Anterior cingulate proton spectroscopy glutamate levels differ as a function of smoking cessation outcome

Abstract

Background Cigarette smoking is the leading preventable cause of death. Unfortunately, the majority of smokers who attempt to quit smoking relapse within weeks. Abnormal dorsal anterior cingulate cortex (dACC) function may contribute to tobacco smoking relapse vulnerability. Growing evidence suggests that glutamate neurotransmission is involved in mediating nicotine dependence. We hypothesized that prior to a cessation attempt, dACC glutamate levels would be lower in relapse vulnerable smokers. Methods Proton magnetic resonance spectra (MRS) were obtained from dACC and a control region, the parieto-occipital cortex (POC), using two-dimensional J-resolved MRS at 4 Tesla and analyzed using LCModel. Nine nicotine-dependent women were scanned prior to making a quit attempt. Subjects then were divided into two groups; those able to maintain subsequent abstinence aided by nicotine replacement therapy (NRT) and those who slipped while on NRT (smoked any part of a cigarette after attaining at least 24 hours of abstinence). Results Slip subjects exhibited significantly reduced dACC MRS glutamate (Glu/Cr) levels (p<0.03) compared to abstinent subjects. This effect was not observed in the POC control region. Conclusions Our preliminary findings suggest that dACC Glu levels as measured with MRS may help identify and/or be a biomarker for relapse vulnerable smokers. Future research following up on these findings may help clarify the role of dACC Glu in smoking dependence that may lead to new treatment strategies.

Lower Glial Metabolite Levels in Brains of Young Children with Prenatal Nicotine Exposure

“…They also did not find group difference on brain CHO between smokers and non-smokers. Contrary to this study and to our study of young children with PNE, another preliminary study of nine women who participated in a smoking cessation program found that those who “slipped” and resumed smoking had lower brain glutamate/tCr level in the ACC, but also normal NAA level, compared to those who remained abstinent (Mashhoon et al 2011). Given the small sample size of these studies and the difference in the developing brain of young children compared to the matured adult brain, the effects of nicotine on neurometabolites are not comparable between these populations.…”

“…However, unlike the children with prenatal methamphetamine exposure (Chang et al 2009), our children with PNE did not show higher levels of neuronal marker NAA, but had trends for lower levels in the thalamus and the basal ganglia. NAA was found to be lower in the frontal white matter of adult smokers who were also recovering alcoholics (Wang et al 2009) but not in the other studies of adult men or women smokers (Mason et al 2006; Mashhoon et al 2011). Therefore, our findings are consistent with studies that found no evidence of neuronal loss (cell numbers in adult rats) in hippocampus or cerebellum after exposed to nicotine prenatally or both prenatally and postnatally (Chen et al 2006).…”

Dorsal anterior cingulate glutamate is associated with engagement of the default mode network during exposure to smoking cues

“…Our prior work suggests that a relationship exists between dACC Glu and treatment outcome as individuals who are more likely to relapse have reduced dACC Glu (Mashhoon et al, 2011). These findings are somewhat in contrast to our current work, which suggests higher dACC Glu enhances self-relevant processing of smoking cues, which could be considered a risk factor for relapse.…”

Acute Shift in Glutamate Concentrations Following Experimentally Induced Panic with Cholecystokinin Tetrapeptide—A 3T-MRS Study in Healthy Subjects

“…Finally, the present study did not control for the genetic background, eg, variation in the NMDA 2B receptor gene (GRIN2B), which has been shown to influence ACC Glx concentration (Arnold et al, 2009). Also, smoking or smoking cessation impacting anterior cingulate proton spectroscopy glutamate levels were not considered as potentially confounding factors (Mashhoon et al, 2011).…”