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.

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Available from: Edythe D London, Aug 19, 2014
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    • "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. "
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    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.
    Drug and alcohol dependence 03/2015; 151. DOI:10.1016/j.drugalcdep.2015.03.004 · 3.42 Impact Factor
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    • "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). "
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    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.
    The International Journal of Neuropsychopharmacology 10/2014; 18(3). DOI:10.1093/ijnp/pyu059 · 4.01 Impact Factor
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    • "Cont. Berman et al. 2008 [108] "
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    ABSTRACT: Methamphetamine (MA) is a potent psychostimulant drug whose abuse has become a global epidemic in recent years. Firstly, this review article briefly discusses the epidemiology and clinical pharmacology of methamphetamine dependence. Secondly, the article reviews relevant animal literature modeling methamphetamine dependence and discusses possible mechanisms of methamphetamine-induced neurotoxicity. Thirdly, it provides a critical review of functional and structural neuroimaging studies in human MA abusers; including positron emission tomography (PET) and functional and structural magnetic resonance imaging (MRI). The effect of abstinence from methamphetamine, both short- and long-term within the context of these studies is also reviewed.
    12/2012; 2(4-4):434-482. DOI:10.3390/brainsci2040434
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