1999). However, there are no obvious microscopic white matter lesions in the cerebral hemispheres of uncomplicated alcoholics, and studies of lipid profiles have revealed only minor alterations (Harper and Kril, 1991; Olsson et al., 1996). An increase in the water content of frontal lobe white matter (Harper, 1998) suggests that the white matter shrinkage in this brain region may reflect demyelination. Consistent with this interpretation, expression of three genes encoding myelin proteins that are required for the highly ordered and compact structure of myelin and are specifically involved in stabilization and compaction of the myelin sheath was lower in the superior frontal cortex of human alcoholic subjects than controls (Lewohl et al., 2005). According to Harper (2009), neural loss may also result in axonal (Wallerian) degeneration and a permanent reduction in white matter volume (Harper et al., 1988). Thus, the pathophysiology of white matter disruption in alcoholics may involve changes in both myelination and axonal integrity (Harper et al., 2005).
