Abstract
Changes in relative regional cerebral glucose metabolism (rCMRglc) and their potential gender differences in abstinent methamphetamine (MA) users were explored. Relative rCMRglc, as measured by 18F-fluorodeoxyglucose positron emission tomography, and frontal executive functions, as assessed by Wisconsin card sorting test (WCST), were compared between 35 abstinent MA users and 21 healthy comparison subjects. In addition, male and female MA users and their gender-matched comparison subjects were compared to investigate potential gender differences. MA users had lower rCMRglc levels in the right superior frontal white matter and more perseveration and nonperseveration errors in the WCST, relative to healthy comparison subjects. Relative rCMRglc in the frontal white matter correlated with number of errors in the WCST in MA users. In the subanalysis for gender differences, lower rCMRglc in the frontal white matter and more errors in the WCST were found only in male MA users, not in female MA users, relative to their gender-matched comparison subjects. The current findings suggest that MA use causes persistent hypometabolism in the frontal white matter and impairment in frontal executive function. Our findings also suggest that the neurotoxic effect of MA on frontal lobes of the brain might be more prominent in men than in women.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Ali SF, Newport GD, Slikker Jr W (1996). Methamphetamine-induced dopaminergic toxicity in mice. Role of environmental temperature and pharmacological agents. Ann NY Acad Sci 801: 187–198.
Chang L, Ernst T, Speck O, Patel H, DeSilva M, Leonido-Yee M et al (2002). Perfusion MRI and computerized cognitive test abnormalities in abstinent methamphetamine users. Psychiatry Res 114: 65–79.
Chang L, Ernst T, Strickland T, Mehringer CM (1999). Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users. Am J Psychiatry 156: 716–722.
Chung AI, Kang HK, Kwon JY, Hwang J, Yune SK, Chang KH et al (2004). Decreased frontal lobe gray matter densities in chronic detoxified methamphetamine user: voxel-based morphometry study. College on Problems of Drug Dependence annual meeting, San Juan, Puerto Rico.
Culmsee C, Vedder H, Ravati A, Junker V, Otto D, Ahlemeyer B et al (1999). Neuroprotection by estrogens in a mouse model of focal cerebral ischemia and in cultured neurons: evidence for a receptor-independent antioxidative mechanism. J Cereb Blood Flow Metab 19: 1263–1269.
Dluzen DE, Anderson LI, Pilati CF (2002). Methamphetamine-gonadal steroid hormonal interactions: effects upon acute toxicity and striatal dopamine concentrations. Neurotoxicol Teratol 24: 267–273.
Dluzen DE, McDermott JL (2002). Estrogen, anti-estrogen, and gender: differences in methamphetamine neurotoxicity. Ann NY Acad Sci 965: 136–156.
Dluzen DE, Tweed C, Anderson LI, Laping NJ (2003). Gender differences in methamphetamine-induced mRNA associated with neurodegeneration in the mouse nigrostriatal dopaminergic system. Neuroendocrinology 77: 232–238.
Ernst T, Chang L, Leonido-Yee M, Speck O (2000a). Evidence for long-term neurotoxicity associated with methamphetamine abuse: A 1H MRS study. Neurology 54: 1344–1349.
Ernst T, Chang L, Oropilla G, Gustavson A, Speck O (2000b). Cerebral perfusion abnormalities in abstinent cocaine abusers: a perfusion MRI and SPECT study. Psychiatry Res 99: 63–74.
Farabee D, Prendergast M, Cartier J (2002). Methamphetamine use and HIV risk among substance-abusing offenders in California. J Psychoactive Drugs 34: 295–300.
Friston KJ, Ashburner J, Frith CD, Poline JB, Heather JD, Frackowiak RSJ (1995a). Spatial registration and normalization of images. Hum Brain Mapp 2: 165–189.
Friston KJ, Holmes AP, Worsley KJ, Poline JP, Frith CD, Frackowiak RSL (1995b). Statistical parametric maps in functional imaging: a general liner approach. Hum Brain Mapp 2: 189–210.
Gao X, Dluzen DE (2001). The effect of testosterone upon methamphetamine neurotoxicity of the nigrostriatal dopaminergic system. Brain Res 892: 63–69.
Garcia-Segura LM, Wozniak A, Azcoitia I, Rodriguez JR, Hutchison RE, Hutchison JB (1999). Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair. Neuroscience 89: 567–578.
Hall JN, Broderick PM (1991). Community networks for response to abuse outbreaks of methamphetamine and its analogs. NIDA Res Monogr 115: 109–120.
Heaton RK, Chelune GJ, Kay KK, Curtiss G (1993). Wisconsin Card Sorting Test Manual: Revised and Expanded. Western Psychological Services: Los Angeles, CA.
Hirata H, Ladenheim B, Carlson E, Epstein C, Cadet JL (1996). Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice. Brain Res 714: 95–103.
Hwang J, Lee HY, Yune SK, Lee DS, Renshaw PF, Lyoo IK (2004). Decreased anterior cingulate activity in intravenous methamphetamine users: a single photon emission computed tomography and neuropsychologic test study. College on Problems of Drug Dependence annual meeting, San Juan, Puerto Rico.
Kalechstein AD, Newton TF, Green M (2003). Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence. J Neuropsychiatry Clin Neurosci 15: 215–220.
Kim JM, Cho GJ, Hong SK, Chang KH, Chung JS, Choi YH et al (2003). Epidemiology and clinical features of HIV infection/AIDS in Korea. Yonsei Med J 44: 363–370.
London ED, Simon SL, Berman SM, Mandelkern MA, Lichtman AM, Bramen J et al (2004). Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers. Arch Gen Psychiatry 61: 73–84.
McLellan AT, Luborsky L, Woody GE, O'Brien CP (1980). An improved diagnostic evaluation instrument for substance abuse patients. The Addiction Severity Index. J Nerv Ment Dis 168: 26–33.
Mermelstein PG, Becker JB, Surmeier DJ (1996). Estradiol reduces calcium currents in rat neostriatal neurons via a membrane receptor. J Neurosci 16: 595–604.
Nabulsi AA, Folsom AR, White A, Patsch W, Heiss G, Wu KK et al (1993). Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. The Atherosclerosis Risk in Communities Study Investigators. N Engl J Med 328: 1069–1075.
Nordahl TE, Salo R, Possin K, Gibson DR, Flynn N, Leamon M et al (2002). Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study. Magnetic resonance spectroscopy. Psychiatry Res 116: 43–52.
Paulus MP, Hozack N, Frank L, Brown GG, Schuckit MA (2003). Decision making by methamphetamine-dependent subjects is associated with error-rate-independent decrease in prefrontal and parietal activation. Biol Psychiatry 53: 65–74.
Paulus MP, Hozack NE, Zauscher BE, Frank L, Brown GG, Braff DL et al (2002). Behavioral and functional neuroimaging evidence for prefrontal dysfunction in methamphetamine-dependent subjects. Neuropsychopharmacology 26: 53–63.
Pope Jr HG, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D (2001). Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry 58: 909–915.
Preston KL, Wagner GC, Schuster CR, Seiden LS (1985). Long-term effects of repeated methylamphetamine administration on monoamine neurons in the rhesus monkey brain. Brain Res 338: 243–248.
Roh JK, Nam H, Lee MC (1998). A case of central pontine and extrapontine myelinolysis with early hypermetabolism on 18FDG-PET scan. J Korean Med Sci 13: 99–102.
Sawada H, Ibi M, Kihara T, Urushitani M, Akaike A, Shimohama S (1998). Estradiol protects mesencephalic dopaminergic neurons from oxidative stress-induced neuronal death. J Neurosci Res 54: 707–719.
Sekine Y, Minabe Y, Ouchi Y, Takei N, Iyo M, Nakamura K et al (2003). Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms. Am J Psychiatry 160: 1699–1701.
Shaw KP (1999). Human methamphetamine-related fatalities in Taiwan during 1991–1996. J Forensic Sci 44: 27–31.
Stout JC, Ellis RJ, Jernigan TL, Archibald SL, Abramson I, Wolfson T et al (1998). Progressive cerebral volume loss in human immunodeficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. HIV Neurobehavioral Research Center Group. Arch Neurol 55: 161–168.
Tarairach J, Tournoux P (1988). Co-Planer Stereotaxic Atlas of the Human Brain. Thieme: New York, NY.
Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y et al (2004). Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci 24: 6028–6036.
Tucker KA, Browndyke JN, Gottschalk PC, Cofrancesco AT, Kosten TR (2004). Gender-specific vulnerability for rCBF abnormalities among cocaine abusers. Neuroreport 15: 797–801.
Volkow ND, Chang L, Wang GJ, Fowler JS, Ding YS, Sedler M et al (2001a). Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. Am J Psychiatry 158: 2015–2021.
Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M et al (2001b). Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci 21: 9414–9418.
Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler MJ et al (2001c). Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers. Am J Psychiatry 158: 383–389.
Vorhees CV, Ahrens KG, Acuff-Smith KD, Schilling MA, Fisher JE (1994). Methamphetamine exposure during early postnatal development in rats: I. Acoustic startle augmentation and spatial learning deficits. Psychopharmacology (Berl) 114: 392–401.
Wagner GC, Tekirian TL, Cheo CT (1993). Sexual differences in sensitivity to methamphetamine toxicity. J Neural Transm Gen Sect 93: 67–70.
Wang GJ, Volkow ND, Chang L, Miller E, Sedler M, Hitzemann R et al (2004). Partial recovery of brain metabolism in methamphetamine abusers after protracted abstinence. Am J Psychiatry 161: 242–248.
Wilson JM, Kalasinsky KS, Levey AI, Bergeron C, Reiber G, Anthony RM et al (1996). Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Nat Med 2: 699–703.
Wirz-Justice A, Hackmann E, Lichtsteiner M (1974). The effect of oestradiol dipropionate and progesterone on monoamine uptake in rat brain. J Neurochem 22: 187–189.
Woolverton WL, Cervo L, Johanson CE (1984). Effects of repeated methamphetamine administration on methamphetamine self-administration in rhesus monkeys. Pharmacol Biochem Behav 21: 737–741.
Yoo HJ, Song WY, Hwang SH, Kim SY, Kang JK, Lee SA et al (2000). Factor analysis of Wisconsin card sorting test as measures of frontal-lobe function in schizophrenia and in temporal lobe epilepsy. Korean J Psychol 19: 873–883.
Acknowledgements
This work was supported by grants from the Health Technology Infrastructure Development Project of Korea Health Industry Development Institute (03-PJ1-PG3-21300-0069).
Author information
Authors and Affiliations
Corresponding author
Additional information
This study was submitted at the 2004 College on Problems of Drug Dependence annual meeting that was held in San Juan, Puerto Rico on June 12–17, 2004
Rights and permissions
About this article
Cite this article
Kim, S., Lyoo, I., Hwang, J. et al. Frontal Glucose Hypometabolism in Abstinent Methamphetamine Users. Neuropsychopharmacol 30, 1383–1391 (2005). https://doi.org/10.1038/sj.npp.1300699
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.npp.1300699
Keywords
This article is cited by
-
Sex differences in behavior, cognitive, and physiological recovery following methamphetamine administration
Psychopharmacology (2024)
-
Aberrant topology of white matter networks in patients with methamphetamine dependence and its application in support vector machine-based classification
Scientific Reports (2023)
-
Influence of Baseline Psychiatric Disorders on Mortality and Suicide and Their Associations with Gender and Age in Patients with Methamphetamine Use Disorder
International Journal of Mental Health and Addiction (2023)
-
Repeated methamphetamine administration produces cognitive deficits through augmentation of GABAergic synaptic transmission in the prefrontal cortex
Neuropsychopharmacology (2022)
-
Genome-wide transcriptional profiling of central amygdala and orbitofrontal cortex during incubation of methamphetamine craving
Neuropsychopharmacology (2018)
