Daily and intermittent smoking are associated with low prefrontal volume and low concentrations of prefrontal glutamate, creatine, myo‐inositol, and N‐acetylaspartate

Abstract

Cigarette smoking is still the largest contributor to disease and death worldwide. Successful cessation is hindered by decreases in prefrontal glutamate concentrations and gray matter volume due to daily smoking. Because nondaily, intermittent smoking also contributes greatly to disease and death, understanding whether infrequent tobacco use is associated with reductions in prefrontal glutamate concentrations and gray matter volume may aid public health. Eighty‐five young participants (41 nonsmokers, 24 intermittent smokers, 20 daily smokers, mean age ~23 years old), underwent 1H‐magnetic resonance spectroscopy of the medial prefrontal cortex, as well as structural magnetic resonance imaging (MRI) to determine whole‐brain gray matter volume. Compared with nonsmokers, both daily and intermittent smokers exhibited lower concentrations of glutamate, creatine, N‐acetylaspartate, and myo‐inositol in the medial prefrontal cortex, and lower gray matter volume in the right inferior frontal gyrus; these measures of prefrontal metabolites and structure did not differ between daily and intermittent smokers. Finally, medial prefrontal metabolite concentrations and right inferior frontal gray matter volume were positively correlated, but these relationships were not influenced by smoking status. This study provides the first evidence that both daily and intermittent smoking are associated with low concentrations of glutamate, creatine, N‐acetylaspartate, and myo‐inositol and low gray matter volume in the prefrontal cortex. Future tobacco cessation efforts should not ignore potential deleterious effects of intermittent smoking by considering only daily smokers. Finally, because low glutamate concentrations hinder cessation, treatments that can normalize tonic levels of prefrontal glutamate, such as N‐acetylcysteine, may help intermittent and daily smokers to quit.

The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study

“…Furthermore, in the healthy volunteer group, we found that Glu/Cr levels were significantly lower in smokers. Previous studies have shown that smokers display lower cortical glutamate levels than non-smokers [64,65]. Thus, our results may be confounded by differences in smoking levels across groups.…”

Effects of Cigarette Smoking on Resting-State Functional Connectivity of the Nucleus Basalis of Meynert in Mild Cognitive Impairment

“…Thus, our result that showed decreased rsFC between the NBM and PFC could potentially reflect the cholinergic dysfunction by cigarette smoking, which might also explain the working memory and attention decline in healthy smokers observed by previous studies ( Chamberlain et al, 2012 ; Zhang et al, 2016 ). Previous findings in healthy smokers suggested that smoking was associated with reduced brain volumes ( Gallinat et al, 2006 ; Fritz et al, 2014 ) or MR spectroscopy markers of neuronal viability ( Durazzo et al, 2016 ; Faulkner et al, 2020 ), particularly in the PFC. In addition, rsfMRI studies ( Janes et al, 2012 ) also demonstrated that PFC network interactions might serve as biomarkers for nicotine dependence severity and treatment efficacy.…”

Relationship between depression, prefrontal creatine and grey matter volume

“…Spectra were analysed using LCModel 6.3-1L, with a basis set consisting of 19 simulated spectra, as in Morgenroth et al (2019) and Faulkner et al (2021) (for the full basis set, see Supplementary Materials ). This basis set was simulated using FID appliance (FID-A) ( Simpson et al, 2017 ) for TE = 8.5 ms, magnetic field strength = ~3 T and assuming ideal radiofrequency pulses.…”

“…Outer volume suppression slabs were applied 5 mm from the edge of each side of the voxel (six slabs in total), both to suppress signals originating outside of the right medial prefrontal voxel of interest, and to minimize motion artefact effects on spectra within the voxel. Spectra were analysed using LCModel 6.3-1L, with a basis set consisting of 19 simulated spectra, as in Morgenroth et al (2019) and Faulkner et al (2021) (for the full basis set, see Supplementary Materials). This basis set was simulated using FID appliance (FID-A) (Simpson et al, 2017) for TE = 8.5 ms, magnetic field strength = ~3 T and assuming ideal radiofrequency pulses.…”

“… Kumar et al, 2002 ), on the basis that creatine was considered to be stable within regions of interest and across individuals ( Li et al, 2003 ). However, prefrontal creatine is influenced by a range of factors, including cigarette smoking ( Durazzo et al, 2016 ; Faulkner et al, 2021 ), cocaine use ( Chang et al, 1997 ), cannabis use ( Prescot et al, 2011 ), anxiety ( Yue et al, 2012 ) and schizophrenia ( Öngür et al, 2009 ), and can be influenced by other pathological conditions such as hepatic encephalopathy ( Braissant et al, 2019 ), and has been shown to be almost absent in the brains of patients with cerebral creatine deficiency syndromes (e.g. Rackayova et al, 2017 ).…”