Preliminary evaluation of a model of stimulant use, oxidative damage and executive dysfunction

Background: Illicit stimulant use increases oxidative stress and oxidative stress has been found to be associated with deficits in memory, attention and problem-solving. Objective: To test a model of the association among oxidative DNA damage, a severe form of oxidative stress, and stimulant use, executive function and stimulant-use outcomes. Methods: Six sites evaluating 12-step facilitation for stimulant abusers obtained peripheral blood samples from methamphetamine-dependent (n=45) and cocaine-dependent (n=120) participants. The blood samples were submitted to a comet assay to assess oxidative DNA damage. Executive Dysfunction was assessed with the Frontal Systems Behavior Scale (FrSBe), which is a reliable and valid self-report assessment of executive dysfunction, disinhibition and apathy. Stimulant-use measures included self-reported stimulant use and stimulant urine drug screens (UDS). Results: While more recent cocaine use (<30 days abstinence) was associated with greater oxidative DNA damage (W=2.4, p<0.05, d=0.36), the results did not support the hypothesized relationship between oxidative DNA damage, executive dysfunction and stimulant use outcomes for cocaine-dependent patients. Support for the model was found for methamphetamine-dependent patients, with oxidative DNA damage significantly greater in methamphetamine-dependent patients with executive dysfunction (W=2.2, p<0.05, d=0.64) and with executive dysfunction being a significant mediator of oxidative DNA damage and stimulant use during active treatment (ab=0.089, p<0.05). As predicted, neither disinhibition nor apathy were significant mediators of oxidative damage and future stimulant use. Conclusion: These findings provide preliminary support for a model in which oxidative damage resulting from methamphetamine use results in executive dysfunction, which in turn increases vulnerability to future stimulant use.