Despite reports of moderate phenotypic association between nicotine use and brain volume (Chen et al. 2006; Longstreth et al. 2000; Seshadri et al. 2004), our understanding of the extent to which any significant relationships are due to common genetic or environmental effects is limited. Cortical volume, a well-studied measure, is the product of cortical thickness and surface area. But, cortical surface area and cortical thickness quantify different aspects of structural development over the lifespan. Studies of inter-individual variation in adult brain size indicate that the majority of differences in cortical gray matter volume are due to differences in cortical surface area rather than cortical thickness (Pakkenberg and Gundersen 1997; Im et al. 2008). At the global level, there is no significant genetic covariance between surface area and thickness (Panizzon et al. 2009). Therefore, surface area and thickness are distinct features of cortical structure and should be examined separately in studies of associations between brain morphology and other phenotypes of interest. However, we are not aware of any studies that have investigated the relationship between nicotine use and these constituent dimensions.
