Citation

Sung YH, Yurgelun-Todd DA, Shi XF, Kondo DG, Lundberg KJ, McGlade EC, Hellem TL, Huber RS, Fiedler KK, Harrell RE, Nickerson BR, Kim SE, Jeong EK, Renshaw PF. Drug Alcohol Depend. 2013; 129(1-2): 102-109.

Affiliation

Department of Psychiatry, University of Utah, Salt Lake City, UT, USA; The Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City, UT, USA. Electronic address: yh.sung@utah.edu.

Copyright

(Copyright © 2013, Elsevier Publishing)

DOI

10.1016/j.drugalcdep.2012.09.015

PMID

23084413

Abstract

BACKGROUND: Mitochondria-related mechanisms have been suggested to mediate methamphetamine (METH) toxicity. However, changes in brain energetics associated with high-energy phosphate metabolism have not been investigated in METH users. Phosphorus-31 ((31)P) magnetic resonance spectroscopy (MRS) was used to evaluate changes in mitochondrial high energy phosphates, including phosphocreatine (PCr) and β-nucleoside triphosphate (β-NTP, primarily ATP in brain) levels. We hypothesized that METH users would have decreased high-energy PCr levels in the frontal gray matter. METHODS: Study participants consisted of 51 METH (age=32.8±6.7) and 23 healthy comparison (age=31.1±7.5) subjects. High-energy phosphate metabolite levels were compared between the groups and potential gender differences were explored. RESULTS: METH users had lower ratios of PCr to total pool of exchangeable phosphate (PCr/TPP) in the frontal lobe as compared to the healthy subjects (p=.001). The lower PCr levels in METH subjects were significantly associated with lifetime amount of METH use (p=.003). A sub-analysis for gender differences revealed that female METH users, who had lower daily amounts (1.1±1.0g) of METH use than males (1.4±1.7g), had significantly lower PCr/TPP ratios than male METH users, controlling for the amount of METH use (p=.02). CONCLUSIONS: The present findings suggest that METH compromises frontal lobe high-energy phosphate metabolism in a dose-responsive manner. Our findings also suggest that the abnormality in frontal lobe high-energy phosphate metabolism might be more prominent in female than in male METH users. This is significant as decreased PCr levels have been associated with depressive symptoms, and poor responses to antidepressant treatment have been reported in those with decreased PCr levels.

Language: en