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.
Highlights
Cigarette smoking is the leading cause of preventable morbidity and premature mortality worldwide [1]
Among nicotine dependent individuals (NDs) compared to Controls, less gray matter volume (GMV) was observed in the thalamus, extending through to the medial orbitofrontal cortex, and bilateral cerebellum whereas greater GMV was observed in bilateral putamen and right parahippocampus
Given the impact that chronic cigarette smoking may have on brain structure, the first goal was to conduct a systematic GMV study in a large cohort of NDs compared to Controls using an advanced registration method that provides greater sensitivity than traditional Voxel-based morphometry (VBM)
Summary
Cigarette smoking is the leading cause of preventable morbidity and premature mortality worldwide [1]. Gallinat et al (2006) reported that greater number of pack-years were associated with less GMV in frontal and temporal lobes; whereas, Zhang et al (2011a) found an association between greater number of PLOS ONE | www.plosone.org pack-years and less GMV in the left prefrontal cortex, but only in high pack-year NDs [14]. These studies, and others, suggest structural abnormalities in ND that may be related to lifetime cigarette exposure and that additional study in larger cohorts is necessary
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