Fourteen subjects (three men and 11 women), who fulfilled DSM-IV criteria for methamphetamine dependence, and 22 healthy volunteers (17 men and five women), had completed the MPQ within two weeks of a PET FDG study. The characteristics of the complete methamphetamine-dependent sample were described previously [8
]. In brief, the methamphetamine-dependent subjects were recruited from drug rehabilitation centers in the Los Angeles area; they used ≥0.5 g/day, at least 5 days/week, for ≥2 years and abstained from any drug use for ≥2 weeks prior to study entry.
Detailed medical and drug use histories, physical, neurological, and psychiatric evaluations were performed for all subjects, including blood test screenings and HIV testing (HIV serology was only performed for the methamphetamine-dependent subjects). Subjects were excluded for history of psychiatric or neurological disorder, history of head trauma, medical illness, and current or past history of dependence on drugs other than nicotine, caffeine, and methamphetamine (dependence on methamphetamine was exclusionary for the comparison subjects). No subject was taking medication at the time of the study, and a prescan urine test was done to ensure the absence of psychoactive drug use in all subjects. Written informed consent was obtained from the subjects after the procedures had been fully explained. The study was approved by the Institutional Review Boards at both Brookhaven National Laboratory and Harbor-UCLA Medical Center.
The psychometric properties of the MPQ, a factor-analytically developed 240-item instrument [6
], are within the well acceptable range. Alpha coefficients for the MPQ harm avoidance scale averaged 0.83 across four samples of college and community men and women. A 30-day test–retest stability coefficient was 0.88 for the harm avoidance scale and 0.89 for the constraint superfactor. External correlations were also high: 0.56 and 0.53 with trait ratings and 0.55 and 0.58 with heritability data, for the harm avoidance scale and constraint superfactor, respectively [6
The harm avoidance scale and constraint superfactor were highly correlated in both study groups (r = 0.82, p < 0.0001 for the comparison subjects and r = 0.75, p < 0.01 for the methamphetamine-dependent subjects). The harm avoidance scale and constraint superfactor also had similar correlations with the negative emotion (NEM) superfactor (r = −0.53, p < 0.0001 for harm avoidance with NEM; r = −0.54, p < 0.0001 for constraint with NEM across all subjects; these correlations were similar within each study group). There were no significant correlations between the harm avoidance scale or constraint superfactor and the positive emotion superfactor for any of the groups or across all subjects.
PET scans were performed with a CTI 931 scanner (Siemens, Knoxville, TN; 15 slices, spatial resolution: 6 × 6 × 6.5 mm full width at half maximum) in all but two subjects, who were scanned with a Siemens Exact HR+ scanner. Details on procedures for positioning, arterial and venous catheterization, quantification of radiotracer, and transmission and emission scans have been published [9
]. Briefly, one 20-min emission scan was taken 35 min after an i.v. injection of 4–6 mCi of FDG. During the study, subjects were kept lying in the PET camera with their eyes open; the room was dimly lit and noise was kept to a minimum. A nurse remained with the subjects throughout the procedure to ensure that the subjects did not fall asleep during the study.
Regions of interest were selected by using a previously published template that locates 115 non-overlapping regions of interest (ROIs) [9
]. In brief, we used small ROIs to minimize the contribution of partial volume effects on the metabolic values. The orbitofrontal gyrus averaged 0.7 cm3
. The size and orientation of the ROIs were the same in all subjects. Placement of the regions was determined by reference to an atlas of axial tomographic anatomy [10
] by an experienced investigator (G.J.W). Three ROIs in the frontal lobe 12 mm below an oblique plane, parallel to the canthomeatal line, were averaged to obtain measures for the orbitofrontal gyrus (). Global metabolism (average metabolism in the 15 planes scanned) was also obtained. Due to the large variability of the absolute regional metabolic measures, we computed ratios of the absolute regional to the global metabolic measures, thus obtaining relative regional measures of metabolism.
Location of the regions of interest used to assess metabolic activity in the orbitofrontal cortex.
Statistical analyses: The methamphetamine-dependent subjects were compared to the controls on select variables. Group differences in continuous variables were examined using unpaired Student’s t-tests (two-tailed). The corrected t statistic and degrees of freedom were used whenever Levene’s test for equality of variance was significant. For dichotomous variables, χ2 tests with Fisher’s exact statistic were used. Pearson product–moment correlation analyses were conducted between the MPQ variables and global and relative (normalized) brain metabolism in the orbitofrontal gyrus separately in each group. All correlations were one-tailed.