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

Abstract

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.

Trial registration: ClinicalTrials.gov identifier: NCT00628927.

• Executive function
• oxidative damage
• stimulant-dependence

Declarations of interest

All authors declare that they have no conflicts of interest.

This study was supported by the following grants from the National Institute on Drug Abuse (NIDA) Clinical Trials Network: U10-DA013036 to Oregon Health and Science University (Dr. McCarty); U10-DA013732 to the University of Cincinnati (Drs. Somoza/Winhusen); U10-DA013720 to the University of Miami School of Medicine (Dr. Szapocznik); U10-DA020024 to the University of Texas Southwestern Medical Center (Dr. Trivedi); and U10-DA013714 to the University of Washington (Dr. Donovan). The data and safety monitoring board (DSMB) of the Center Clinical Trials Network (CCTN) of the National Institute on Drug Abuse (NIDA) provided guidance and final approval for the study design. The director and deputy director of the CCTN, the DSMB of the CCTN and a quality assurance subcontractor to the CCTN monitored study conduct, data collection and data management. A subcontractor to the CCTN was responsible for data management. The publications committee of the Clinical Trials Network (CTN) gave final approval of the analysis and interpretation of the data and approved the manuscript.

ClinicalTrials.gov Identifier: NCT00628927