Decreased frontal lobe phosphocreatine levels in methamphetamine users.
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.
Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA. yh.sung@utah.edu
Young-Hoon
YH
Sung
Deborah A
DA
Yurgelun-Todd
Xian-Feng
XF
Shi
Douglas G
DG
Kondo
Kelly J
KJ
Lundberg
Erin C
EC
McGlade
Tracy L
TL
Hellem
Rebekah S
RS
Huber
Kristen K
KK
Fiedler
Renee E
RE
Harrell
Bethany R
BR
Nickerson
Seong-Eun
SE
Kim
Eun-Kee
EK
Jeong
Perry F
PF
Renshaw
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D000697:Central Nervous System Stimulants; D002540:Cerebral Cortex / Q000737:chemistry; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004522:Educational Status; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008694:Methamphetamine; D008875:Middle Aged; D010725:Phosphocreatine / Q000378:metabolism*; D010759:Phosphorus Isotopes; D012959:Socioeconomic Factors; D019966:Substance-Related Disorders / Q000378:metabolism; D055815:Young Adult
D000697:Central Nervous System Stimulants; D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D008694:Methamphetamine