Gray-Matter Volume in Methamphetamine Dependence: Sources of Variability and Behavioral Relevance
There are currently no approved medications for the treatment of methamphetamine dependence, and the efficacy of psychosocial interventions for substance use disorders may be hindered by impairments in self-control or by excessive drug craving. Differences in brain structure between methamphetamine-dependent and healthy research participants have been reported; however, more work is necessary to determine how these differences arise and if they contribute to cognitive processes and behaviors that undermine treatment outcomes.
Although most methamphetamine-abusing individuals also smoke tobacco cigarettes, the effects of smoking on brain structure have not been distinguished from those of methamphetamine. Changes in brain structure with abstinence from methamphetamine have also been unexplored. Studies 1 and 2, therefore, attempted to account for effects of cigarette smoking and brief abstinence from methamphetamine on gray-matter volume in methamphetamine-dependent research participants. As cross-sectional studies cannot distinguish the extent to which structural abnormalities observed in individuals with methamphetamine dependence result from drug use or reflect neurobiological risk factors that predate drug use, the purpose of Study 3 was to determine how a chronic escalating dosing regimen of methamphetamine (or a saline, as a control) affects corticostriatal structure in vervet monkeys. Problematic drug use is associated with difficulty in exerting self-control over behaviors and drug craving, these difficulties may be a consequence of atypical morphometric characteristics that are exhibited by methamphetamine-dependent individuals. Study 4, therefore, examined the relationships between impulsivity, craving for methamphetamine, and gray-matter volume.
Study 1 demonstrated that cigarette smokers (control or methamphetamine-dependent) have smaller gray-matter volume in the orbitofrontal cortex and caudate nucleus than individuals with no prior history of cigarette or methamphetamine abuse. Individuals concurrently abusing methamphetamine and cigarettes also have smaller gray-matter volumes in frontal, parietal and temporal cortices than control participants (cigarette nonsmokers or smokers), and smaller gray-matter volume in insula than control nonsmokers. Findings from Study 1 provide new information about the regional distribution of gray-matter deficits associated with methamphetamine dependence and suggest that cigarette smoking or neurobiological risk factors that promote drug use may explain differences between methamphetamine-dependent and control participants. In Study 2, gray matter increased in inferior frontal, angular, and superior temporal gyri, precuneus, insula, occipital pole in individuals who maintained abstinence from methamphetamine for ~30 days, but not control participants; the cerebellum showed a decrease in volume with abstinence from methamphetamine. Study 3 provides the first evidence that exposure to a methamphetamine dosing regimen that resembles human use alters the structural integrity of the striatum and suggests that gray-matter abnormalities detected in human methamphetamine users are due, at least in part, to the pharmacological effects of drug experience. Finally, Study 4 shows that impulsivity is negatively associated with prefrontal gray-matter volume in methamphetamine-dependent individuals, while craving for methamphetamine is negatively associated with gray-matter volume in prefrontal, insular, temporal and occipital cortices. These findings suggest that individual differences in gray-matter volume may influence cognitive processes that play a critical role in substance use disorders. Interventions designed to induce neuroplastic changes in these brain regions may also produce corresponding changes in impulsivity or craving, potentially leading to improved treatment outcomes from methamphetamine dependence.