☆ 4.6 Article

The Effects of Chronic Cigarette Smoking on Gray Matter Volume: Influence of Sex

PLOS ONE (2014)

Journal

PLOS ONE

Volume 9, Issue 8, Pages -

Publisher

PUBLIC LIBRARY SCIENCE

DOI: 10.1371/journal.pone.0104102

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Funding

National Institutes of Health [R21 DA032022, R21 DA25882, R03 DA027098, R01 HL102119, R01 DA029845, R01 DA030394-01A1]
Pfizer Pharma
Institute for Translational Medicine and Therapeutics (ITMAT) of the University of Pennsylvania

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Abstract

Cigarette smoke contains nicotine and toxic chemicals and may cause significant neurochemical and anatomical brain changes. Voxel-based morphometry studies have examined the effects of smoking on the brain by comparing gray matter volume (GMV) in nicotine dependent individuals (NDs) to nonsmoking individuals with inconsistent results. Although sex differences in neural and behavioral features of nicotine dependence are reported, sex differences in regional GMV remain unknown. The current study examined sex differences in GMV in a large sample of 80 NDs (41 males) and 80 healthy controls (41 males) using voxel-based morphometry. Within NDs, we explored whether GMV was correlated with measures of cigarette use and nicotine dependence. High-resolution T1 structural scans were obtained from all participants. Segmentation and registration were performed in SPM8 using the optimized DARTEL approach. Covariates included age and an estimate of total global GMV. Differences were considered significant at p <= 0.001, with a whole brain FWE-corrected cluster probability of p<0.025. Among NDs compared to Controls less GMV was observed in the thalamus and bilateral cerebellum and greater GMV was observed in the bilateral putamen and right parahippocampus. Lower thalamic GMV was observed in both female and male NDs compared to Controls. Female NDs also had lower GMV in the left cerebellum and in the ventral medial and orbitofrontal cortices with no areas of greater GMV. Male NDs had lower GMV in bilateral cerebellum and greater GMV in bilateral parahippocampus and left putamen. Within male NDs, GMV in the left putamen was correlated with number of pack years. This study, conducted in a large cohort, contributes to our knowledge of brain morphology in nicotine addiction and provides additional evidence of sex-specific effects on GMV in NDs. Identifying brain vulnerabilities with respect to sex provides a methodological framework for personalized therapies to improve relapse rates for both sexes.

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Association between vmPFC gray matter volume and smoking initiation in adolescents

Shitong Xiang, Tianye Jia, Chao Xie, Wei Cheng, Bader Chaarani, Tobias J. Banaschewski, Gareth Barker, Arun L. W. Bokde, Christian Buechel, Sylvane Desrivieres, Herta Flor, Antoine A. Grigis, Penny Gowland, Ruediger Bruehl, Jean-Luc Martinot, Marie-Laure Paillere Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah H. Hohmann, Juliane N. Froehner, Michael Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Hugh Garavan, Gunter J. Schumann, Barbara W. Sahakian, Trevor Robbins, Jianfeng Feng, IMAGEN Consortium

Summary: Smoking initiation and maintenance during adolescence are associated with altered brain development, particularly in the ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV). Rule-breaking behavior mediates the association between smaller left vmPFC GMV and smoking behavior, while a reward-based mechanism involving right vmPFC GMV and sensation seeking is implicated in sustaining addictive behavior. These findings highlight the importance of vmPFC GMV as a possible biomarker for nicotine addiction prevention and treatment.

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