Effects of sleep deprivation on sleep homeostasis and restoration during methadone-maintenance: A [31]P MRS brain imaging study

Abstract

SUMMARYInsomnia afflicts many individuals, but particularly those in chronic methadone treatment. Studies examining sleep deprivation (SD) have begun to identify sleep restoration processes involving brain bioenergetics. The technique [31]P magnetic resonance spectroscopy (MRS) can measure brain changes in the high-energy phosphates: alpha-, beta-, and gamma-nucleoside triphosphate (NTP). In the present study, 21 methadone-maintained (MM) and 16 control participants underwent baseline (BL), SD (40 wakeful hrs), recovery1 (RE1), and recovery2 (RE2) study nights. Polysomnographic sleep was recorded each night and [31]P MRS brain scanning conducted each morning using a 4T MR scanner (dual-tuned proton/phosphorus headcoil). Interestingly, increases in total sleep time (TST) and sleep efficiency index (SEI) commonly associated with RE sleep were not apparent in MM participants. Analysis of methadone treatment duration revealed that the lack of RE sleep increases in TST and SEI were primarily exhibited by short-term MM participants (methadone<12 months), while RE sleep in long-term MM (methadone>12 months) participants was more comparable to control participants. Slow wave sleep increased during RE1, but there was no difference between MM and control participants. Spectral power analysis revealed that compared to control participants; MM participants had greater delta, theta, and alpha spectral power during BL and RE sleep.[31]P MRS revealed that elevations in brain beta-NTP (a direct measure of ATP) following RE sleep were greater in MM compared to control participants. Results suggest that differences in sleep and brain chemistry during RE in MM participants may be reflective of a disruption in homeostatic sleep function.

The Utility of Magnetic Resonance Spectroscopy for Understanding Substance Use Disorders

“…One study noted reduced levels of phosphocreatine found in the orbitofrontal and occipital cortices in heroin users initiating methadone maintenance therapy but not in a healthy comparison group (Silveri et al, 2004), whereas another study demonstrated no differences in concentrations of whole brain phosphocreatine in individuals on methadone maintenance therapy compared with healthy controls (Trksak et al, 2010). Length of methadone maintenance therapy might explain the discrepancy in these findings, as in one of the studies, methadone was recently initiated (Silveri et al, 2004), while in the other study, the duration of methadone maintenance ranged from 8 to 28 months (Trksak et al, 2010). Because of the limited number of MRS studies in opiate use, it is difficult to assess the impact of opiate use on the brain; however, the few published reports provide some evidence that there are differences in neurochemistry in opiate users starting opiate maintenance therapy in comparison to nonopiate users.…”

Response inhibition and psychomotor speed during methadone maintenance: impact of treatment duration, dose, and sleep deprivation

“…These data were collected as part of a larger study assessing effects of SD on sleep architecture (polysomnography) and brain bioenergetics (magnetic resonance spectroscopy) (Trksak et al, 2010). These previous analyses found no effect of methadone dose, but an effect of MM duration with long-term MM participants recovering from SD more similarly to HCs.…”

“…Finally, participants on a high dose of methadone would perform the most poorly, however after SD both high- and low-dose groups would perform at a similar level. These data were collected as part of a larger study to assess the effects of SD on sleep architecture and brain bioenergetics in MM participants (Trksak et al, 2010). …”

Sleep disturbances and pain among individuals with prescription opioid dependence

“…In a study of opioid naïve individuals, sleep architecture was significantly altered after a single opioid medication administration, with participants evidencing increases in the percentage of time spent in light sleep stages, and a marked reduction in the percentage of time spent in deep sleep stages (Dimsdale et al, 2007). Multiple mechanisms of action leading to disturbed sleep in those abusing opioids have been theorized, including decreased REM sleep (Lydic and Baghdoyan, 2005), altered GABA functioning (Watson et al, 2007), and lowered levels of adenosine (Trksak et al, 2010). Though sleep has become a focus of substance use research, no known studies to date have utilized actigraphy with a group of current PO dependent individuals.…”