Factors underlying prefrontal and insula structural alterations in smokers

Abstract

Based upon previous reports of alterations in white matter integrity and gray matter density in smokers, we examined these markers in a large, well-matched sample of smokers and non-smokers. We further investigated the effect of heavy cigarette exposure by using pack-years and the effects of two relatively stable, highly heritable traits in smokers (Fagerström Test of Nicotine Dependence (FTND), a measure of severity of nicotine dependence so and Toronto Alexithymia Scale (TAS-20), measuring a stable personality trait related to smoking. Forty-eight nicotine-dependent subjects and 48 matched controls were included in the analyses, with smokers also subdivided into high/low dependence and high/low pack-years smokers. White matter integrity (fractional anisotropy (FA)) and gray matter density (voxel-based morphometry (VBM)) were measured and compared across groups. Gray matter density was lower in left prefrontal cortex (PFC) in high pack-years smokers and was inversely related to pack-years. In contrast, left insular cortex gray matter density was higher in smokers and associated with TAS-20 total score and with difficulty-identifying-feelings factor. Further, the most highly dependent smokers showed lower prefrontal FA, which was negatively correlated with FTND. There was no correlation between pack-years and FTND in our smoker population. These data suggest chronic tobacco use is correlated with prefrontal gray matter damage , while differences in insula gray matter and PFC white matter appear to reflect stable and heritable differences between smokers and non-smokers.

Cigarette Exposure, Dependence, and Craving Are Related to Insula Thickness in Young Adult Smokers

“…Effects of continued exposure may explain reports of lower gray-matter density in insula in adult smokers than nonsmokers (Gallinat et al, 2006;Zhang et al, 2011a). Although one study reports greater insula graymatter density in adult smokers than nonsmokers, left insula density was correlated with symptoms of alexithymia, but not with cigarette exposure or dependence (Zhang et al, 2011a), suggesting that other factors comorbid with smoking may contribute to the discrepant results. Differences in the methods used to index gray-matter integrity could also contribute to the heterogeneity in the literature.…”

“…Participants in this study began smoking in adolescence (mean age of initiation: 15.1 years old), and studies in animals indicate that exposure to nicotine during adolescence reduces the number of cells in the cerebral cortex by 5-10% as indexed by DNA content; however, DNA content was measured in fairly gross anatomical regions precluding determination of anatomical specificity and possibly masking the true magnitude of the effect (Slotkin, 2002). Effects of continued exposure may explain reports of lower gray-matter density in insula in adult smokers than nonsmokers (Gallinat et al, 2006;Zhang et al, 2011a). Although one study reports greater insula graymatter density in adult smokers than nonsmokers, left insula density was correlated with symptoms of alexithymia, but not with cigarette exposure or dependence (Zhang et al, 2011a), suggesting that other factors comorbid with smoking may contribute to the discrepant results.…”

“…The majority of studies in adult smokers find that individuals who smoke have lower regional gray-matter volume or density than nonsmokers in various brain regions (Brody et al, 2004;Morales et al, 2012) including the insular cortex (Gallinat et al, 2006;Zhang et al, 2011b). A single study, however, found greater gray-matter density in the left insula in smokers than nonsmokers (Zhang et al, 2011a). Inconsistencies in the literature may be attributable to the structural and functional heterogeneity of the insula.…”

Sex differences in impulsivity and brain volumes in methamphetamine users

“…However, previous studies have shown mixed results as to whether drug addiction was associated with increased or decreased gray matter volume in the insula. One study found that METH-dependent subjects had smaller left insula compared to CON (Morales et al, 2012), but another study found higher gray matter density in cigarette smokers in the left anterior insula compared to nonsmokers (Zhang et al, 2011). The inconsistencies could be due to differences in methodologies.…”

Non-invasive Brain Stimulation for the Treatment of Nicotine Addiction: Potential and Challenges

“…Besides physical health problems, chronic smoking causes functional and structural abnormalities in the brain [2][3][4][5]. However, most chronic smokers, including those who are willing to quit, find it difficult to become free of tobacco usage even with the help of intervention methods such as pharmacotherapy [6].…”