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Neurobiology of Disease

Structural Abnormalities in the Brains of Human Subjects Who Use Methamphetamine

Paul M. Thompson, Kiralee M. Hayashi, Sara L. Simon, Jennifer A. Geaga, Michael S. Hong, Yihong Sui, Jessica Y. Lee, Arthur W. Toga, Walter Ling and Edythe D. London
Journal of Neuroscience 30 June 2004, 24 (26) 6028-6036; DOI: https://doi.org/10.1523/JNEUROSCI.0713-04.2004
Paul M. Thompson
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Kiralee M. Hayashi
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Sara L. Simon
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Jennifer A. Geaga
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Michael S. Hong
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Yihong Sui
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Jessica Y. Lee
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Arthur W. Toga
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Walter Ling
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Edythe D. London
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  •   Figure 1.
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    Figure 1.

    Gray-matter differences on the medial brain surface. Group difference maps (c) show mean percentage differences in gray-matter volumes between the control group average (a) and the methamphetamine group average (b), according to the color bar. The significance of these reductions is plotted in d as a map of p values. The cingulate gyrus shows highly significant gray-matter deficits (red colors; p < 0.034, corrected), whereas other brain regions are comparatively spared (blue colors). e is from London et al. (2004) (reprinted with permission). It shows the locations of MA (n = 17) and control (n = 18) group differences in relative regional cerebral metabolic glucose rate, assessed with PET. This PET sample partially overlaps with the current sample assessed with MRI. Briefly, in e, statistical parametric maps reveal regions in which the MA group has greater (red colors) or lesser (blue colors) glucose metabolism. Colors superimposed on a gray-scale MRI template indicate areas in which the significance of the group difference was t ≥ 1.69 (p = 0.049). The region of greatest gray-matter deficit (b, d) is in the right hemisphere posterior cingulate cortex (pCING), and so is the region of greatest metabolic increase in the MA group (e). This suggests an anatomical congruence of the MRI-based deficits with metabolic differences observed with PET. igACC and pgACC denote the inferior and perigenual anterior cingulate cortex, respectively. CTL, Control; R hem, right hemisphere; L hem, left hemisphere.

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    Figure 2.

    Gray-matter differences on the lateral brain surfaces. The mean reduction in gray matter in the MA group, relative to healthy controls, is expressed as a percentage and shown color-coded (blue colors, no reduction; red colors, greater reduction). In the left medial wall (a) and right-lateral (b) and left-lateral (c) brain surfaces, gray-matter differences are not pronounced. The significance of these differences is plotted in d-f. Differences were not significant after correction for multiple comparisons.

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    Figure 3.

    Comparison of brain structure volumes in MA abusers and healthy controls (CTL). Means and SE measures (error bars) are shown for the volumes of the hippocampus (a), frontal horn of the lateral ventricles (b), total cerebral gray matter (GM) (c), and total cerebral white matter (WM) (d). MA abusers show reductions in hippocampal volumes without significant reductions in gray-matter volume overall (c). They also show volume expansions in some ventricular regions (b) and increases in white-matter volume (d). e shows that mean gray-matter density in the cingulate gyrus is reduced in MA abusers (by 11.3%; p < 0.034), erasing the normal right > left asymmetry in gray-matter density that is found here and has been documented previously in healthy subjects. In agreement with the maps, this deficit pattern is not found in the adjacent medial frontal cortex.

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    Figure 4.

    Hippocampal atrophy in MA abusers is linked with poorer memory performance. Each individual's hippocampus is traced in coronal MRI sections (a) and converted to a mesh surface representation (b) in which the radial size of the hippocampus is measured from a centerline and plotted in color on the surface to index radial atrophy. Arrows in b represent vectors from the centerline to various points on the hippocampal surface. These meshes are averaged across subjects (c), and atrophy relative to the control mean is computed at each surface grid point (d). Shown in millimeters in e and f, the average radial size of the hippocampus in MA abusers (e) is smaller in some regions [red colors in g] than corresponding regions in healthy controls (f). h shows hippocampal regions (in red colors) in which word-recall performance is significantly linked with radial atrophy.

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    Table 1.

    Characteristics of research participants

    Controls (n = 21) MA abusers (n = 22)
    Age (years)a 31.9 (1.47) 35.3 (1.66)
    Gender (males/females) 10/11 15/7
    Education (years)a 15.2 (0.50) 12.8 (0.42)*
    Mother's education (years)a,b* 14.2 (0.48) 13.0 (0.68)
    Race
    Caucasian (non-Hispanic) 14 13
    Caucasian (Hispanic) 3 5
    African American 3 2
    Asian 1 2
    Handedness (right handed)c 16 17
    • ↵ a Data shown are means (SEM); n = 21 for controls; n = 22 for MA abusers.

    • ↵ b n = 20 for controls.

    • ↵ c Handedness was determined according to the Lateral Preference Pattern Assignment subtest of the Physical and Neurological Examination for Soft Signs (Denckla, 1985). To qualify as right handed, a participant had to write and to perform all or all but 1 of 11 items other than writing with the right hand.

    • ↵* Significantly different from controls; p <0.001 by Student's t test.

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    Table 2.

    Self-reported drug use a

    Controls (n = 21) MA abusers (n = 22)
    Methamphetamine use
    Duration (year) 10.5 (1.09); n = 21
    Average (gm/week) 3.44 (0.79); n = 19
    Days used in last 30 d 18.9 (1.75); n = 21
    Age of first use (year) 26.1 (1.77); n = 12
    Tobacco smokers
    (>5 cigarettes/d) n = 2 n = 15*
    Marijuana use
    Days used in last 30 d 0.14 (0.08); n = 21 2.38 (0.91);** n = 21
    Alcohol use
    Days used in last 30 d 2.38 (0.69); n = 21 3.24 (0.85); n = 21
    • ↵ a Data shown are means (SEM) of self-reported drug use from an intake questionnaire, a drug-use survey, and the Addiction Severity Index (McLellan et al., 1992).

    • ↵* Significantly different from controls by Pearson ϰ2 analysis.

    • ↵** Significantly different from control group; p <0.05 by Student's t test.

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    Table 3.

    Self reports of mood and feeling state a

    Control subjects (n = 21) MA abusers (n = 22)
    Beck Depression Inventory
    Sample size 20 22
    Mean score 1.25 (1.25) 9.77 (1.89)b*
    Mean days abstinent (SD) 6.64 (5.2)
    Spielberger State-Trait Anxiety Inventory
    Sample size 15 15
    State anxiety score 31.4 (3.77) 38.67 (2.64)**
    Trait anxiety score 31.9 (2.41) 38.7 (2.63)***
    • ↵ a Data are expressed as means (SEM). Beck Depression Inventory scores range from 0 to 63. Spielberger State-Trait Anxiety Inventory scores are reported as the sum of 20 questions ranking anxiety on a scale of 1-4.

    • ↵ b Beck Depression Inventory scores were closely correlated with the days of abstinence at time of assessment; p < 0.05 by regression.

    • ↵* Significantly different from controls; p < 0.0005 by Student's t test.

    • ↵** Not significantly different from controls; p = 0.0506.

    • ↵*** Significantly different from controls; p < 0.001 by Student's t test.

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The Journal of Neuroscience: 24 (26)
Journal of Neuroscience
Vol. 24, Issue 26
30 Jun 2004
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Structural Abnormalities in the Brains of Human Subjects Who Use Methamphetamine
Paul M. Thompson, Kiralee M. Hayashi, Sara L. Simon, Jennifer A. Geaga, Michael S. Hong, Yihong Sui, Jessica Y. Lee, Arthur W. Toga, Walter Ling, Edythe D. London
Journal of Neuroscience 30 June 2004, 24 (26) 6028-6036; DOI: 10.1523/JNEUROSCI.0713-04.2004

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Structural Abnormalities in the Brains of Human Subjects Who Use Methamphetamine
Paul M. Thompson, Kiralee M. Hayashi, Sara L. Simon, Jennifer A. Geaga, Michael S. Hong, Yihong Sui, Jessica Y. Lee, Arthur W. Toga, Walter Ling, Edythe D. London
Journal of Neuroscience 30 June 2004, 24 (26) 6028-6036; DOI: 10.1523/JNEUROSCI.0713-04.2004
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