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Dear Pedro, > I am currently running a series of structural MRI analysis using a large sample of subjects with psychosis, and I found myself in trouble. > Do you think it is problematic to include several (three or four) nuisances at a two-group / full factorial analysis in SPM8? I don't think it is necessarily a problem to include multiple covariates in an analysis; however, there are two issues probably worth keeping in mind. One is that if these factors differ across groups, including them as covariates can be problematic. See e.g.: Miller GA, Chapman JP (2001) Misunderstanding analysis of covariance. Journal of Abnormal Psychology 110:40-48. The second is that the way in which global gray matter effects are accounted for influences how the results can be interpreted. We have a recent paper that addresses this issue in the context of normal aging, but it's applicable in other situations as well. Peelle JE, Cusack R, Henson RNA (2012) Adjusting for global effects in voxel-based morphometry: Gray matter decline in normal aging. NeuroImage 60:1503-1516. http://dx.doi.org/10.1016/j.neuroimage.2011.12.086 Hope this helps! Best regards, Jonathan -- Dr. Jonathan Peelle Department of Neurology University of Pennsylvania 3 West Gates 3400 Spruce Street Philadelphia, PA 19104 USA http://jonathanpeelle.net/