Decreased frontal lobe phosphocreatine levels in methamphetamine users

Abstract

BACKGROUND Mitochondria-related mechanisms have been suggested to mediate methamphetamine (METH) toxicity. However, changes in brain energetics associated with highenergy phosphate metabolism have not been investigated in METH users. Phosphorus-31 (31P) 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=0.001). The lower PCr levels in METH subjects were significantly associated with lifetime amount of METH use (p=0.003). A sub-analysis for gender differences revealed that female METH users, who had lower daily amounts (1.1±1.0 gram) of METH use than males (1.4±1.7 gram), had significantly lower PCr/TPP ratios than male METH users, controlling for the amount of METH use (p=0.02). 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.

Hippocampal volume reduction in female but not male recent abstinent methamphetamine users

“…For example, an animal study found that altered hippocampal integrity by even modest doses of MA could account for pronounced brain pathology linked to MA abuse (12). Another human imaging study reported that MA compromised frontal lobe high-energy phosphate metabolism in a dose-responsive manner, and also suggested that this abnormality might be more prominent in female than in male MA users (32). …”

Preliminary Psychometric Evaluation of the Hamilton Depression Rating Scale in Methamphetamine Dependence

“…When screened for study eligibility, the Structured Clinical Interview for DSM-IV Disorders (SCID-IV; Sung et al, 2013; or the Psychiatric Research Instrument for Substance and Mental Disorders (PRISM; ClinicalTrials.gov ID NCT02568878 and NCT02192931) and the 17-item HAM-D were administered. Data on demographics, HAM-D, SCID-IV, and PRISM diagnosis (MDD or no MDD) were used in the current study.…”

“…Trained study personnel administered the SCID-IV (Sung et al, 2013; or PRISM (ClinicalTrials.gov ID NCT02568878 and NCT02192931) after written informed consent was obtained. Participants meeting SCID-IV or PRISM criteria for study inclusion completed the remaining screening procedures, including the HAM-D. A waiver of informed consent was issued by both IRBs for the current analysis, as data were collected retrospectively.…”

“…Data were collected at screening visits from four separate studies (see Sung et al, 2013;ClinicalTrials.gov ID NCT02568878 and NCT02192931). Three studies required participants to meet Diagnostic and Statistical Manual (DSM)-IV criteria (American Psychiatric Association, 2000) for current methamphetamine abuse or dependence (Sung et al, 2013;ClinicalTrials.gov ID NCT02568878 and NCT02192931) and one for methamphetamine abuse or dependence within the last 12 months . Further, three studies ; ClinicalTrials.gov ID NCT02568878 and NCT02192931) required participants to meet DSM-IV criteria for MDD with a screening HAM-D score of 15 or 16 (ClinicalTrials.gov ID NCT02568878 and NCT02192931).…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…Furthermore, magnetic resonance spectroscopy has been employed to detect changes in chemical markers, such as N-acetylaspartate, choline, creatine, and phosphocreatine, putatively reflecting abnormalities in neuronal cell membrane integrity or metabolism (Panenka et al, 2013). Decreases in phosphocreatine and correlations between N-acetylaspartate/creatine ratio and verbal memory performance have been reported in METH and MDMA users, respectively (Reneman et al, 2001b;Sung et al, 2013).…”