title: Glutamatergic neurometabolites during early abstinence from chronic methamphetamine abuse.
abstract: BACKGROUND
  The acute phase of abstinence from methamphetamine abuse is critical for rehabilitation success. Proton magnetic resonance spectroscopy has detected below-normal levels of glutamate+glutamine in anterior middle cingulate 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.
  
  
  METHODS
  We measured glutamate+glutamine in additional cortical regions (midline posterior cingulate, midline precuneus, and bilateral inferior frontal cortex) putatively affected by methamphetamine. We examined the relationship between glutamate+glutamine 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.
  
  
  RESULTS
  In the methamphetamine group, small but significant (5-15%, P<.05) decrements (vs control) in glutamate+glutamine were observed in posterior cingulate, precuneus, and right inferior frontal cortex; glutamate+glutamine in posterior cingulate was negatively correlated (P<.05) with years of methamphetamine abuse. The Beck Depression Inventory score was negatively correlated (P<.005) with glutamate+glutamine in right inferior frontal cortex.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Child and Adolescent Psychiatry (Drs O'Neill, Tobias, and Hudkins), and Department of Psychiatry and Biobehavioral Sciences (Drs O'Neill and London), Semel Institute for Neuroscience, and Department of Molecular and Medical Pharmacology (Dr London), and Brain Research Institute (Dr London), University of California, Los Angeles, CA joneill@mednet.ucla.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Neill
authors.affiliation: Division of Child and Adolescent Psychiatry (Drs O'Neill, Tobias, and Hudkins), and Department of Psychiatry and Biobehavioral Sciences (Drs O'Neill and London), Semel Institute for Neuroscience, and Department of Molecular and Medical Pharmacology (Dr London), and Brain Research Institute (Dr London), University of California, Los Angeles, CA.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Tobias
authors.affiliation: Division of Child and Adolescent Psychiatry (Drs O'Neill, Tobias, and Hudkins), and Department of Psychiatry and Biobehavioral Sciences (Drs O'Neill and London), Semel Institute for Neuroscience, and Department of Molecular and Medical Pharmacology (Dr London), and Brain Research Institute (Dr London), University of California, Los Angeles, CA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hudkins
authors.affiliation: Division of Child and Adolescent Psychiatry (Drs O'Neill, Tobias, and Hudkins), and Department of Psychiatry and Biobehavioral Sciences (Drs O'Neill and London), Semel Institute for Neuroscience, and Department of Molecular and Medical Pharmacology (Dr London), and Brain Research Institute (Dr London), University of California, Los Angeles, CA.
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011522:Protons; D013223:Statistics as Topic; D019966:Substance-Related Disorders / Q000378:metabolism*; D055815:Young Adult
chemical_list: D011522:Protons; D005973:Glutamine; D018698:Glutamic Acid
keywords: abstinence; depression; glutamate; magnetic resonance spectroscopy; methamphetamine