of depressive symptoms and relative activity in the ventral striatum may have great relevance to treatment success because of the role of this region in drug abuse-related behaviors. Shifts in cortical-subcortical metabolic balance either reflect new processes that occur during early abstinence, or the unmasking of effects of chronic methamphetamine abuse that are obscured by suppression of cortical glucose metabolism that continues for at least 5-9 days after cessation of methamphetamine self-administration.

Download full-text


Available from: Edythe D London, Aug 19, 2014
    • "In chronic methamphetamine users, mood disorders and anxiety disorders are fairly frequent (Conway, Compton, Stinson, & Grant, 2006), and a smaller proportion of these have been attributed directly to the use of the drug (Salo et al., 2011). Changes in selfreported depressive symptoms were in strong correlation with relative deoxyglucose uptake in ventral striatum, in a study with two measurements 4 weeks of supervised abstinence apart (Berman, Voytek, et al., 2008). Striatal dopamine D 2 receptor availability in striatum, at baseline or after amphetamine administration, was however not associated with depression (Parsey et al., 2001), but this remains to be investigated in drug users. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors. © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Dec 2015 · International Review of Neurobiology
  • Source
    • "While few other studies have examined relationships between denial and the brain in addiction, the cortical and limbic regions identified in the current study have been variously associated with other abnormalities in methamphetamine users. Compared to healthy control subjects, methamphetamine-dependent participants have exhibited hypoactivity of the ACC associated with inhibitory control deficits (Nestor et al., 2011), increase in cerebral glucose metabolism in the precuneus during early abstinence (Berman et al., 2007), gray matter deficits in the ACC, OFC, precuneus, amygdala and hippocampus (Morales et al., 2012; Thompson et al., 2004), and aberrant relative glucose metabolism in the ACC, OFC and amygdala associated with inattention and mood disturbances (London et al., 2004, 2005). Future studies are needed to investigate mechanisms by which these abnormalities may, in isolation or combination, contribute to reduced insight/denial. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite harmful consequences of drug addiction, it is common for individuals with substance use disorders to deny having problems with drugs. Emerging evidence suggests that some drug users lack insight into their behavior due to neurocognitive dysfunction, but little research has examined potential neurocognitive contributions to denial. This study explored the relationship between denial, cognitive performance and functional connectivity in brain. The participants were 58 non-treatment-seeking, methamphetamine-dependent participants who completed the URICA precontemplation scale, a self-report measure of denial of drug problems warranting change, as well as a cognitive test battery. A subset of participants (N=21) had functional MRI scans assessing resting-state functional connectivity. Given literature indicating roles of the rostral anterior cingulate (rACC), anterior insula and precuneus in self-awareness, relationships between denial and resting-state connectivity were tested using seeds placed in these regions. The results revealed a negative relationship between denial and an overall cognitive battery score (p=0.001), the effect being driven particularly by performance on tests of memory and executive function. Denial was negatively associated with strength of connectivity between the rACC and regions of the frontal lobe (precentral gyri, left ventromedial prefrontal cortex, left orbitofrontal cortex), limbic system (left amygdala, left hippocampus and left parahippocampal gyrus), occipital lobes and cerebellum; and between the precuneus and the midbrain and cerebellum. Anterior insula connectivity was unrelated to denial. These findings suggest that denial by methamphetamine users is linked with a cognitive and neural phenotype that may impede the development of insight into their behavior. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Mar 2015 · Drug and alcohol dependence
  • Source
    • "FDG-PET previously demonstrated elevated glucose metabolism in methamphetamine-abusing subjects following up to14 days (London et al. 2004) or 14 days to 2 years (Volkow et al. 2001; Berman et al. 2008) abstinence from drug. In combination with these findings, the present results reinforce the view that methamphetamine abuse is associated with dysfunction in brain areas, such as medial parietal cortex, with sparse dopaminergic innervation (Descarries et al. 1987). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The acute phase of abstinence from methamphetamine abuse is critical for rehabilitation success. Proton magnetic resonance spectroscopy (MRS) has detected below-normal levels of glutamate+glutamine (Glx) in anterior middle cingulate cortex of chronic methamphetamine abusers during early abstinence, attributed to abstinence-induced downregulation of the glutamatergic systems in the brain. This study further explored this phenomenon. We measured Glx in additional cortical regions (midline posterior cingulate, midline precuneus, and bilateral inferior frontal cortex) putatively impacted by methamphetamine. We examined the relationship between Glx in each region with duration of methamphetamine abuse as well as the depressive symptoms of early abstinence. Magnetic resonance spectroscopic imaging was acquired at 1.5 T from a Methamphetamine group of 44 adults who had chronically abused methamphetamine and a Control group of 23 age-, sex-, and tobacco smoking-matched healthy volunteers. Participants in the Methamphetamine group were studied as inpatients during the first week of abstinence from the drug, and were not receiving treatment. In the Methamphetamine group, small but significant (5-15%, P<0.05) decrements (vs. Control) in Glx were observed in posterior cingulate, precuneus, and right inferior frontal cortex; Glx in posterior cingulate was correlated negatively (P<0.05) with years of methamphetamine abuse. The Beck Depression Inventory score was correlated negatively (P<0.005) with Glx in right inferior frontal cortex. Our findings support the idea that glutamatergic metabolism is downregulated in early abstinence in multiple cortical regions. The extent of downregulation may vary with length of abuse and may be associated with severity of depressive symptoms emergent in early recovery. © The Author 2014. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · Oct 2014 · The International Journal of Neuropsychopharmacology
Show more