Glutamatergic neurometabolites during early abstinence from chronic methamphetamine abuse

Joseph O'Neill; Marc C Tobias; Matthew Hudkins; Edythe D London

doi:10.1093/ijnp/pyu059

Glutamatergic neurometabolites during early abstinence from chronic methamphetamine abuse

Int J Neuropsychopharmacol. 2014 Oct 31;18(3):pyu059. doi: 10.1093/ijnp/pyu059.

Authors

Joseph O'Neill¹, Marc C Tobias², Matthew Hudkins², Edythe D London²

Affiliations

¹ 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.
² 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.

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.

Keywords: abstinence; depression; glutamate; magnetic resonance spectroscopy; methamphetamine.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Amphetamine-Related Disorders / metabolism*
Brain / metabolism*
Case-Control Studies
Female
Glutamic Acid / metabolism*
Glutamine / metabolism*
Humans
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Male
Protons
Statistics as Topic
Substance-Related Disorders / metabolism*
Young Adult

Substances

Protons
Glutamine
Glutamic Acid

Abstract

Publication types

MeSH terms

Substances

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