Skip to main content

Advertisement

Log in

Effects of human immunodeficiency virus and methamphetamine on cerebral metabolites measured with magnetic resonance spectroscopy

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Human immunodeficiency virus (HIV) and methamphetamine (METH) use disorders are associated with cerebral dysfunction. To determine whether these effects were evident on in vivo neuroimaging, quantitative, single voxel magnetic resonance (MR) spectroscopy was used to assess frontal white matter, frontal gray matter, and basal ganglia in 40 HIV+/METH+, 66 HIV+/METH-, 48 HIV-/METH+, and 51 HIV-/METH-participants. HIV was associated with lower N-acetylaspartate (NAA) in frontal white and frontal gray matter but METH was not associated with cerebral metabolite differences in any region. Among HIV+ individuals, lower CD4 counts and higher plasma HIV viral loads were associated with lower NAA in frontal gray matter and basal ganglia. The relationship between detectable plasma HIV viral load and NAA in frontal white matter was significantly stronger in the HIV+/METH+ group, compared to HIV+/METH-. Higher detectable plasma HIV viral load was significantly associated with higher myo-inositol (MI) in frontal white and gray matter for HIV+/METH+, but not HIV+/METH-. For the HIV-/METH+ group, lifetime duration of METH use was associated with higher choline levels in frontal gray matter and higher MI levels in basal ganglia. Our findings are consistent with significant disruption of neuronal integrity in the frontal lobes of HIV-infected individuals. Although METH was not associated with cerebral metabolite levels, other findings suggested that METH use did affect the brain. For example, the relationship between detectable plasma HIV viral load and NAA levels was limited to HIV+/METH+ individuals. This evidence indicates when HIV is poorly suppressed, METH may modify the effects of the virus on neuronal integrity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Chang L, Ernst T, Speck O, Grob CS (2005). Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities. Am J Psychiatry 162: 361–369.

    Article  PubMed  Google Scholar 

  • Chang L, Ernst T, Witt MD, Ames N, Gaiefsky M, Miller E (2002). Relationships among brain metabolites, cognitive function, and viral loads in antiretroviral-naive HIV patients. Neuroimage 17: 1638–1648.

    Article  PubMed  Google Scholar 

  • Chang L, Ernst T, Witt MD, Ames N, Walot I, Jovicich J, DeSilva M, Trivedi N, Speck O, Miller EN (2003). Persistent brain abnormalities in antiretroviral-naive HIV patients 3 months after HAART. Antiviral Ther 8: 17–26.

    CAS  Google Scholar 

  • Chang L, Lee PL, Yiannoutsos CT, Ernst T, Marra CM, Richards T, Kolson D, Schifitto G, Jarvik JG, Miller EN, Lenkinski R, Gonzalez G, Navia BA (2004). A multicenter in vivo proton-MRS study of HIV—associated dementia and its relationship to age. Neuroimage 23: 1336–1347.

    Article  CAS  PubMed  Google Scholar 

  • Chong WK, Paley M, Wilkinson ID, Hall-Craggs MA, Sweeney B, Harrison MJ, Miller RF, Kendall BE (1994). Localized cerebral proton MR spectroscopy in HIV infection and AIDS. AJNR Am J Neuroradiol 15: 21–25.

    CAS  PubMed  Google Scholar 

  • Chong WK, Sweeney B, Wilkinson ID, Paley M, Hall-Craggs MA, Kendall BE, Shepard JK, Beecham M, Miller RF, Weller IV, et al (1993). Proton spectroscopy of the brain in HIV infection: correlation with clinical, immunologic, and MR imaging findings. Radiology 188: 119–124.

    CAS  PubMed  Google Scholar 

  • Cohen J, Cohen P (1983). Applied multiple regression/correlation analysis for the behavioral sciences. Hillsdale, NJ: Lawrence Erlbaum.

    Google Scholar 

  • Davidson C, Gow AJ, Lee TH, Ellinwood EH (2001). Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Res Brain Res Rev 36: 1–22.

    CAS  PubMed  Google Scholar 

  • Demougeot C, Garnier P, Mossiat C, Bertrand N, Giroud M, Beley A, Marie C (2001). N-acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its relevance to studies of acute brain injury. J Neurochem 77: 408–415.

    Article  CAS  PubMed  Google Scholar 

  • Eisch AJ, O’Dell SJ, Marshall JF (1996). Striatal and cortical NMDA receptors are altered by a neurotoxic regimen of methamphetamine. Synapse 22: 217–225.

    Article  CAS  PubMed  Google Scholar 

  • Ellis RJ, Childers ME, Cherner M, Lazzaretto D, Letendre S, Grant I (2003). Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy. J Infect Dis 188: 1820–1826.

    Article  PubMed  Google Scholar 

  • Ernst T, Chang L, Leonido-Yee M, Speck O (2000). Evidence for long-term neurotoxicity associated with methamphetamine abuse: a 1H MRS study. Neurology 54: 1344–1349.

    CAS  PubMed  Google Scholar 

  • Everall I, Salaria S, Roberts E, Corbeil J, Sasik R, Fox H, Grant I, Masliah E (2005). Methamphetamine stimulates interferon inducible genes in HIV infected brain. J Neuroimmunol 170: 158–171.

    Article  CAS  PubMed  Google Scholar 

  • First MB, Spitzer RL, Gibbon M, Williams JB (1996). Structured clinical interview for DSM-IV Axis I disorders. New York: Biometrics Research Department.

    Google Scholar 

  • Flora G, Lee YW, Nath A, Hennig B, Maragos W, Toborek M (2003). Methamphetamine potentiates HIV—1 Tat protein-mediated activation of redox-sensitive pathways in discrete regions of the brain. Exp Neurol 179: 60–70.

    Article  CAS  PubMed  Google Scholar 

  • Itoh K, Mehraein P, Weis S (2000). Neuronal damage of the substantia nigra in HIV—1 infected brains. Acta Neuropathol (Berl) 99: 376–384.

    Article  CAS  Google Scholar 

  • Jarvik JG, Lenkinski RE, Grossman RI, Gomori JM, Schnall MD, Frank I (1993). Proton MR spectroscopy of HIV—infected patients: characterization of abnormalities with imaging and clinical correlation. Radiology 186: 739–744.

    CAS  PubMed  Google Scholar 

  • Jernigan TL, Gamst AC, Archibald SL, Fennema-Notestine C, Mindt MR, Marcotte TD, Heaton RK, Ellis RJ, Grant I (2005). Effects of methamphetamine dependence and HIV infection on cerebral morphology. Am J Psychiatry 162: 1461–1472.

    Article  PubMed  Google Scholar 

  • Langford D, Adame A, Grigorian A, Grant I, McCutchan JA, Ellis RJ, Marcotte TD, Masliah E (2003). Patterns of selective neuronal damage in methamphetamine-user AIDS patients. J Acquir Immune Defic Syndr 34: 467–474.

    Article  CAS  PubMed  Google Scholar 

  • Laubenberger J, Haussinger D, Bayer S, Thielemann S, Schneider B, Mundinger A, Hennig J, Langer M (1996). HIV—related metabolic abnormalities in the brain: depiction with proton MR spectroscopy with short echo times. Radiology 199: 805–810.

    CAS  PubMed  Google Scholar 

  • Lee PL, Yiannoutsos CT, Ernst T, Chang L, Marra CM, Jarvik JG, Richards TL, Kwok EW, Kolson DL, Simpson D, Tang CY, Schifitto G, Ketonen LM, Meyerhoff DJ, Lenkinski RE, Gonzalez RG, Navia BA (2003). A multi-center 1H MRS study of the AIDS dementia complex: validation and preliminary analysis. J Magn Reson Imaging 17: 625–633.

    Article  PubMed  Google Scholar 

  • Lopez-Villegas D, Lenkinski RE, Frank I (1997). Biochemical changes in the frontal lobe of HIV—infected individuals detected by magnetic resonance spectroscopy. Proc Natl Acad Sci USA 94: 9854–9859.

    Article  CAS  PubMed  Google Scholar 

  • Maragos WF, Young KL, Turchan JT, Guseva M, Pauly JR, Nath A, Cass WA (2002). Human immunodeficiency virus-1 Tat protein and methamphetamine interact synergistically to impair striatal dopaminergic function. J Neurochem 83: 955–963.

    Article  CAS  PubMed  Google Scholar 

  • Marshall JF, O’Dell SJ, Weihmuller FB (1993). Dopamine-glutamate interactions in methamphetamine-induced neurotoxicity. J Neural Transm Gen Sect 91: 241–254.

    Article  CAS  PubMed  Google Scholar 

  • McLean MA, Woermann FG, Barker GJ, Duncan JS (2000). Quantitative analysis of short echo time (1)H-MRSI of cerebral gray and white matter. Magn Reson Med 44: 401–411.

    Article  CAS  PubMed  Google Scholar 

  • Meyerhoff DJ, Weiner MW, Fein G (1996). Deep gray matter structures in HIV infection: a proton MR spectroscopic study. AJNR Am J Neuroradiol 17: 973–978.

    CAS  PubMed  Google Scholar 

  • Moller HE, Vermathen P, Lentschig MG, Schuierer G, Schwarz S, Wiedermann D, Evers S, Husstedt IW (1999). Metabolic characterization of AIDS dementia complex by spectroscopic imaging. J Magn Reson Imaging 9: 10–18.

    Article  CAS  PubMed  Google Scholar 

  • Nordahl TE, Salo R, Natsuaki Y, Galloway GP, Waters C, Moore CD, Kile S, Buonocore MH (2005). Methamphetamine users in sustained abstinence: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry 62: 444–452.

    Article  PubMed  Google Scholar 

  • Nordahl TE, Salo R, Possin K, Gibson DR, Flynn N, Leamon M, Galloway GP, Pfefferbaum A, Spielman DM, Adalsteinsson E, Sullivan EV (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.

    Article  CAS  PubMed  Google Scholar 

  • Ohmori T, Abekawa T, Koyama T (1996). The role of glutamate in behavioral and neurotoxic effects of methamphetamine. Neurochem Int 29: 301–307.

    Article  CAS  PubMed  Google Scholar 

  • Paley M, Cozzone PJ, Alonso J, Vion-Dury J, Confort-Gouny S, Wilkinson ID, Chong WK, Hall-Craggs MA, Harrison MJ, Gili J, Rovira A, Capellades J, Rio J, Ocana I, Nicoli F, Dhiver C, Gastaut JL, Gastaut JA, Wicklow K, Sauter R (1996). A multicenter proton magnetic resonance spectroscopy study of neurological complications of AIDS. AIDS Res Hum Retroviruses 12: 213–222.

    Article  CAS  PubMed  Google Scholar 

  • Provencher SW (1993). Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30: 672–679.

    Article  CAS  PubMed  Google Scholar 

  • Reyes MG, Faraldi F, Senseng CS, Flowers C, Fariello R (1991). Nigral degeneration in acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 82: 39–44.

    Article  CAS  Google Scholar 

  • Rippeth JD, Heaton RK, Carey CL, Marcotte TD, Moore DJ, Gonzalez R, Wolfson T, Grant I (2004). Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons. J Int Neuropsychol Soc 10: 1–14.

    Article  CAS  PubMed  Google Scholar 

  • Robinson TE, Kolb B (1997). Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine. J Neurosci 17: 8491–8497.

    CAS  PubMed  Google Scholar 

  • Robinson TE, Kolb B (1999). Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur J Neurosci 11: 1598–1604.

    Article  CAS  PubMed  Google Scholar 

  • Schweinsburg BC, Taylor MJ, Alhassoon OM, Videen JS, Brown GG, Patterson TL, Berger F, Grant I (2001). Chemical pathology in brain white matter of recently detoxified alcoholics: a 1H magnetic resonance spectroscopy investigation of alcohol-associated frontal lobe injury. Alcohol Clin Exp Res 25: 924–934.

    Article  CAS  PubMed  Google Scholar 

  • Schweinsburg BC, Taylor MJ, Videen JS, Alhassoon OM, Patterson TL, Grant I (2000). Elevated myo-inositol in gray matter of recently detoxified but not long-term abstinent alcoholics: a preliminary MR spectroscopy study. Alcohol Clin Exp Res 24: 699–705.

    Article  CAS  PubMed  Google Scholar 

  • Sekine Y, Minabe Y, Kawai M, Suzuki K, Iyo M, Isoda H, Sakahara H, Ashby CR Jr, Takei N, Mori N (2002). Metabolite alterations in basal ganglia associated with methamphetamine-related psychiatric symptoms. A proton MRS study. Neuropsychopharmacology 27: 453–461.

    CAS  Google Scholar 

  • Simon SL, Richardson K, Dacey J, Glynn S, Domier CP, Rawson RA, Ling W (2002). A comparison of patterns of methamphetamine and cocaine use. J Addict Dis 21: 35–44.

    Article  PubMed  Google Scholar 

  • Soher BJ, Hurd RE, Sailasuta N, Barker PB (1996). Quantitation of automated single-voxel proton MRS using cerebral water as an internal reference. Magn Reson Med 36: 335–339.

    Article  CAS  PubMed  Google Scholar 

  • Stankoff B, Tourbah A, Suarez S, Turell E, Stievenart JL, Payan C, Coutellier A, Herson S, Baril L, Bricaire F, Calvez V, Cabanis EA, Lacomblez L, Lubetzki C (2001). Clinical and spectroscopic improvement in HIV—associated cognitive impairment. Neurology 56: 112–115.

    CAS  PubMed  Google Scholar 

  • Stephans SE, Yamamoto BK (1994). Methamphetamine-induced neurotoxicity: roles for glutamate and dopamine efflux. Synapse 17: 203–209.

    Article  CAS  PubMed  Google Scholar 

  • Suwanwelaa N, Phanuphak P, Phanthumchinda K, Suwanwela NC, Tantivatana J, Ruxrungtham K, Suttipan J, Wangsuphachart S, Hanvanich M (2000). Magnetic resonance spectroscopy of the brain in neurologically asymptomatic HIV—infected patients. Magn Reson Imaging 18: 859–865.

    Article  CAS  PubMed  Google Scholar 

  • Tarasow E, Wiercinska-Drapalo A, Kubas B, Dzienis W, Orzechowska-Bobkiewicz A, Prokopowicz D, Walecki J (2003). Cerebral MR spectroscopy in neurologically asymptomatic HIV—infected patients. Acta Radiol 44: 206–212.

    Article  CAS  PubMed  Google Scholar 

  • Taylor MJ, Alhassoon OM, Schweinsburg BC, Videen JS, Grant I (2000). MR spectroscopy in HIV and stimulant dependence HNRC Group. HIV Neurobehavioral Research Center. J Int Neuropsychol Soc 6: 83–85.

    Article  CAS  PubMed  Google Scholar 

  • Theodore S, Cass WA, Nath A, Steiner J, Young K, Maragos WF (2006). Inhibition of tumor necrosis factor-alpha signaling prevents human immunodeficiency virus-1 protein Tat and methamphetamine interaction. Neurobiol Dis 23: 663–668.

    Article  CAS  PubMed  Google Scholar 

  • Tracey I, Carr CA, Guimaraes AR, Worth JL, Navia BA, Gonzalez RG (1996). Brain choline-containing compounds are elevated in HIV—positive patients before the onset of AIDS dementia complex: a proton magnetic resonance spectroscopic study. Neurology 46: 783–788.

    CAS  PubMed  Google Scholar 

  • von Giesen HJ, Wittsack HJ, Wenserski F, Koller H, Hefter H, Arendt G (2001). Basal ganglia metabolite abnormalities in minor motor disorders associated with human immunodeficiency virus type 1. Arch Neurol 58: 1281–1286.

    Article  Google Scholar 

  • Wilkinson ID, Miller RF, Miszkiel KA, Paley MN, Hall-Craggs MA, Baldeweg T, Williams IG, Carter S, Newman SP, Kendall BE, Catalan J, Chinn RJ, Harrison MJ (1997). Cerebral proton magnetic resonance spectroscopy in asymptomatic HIV infection. AIDS 11: 289–295.

    Article  CAS  PubMed  Google Scholar 

  • Wilson JM, Kalasinsky KS, Levey AI, Bergeron C, Reiber G, Anthony RM, Schmunk GA, Shannak K, Haycock JW, Kish SJ (1996). Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Nat Med 2: 699–703.

    Article  CAS  PubMed  Google Scholar 

  • Yiannoutsos CT, Ernst T, Chang L, Lee PL, Richards T, Marra CM, Meyerhoff DJ, Jarvik JG, Kolson D, Schifitto G, Ellis RJ, Swindells S, Simpson DM, Miller EN, Gonzalez RG, Navia BA (2004). Regional patterns of brain metabolites in AIDS dementia complex. Neuroimage 23: 928–935.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Michael J. Taylor.

Additional information

This work was supported by DA12065 from the National Institute of Drug Abuse. The HIV Neurobehavioral Research Center (HNRC) is supported by Center award MH 62512 from NIMH.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taylor, M.J., Schweinsburg, B.C., Alhassoon, O.M. et al. Effects of human immunodeficiency virus and methamphetamine on cerebral metabolites measured with magnetic resonance spectroscopy. Journal of NeuroVirology 13, 150–159 (2007). https://doi.org/10.1080/13550280701194230

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280701194230

Keywords

Navigation