White-matter abnormalities in brain during early abstinence from methamphetamine abuse

Abstract

Background: Previous studies revealed microstructural abnormalities in prefrontal white matter and corpus callosum of long-term abstinent chronic methamphetamine abusers. In view of the importance of the early abstinence period in treatment retention, we compared 23 methamphetamine-dependent subjects abstinent from methamphetamine for 7-13 days with 18 healthy comparison subjects. As certain metabolic changes in the brain first manifest after early abstinence from methamphetamine, it is also possible that microstructural white-matter abnormalities are not yet present during early abstinence.

Methods: Using diffusion tensor imaging at 1.5 T, fractional anisotropy (FA) was measured in prefrontal white matter at four inferior-superior levels parallel to the anterior commissure-posterior commissure (AC-PC) plane. We also sampled FA in the corpus callosum at the midline and at eight bilateral, fiber-tract sites in other regions implicated in effects of methamphetamine.

Results: The methamphetamine group exhibited lower FA in right prefrontal white matter above the AC-PC plane (11.9% lower; p = 0.007), in midline genu corpus callosum (3.9%; p = 0.019), in left and right midcaudal superior corona radiata (11.0% in both hemispheres, p's = 0.020 and 0.016, respectively), and in right perforant fibers (7.3%; p = 0.025). FA in left midcaudal superior corona radiata was correlated with depressive and generalized psychiatric symptoms within the methamphetamine group.

Conclusions: The findings support the idea that methamphetamine abuse produces microstructural abnormalities in white matter underlying and interconnecting prefrontal cortices and hippocampal formation. These effects are already present during the first weeks of abstinence from methamphetamine and are linked to psychiatric symptoms assessed during this period.

Fig. 1

DTI FA whole-brain color map of an experimental subject. In the left, an axial-oblique (at the AC–PC plane) section. The white box in left prefrontal white matter (PFWM) indicates the boundaries of a 3-mm deep 9 × 9-mm² slab across which FA values were sampled and averaged in postprocessing. A similar average was obtained for the right PFWM. In the right, a parasagittal section of the same color map depicts the position of the four parallel prefrontal white-matter slabs (white bars) located at the level of the AC–PC plane (C), 6 mm below (D), and 6 (B) and 9 (A) mm above. Left and right PFWM FA averages were obtained at each level

Fig. 2

Axial-oblique (parallel to AC–PC plane) DTI FA brain map at level of the upper lateral ventricles from a study subject. The same image is shown in both left and right. In the left, the green arrow indicates typical site of DTI voxel selection for the midcaudal cross section of the right superior corona radiata white-matter region. In the right, the green arrow indicates typical site for the caudal cross section of the right superior corona radiata

Fig. 3

Axial-oblique (parallel to AC–PC plane) DTI FA brain map at level of the basal ganglia from a selected subject. The same image is shown in all three panels. In the upper left, the green arrow indicates typical site of DTI voxel selection for the anterior limb of the right internal capsule white-matter tract. At the upper right, the arrow indicates the genu of the right internal capsule. At bottom left, the arrow indicates the posterior limb of the right internal capsule

Fig. 4

Key findings for FA obtained in right prefrontal white matter using the methods of Chung et al. (; left) and Ringman et al. (; right) in MA (solid diamonds) and age-matched HC (open squares) subjects. Group means given by horizontal bars. Mean FA of MA subjects was significantly below that of the HC group in an axial-oblique slab of right prefrontal white matter centered 6 mm above the anterior commissure–posterior commissure (AC–PC) plane. Lower FA of MA subjects than HC subjects at a midcaudal site along the superior portion of the right corona radiata indicates that this specific tract may be vulnerable to MA abuse

Fig. 5

Relationship of fractional anisotropy (FA) in left midcaudal corona radiata to psychiatric symptoms in MA subjects (solid diamonds). Symptoms were evaluated within 7 days of admission for supervised MA abstinence. Rather than the anticipated negative association, FA was significantly positively related to depressive symptoms (BDI score; r = 0.44, p = 0.038) and with generalized psychiatric symptoms (Brief Symptom Inventory Positive Symptom Total; r = 0.51, p = 0.014)