Global and local morphometric differences in recently abstinent methamphetamine-dependent individuals

Abstract

Methamphetamine (MA) is associated with behavioral and cognitive deficits that may be related to macrostructural abnormalities. Quantitative anatomical comparisons between controls and methamphetamine-dependent individuals have produced conflicting results. We examined local and global differences in brain structure in 61 abstinent methamphetamine-dependent individuals and 44 controls with voxel-based morphometry and tissue segmentation. We related regional differences in gray matter density and whole brain segmentation volumes to performance on a behavioral measure of impulsivity and group membership using multiple linear regression. Within the MA group, we related cortical and subcortical gray matter density to length of abstinence. Controls had greater density relative to MA in bilateral insula and left middle frontal gyrus. Impulsivity was higher in the MA group and, within all subjects, impulsivity was positively correlated with gray matter density in posterior cingulate cortex and ventral striatum and negatively correlated in left superior frontal gyrus. Length of abstinence from MA was associated with greater amygdalar density. Earlier age of first use of MA (in subjects who initiated use before age 21) was associated with smaller intracranial volume. The findings are consistent with multiple possible mechanisms including neuroadaptations due to addictive behavior, neuroinflammation as well as dopaminergic and serotonergic neurotoxicity.

Figure 1

A. Regions where cortical density for MA was significantly less than for CS, t-statistic corrected for multiple comparisons shown. B. The average cortical density in the significant voxels only in the left insula VOI circled are graphed for each subject, the means and standard errors are 0.72 ± 0.01 and 0.80 ± 0.02 for MA and CS, respectively (t⁽¹⁰³⁾ = 4.42, p <.0001).

Figure 2

A map of the regression coefficient for group membership after controlling for age and gender. CS > MA, red; MA > CS, blue. Green circles indicate significant regions shown in Figure 1, numbered by occurrence in Table 2.

Figure 3

A. Map of the significant t-statistic map for the regression coefficient of IMP, corrected for multiple comparisons. B. Average cortical density value in significant voxels within circled VOI vs IMP. Blue diamonds CS; red squares MA. Line (n = 105) represents the ordinary least squares fit (F(1,104) = 15.37, p < .001).

Figure 4

A map of the regression coefficient for IMP after controlling for age and gender. Positive correlations are shown in red, negative correlations are shown in blue. Green circles indicate significant regions shown in Figure 3, numbered by occurrence in Table 2.

Figure 5

A. Regions of significance for the t-statistic associated with the regression coefficient of ABS in MA group, corrected for multiple comparisons. B. Days of abstinence versus average cortical density in the significant voxels in right amygdalar/right putamen volume (circled). Line (n = 61) represents the ordinary least squares fit (F(1,60) = 21.81, p < .001).

Figure 6

A map of the regression coefficient for ABS after controlling for age and gender. Positive correlations are shown in red, negative correlations are shown in blue. Green circles indicate significant regions shown in Figure 5, numbered by occurrence in Table 2.

Figure 7

Square root of Age of First Use (AFU) vs Inverse Volumetric Scaling Factor (1/VSF). Smaller 1/VSF is equivalent to smaller head size. Pearson's r² is shown for the left (first stage) regression line.